CHAPTER 13 DERMATOLOGICAL DRUGS

13.01 DRUGS FOR ECZEMA

Eczema
Eczema (dermatitis) includes a wide range of conditions characterised by skin inflammation.
Principal features include itch, redness, scaling and excoriations.
Eczema may be classified as endogenous or exogenous (which requires removal of precipitating factors).
The principles of management are generally the same irrespective of cause.
Rationale for drug use
Relieve symptoms.
Optimise skin hydration.
Suppress inflammation.
Prevent or eliminate infection.
Before starting treatment

Identify and eliminate potential trigger factors including:

·         environmental irritants, eg wool, synthetic clothing, soaps, detergents (including bubble bath), carpets, sand, grass, raised temperatures, sweating

·         environmental allergens, eg preservatives, fragrances, deodorants, lanolin, nickel, photosensitising drugs, animal hair, inhaled allergens.

A link between food allergens and eczema has not been confirmed. Exclusion diets are controversial and should only be considered after immunological assessment and advice from a dietitian.

 The role of house dust mites in eczema and other non-pulmonary conditions is unclear. There is evidence that control of house dust mite reduces severity of symptoms, especially in patients with positive mite RAST scores or skin prick testing, but only if very low levels of mite are achieved. Covering bedding is the most effective control method.
Time to resolution following removal of trigger depends on numerous factors and, while usually rapid, may take up to 3 weeks or more.
Treatment
Hydration: Use tepid rather than hot water, bath oil or colloidal oatmeal, and soap substitutes; if soaps are used they should have a neutral pH (mild soaps) and time spent bathing should be minimised to reduce resultant dehydration.
Soaking baths (containing bath oil or colloidal oatmeal) of 10–15 minutes duration may be taken once a day in the maintenance treatment of moderate-to-severe eczema and up to 4 times a day during disease flares to remove crusts and dry blisters.
Wet compresses: Wet compresses are usually soaked in tap water. Solutions of aluminium acetate (Burow's solution) or potassium permanganate (Condy's crystals) may be used, but are usually reserved for acute infected eczema. Immediately after hydration and applying emollient and/or topical corticosteroids, apply wet compresses for 15–60 minutes to increase the benefits of topical treatment. Reserve wet compresses for severely affected or persistent areas of eczema (exudative or crusting lesions); inappropriate use may lead to secondary infection (folliculitis), maceration or excessive dryness.
Moisturisers
Moisturisers may prevent exacerbation of eczema already under optimal control; apply liberally at least twice a day; most effective when applied after bathing (water content of skin is at its greatest).
Apply moisturisers 10–15 minutes before topical corticosteroids.
Creams and ointments are more effective than lotions; lotions may be substituted as condition improves. Lotions can be applied without friction and are more cosmetically acceptable.
Topical corticosteroids
Use corticosteroids where moisturisers do not provide adequate relief.
The patient's age, site of involvement and disease extent determine the type and strength of preparation and method of application; use the least potent preparation required to bring disease under control.
Topical immunomodulators
Pimecrolimus is marketed as an alternative to corticosteroids for short term or intermittent treatment of mild-to-moderate eczema. Data comparing pimecrolimus with mild or moderate potency corticosteroids in either children or adults are limited. Its place in therapy is presently unclear. It is best reserved for patients >2 years of age as there are some concerns about toxicity in infants.
Tacrolimus ointment is marketed overseas (as 0.03% and 0.1% ointment). Trial data indicate that it may be as effective as potent corticosteroids but it is expensive.
Tar and ichthammol
Have longer lasting anti-inflammatory properties and fewer adverse effects than topical corticosteroids, but are less potent and messier to use, leading to reduced compliance; should not be applied to acutely inflamed skin, face, flexures or genitals because of the potential for irritation; useful for chronic or lichenified lesions.
Antihistamines
Although commonly believed to have antipruritic effects, their therapeutic value is primarily due to their sedative properties; newer, less sedating antihistamines are of little value, unless allergic triggers are involved, eg house dust mite.
Sedating antihistamines are useful at night in patients having trouble getting to sleep or waking regularly because of excessive itching.
May be used as short term adjuvants to topical corticosteroid treatment.
Systemic immunomodulators
May be used for patients with severe, disabling disease unresponsive to other treatment; their use should be initiated and monitored by a dermatologist.
Systemic corticosteroids are useful in controlling widespread disease and severe generalised disease flares; they produce dramatic clinical improvement but may be associated with rebound flaring after stopping; they should be avoided in children, to reduce the risk of permanent growth retardation.
Cyclosporin may be used; azathioprine and other immunomodulating drugs have also been used.
Phototherapy
UVB phototherapy and photochemotherapy (methoxsalen and ultraviolet A irradiation, PUVA) are effective in unresponsive eczema, but there are concerns about long term safety.
Other treatment
Oral evening primrose oil has been claimed to be effective in atopic disease, but studies have shown no therapeutic benefit.
Herbal and complementary medicines have been used, but product quality may be variable; there are reports of hepatotoxicity and of potent corticosteroid contaminants.
Dietary manipulation, prolonged breastfeeding of predisposed infants and dietary restriction of breastfeeding mothers have unknown efficacy. Dietary restriction may lead to vitamin deficiency, particularly in children.
Special cases
Atopic dermatitis: Occurs in genetically predisposed individuals; diagnosed by the presence of atopy and the pattern and distribution of eczema. Generally managed by keeping skin hydrated and using topical therapy (especially moisturisers) for symptomatic relief.
Limit topical corticosteroid to sites of inflammation.
Nappy dermatitis: Advise parents to use highly absorbent disposable nappies, change nappies frequently, avoid use of plastic pants (because of occlusive effect) and maximise nappy free periods. Applying a protective agent (eg zinc or dimethicone cream) after each nappy change is also useful. Topical hydrocortisone can be used in more severe cases or when the above measures are inadequate.
Nappy dermatitis may be complicated by candidal infection. Treat such infections with a topical azole or nystatin and topical hydrocortisone.
Secondary infection: Treat according to the cause, whether bacterial (usually S. aureus), viral or fungal.
Seborrhoeic dermatitis in adults: Regular use of shampoo containing ketoconazole, miconazole, selenium sulfide, pyrithione zinc, ciclopirox or coal tar is the mainstay of treatment; can also be applied to eyebrows, ears, central face and trunk.
Coal tar preparations containing salicylic acid and/or sulfur may be used to reduce scale.
Topical corticosteroids may be used to reduce inflammation and itch, but should not be used long term. They may also be used intermittently in combination with a topical antifungal agent.

 

13.01.01 Corticosteroids (Skin)

BETAMETHASONE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Useful in a range of skin conditions including insect bite reactions, sunburn and as adjuncts to other treatments.
Indications
Inflammatory skin conditions, e.g. eczema, and psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate; ADEC category A.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
Relative potency, patient age, site and extent of disease, preparation type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia.
Infrequent: allergic contact dermatitis.
Rare: hyperaesthesia, subcutaneous tissue atrophy, systemic effects (hypothalamic-pituitary-adrenal axis suppression, hyperglycaemia, growth retardation, Cushing's syndrome, cataract).
Dosage
Apply sparingly 1–2 times a day.
Practice points

·         use an appropriately potent preparation for the shortest time required to control skin disorder then stop corticosteroid

·         therapy can be staged (eg remove precipitating factors and use a moisture care plan, then add topical corticosteroids, sedating antihistamines and tar, in order) with the aim of using the fewest number of treatments to control the disease

·         apply sparingly in thin layers by smoothing gently into skin, preferably after bathing

·         avoid tolerance by applying corticosteroid on alternate days or instituting medication-free periods (eg 5 days on then 2 days off) during treatment of chronic dermatoses

Nappy dermatitis

·         treat with a mild topical corticosteroid initially

·         advise parents to use highly absorbent disposable nappies and change nappy frequently; avoid plastic pants because of occlusive effect; nappy free periods should be maximised

·         use a protective agent (eg zinc cream)

·         often complicated by candidal infection (treat with a topical antifungal).

Products

BETAMETHASONE CREAM 0.1 % (AS VALERATE)   30 GM TUBE (BETAVAL®, BETNOVATE®, VALEDERM®)

BETAMETHASONE LOTION 0.1 % (AS VALERATE)   20 ML BOTTLE (BETNOVATE®)

BETAMETHASONE OINTMENT 0.1 % (AS VALERATE)   30 GM TUBE (BETAVAL®, BETNOVATE®)

BETAMETHASONE SCALP LOTION 0.1 % (AS VALERATE)   30 ML BOTTLE (BEMETSON®, BETNOVATE SCALP APPLICATION®)

 

CLOBETASOL (SKIN)

Mode of action

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin, while inflammation and/or other disease processes in the skin may increase percutaneous absorption. Greater absorption was observed for the clobetasol propionate gel formulation as compared to the cream formulation in in vitro human skin penetration studies.

Indications

Clobetasol is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use in children under 12 years of age is not recommended.

Contraindications

Clobetasol is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Specific considerations

General:  Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g per day.

Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.

Patients receiving a large dose applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, a.m. plasma cortisol, and urinary free cortisol tests. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA suppression.

If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur that require supplemental systemic corticosteroids.

Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios.

If irritation develops, Clobetasol should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Clobetasol should be discontinued until the infection has been adequately controlled.

Clobetasol should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Lactation: Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clobetasol is administered to a nursing woman.

Children: Safety and effectiveness of Clobetasol in children and infants have not been established; therefore, use in children under 12 years of age is not recommended. Because of a higher ratio of skin surface area to body mass, children are at a greater risk than adults of HPA axis suppression when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing's syndrome while on treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Adverse effects

In a controlled trial with Clobetasol, the only reported adverse reaction that was considered to be drug related was a report of burning sensation (1.8% of treated patients).

In larger controlled clinical trials with other clobetasol propionate formulations, the most frequently reported adverse reactions have included burning, stinging, irritation, pruritus, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, skin atrophy, and telangiectasia (all less than 2%).

Cushing's syndrome has been reported in infants and adults as a result of prolonged use of topical clobetasol propionate formulations.

Clobetasol is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks, and amounts greater than 50 g per week should not be used.

As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Clobetasol should not be used with occlusive dressings.

Products

CLOBETASOL BUTYRATE CREAM 0.05 %   25 GM TUBE (EUMOVATE®)

CLOBETASOL BUTYRATE OINTMENT 0.05 %    25 GM TUBE (EUMOVATE®)

CLOBETASOL PROPIONATE CREAM 0.05 %   25 GM TUBE (CLODERM®, DELOR®, DERMOVATE®, MEDODERMONE®)

CLOBETASOL PROPIONATE OINTMENT 0.05 %   15-25 GM TUBE (CLODERM®, DELOR®, DERMOVATE®, MEDODERMONE®)

 

DEXAMETHASONE (SKIN)

Adverse Effects, Treatment, Withdrawal, and Precautions

As for corticosteroids in general

When applied topically, particularly to large areas, when the skin is broken, or under occlusive dressings, or when given intranasally, corticosteroids may be absorbed in sufficient amounts to cause systemic effects. Prolonged application to the eye of preparations containing corticosteroids has caused raised intra-ocular pressure and reduced visual function.

Products

DEXAMETHASONE 0.12 % + SALICYLIC ACID 2 % SCALP LOTION   30 ML BOTTLE (DEXASALYL®,  SALIDEX®)

DEXAMETHASONE 0.12 % + SALICYLIC ACID 3 % OINTMENT    20 GM TUBE (DEXASALYL®)

 

FLUOCINOLONE ACETONIDE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Indications
Inflammatory skin conditions, eg eczema, psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate; ADEC category A.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
spread and worsening of untreated infection; thinning of the skin which may be restored over a period after stopping treatment but the original structure may never return; irreversible striae atrophicae and telangiectasia; contact dermatitis; perioral dermatitis; acne, or worsening of acne or rosacea; mild depigmentation which may be reversible; hypertrichosis also reported.

Dosage
Apply sparingly 1–2 times a day.
Practice points

·         use an appropriately potent preparation for the shortest time required to control skin disorder then stop corticosteroid

·         therapy can be staged (eg remove precipitating factors and use a moisture care plan, then add topical corticosteroids, sedating antihistamines and tar, in order) with the aim of using the fewest number of treatments to control the disease

·         apply sparingly in thin layers by smoothing gently into skin, preferably after bathing

·         avoid tolerance by applying corticosteroid on alternate days or instituting medication-free periods (eg 5 days on then 2 days off) during treatment of chronic dermatoses

Nappy dermatitis

·         treat with a mild topical corticosteroid initially

·         advise parents to use highly absorbent disposable nappies and change nappy frequently; avoid plastic pants because of occlusive effect; nappy free periods should be maximised

·         use a protective agent (eg zinc cream)

·         often complicated by candidal infection (treat with a topical antifungal).

Products

FLUOCINOLONE ACETONIDE CREAM OR OINTMENT 0.025% (15-30)GM (PETRALAR®, SYNALAR®)

 

HYDROCORTISONE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Useful in a range of skin conditions including insect bite reactions, sunburn and as adjuncts to other treatments.
Indications
Inflammatory skin conditions, e.g. eczema, psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate; ADEC category A.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
Relative potency, patient age, site and extent of disease, preparation type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia.
Infrequent: allergic contact dermatitis.
Rare: hyperaesthesia, subcutaneous tissue atrophy, systemic effects (hypothalamic-pituitary-adrenal axis suppression, hyperglycaemia, growth retardation, Cushing's syndrome, cataract).
Dosage
Apply sparingly 1–2 times a day.
Practice points

Same as fluocinolone

 

Products

HYDROCORTISONE ACETATE CREAM 1 % (ALFACORT®, HYDROCORT®)

HYDROCORTISONE ACETATE OINTMENT 1 % (ALFACORT®)

HYDROCORTISONE BUTYRATE CREAM 0.1 % (LOCOID LIPO®, ZONA®)

HYDROCORTISONE BUTYRATE SKIN LOTION 0.1 %   100 ML BOTTLE (LOCOID LIPO®)

 

METHYLPREDNISOLONE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Useful in a range of skin conditions including insect bite reactions, sunburn and as adjuncts to other treatments.
Indications
Inflammatory skin conditions, e.g. eczema, psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate; ADEC category A.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
Relative potency, patient age, site and extent of disease, preparation type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia.
Infrequent: allergic contact dermatitis.
Rare: hyperaesthesia, subcutaneous tissue atrophy, systemic effects (hypothalamic-pituitary-adrenal axis suppression, hyperglycaemia, growth retardation, Cushing's syndrome, cataract).
Dosage
Apply sparingly once a day.
Practice points

·         use an appropriately potent preparation for the shortest time required to control skin disorder then stop corticosteroid

·         therapy can be staged (eg remove precipitating factors and use a moisture care plan, then add topical corticosteroids, sedating antihistamines and tar, in order) with the aim of using the fewest number of treatments to control the disease

·         apply sparingly in thin layers by smoothing gently into skin, preferably after bathing

·         avoid tolerance by applying corticosteroid on alternate days or instituting medication-free periods (eg 5 days on then 2 days off) during treatment of chronic dermatoses

Products

METHYLPREDNISOLON CREAM 1 % (AS OXYPONATE)   20 GM TUBE (ADVANTAN®)

METHYLPREDNISOLON OINTMENT 1 % (AS OXYPONATE)   20 GM TUBE (ADVANTAN®)

 

MOMETASONE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Useful in a range of skin conditions including insect bite reactions, sunburn and as adjuncts to other treatments.
Indications
Inflammatory skin conditions, eg eczema, psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate. Safety data are lacking; ADEC category B3.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
Relative potency, patient age, site and extent of disease, preparation type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia.
Infrequent: allergic contact dermatitis.
Rare: hyperaesthesia, subcutaneous tissue atrophy, systemic effects (hypothalamic-pituitary-adrenal axis suppression, hyperglycaemia, growth retardation, Cushing's syndrome, cataract).
Dosage
Apply sparingly once a day.
Practice points

·         use an appropriately potent preparation for the shortest time required to control skin disorder then stop corticosteroid

·         therapy can be staged (eg remove precipitating factors and use a moisture care plan, then add topical corticosteroids, sedating antihistamines and tar, in order) with the aim of using the fewest number of treatments to control the disease

·         apply sparingly in thin layers by smoothing gently into skin, preferably after bathing

·         avoid tolerance by applying corticosteroid on alternate days or instituting medication-free periods (eg 5 days on then 2 days off) during treatment of chronic dermatoses

Products

MOMETASONE CREAM 0.1 % 15-30 GM TUBE (ELICA®, ELISONE®, ELNA®, ELOCOM®, MESONE®)

MOMETASONE OINTMENT 0.1 % 15-30 GM TUBE (ELICA®, ELOCOM®, MESONE®)

 

TRIAMCINOLONE (SKIN)

Mode of action
Anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells.
They also cause vasoconstriction which has been used to measure their potency.
Useful in a range of skin conditions including insect bite reactions, sunburn and as adjuncts to other treatments.
Indications
Inflammatory skin conditions, e.g. eczema, psoriasis.
Contraindications
Rosacea; Acne vulgaris; Allergy to corticosteroids or preservatives in vehicle; Ulcerative conditions and/or impaired circulation; Uncontrolled infection in area to be treated.
Specific considerations
Pregnancy: Use the lowest potency for the shortest time necessary where emollients and other simple measures are inadequate; ADEC category A.
Skin atrophy: increases systemic absorption and skin atrophy; avoid use.
Diabetes: systemic absorption increases blood glucose; avoid extensive use.
Impaired T cell function: systemic absorption results in immunosuppression; avoid extensive use.
Elderly: Skin atrophy makes cutaneous adverse effects more likely.
Children: More susceptible to systemic absorption due to higher surface area/bodyweight ratio.
Hydrocortisone is adequate initial treatment for most children with mild-to-moderate disease. Use stronger preparations for short periods under close supervision.
Consider a corticosteroid-free period of at least 2 weeks after each 2–3 week period of daily use.
Lactation: Safe to use; ensure breast area is free of corticosteroid before nursing.
Adverse effects
Relative potency, patient age, site and extent of disease, preparation type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia.
Infrequent: allergic contact dermatitis.
Rare: hyperaesthesia, subcutaneous tissue atrophy, systemic effects (hypothalamic-pituitary-adrenal axis suppression, hyperglycaemia, growth retardation, Cushing's syndrome, cataract).
Dosage
Apply sparingly 1–2 times day.
Practice points

Same as betamethasone.

Products

TRIAMCINOLONE OINTMENT 0.1 % (KENACIN A®)

 

13.01.02 Coal Tar (Skin)

COAL TAR (SKIN)

Mode of action
Exact mechanism unknown. Tars suppress DNA synthesis, reduce epidermal thickness, are antipruritic and may be weakly antiseptic.
Indications
Eczema, particularly chronic or lichenified eczema; Seborrhoeic dermatitis; Stable chronic plaque psoriasis; Dandruff.

Contraindications
Inflamed, broken skin; Infection; Previous allergic reaction to coal tar; Conditions characterised by photosensitivity, e.g. lupus erythematosus, polymorphic light eruption (coal tars contraindicated because of photosensitising action); Unstable psoriasis.
Specific considerations
Treatment with photosensitising medications: increases risk of phototoxic reactions; avoid combinations.
Children: Safety and efficacy of coal tar preparations have not been established. Should not be used in children <2 years, except under the direction and supervision of a dermatologist.
Pregnancy: Data lacking, unlikely to be a concern.
Lactation: Safe to use.
Adverse effects
Common: mild stinging.
Rare: folliculitis, irritant reactions, allergic reactions, photosensitivity, acneiform eruptions.
Others: staining of skin, hair (especially in patients with fair, bleached or grey hair) and clothing
Carcinogenicity: Conflicting evidence.
Dosage
Shampoo, once a week to once a day.
Cream, lotion, 2–4 times a day.
Gel, 2–4 times a day.
Medicated bar, use as soap.
Dose equivalence
Extemporaneous products, 1% crude coal tar is
equivalent to 5% coal tar solution.
Administration instructions
Shampoo, apply to wet hair, massage vigorously into scalp and leave for 3–5 minutes; rinse thoroughly; repeat application and rinse.
Cream, gel, apply enough to cover affected area and rub in gently.
Patient counselling
Do not use near eyes.
May stain skin, hair and clothes.
Avoid exposure to direct sunlight or sunlamps for at least 24 hours after application. Completely remove coal tar preparations before exposure to sunlight.
Practice points

·         may be used alone in treatment of psoriasis, or combined with dithranol and/or ultraviolet light

·         use low concentrations (0.5–1%) on face, flexures and genitals to reduce potential for irritation

·         patient acceptance may be poor due to the messiness, smell and staining properties of some preparations

·         salicylic acid, sulfur and allantoin have keratolytic properties and may be used in combination with coal tar in the treatment of psoriasis, seborrhoeic dermatitis and dandruff

·         pyrithione zinc has bacteriostatic and fungistatic properties and is available with coal tar for the treatment of seborrhoeic dermatitis and dandruff

Products

COAL TAR SHAMPOO®

 

13.01.03 Other Drugs for Eczema

 

DIMETINDENE (SKIN)

Dimetindene maleate, an alkylamine derivative, is a sedating antihistamine; it is mildly sedative and is reported to have mast-cell stabilising properties. It is used for the s relief of allergic conditions including urticaria, and in pruritic skin disorders.

Products

DIMETINDENE GEL 1 %   30 GM TUBE (FENISTIL®)

 
PIMECROLIMUS (SKIN)

Mode of action
Anti-inflammatory, but precise mechanism unknown.
Inhibits calcineurin thus blocking T-cell activation, prevents release of inflammatory mediators from mast cells.
Indications
Short term treatment of active mild-to-moderate eczema in children >3 months and adults.

Contraindications
Cutaneous viral infection.

Specific considerations
Immunosuppression, skin cancer: avoid use, theoretical risk of toxicity.
Bacterial or fungal skin infections: treat area before starting pimecrolimus.
Pregnancy: Limited data; ADEC category B3.
Lactation: No data, seek specialist advice.
Adverse effects
Common: local irritation, burning sensation, itch, erythema, skin infections.
Infrequent: local rash, aggravation of eczema, herpes simplex dermatitis, impetigo.
Dosage
Apply twice a day in a thin film to affected areas.
Administration instructions
Apply to clean, dry skin.
Patient counselling
Avoid contact with eyes, mouth and other mucous surfaces.

Avoid exposure to sun, use an effective sunscreen.
Practice points

·         due to concerns about possible increased incidence of adverse effects (upper respiratory tract infections, otitis media, diarrhoea, asthma, irritability), pimecrolimus is not approved for use in children <2 years in the USA or the UK

·         stop treatment if condition deteriorates or there is no noticeable improvement after 6 weeks

·         if irritation occurs, apply less frequently; if it persists or is severe, stop treatment

·         data comparing pimecrolimus with topical corticosteroids is limited; it is much more expensive than topical corticosteroid treatment and benefit over such agents has not been confirmed

·         safety of long term use has not been clearly established

Products

PIMECROLIMUS CREAM 1 %   30 GM TUBE (ELIDEL®)

 

TACROLIMUS

Mode of Action

The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This effect has been shown to prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-(alpha), all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of Fc[egr ]Rl on Langerhans cells.

Indication and usage

Tacrolimus Ointment 0.1% for adults, is indicated for short-term and intermittent long-term therapy in the treatment of patients with moderate to severe atopic dermatitis in whom the use of alternative, conventional therapies are deemed inadvisable because of potential risks, or in the treatment of patients who are not adequately responsive to or are intolerant of alternative, conventional therapies.

Contraindications

Contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the preparation.

Precautions

General

Studies have not evaluated the safety and efficacy in the treatment of clinically infected atopic dermatitis. Before commencing treatment, clinical infections at treatment sites should be cleared.

While patients with atopic dermatitis are predisposed to superficial skin infections including eczema herpeticum (Kaposi's varicelliform eruption), treatment may be associated with an increased risk of varicella zoster virus infection (chicken pox or shingles), herpes simplex virus infection, or eczema herpeticum. In the presence of these infections, the balance of risks and benefits associated with Tacrolimus Ointment use should be evaluated.

In clinical studies, 33 cases of lymphadenopathy (0.8%) were reported and were usually related to infections (particularly of the skin) and noted to resolve upon appropriate antibiotic therapy. Of these 33 cases, the majority had either a clear etiology or were known to resolve. Transplant patients receiving immunosuppressive regimens (e.g., systemic tacrolimus) are at increased risk for developing lymphoma; therefore, patients who develop lymphadenopathy should have the etiology of their lymphadenopathy investigated. In the absence of a clear etiology for the lymphadenopathy, or in the presence of acute infectious mononucleosis, discontinuation should be considered. Patients who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.

The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. Despite the absence of observed phototoxicity in humans, Tacrolimus Ointment shortened the time to skin tumor formation in an animal photocarcinogenicity study. Therefore, it is prudent for patients to minimize or avoid natural or artificial sunlight exposure.

The use of Tacrolimus Ointment may cause local symptoms such as skin burning (burning sensation, stinging, soreness) or pruritus. Localized symptoms are most common during the first few days of application and typically improve as the lesions of atopic dermatitis heal. With Tacrolimus Ointment 0.1%, 90% of the skin burning events had a duration between 2 minutes and 3 hours (median 15 minutes). Ninety percent of the pruritus events had a duration between 3 minutes and 10 hours (median 20 minutes).

Patients counseling
Patients using Tacrolimus Ointment should receive the following information and instructions:

Patients should use Tacrolimus Ointment as directed by the physician.

As with any topical medication, patients or caregivers should wash hands after application if hands are not an area for treatment.

Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using Tacrolimus Ointment.

Patients should not use this medication for any disorder other than that for which it was prescribed.

Patients should report any signs of adverse reactions to their physician.

Pregnancy:

Teratogenic Effects: Pregnancy Category C

Pediatric Use: Tacrolimus Ointment 0.03% may be used in pediatric patients 2 years of age and older. Two phase 3 pediatric studies were conducted involving 606 patients 2-15 years of age: one 12-week randomized vehicle-controlled study and one open-label, 1 year, long-term safety study. Three hundred and thirty (330) of these patients were 2 to 6 years of age.

Geriatric Use: Twenty-five (25) patients >/= 65 years old received Tacrolimus Ointment in phase 3 studies. The adverse event profile for these patients was consistent with that for other adult patients.

Adverse effects

No phototoxicity and no photoallergenicity was detected in clinical studies of 12 and 216 normal volunteers, respectively. One out of 198 normal volunteers showed evidence of sensitization in a contact sensitization study.

In three randomized vehicle-controlled studies and two long-term safety studies, 655 and 571 patients respectively, were treated with Tacrolimus Ointment.

The following table depicts the adjusted incidence of adverse events pooled across the 3 identically designed 12 week studies for patients in vehicle, Tacrolimus Ointment 0.03%, and Tacrolimus Ointment 0.1% treatment groups, and the unadjusted incidence of adverse events in two one year long-term safety studies, regardless of relationship to study drug.

Dosage and administration

Adults: Apply a thin layer to the affected skin areas twice daily and rub in gently and completely. Treatment should be continued for one week after clearing of signs and symptoms of atopic dermatitis.

Pediatric: Apply a thin layer of Tacrolimus Ointment 0.03% to the affected skin areas twice daily and rub in gently and completely. Treatment should be continued for one week after clearing of signs and symptoms of atopic dermatitis.

Products

TACROLIMUS OINTMENT 0.1 % (PROTOPEC®)

TACROLIMUS OINTMENT 0.03 % (PROTOPEC®)

13.02 DRUGS FOR ACNE

Acne
Acne vulgaris is a common skin disease caused by increased sebum production, abnormal follicular keratinization, proliferation of Propionibacterium acnes and inflammation. Management is directed at these factors.
Mild acne is characterised by comedones with some papules and pustules. In moderate acne, the papules and pustules are more widespread and there may be mild scarring.
Severe acne is characterised by nodular abscesses and cysts in addition to widespread papules and pustules and may lead to extensive scarring.
Rationale for drug use
Improve complexion, reduce the number of lesions.
Prevent scarring.
Limit disease duration.
Reduce psychological stress (depression and low self esteem) related to acne.
Before starting treatment
Hormonal evaluation is indicated if hirsutism, alopecia or menstrual irregularities are present.
When to start treatment
Start early to prevent scarring; tailor treatment according to severity.

Choice of topical treatment
Retinoids, benzoyl peroxide or azelaic acid are used as first line treatments in mild acne and with oral antibacterials in moderate acne. Apply to entire affected area and not just to individual lesions.
Retinoids
Tretinoin, adapalene or isotretinoin (skin) are the treatment of choice for comedonal acne. May be used with other topical and oral (antibacterial or hormonal) treatments. Irritation may increase with use of >1 topical treatment. Do not use during pregnancy because of potential risk of teratogenicity.
Benzoyl peroxide and azelaic acid
Benzoyl peroxide has antibacterial activity and is mildly comedolytic; first line treatment in comedonal and mild inflammatory acne. May be used with topical or oral antibacterials; can be used on alternate days with topical retinoids; some patients can tolerate same day applications of benzoyl peroxide and a topical retinoid.
Azelaic acid has antibacterial activity and is comedolytic; it is a less irritating alternative to benzoyl peroxide in mild inflammatory acne. Should be used cautiously in patients with dark complexions (may cause hypopigmentation). Hypopigmentation effects may be useful if acne has caused hyperpigmented scars.
Antibacterials
Clindamycin and erythromycin (skin) may also have indirect effects on comedogenesis; clinical efficacy is similar. Development of antibacterial resistance by skin flora is an increasing problem. Add to topical retinoid, benzoyl peroxide or azelaic acid in mild acne after 6–8 weeks if there is inadequate response.
Choice of oral treatment
Includes antibacterials, hormonal treatments and isotretinoin.

Antibacterials
Are useful in treatment of moderate acne; doxycycline and tetracycline are the drugs of choice. Minocycline, although widely used, is less well tolerated and has been associated more commonly with CNS adverse effects, including benign intracranial hypertension; may also cause hepatitis, a lupus-like syndrome and altered skin pigmentation. Erythromycin may be used if tetracyclines are not tolerated or are contraindicated.
Antibacterials may be used with topical agents. Improvement may not begin until after 4–8 weeks of treatment. Treatment should be changed if there is no response after 3 months. They must be taken for at least 3–6 months to obtain a good response; in some patients longer term treatment may be necessary.
Hormonal treatments
Are limited to treatment of acne in females; they reduce sebum secretion which is under androgen control. Several months of treatment are usually required before benefit occurs; prolonged treatment is needed to maintain improvement.
Oestrogens suppress ovarian androgen production; usually prescribed as combined oral contraceptive (COC). Beneficial effect is most apparent at doses of 50 micrograms or more of ethinyloestradiol (or equivalent), but even a low dose COC (particularly one that contains a less androgenic progestogen, such as desogestrel) may be effective. Consider adding to topical retinoid, benzoyl peroxide or azelaic acid in moderate acne either in addition to, or instead of, an oral antibacterial.
Cyproterone is an antiandrogen and is used with ethinyloestradiol for the control of severe acne refractory to prolonged oral antibacterial treatment, see Cyproterone with ethinyloestradiol. Higher doses of cyproterone are occasionally recommended by specialists, particularly if seborrhoea or hirsutism are also present.
Spironolactone has potent antiandrogen activity and has been used by specialists to treat severe acne.
Isotretinoin

Acts primarily by reducing sebum secretion; used in severe acne or in moderate acne unresponsive to conventional treatment.

Known teratogen; pregnancy and blood donation should be avoided during treatment and for at least 1 month after stopping treatment.
Other drug treatments
Include abrasive agents, eg aluminium oxide; degreasing agents, eg triclosan; and preparations containing sulfur, salicylic acid, resorcinol and allantoin. Although widely used, effectiveness is questionable.
Exfoliants may limit tolerance to other more effective agents and have no effect on sebaceous gland activity.
Special cases
Acne conglobata, acne fulminans and pyoderma faciale are severe forms of inflammatory acne that require urgent specialist referral for treatment with isotretinoin and oral corticosteroids.
Patient counselling
Wash affected areas gently; avoid vigorous scrubbing and abrasive cleansers, which may cause more inflammation and make acne worse.
Avoid using toners and oil-based moisturisers.
Do not squeeze or pick the acne lesions (pimples).
Eat a healthy balanced diet; there is no relationship between particular foods and acne.
Practice points

·         consider using 2 or 3 agents that act in different ways

·         avoid systemic antibiotics if a topical medication will suffice

·         do not switch or rotate antibiotics in patients who are responding to therapy (response indicates efficacy and changing antibiotics may promote resistance)

 

13.02.01 Keratolytics

BENZOYL PEROXIDE

Mode of action
Antibacterial action probably due to oxidising effect; mild keratolytic properties.

Indications
Acne vulgaris.

Contraindications
Allergy to benzoyl peroxide.

Specific considerations
Inflamed or broken skin: increases systemic absorption.
Children: Safety and efficacy are not established in children, but problems are not expected.
Pregnancy: Safe to use.
Lactation: Safe to use.
Adverse effects
Common: skin dryness or peeling, feeling of warmth, mild stinging or erythema.
Rare: allergic contact dermatitis.
Dosage
Apply once or twice a day; begin treatment with 2.5% or 5% product, then change to 10% strength after 3–4 weeks, or sooner if tolerance to the lower strengths develops.
Administration instructions
Before applying, wash affected area with mild soap or soap substitute and warm water; gently pat dry. Apply enough medication to cover affected area and rub in gently.
Patient counselling
Avoid contact with eyes, mouth and other mucous membranes.

Avoid contact with hair and coloured fabric as bleaching or discolouration may result.
Practice points

·         cumulative irritant or drying effects with other topical anti-acne preparations; combinations may be used if tolerated by patient

·         benzoyl peroxide inactivates topical tretinoin; apply 12–24 hours apart

·         effective first line treatment for mild acne when used alone; may be used on alternate days with topical retinoids and with topical or oral antibacterials in more severe acne; however, irritation may be a problem with such combinations

·         if irritation occurs, apply less frequently or use a lower strength preparation; if it persists, is severe or is thought to be due to allergy, stop treatment

Products

BENZOYL PEROXIDE GEL 5 %   40-60 GM TUBE (BENZAC®, BENOXYPHIL®, PANOXYL®)

 

13.02.02 Antibacterials

CLINDAMYCIN (SKIN)
Mode of action
Lincosamide antibacterial; inhibits growth of Propionibacterium acnes.
Indications
Acne vulgaris, mild-to-moderate.

Specific considerations
History of antibacterial-associated colitis, regional enteritis or ulcerative colitis: small risk of systemic adverse effects, eg colitis, following topical application.
Pregnancy: Safe to use; ADEC category A.
Lactation:Safe to use; low topical absorption.
Drug interactions
See Clindamycin.

Adverse effects
Common:dry, scaly or peeling skin.
Infrequent:contact dermatitis.
Rare: pseudomembranous colitis.
Dosage
Apply twice a day. Application to the entire face is equivalent to approximately 2 mL of liquid or lotion.
Administration instructions
Before applying, wash affected areas with mild soap or soap substitute and warm water; rinse and pat dry.
Patient counselling
Do not use near heat, open flame or if smoking (products contain alcohol).
Avoid contact with eyes, mouth and other mucous membranes.
Stop use and tell your doctor if GI symptoms such as diarrhoea occur.
Practice points

·         noticeable improvement is usually seen after about 6 weeks in most patients; however, 8–12 weeks of treatment may be required before maximum benefit is seen

·         avoid combination with topical erythromycin preparation (antagonistic mode of action)

·         cumulative irritant or drying effects may occur if used with other topical anti-acne preparations; combinations may be used if tolerated by patient

Products

CLINDAMYCIN SOLUTION 1 % 30 ML BOTTLE (CLINADERM®, CLINDOX®, CLINDACIN-T®, DALACIN-T®, DERMOVATE®, LINDASOL®)


ERYTHROMYCIN (SKIN)

Mode of action
Macrolide antibacterial; inhibits growth of Propionibacterium acnes.
Indications
Marketed: Acne vulgaris, mild-to-moderate.
Accepted: Minor bacterial skin infections.
Specific considerations
Pregnancy: Safe to use; ADEC category A.
Lactation: Safe to use.
Adverse effects
Common: dry or scaly skin, itch, stinging or burning feeling.
Infrequent: desquamation, erythema.
Dosage
Apply twice a day in a thin film to affected areas.
Administration instructions
Before application, wash affected area with a mild soap or soap substitute and warm water; rinse thoroughly and pat dry.
Patient counselling
Avoid contact with eyes, mouth and other mucous surfaces.

Do not use near heat or open flame or if smoking (contains alcohol).
Practice points

·         noticeable improvement may be seen in 3–4 weeks; however, 8–12 weeks of treatment may be required before maximum benefit is seen

·         if irritation occurs, apply less frequently; if it persists or is severe, stop treatment

·         combination treatment with benzoyl peroxide and topical erythromycin may prevent resistance; use with caution due to cumulative irritant effects

·         avoid combination with topical clindamycin preparation (antagonistic mode of action)

·         cumulative irritant or drying effects may occur if used with other topical anti-acne preparations; combinations may be used if tolerated by patient

Products

ERYTHROMYCIN LOTION 40 MG/ML + ZINC ACETATE 12 MG/ML 30 GM BOTTLE (ZINYRET®)

ERYTHROMYCIN SOLUTION 2 %   25 ML BOTTLE (AKNE-MYCIN®, PHILAMYCIN®, STIEMYCIN®)

 

13.02.03 Retinoids (Oral)

ACITRETIN (ORAL)

Mode of action
Reverses the epidermal proliferation and increased keratinization seen in hyperkeratotic disorders.
Indications
Psoriasis, severe; Keratinization disorders, severe.

Contraindications
Pregnancy; Breastfeeding; Hepatic impairment.

Specific considerations
Renal impairment: Avoid in endstage renal disease; use lower doses in patients with renal impairment.
Children: Because of the unknown effects of acitretin on growth and skeletal development and the risk of premature epiphyseal closure, acitretin should be used in people <18 years only in:

life-threatening circumstances where other treatment cannot be used or is ineffective (eg widespread pustular psoriasis), severe disorders for which there is no alternative treatment.

Growth parameters and bone development must be closely monitored by regular measurement and x-ray in all children on long term treatment.
Pregnancy: Contraindicated; ADEC category X.
Acitretin is the active metabolite of etretinate which has been reported to cause major human fetal abnormalities if administered during pregnancy. Acitretin may also be converted to etretinate in the body. Alcohol intake may increase this conversion.
Breastfeeding: Contraindicated.
Hyperlipidaemia, obesity, excessive alcohol intake, diabetes: oral retinoids are associated with increased risk of hypertriglyceridaemia and cardiovascular disease; avoid use or monitor carefully because of further risk of triglyceride elevation.
Women of child-bearing age

Treatment with tetracyclines: increases risk of benign intracranial hypertension; avoid combination (contraindicated by manufacturer).
Treatment with topical retinoids: increases risk of adverse effects; avoid combination.
Treatment with photosensitising medications: increases risk of phototoxic reactions; avoid combination.
Elderly: Arthralgias are more common; monitor carefully.
Children: Risk of premature epiphyseal closure; seek specialist advice.
Pregnancy: The elimination half-life for isotretinoin is 20 hours and for acitretin, 50 hours. However, due to possible conversion of acitretin to etretinate, which has an elimination half-life of 120 days or more, the recommended contraception period is significantly longer with acitretin.
Breastfeeding: Contraindicated.
Adverse effects
Common: nail fragility, sticky skin, taste disturbance, blurred vision and impaired night vision.
Infrequent: vertigo, somnolence.
Rare: granulomatous lesions, bullous eruptions
Most patients experience adverse effects which generally resemble excess vitamin A intake.
Dosage
Adult
Initially, 25–30 mg once a day for 2–4 weeks.
Maintenance, based on clinical efficacy and tolerance; generally 25–50 mg once a day for a further 6–8 weeks. Longer courses using lower doses have been used.
Treatment may be stopped if lesions have resolved sufficiently.
Child: 0.5–1 mg/kg daily; maximum daily dose 35 mg.
Patient counselling
Do not donate blood during, and for at least 2 years after, treatment.
Female patients, it is important that you use adequate contraception before, during and for 2 years after, treatment, because birth defects have occurred during this time.
Avoid alcohol during, and for 2 months after, treatment.
Psoriasis, sometimes psoriasis becomes worse for a short time after starting treatment.
Practice points

·         confirm a negative pregnancy test in the 2 weeks before starting treatment, then start on the second or third day of the next normal menstrual period

·         ensure effective contraception before, during and after treatment; an oestrogen–progestogen combined pill is the contraceptive method of choice; another method of contraception may be used as well, eg condoms or diaphragm, to minimise pregnancy risk

·         complete blood count, biochemical profile, liver function and fasting blood lipids should be measured at baseline, after the first month of treatment and then as required

·         blood glucose should be monitored throughout treatment in patients who either have, or are predisposed to, type 1 diabetes

·         consider radiological evaluation for skeletal hyperostosis in patients receiving long term treatment (>1 year)

 Products

ACITRETIN CAPS 10 MG (NEOTIGASON®)

ACITRETIN CAPS 25 MG (NEOTIGASON®)

 

ISOTRETINOIN (ORAL)

Mode of action
Modulates cell proliferation and differentiation.
Reduces sebum excretion, Propionibacterium acnes numbers, inflammation and cyst formation.
Indications
Marketed: Cystic acne, severe.
Accepted: Neoplastic disorders, e.g. squamous cell carcinoma; Disorders of keratinization.
Contraindications
Pregnancy; Lactation; Hepatic impairment.

Specific considerations
Pregnancy: Contraindicated; ADEC category X.
Lactation: Contraindicated.
Contraindicated.
Hyperlipidaemia, obesity, excessive alcohol intake, diabetes: oral retinoids are associated with increased risk of hypertriglyceridaemia and cardiovascular disease; avoid use or monitor carefully because of further risk of triglyceride elevation.
Women of child-bearing age.
Treatment with tetracyclines: increases risk of benign intracranial hypertension; avoid combination (contraindicated by manufacturer).
Treatment with topical retinoids: increases risk of adverse effects; avoid combination.
Treatment with photosensitising medications: increases risk of phototoxic reactions; avoid combination.
Elderly: Arthralgias are more common; monitor carefully.
Children: Risk of premature epiphyseal closure; seek specialist advice.
Pregnancy: ISOTRETINOIN is contraindicated; and is teratogenic; ADEC category X. Women should use effective contraceptive measures for 1 month before starting treatment, during treatment, for 1 month after stopping isotretinoin and for at least 2 years after stopping acitretin. Should women conceive during this period there is a high risk of birth defects.

Lactation: Contraindicated.
Adverse effects
Common: dryness of skin, lips and mucous membranes; cheilitis, mild acne flare, conjunctivitis and epistaxis, reduced tolerance to contact lenses, raised blood glucose (diabetics), photosensitivity.
Infrequent: depression, hair thinning, myalgias, arthralgias, fatigue, headache, severe acne flare, menstrual disturbances, raised liver enzymes.
Rare: corneal opacities, cataracts, papilloedema, decreased night vision, optic neuritis, benign intracranial hypertension, skeletal hyperostosis, inflammatory bowel disease, hepatitis
Hyperlipidaemia
Increases in serum triglycerides and total cholesterol and decreases in high density lipoproteins, may occur; these effects are dose-dependent, occur early during treatment and are usually reversible within a few weeks of stopping therapy.
Dosage
Initially, up to 0.5 mg/kg each day as a single dose or in 2 divided doses. Dosage may be increased to 1 mg/kg after 4 weeks according to response and tolerance.
Treatment should be continued until total cumulative dose is 100 mg/kg for moderate acne, or 150 mg/kg for severe acne. A treatment course is usually 4–6 months.
Patients with acne primarily on the body instead of the face may require a total cumulative dose of up to 150 mg/kg.
Patient counselling
Hair removal by waxing may tear your skin during, and for 2 months after stopping, treatment because of fragile skin.
Do not give blood during treatment or for 1 month after stopping treatment.
Use white soft paraffin, eg Vaseline®, to treat dry lips; use lubricating eye drops to treat eye irritation.
Tell your doctor if you are unable to manage dry skin, dry lips or dry eyes, or if during the initial treatment period your contact lenses become uncomfortable.
Report promptly any nausea, headaches or visual changes (including impaired night vision or blurring) to your doctor.
Tell your doctor if you notice a change in your moods.
Avoid taking vitamin A supplements.
Protect skin from sunlight with protective clothing or sunscreen. Broad spectrum sunscreen, at least factor 15+, and containing a physical barrier (eg titanium dioxide or zinc oxide) is recommended. Avoid sunlamps and tanning beds.
Do not share medication with others.
Practice points

·         a mild flare of acne commonly occurs after 2–4 weeks of treatment, but improves after 1–2 months of continued treatment; severe flares occur infrequently

·         most patients remain disease-free after a single course or have long remissions; approximately 10% of patients relapse; repeated courses of isotretinoin are not usually recommended unless recurrence is severe

·         allow at least 2 months after completing a course to see whether further treatment is necessary, as improvement may continue for several months after stopping

·         use of isotretinoin with antibacterials and antiandrogens does not markedly improve efficacy; if concomitant antibacterial treatment is contemplated, erythromycin is preferred, as use of isotretinoin with tetracyclines can increase the risk of benign intracranial hypertension

Products

ISOTRETINOIN CAPS 10 MG (ISOSUPRA®, ROACCUTANE®)

ISOTRETINOIN CAPS 20 MG (CURANCE®, ISOSUPRA®, ROACCUTANE®, RUATINE®)

 

13.02.04 Retinoids (Skin)

ADAPALENE

Mode of action
Modulate cell proliferation and differentiation; decrease new comedone formation and inflammatory lesions.
Indications
Acne vulgaris, especially early comedonal acne, although may be used adjunctively in the management of comedones associated with inflammatory acne.
Contraindications
Allergy to topical retinoids; Pregnancy; Sunburn; Unprotected sun exposure.
Specific considerations
Children: Contraindicated in neonates; may be used in young children with comedonal acne.
Eczema: severe irritation to eczematous skin may occur; use with caution.
Women of child-bearing age.
Treatment with oral retinoids: increases risk of adverse effects; avoid combination.
Treatment with photosensitising medications: increases risk of phototoxic reactions; avoid combination.
Pregnancy: Contraindicated. Although absorption via skin is minimal, in view of teratogenicity of systemic retinoids, topical retinoids should not be used in pregnancy. ADEC category D.
Lactation: No data available but unlikely to be a concern.
Adverse effects
Common: erythema, peeling, irritation.
Infrequent: pigmentation changes, photoirritation.
Rare: allergic contact dermatitis.
Dosage
Apply once a day at bedtime.
Patient counselling
Before applying, wash with mild soap or soap substitute and warm water; rinse and gently pat dry; wait 20–30 minutes for complete drying of skin to occur. Apply enough to cover affected areas and rub in gently.
Do not apply to eyes, lips or in nostrils.
Protect treated areas from sunlight with protective clothing or sunscreen. Use broad spectrum sunscreen, at least factor 15+ (30+ is preferable), containing a physical agent (eg titanium dioxide). Avoid sunlamps and tanning beds.
Cosmetics may be used but skin must be washed thoroughly before applying medication.
Practice points

·         cumulative irritant or drying effects may occur with other topical anti-acne preparations; combinations may be used if tolerated by patient

·         confirm a negative pregnancy test in the 2 weeks before starting treatment, then start treatment on the second or third day of the next normal menstrual period

·         during early weeks of treatment, an apparent flare of acne may occur; this is due to actions on deep lesions and is not a reason to stop treatment; benefit does not generally become evident for some weeks or even months

·         if patients have been using keratolytics, allow sufficient time for their effects to subside before initiating treatment with topical retinoids

·         adverse effects may decrease with time and can be minimised by using a moisturiser

·         excessive application does not increase therapeutic effect and may produce marked inflammation

·         if severe erythema, oedema, blistering or crusting occurs, apply less frequently or stop until skin integrity is restored

Products

ADAPALENE GEL 0.1 %   30 GM (DIFFERIN GEL®)

 

ISOTRETINOIN (SKIN)

Mode of action
Modulate cell proliferation and differentiation; decrease new comedone formation and inflammatory lesions.
Indications
Acne vulgaris, especially comedonal acne, although may be used adjunctively in the management of comedones associated with inflammatory acne.
Contraindications
Allergy to topical retinoids; Pregnancy; Sunburn; Unprotected sun exposure.
Specific considerations
Children: Contraindicated in neonates; may be used in young children with comedonal acne.
Eczema: severe irritation to eczematous skin may occur; use with caution.
Women of child-bearing age.
Treatment with oral retinoids: increases risk of adverse effects; avoid combination.
Treatment with photosensitizing medications: increases risk of phototoxic reactions; avoid combination.
Pregnancy: Contraindicated. Although absorption via skin is minimal, in view of teratogenicity of systemic retinoids, topical retinoids should not be used in pregnancy. ADEC category D.
Lactation: No data available but unlikely to be a concern.
Adverse effects
Common: erythema, peeling, irritation.
Infrequent: pigmentation changes, photoirritation.
Rare: allergic contact dermatitis.
Dosage
Apply once a day at bedtime.
Patient counselling
Before applying, wash with mild soap or soap substitute and warm water; rinse and gently pat dry; wait 20–30 minutes for complete drying of skin to occur. Apply enough to cover affected areas and rub in gently.
Do not apply to eyes, lips or in nostrils.
Protect treated areas from sunlight with protective clothing or sunscreen. Use broad spectrum sunscreen, at least factor 15+ (30+ is preferable), containing a physical agent (eg titanium dioxide). Avoid sunlamps and tanning beds.
Cosmetics may be used but skin must be washed thoroughly before applying medication.
Practice points

·         cumulative irritant or drying effects may occur with other topical anti-acne preparations; combinations may be used if tolerated by patient

·         confirm a negative pregnancy test in the 2 weeks before starting treatment, then start treatment on the second or third day of the next normal menstrual period

·         during early weeks of treatment, an apparent flare of acne may occur; this is due to actions on deep lesions and is not a reason to stop treatment; benefit does not generally become evident for some weeks or even months

·         if patients have been using keratolytics, allow sufficient time for their effects to subside before initiating treatment with topical retinoids

·         adverse effects may decrease with time and can be minimised by using a moisturiser

·         excessive application does not increase therapeutic effect and may produce marked inflammation

·         if severe erythema, oedema, blistering or crusting occurs, apply less frequently or stop until skin integrity is restored

Products

ISOTRETINION GEL 0.05 % + ERYTHROMYCIN 2 %   30 GM TUBE (ISOTREXIN®)

 

TRETINOIN (SKIN)

Mode of action
Modulate cell proliferation and differentiation; decrease new comedone formation and inflammatory lesions.
Indications
Marketed: Acne vulgaris, especially comedonal acne, although may be used adjunctively in the management of comedones associated with inflammatory acne.
Accepted: Photoageing.
Contraindications
Allergy to topical retinoids; Pregnancy; Sunburn; Unprotected sun exposure.
Specific considerations
Children: Contraindicated in neonates; may be used in young children with comedonal acne.
Eczema: severe irritation to eczematous skin may occur; use with caution.
Women of child-bearing age.
Treatment with oral retinoids: increases risk of adverse effects; avoid combination.
Treatment with photosensitising medications: increases risk of phototoxic reactions; avoid combination.
Pregnancy: Contraindicated. Although absorption via skin is minimal, in view of teratogenicity of systemic retinoids, topical retinoids should not be used in pregnancy. ADEC category D.
Lactation: No data available but unlikely to be a concern.
Adverse effects
Common: erythema, peeling, irritation.
Infrequent: pigmentation changes, photoirritation.
Rare: allergic contact dermatitis.
Dosage
Apply once a day at bedtime.
Patient counselling
Before applying, wash with mild soap or soap substitute and warm water; rinse and gently pat dry; wait 20–30 minutes for complete drying of skin to occur. Apply enough to cover affected areas and rub in gently.
Do not apply to eyes, lips or in nostrils.
Protect treated areas from sunlight with protective clothing or sunscreen. Use broad spectrum sunscreen, at least factor 15+ (30+ is preferable), containing a physical agent (e.g. titanium dioxide). Avoid sunlamps and tanning beds.
Cosmetics may be used but skin must be washed thoroughly before applying medication.
Practice points

·         start with the lowest strength cream or gel

·         benefit may be noticed after 2–3 weeks, but >6 weeks treatment is usually required

·         there may be a symptomatic flare in the first 4–6 weeks of treatment

·         after achieving satisfactory response, it may be possible to maintain efficacy with less frequent application

·         tretinoin and benzoyl peroxide can be applied with a 12–24 hour interval between applications

·         topical tretinoin may increase the systemic absorption of topical minoxidil; avoid applying to same area of skin

Products

TRETINOIN GEL 0.025 %   30 GM TUBE (OPTIMAL®, RETIN-A®)

 

13.03 DRUGS FOR FUNGAL AND YEAST INFECTIONS

Tinea
Tinea is a superficial fungal infection of the skin, hair or nails caused by dermatophytes. It is classified according to the area affected, eg scalp and hair (tinea capitis), trunk (tinea corporis, ringworm), groin (tinea cruris) and foot (tinea pedis, athlete's foot). Infection involving the nail (tinea unguium) is discussed in Nail infections.
Before starting treatment
Skin scrapings from edge of lesion should be taken for microscopy and culture.
Confirmation of fungal infection is warranted as the clinical picture may be very similar to non-fungal conditions (exclude discoid eczema when ringworm-like lesions are present; this is a common misdiagnosis).
When to start treatment
Obvious clinical picture or positive microscopy result; it is not necessary to wait for culture results.
Drug choice
Topical treatment
Mild localised skin infections usually respond to topical treatments, including azoles, terbinafine and tolnaftate. Topical treatment is not usually successful for infections involving the nails and hair. Hyperkeratotic lesions also respond poorly.
Azoles (eg clotrimazole, miconazole) are the treatment of choice; fungistatic; available as cream, lotion, solution, spray and powder; well tolerated.
Terbinafine is more expensive but produces a more rapid response than azoles; fungicidal; available as gel and cream.
Tolnaftate may irritate skin; less effective than azoles and terbinafine; available as cream, solution, ointment, powder and spray.
Miscellaneous agents such as benzoic acid with salicylic acid (Whitfield's ointment), undecanoic acid salts, selenium sulfide and crystal violet are less effective than azoles, terbinafine and tolnaftate.
Systemic treatment
Griseofulvin, itraconazole or terbinafine are used for tinea capitis, extensive infection, infections in heavily keratinised areas, eg palms and soles, and disseminated disease. They may also be used for tinea pedis, tinea corporis and tinea cruris when there is poor response to topical therapy. Fluconazole may be used but is more commonly reserved for candidal infection.
Griseofulvin has a narrow spectrum of activity confined largely to dermatophytes, so accurate diagnosis is essential. As tissue concentration drops quickly after stopping, it should be continued until condition is cured (typically several weeks or months).
Other drug treatment
Drying agents and/or antibacterial agents (such as solution of Condy's crystals or Burow's solution) may be needed for severe forms of interdigital infection.
Saline compresses/drying agents and sometimes topical corticosteroids may be necessary for acute vesicular tinea pedis.
Treatment endpoints
Continue topical treatment for 2 weeks after clinical signs resolve. Continue oral treatment until mycological and clinical cures are obtained.
Practice points

·         good personal hygiene is an important adjunct to antifungal treatment, eg drying between toes, using a separate towel for infected area, wearing thongs in public showers and change rooms, changing socks (preferably cotton) daily, avoiding sharing combs, hats and towels

·         discard old shoes that may have a high density of fungal spores

·         creams are generally preferred; lotions or sprays may be applied to large and/or hairy areas; powders may be used on feet, groin and other intertriginous areas (also inside socks and shoes)

·         family members should be evaluated for asymptomatic carriage, particularly if infection is persistent or recurrent

Cutaneous candidiasis
Usually caused by the yeast, C. albicans, although other Candida species are occasionally responsible. Infections commonly occur in the groin, axillae, beneath the breasts, in abdominal folds in obese people, or in the umbilicus. Infections involving the nail are discussed in Nail infections.
Before starting treatment
Confirm diagnosis by microscopy and culture when systemic treatment is anticipated.

Manage predisposing factors such as diabetes, obesity, use of systemic corticosteroids or antibacterials, neutropenia, HIV, other immunocompromised states, occlusion, warm or moist environments, mechanical irritation and skin diseases, eg psoriasis.
Drug choice
Topical treatment
Immunocompetent patients can usually be treated with topical antifungal agents, including the azoles, nystatin and terbinafine.
Azoles (eg clotrimazole, miconazole) are the treatment of choice; are relatively broad spectrum, primarily fungistatic, generally considered more effective than topical nystatin and well tolerated; available as cream, lotion, solution, spray and powder.
Nystatin is available as a cream or ointment; not active against dermatophytes.
Terbinafine is fungistatic against Candida spp.; alternative to topical azoles, but more expensive; available as gel and cream.
Systemic treatment
Systemic treatment with azole antifungals is indicated for widespread or unresponsive disease and immunocompromised patients.
Fluconazole is the treatment of choice.
Itraconazole has similar safety profile to fluconazole; its use in candidal infections is less well studied.
Ketoconazole is highly effective, but due to its serious adverse effects, other oral azoles are preferred.
Other drug treatment
Topical corticosteroids may be used sparingly for short periods with topical and/or systemic antifungals, to reduce inflammation.
Practice points

·         give advice about good hygiene, keeping the skin as clean and dry as possible (particularly the groin, armpits and skin folds) and avoiding occlusion

·         creams are generally preferred; lotions or sprays may be applied to large and/or hairy areas; powders may be used on feet, groin and other intertriginous areas as well as inside socks and shoes

·         continue treatment with topical azoles or nystatin for 2 weeks after symptoms resolve

·         regular application of topical drugs is essential for successful treatment

 

13.03.01 Imidazoles (Skin)

CLOTRIMAZOLE (SKIN)
Mode of action
Impair biosynthesis of ergosterol for cytoplasmic membrane, inhibiting fungal growth; fungistatic.
Indications
Dermatophytoses; Mucocutaneous candidiasis, including paronychia; Pityriasis versicolor.

Specific considerations
Pregnancy: Safe to use; ADEC category A.
Lactation: Safe to use.
Adverse effects
Topical imidazoles are generally well tolerated.
Infrequent: burning, stinging, itch, erythema.
Rare: allergic reactions.
Dosage
Apply sparingly twice a day.
Patient counselling
Regular application is essential for successful treatment.
Complete the full treatment course even if signs of infection have gone.
Attention to hygiene is important in the management of fungal disease of the feet; after washing, dry feet thoroughly, especially between toes.
Practice points

·         continue treatment for 2–4 weeks in dermatophytoses

·         use sparingly, especially in intertriginous areas, to avoid maceration

·         creams are preferred; powders may be used on feet, moist lesions of the groin and intertriginous areas with creams or to prevent reinfection

·         intractable candidiasis may be the presenting symptom of undiagnosed diabetes; appropriate urine and blood tests may be indicated in patients not responding to treatment

·         topical imidazoles are not usually successful in treating infections of the nails or hair

Products

CLOTRIMAZOLE CREAM   20-30 GM TUBE (CLOTREX®, CLOTRIM®)

 

ECONAZOLE (SKIN)
Mode of action
Impair biosynthesis of ergosterol for cytoplasmic membrane, inhibiting fungal growth; fungistatic.
Indications
Dermatophytoses; Mucocutaneous candidiasis, including paronychia.

Specific considerations
Pregnancy: Safe to use; ADEC category A.
Lactation: Safe to use.
Adverse effects
Topical imidazoles are generally well tolerated.
Infrequent: burning, stinging, itch, erythema.
Rare: allergic reactions.
Dosage
Dermatophytoses and cutaneous candidiasis
Cream, apply a thin layer 2–3 times a day.
Pityriasis versicolor
Foaming liquid, apply to wet body on 3 consecutive nights and allow to dry. May be rinsed off the next morning. To prevent relapse, repeat 1 and 3 months after initial course.
Patient counselling
Apply a thin layer to the affected skin and surrounding area; pay particular attention to skin folds.
For this treatment to be successful you have to use it regularly.
Continue using the treatment for 2 weeks after symptoms have gone.
Practice points

·         topical azoles are not usually successful in treating infections of the nails or hair

·         intractable candidiasis may be the presenting symptom of undiagnosed diabetes; consider this possibility in patients not responding to treatment

Products

ECONAZOLE NITRATE CREAM 1% + TRIAMCINOLONE ACETONIDE 0.1%  (15-30) GM  TUBE (ECOREX PLUS®, PEVISON®)

 

ISOCONAZOLE (SKIN)

Antimicrobial Action

Isoconazole is an imidazole antifungal active against a wide spectrum of fungi including Candida spp., dermatophytes, and Malassezia furfur. It is also active against some Gram-positive bacteria.

Uses and Administration

Isoconazole nitrate is an imidazole antifungal used locally in the treatment of vaginal mycoses, particularly due to Candida spp. and in fungal skin infections. For vaginal infections it is usually given as pessaries in a single dose of 600 mg or 300 mg daily for 3 days, or as a 1% vaginal cream daily for 7 days. For skin infections a 2% cream or other topical formulation has been used.

Adverse Effects and Precautions

Local reactions including burning or itching may occur following the application of isoconazole.

Intravaginal preparations of azole antifungals may damage latex contraceptives and additional contraceptive measures are therefore necessary during local administration of isoconazole.

Precautions

See Fluconazole.

Products

ISOCONAZOLE CREAM 1 %  (AS NITRATE)   20 GM TUBE (AZONIT®, TRAVOGEN®)

 

KETOCONAZOLE (SKIN)

Mode of action
Impair biosynthesis of ergosterol for cytoplasmic membrane, inhibiting fungal growth; fungistatic.

Indications
Dermatophytoses; Mucocutaneous candidiasis, including paronychia
Pityriasis versicolor; Seborrhoeic dermatitis.

Specific considerations
Pregnancy: Avoid use; use alternative imidazole; ADEC category B3.
Lactation: Safe to use.
Adverse effects
Topical imidazoles are generally well tolerated.
Infrequent: burning, stinging, itch, erythema.
Rare: allergic reactions.
Dosage
Dermatophytoses and cutaneous candidiasis
Apply sparingly twice a day.
Seborrhoeic dermatitis
Use shampoo twice a week for 4 weeks.

Patient counselling
Regular application is essential for successful treatment.
Complete the full treatment course even if signs of infection have gone.
Attention to hygiene is important in the management of fungal disease of the feet; after washing, dry feet thoroughly, especially between toes.
Practice points

·         continue treatment for 2–4 weeks in dermatophytoses

·         use sparingly, especially in intertriginous areas, to avoid maceration

·         creams are preferred; powders may be used on feet, moist lesions of the groin and intertriginous areas with creams or to prevent reinfection

·         intractable candidiasis may be the presenting symptom of undiagnosed diabetes; appropriate urine and blood tests may be indicated in patients not responding to treatment

·         topical imidazoles are not usually successful in treating infections of the nails or hair

Products

KETOCONAZOLE SHAMPOO 0.02 %   100 ML BOTTLE (FUNGIPAN®,  KETODAR®, NIZORAL®, PHILAZOLE®)

 

MICONAZOLE (SKIN)

Mode of action
Impair biosynthesis of ergosterol for cytoplasmic membrane, inhibiting fungal growth; fungistatic.

Indications
Dermatophytoses; Mucocutaneous candidiasis, including paronychia; Pityriasis versicolor; Seborrhoeic dermatitis (shampoo).

Specific considerations
Pregnancy: Safe to use; ADEC category A.
Lactation: Safe to use.
Adverse effects
Topical imidazoles are generally well tolerated.
Infrequent: burning, stinging, itch, erythema
Rare: allergic reactions
Dosage
Apply sparingly twice a day.
Patient counselling
Regular application is essential for successful treatment.
Complete the full treatment course even if signs of infection have gone.
Attention to hygiene is important in the management of fungal disease of the feet; after washing, dry feet thoroughly, especially between toes.
Practice points

·         continue treatment for 2–4 weeks in dermatophytoses

·         use sparingly, especially in intertriginous areas, to avoid maceration

·         creams are preferred; powders may be used on feet, moist lesions of the groin and intertriginous areas with creams or to prevent reinfection

·         intractable candidiasis may be the presenting symptom of undiagnosed diabetes; appropriate urine and blood tests may be indicated in patients not responding to treatment

·         topical imidazoles are not usually successful in treating infections of the nails or hair

Products

MICONAZOLE CREAM 2 % (AS NITRATE)   15 GM TUBE (CANDIPLAS®, CANDIZOL®, CYPROZOL®, DAKTARIN®, MECONAZOL®, MICOVER®, MYCODERM®)

MICONAZOLE LOTION 2 %  (AS NITRATE)   30 GM BOTTLE (DAKTARIN®)

HYDROCORTISONE ACETATE CREAM 1 % + MICONAZOLE 2 %  CREAM   15 GM TUBE  (CANDICORT®, MICOVER -H®, MYCOHEAL -HC®)

 

TERBINAFINE (SKIN)

Mode of action
Inhibits fungal sterol synthesis; fungicidal against dermatophytes and some yeasts, but only fungistatic against C. albicans.
Indications
Dermatophyte infections of the skin; Cutaneous candidiasis; Pityriasis versicolor (gel).

Contraindications
Allergy to terbinafine.

Specific considerations
Pregnancy: Safe to use; ADEC category B1.
Lactation: Data lacking, unlikely to be a concern.
Adverse effects
Infrequent: redness, itch and stinging.
Rare: allergic reactions.
Dosage
Apply once or twice a day:
Tinea corporis, tinea cruris, for 1–2 weeks.
Tinea pedis, interdigital, for 1 week.
Tinea pedis, plantar/moccasin type, for 2–4 weeks.
Cutaneous candidiasis, for 2 weeks.
Pityriasis versicolor, for 1 week.
Patient counselling
Clean and dry affected areas thoroughly before applying a thin layer to the affected skin and surrounding area.
Rub in lightly.
For this treatment to be successful you have to use it regularly.
Do not use occlusive dressings or wrappings unless you have been told by your doctor.
Continue using the treatment for the full course even if your skin looks better.
Practice points

·         rapid action usually allows a shorter duration of treatment than with topical azoles, but is more expensive

·         symptoms are usually relieved within a few days

·         optimum clinical response to topical terbinafine generally is delayed for a week or more after completing a short course of treatment

·         may be useful when patient compliance beyond 1 week cannot be ensured

·         topical treatment course generally should not exceed 4 weeks

Products

TERBINAFINE CREAM  1 %  (AS HCL)   15 GM TUBE (LAMIFEN®, LAMISIL®, SOLVEASY TINEA®, TERFINIL®, TINASIL®)

TERBINAFINE SPRAY  1 % (LAMISIL®)

 

13.04 SCABICIDES AND PEDICULICIDES

Scabies
Rationale for drug use
Scabies eradication.
Symptom relief.
Prevent secondary infection.
Prevent transmission.
Before starting treatment
Confirm diagnosis by demonstrating the typical burrows; or definitively, the mite, an ovum or scybalum (faecal pellet) by microscopy.
Dermatoscopy may also be useful.
Drug choice
Permethrin 5%: treatment of choice (including in pregnancy and breastfeeding); pyrethroid insecticide; low toxicity and high efficacy; may cause irritation or allergic reaction.
Benzyl benzoate: messy; irritant; dilution required if used in children.
Crotamiton: other more effective agents preferred; may be used to control itch after treatment with a more effective scabicide; may cause irritation.
Maldison: alcohol-based lotion may cause irritation.
Special cases
Norwegian scabies is a severe crusted form that occurs rarely; immunocompromised or incapacitated patients are more susceptible; multiple applications are needed and combination treatment with keratolytics may be required.
Resistant cases or immunocompromised, oral ivermectin may be beneficial.
Patient counselling
The affected person, all household/family members and close contacts should be treated at the same time to avoid becoming infected again. Even contacts who don't have any symptoms need to be treated.
Treatment with permethrin requires 2 applications 1 week apart.
Soft toys, bed linen and clothing should be washed and dried on hot machine settings the morning after each treatment or stored in tightly sealed plastic bags for 1–2 weeks.
Practice points

·         examine patients 2 weeks after start of treatment to monitor adequacy; assess for irritant dermatitis and treat residual itch

·         evidence of a cure requires follow-up for about 1 month; this is the time it takes for lesions to heal and for any eggs and mites to reach maturity if treatment fails

·         improvement usually occurs within 1 or 2 days of treatment; itch generally lasts 2–3 weeks and patients should be warned not to mistake this for ongoing infection; manage the itch with moisturiser, topical corticosteroids, crotamiton or an antihistamine; patients should see a doctor if itching continues longer than 2–3 weeks

Head lice
Pediculosis or infestation by the head louse, Pediculus humanus capitis, can occur at any age but is most common in school-age children.
Before starting treatment
A living, moving louse must be found to confirm infestation. Itching or the presence of eggs (nits) does not necessarily indicate active infestation.
Examine family members and close contacts for infestation. Family members with head lice should be treated at the same time.
Drug choice
If using chemical treatment use only products containing the insecticides mentioned below. Chemical resistance is common; check lice are killed the day after the first treatment and repeat successful treatment; if lice are not killed use a different insecticide as soon as possible.
Permethrin 1%: safe and effective; short application time (10 minutes); treatment of choice in pregnancy and breastfeeding.
Maldison: organophosphate pesticide; safe and effective when used as directed; avoid use in pregnancy and infants <12 months; smelly; requires long application time (12 hours).
Pyrethrins with piperonyl butoxide: probably as effective as other insecticide treatments.
Other treatment
'Bug busting': meticulous wet combing (using a special fine-tooth comb) with conditioner, can be used to detect and treat head lice. Although it provides an alternative to insecticide treatment evidence for benefit is unreliable and it requires motivation to be effective. Repeat every 2 days until there are no head lice seen for 10 consecutive days.
Electrified comb: despite a lack of clinical evidence there is anecdotal evidence that regular use of an electrified comb (available at most pharmacies) may be a useful non-drug alternative. This technique has the advantage of being less time consuming, does not damage hair and avoids the smell and cosmetic problems associated with topical preparations.
Essential oils, herbal products: there is insufficient evidence to support their use in eradicating lice.
Treatment failure
May result from inadequate or incorrect application, reinfection or pediculicide resistance.
Patient counselling
Check other family members for head lice. Only treat if a live louse is found.
Chemical treatment requires 2 applications 7 days apart. The second treatment kills the lice that have hatched since the first application.
Wet combing (using a special fine-tooth comb and conditioner) every 2 days in between chemical treatments may increase effectiveness, but avoid using conditioner for at least 1 day before and after chemical treatment. Wet combing, unlike chemical treatment, also helps to remove nits.
Do not use a hair dryer following chemical treatment as heat can destroy the active ingredient.
Children can be sent back to school after the first treatment. Tell children not to share hats and hairbrushes. Long hair should be tied back or plaited, especially while at school.
Soak combs and hairbrushes in hot water (>60°C) for 30 seconds and wash pillowcases in hot water or put in a clothes dryer for 15 minutes.
Do not overuse chemical treatments or use them to prevent head lice infestation. Overuse can cause irritation and result in lice that are resistant to chemical treatment.

 

BENZYL BENZOATE

Mode of action
Unknown.

Indications
Scabies; Pediculosis.

Contraindications
Acutely inflamed skin, or raw, weeping skin; Allergy to benzyl benzoate.
Specific considerations
Elderly: Age-related dryness of skin increases susceptibility to drying effects of benzyl benzoate; irritation may be worse in this age group.
Children: Dilute with an equal quantity of water for children <12 years and with 3 parts of water for infants. Dilution reduces irritation, but also efficacy.
Pregnancy: Although no problems in humans have been documented with benzyl benzoate, use of permethrin is preferred; ADEC category B2.
Lactation: Data lacking, permethrin preferred.
Adverse effects
Infrequent: burning sensation, itch and dermatitis.
Rare: CNS stimulation, eg convulsions (with excessive topical use), allergic reaction.
Dosage and administration instructions
Test on small area of skin for 10 minutes before using. If excessive stinging occurs, it should be diluted with an equal quantity of water, then retested before using.
Scabies
Apply to cool skin (not hot after bathing) from chin down; repeat without bathing on the following day and wash off 24 hours later; a third application may be required in some cases.
In infants and young children up to 2 years, also apply to the scalp, neck, face and ears; avoid eyes, mouth and mucous membranes.
Pediculosis: Coat affected region and leave on for 24 hours, then wash with soap and water.
Patient counselling
Do not use on face unless advised by your doctor; avoid contact with eyes, mouth and mucous membranes.
If you wash your hands or any other part of your body during the treatment period for scabies, you should reapply the lotion to the washed areas.
Itch may persist for some months after scabies treatment (7–10 days after lice treatment); this may not be ongoing infection although persisting itch could mean scabies that has not responded. Symptomatic itch treatment may be required.
Practice points
Scabies

·         benzyl benzoate has been superseded by more effective products for the treatment of scabies (50% cure rate with benzyl benzoate versus 80% with permethrin)

·         improvement usually occurs within 1 or 2 days of treatment

·         traditionally applied after a bath, but this is unnecessary and may increase transdermal absorption, removing drug from site of action and increasing the risk of systemic toxicity

·         special attention should be given to the finger and toe webs, under nails, umbilicus, intertriginous areas and intergluteal cleft

·         application to the genitals is irritant; use another insecticide (eg permethrin) or relieve with hydrocortisone 1% cream

·         scalp, neck, face and ears may also need to be treated in elderly, immunocompromised, people who have had treatment failure or those with atypical or crusted scabies; stinging is significant; an alternative agent may be preferable

·         do not use to prevent scabies

Pediculosis

·         efficacy is questionable; other agents are more effective

Products

BENZYL BENZOATE LOTION 25 %   100 ML BOTTLE (BENZYL BENZOATE®)

 

CROTAMITON

Mode of action
Unknown.

Indications
Scabies (but not pediculosis); Itch from various causes, eg post-scabies and post-pediculosis itch, insect bites (claims of drug's antipruritic activity based largely on uncontrolled studies).
Contraindications
Acutely inflamed skin or raw, weeping skin; Allergy to crotamiton.
Specific considerations
Pregnancy: Safe to use; ADEC category B2.
Lactation: Safe to use (avoid nipple region).
Adverse effects
Infrequent: irritation.
Rare: allergic reaction.
Dosage
Scabies, apply once a day for 2–5 days, preferably in the evening; do not wash off until next application is due.
Itch, apply 2–3 times a day.
Administration instructions
Scabies, after bathing and drying, allow skin to cool before applying to body from chin down.
Special attention should be given to the finger and toe webs, under nails, umbilicus, intertriginous areas and intergluteal cleft.
Itch, rub into affected areas.
Patient counselling
Do not use on face; avoid contact with eyes, mouth and mucous membranes.
Massage into skin until dry, do not wash off for 24 hours.
If you wash your hands or any other part of your body during the treatment period for scabies, you should reapply the lotion/cream to the washed areas.
Do not apply to entire body surface of small children more than once daily.
Practice points

·         other more effective agents, eg permethrin, are usually preferred in the treatment of scabies

·         if used correctly, 2 applications of crotamiton may be effective in eradicating scabies

Products

CROTAMITON CREAM 10 %   20-25 GM TUBE (CROTAPHIL®, EURAX®)

CROTAMITON LOTION 10 %   50 ML BOTTLE (CROTAPHIL®, EURAX®)

 

PYRETHRIN 

Mode of action
Pyrethrins are absorbed through the chitinous exoskeleton of arthropods and stimulate the nervous system. Nerve impulse transmission is blocked, resulting in paralysis and death.
Piperonyl butoxide inhibits pyrethrin metabolism in arthropods (it has little or no insecticidal activity).
Indications
Pediculosis.

Contraindications
Allergy to pyrethrins or pyrethroids; Acutely inflamed skin.
Specific considerations
Pregnancy: Permethrin preferred; ADEC category B3.
Lactation: Safe to use.
Adverse effects
Rare: allergic reaction, skin infection, skin irritation.
Dosage
Following initial treatment, a second treatment is required in 7–10 days to kill any newly hatched lice.
Administration instructions
Mousse: Apply to dry hair and massage in until wet; leave for 10 minutes, then wash out with shampoo.
Aerosol spray: Moisten whole scalp by spraying in short bursts (2–3 seconds); leave for 30 minutes (do not cover head), then wash out with shampoo.
Patient counselling
Apply aerosol in a well ventilated room.
Avoid contact with eyes, mouth and mucous membranes.
Avoid excessive treatment, as irritation can occur.
Do not use on eyelashes or eyebrows; check with your doctor or pharmacist if they become infested.
Wash hands immediately after using medication.
Practice points

·         treatment should be repeated in 7–10 days to kill any newly hatched lice

Products

PYRETHRINE SHAMPOO 0.165 %   100 ML BOTTLE (LICESOL®)

 

13.05 DRUGS FOR OTHER SKIN INFECTONS

13.05.01 Antibacterials (Skin)

FUSIDIC ACID (SODIUM FUSIDATE) (SKIN)

Indications
Staphylococcal skin infections
Specific considerations
Pregnancy: Avoid use during the last month of pregnancy; ADEC category C.
Adverse effects
Rare: hypersensitivity reactions including rash and irritation.
Dosage
Apply 2–3 times daily for 7 days.
If using a protective dressing, apply once daily.
Patient counselling
Avoid contact with eyes.

Exclude child with impetigo from school until appropriate treatment is started. Sores on exposed surfaces must be covered with a watertight dressing.
Practice points

·         avoid use in chronic skin conditions because of doubtful efficacy and risk of resistance emerging during treatment

·         studies comparing topical sodium fusidate and mupirocin show no significant difference in efficacy in staphylococcal skin infections; mupirocin is preferred for mild impetigo

Products

FUSIDIC ACID CREAM 2 %   15 GM TUBE (DERMOFUCIN®, FUCIDIN®, FUSIDERM®, FUSIVER®, TOPIDIC®, UCIDERM®)

FUSIDIC ACID CREAM 2 % + BETAMETHASONE (AS VALERATE) CREAM 0.1 %   15 GM TUBE (FUCICORT®)

FUSIDIC ACID GEL 2 %   15 GM TUBE (DERMOFUCIN®, FUCIDIN®, TOPIDIC®, UCIDERM®)

FUSIDIC ACID OINTMENT 2 %   15 GM TUBE (DERMOFUCIN®, FUCIDIN®, FUSIDERM®, FUSIVER®, TOPIDIC®, UCIDERM®, ZETA®)

 

METRONIDAZOLE (SKIN)

Indications
Acne rosacea.

Specific considerations
Pregnancy: Safe to use; ADEC category B2.
Lactation: Safe to use.
Adverse effects
Common: local reactions include eye irritation (watering), redness, dryness and skin irritation.
Dosage
Rub a thin film of gel or cream into affected areas twice a day.
Administration instructions
Apply to clean, dry skin. Avoid eye area.
Practice points

·         use with systemic treatment or alone for mild rosacea and maintenance therapy

·         there should be improvement within 3 weeks; continue treatment for 8–9 weeks

·         continued topical therapy after oral tetracycline is stopped lowers the relapse rate

Products

METRONIDAZOLE GEL 0.75 % 15-25 GM TUBE (FLANIZOL®, METROZA®)

 

NEOMYCIN with BACITRACIN

Indications
Otitis externa.

Specific considerations
Perforated eardrum, tympanostomy tube—slight risk of inner ear damage; only use neomycin with bacitracin if there is no appropriate alternative. Limit treatment to 5–7 days; refer to ENT specialist if discharge continues.
Adverse effects
Common: allergic dermatitis.
Infrequent: fungal overgrowth (with prolonged use).
Rare: inner ear damage.
Dosage
Use in the affected ear 2–4 times daily.

Patient Councelling
If you develop ringing in the ears, hearing loss or difficulty with balance, stop using this medication and tell your doctor.

Products

NEOMYCIN 0.5%+BACITRACIN 250 IU/GM OINTMENT 15-30 GM TUBE (BANEOCIN®, MULTICIN Z CENTER®, NEOBACIN®)

 

NITROFURAZONE (SKIN)

Mode of action

Nitrofurazone inhibits several bacterial enzymes, especially those involved in the aerobic and anaerobic degradation of glucose and pyruvate.

Indications
Burns (treatment)—Topical nitrofurazone is indicated as an adjunctive therapy for second and third degree burns when resistance to other agents is a real or potential problem.
Skin infections (treatment)—Nitrofurazone is indicated in skin grafting when bacterial contamination may cause graft rejection or donor site infection, especially in hospitals with a history of resistant bacteria.
Contraindications
Serious allergic reaction to nitrofurazone.

Specific considerations.
Pregnancy: Avoid use; ADEC category C.
Adverse effects
Contact dermatitis (itching; rash; swelling)
Dosage
Nitrofurazone should be applied directly to affected area  or on gauze to cover affected area.
The drug should be reapplied once daily or every few days, depending on the usual dressing technique..
Practice points

·         The use of nitrofurazone occasionally allows overgrowth of nonsusceptible organisms including fungi  and Pseudomonas If this occurs, or if irritation, sensitization, or superinfection develops, treatment should be discontinued

Products

NITROFURAZONE OINTMENT 0.2% (BACTAZONE®)

 

SILVER SULFADIAZINE (SKIN)

Mode of action

Bactericidal; binds to cell membranes; effective against many Gram-positive and Gram-negative bacteria. Indications
Prevention and treatment of infection in severe burns, leg ulcers and pressure sores; Prevention and treatment of infection in epidermolysis bullosa.

Contraindications
Serious allergic reaction to sulfonamide or related drugs or to chlorhexidine; Neonates <4 weeks old.

Specific considerations
G6PD deficiency—increases risk of haemolysis.
Renal impairment: Use with caution in patients with impaired renal function, particularly those receiving treatment for extensive burns.
Pregnancy: Avoid use during last month of pregnancy if possible because of the theoretical risk of kernicterus, jaundice and haemolytic anaemia in the neonate; ADEC category C.
Adverse effects
Common: burning, itch, rash.
Rare: skin discolouration due to deposition of silver, transient neutropenia, development of bacterial resistance, hypersensitivity reactions.
Dosage
Rub a thin film of gel or cream into affected areas twice a day.
Administration instructions
Apply a 3–5 mm thick layer every 24 hours or more frequently.
Practice points

·         silver sulfadiazine cream is formulated with the disinfectant, chlorhexidine

·         chlorhexidine (cation) is inactivated by anionic agents such as soap; do not use together

·         silver sulfadiazine may inactivate enzymatic debriding agents

Products

SILVER SULFADIAZINE CREAM 1% (FLAMAZINE®, NO-BURN®, SILVABURN®, SIDILAZINE®, SILVERIN®)

SILVER SULFADIAZINE CREAM 1% + CERIUM NITRATE (FLAMMACERIUM®)

 

 

13.05.02 Antivirals (Skin)

ACICLOVIR (SKIN)

Indications
Labial herpes simplex (cold sores), initial and recurrent.

Specific considerations
Immunocompromised patients: oral aciclovir is more effective than topical.
Pregnancy: Safe to use; ADEC category B3.
Lactation: Safe to use.
Adverse effects
Common: dry or flaking skin, transient stinging or burning.
Infrequent: erythema, itch.
Rare: allergic dermatitis.
Dosage
Apply at first sign of lesion; apply 5 times a day (every 4 hours while awake) for 5 days.
Administration instructions
Avoid contact with eyes and mucous membranes.
Practice points

·         treat as early as possible in the course of infection

·         treatment of primary infections relieves symptoms and reduces duration of viral shedding, but does not affect recurrence rate

·         more effective for primary infections than for recurrences

·         in genital herpes, topical antivirals are less effective than oral treatment

·         in immunocompromised patients, oral aciclovir is more effective than topical; severe infections should be treated with IV aciclovir

Products

ACICLOVIR CREAM 5 %   2 GM TUBE (CYCLOHERP®, CUSIVIRAL®, HERPAVIR®,  ZOVIRAX®,  SUPRAVIRAN®)

 

TROMANTADINE (SKIN)

Indications
treatment of the initial symptoms of herpes simplex infections of the skin and mucous membrane and dermal manifestation of herpes zoster.

Specific considerations.
Pregnancy: no data available.
Lactation: no data available.
Adverse effects
Common: contact dermatitis.
Dosage
Apply at first sign of lesion; apply 3-5 times a day.
Administration instructions
Avoid contact with eyes and mucous membranes.
Practice points

·         treat as early as possible in the course of infection

·         treatment of primary infections relieves symptoms and reduces duration of viral shedding, but does not affect recurrence rate

·         more effective for primary infections than for recurrences

Products

TROMANTADINE GEL  1 %  10 GM TUBE (VIRU-MERZ®)

 

13.06 DRUGS FOR PSORIASIS

Psoriasis
Psoriasis is a common inflammatory and proliferative disease. Several morphological variants exist; plaque psoriasis is the most common and classically affects elbows, knees, buttocks and scalp.
Rationale for drug use
Induce remission.
Reduce the severity and extent of psoriasis to a tolerable level.
Relieve symptoms, including itch, excessive scale, pain.
Before starting treatment
Minimise or eliminate potential trigger factors where possible, eg stress, trauma, smoking, alcohol, infection (streptococcal throat infection may precipitate guttate psoriasis). Drugs known to exacerbate or trigger psoriasis include lithium, quinolines, ACE inhibitors, NSAIDs and beta-blockers.
Consider referral to a dermatologist if the diagnosis is in doubt, therapy fails, or when treatment with phototherapy or systemic agents is indicated.
When to start treatment
Troubling local symptoms, eg pain, itch, reduced manual dexterity, flexural intertrigo.

Cosmetic problems, eg prominent hand, arm, leg or facial lesions.
Drug choice
Topical treatment
Should be the initial treatment for stable plaque psoriasis, except when large areas of involvement make this impractical or expensive. Topical agents are commonly used in combination. A patient who does not respond to a particular agent may respond to it in the future.
Moisturisers
Moisturisers hydrate and soften the scaly, hyperkeratotic surface of psoriatic plaques and may suffice in mild disease or in some patients with more extensive disease who prefer a treatment with minimal adverse effects.
Keratolytics
Include salicylic acid. They help to remove accumulated scale and allow other topical agents such as coal tar, dithranol and corticosteroids to penetrate lesions. They can cause irritation.
Coal tar
Coal tar is generally preferred for limited or scalp psoriasis but can be effective in widespread psoriasis, eg guttate psoriasis. May not clear psoriasis as quickly as other topical agents but remission may be longer. Crude tar preparations are difficult to apply, stain clothing and smell unpleasant; newer, more refined preparations are less messy but may be less effective. It is photosensitising and may be irritant to face, genitals, flexures and in unstable psoriasis.
Dithranol
Dithranol may be used in increasing strength and contact duration according to patient response and tolerance. Treatment is more feasible when plaques are large or few. Short contact treatment with higher dithranol concentrations is as effective as overnight application of lower concentrations. It is irritant and stains clothing, skin and hair.
Topical corticosteroids
Topical corticosteroids have quicker onset of action than coal tar and dithranol. May be useful when treating face, flexures and genitals (where coal tar and dithranol are contraindicated), in localised disease and in scalp psoriasis. Tachyphylaxis develops with continued use and relapse occurs faster than with other topical treatments. There is a risk of local and systemic adverse effects; should not be used in extensive disease or in large amounts for periods >4–6 weeks (trunk), >4 weeks (palms or soles) or >few days to 1 week (face or flexures). Potent topical corticosteroids should be used with caution. Systemic corticosteroids are not prescribed due to the risk of rebound flare.
Calcipotriol
Calcipotriol is useful in the treatment of resistant plaque psoriasis; similar efficacy to moderate potency corticosteroids and coal tar; tolerance does not occur; continuous use beyond 12 months has not been studied. Can cause irritation particularly if applied to face or skin folds.
Phototherapy
UVB light
Narrow band UVB is the preferred form of phototherapy for psoriasis. Safer, simpler and cheaper than photochemotherapy. UVB may be used alone or with topical treatments, eg coal tar, dithranol or calcipotriol. Particularly effective in guttate psoriasis when used alone.
Photochemotherapy (PUVA)
Combines topical or oral methoxsalen with UVA; probably the least toxic of all systemic agents. Its advantages are a high likelihood of response and no need for topical medication between treatments. There is a potential risk of non-melanoma skin cancer with PUVA. It is reserved for severe psoriasis unresponsive to other treatments.
Systemic treatment
Acitretin and immunomodulators have potentially serious adverse effects and drug interactions; they should not be used in pregnancy and their use should be overseen by a dermatologist.
Acitretin
Acitretin is most effective in treating pustular and erythrodermic psoriasis; less effective in treating plaque psoriasis. 10–20% discontinuation rate due to adverse effects and risk of teratogenicity make acitretin less acceptable to women who may become pregnant. May be combined with phototherapy or calcipotriol, providing increased efficacy and an acitretin-sparing effect.
Immunomodulators
Methotrexate and cyclosporin are used most frequently; they are indicated in extensive plaque psoriasis and psoriasis refractory to topical treatment, generalised pustular or erythrodermic psoriasis and severe psoriatic arthritis.
Mycophenolate mofetil and tacrolimus are newer agents that may be useful in selected patients, seek specialist advice.
Hydroxyurea is used occasionally but is less effective than methotrexate or cyclosporin.
Alefacept and efalizumab have recently been approved for the treatment of moderate-to-severe psoriasis. They have not been directly compared with other systemic agents and long term safety and efficacy have not been established. Reserve for patients with contraindications to, or who are unresponsive to, phototherapy or systemic therapy.
Other treatments
Antimicrobials
Indications include secondary skin infections and psoriasis precipitated by infection.
Combination therapy
Useful when monotherapy has failed, to limit toxicities of individual agents (lower dosages can be used) and to improve therapeutic outcome (combination more effective than either agent alone). Usually one agent is stopped after psoriasis has cleared and the safer agent is continued as maintenance treatment.
Examples of combinations include coal tar or dithranol with UVB, acitretin with UVB or PUVA, methotrexate with UVB or cyclosporin.
Rotational therapy
Rotating treatment regimens, before significant individual drug toxicities occur, minimizes chronic toxicity and facilitates long term treatment.
Primary agents include PUVA, methotrexate, acitretin, UVB (with or without coal tar or dithranol) and cyclosporin. Secondary agents such as hydroxyurea may be tried when the primary agents are no longer effective or have unacceptable side effects.
Special cases
Unstable psoriasis: Trigger factors include intensive systemic and topical corticosteroids, infection and overtreatment with tar, dithranol or ultraviolet irradiation. It often warrants hospitalisation for systemic treatment with retinoids or immunosuppressants and skilled nursing.
Scalp psoriasis: Coal tar and dithranol preparations with or without salicylic acid and/or sulfur, calcipotriol or corticosteroid scalp lotions may be used.

 

CALCIPOTRIOL
Vitamin D analogue
Also known as calcipotriene
.
Mode of action
Vitamin D analogue.
Induces differentiation and suppresses proliferation of keratinocytes, reversing the abnormal keratinocyte changes in psoriasis.
Indications
Psoriasis vulgaris, chronic stable plaque type.

Contraindications
Disorders of calcium metabolism; Previous allergic reaction to calcipotriol; Severe, extensive psoriasis (in view of the risk of hypercalcaemia secondary to excessive absorption)
Specific considerations
Renal impairment: Data lacking, unlikely to be of concern; monitor plasma concentrations.
Hepatic impairment: Safety not established.
Pregnancy: Data lacking; contact specialised information service.
Lactation: Ensure chest area is free from calcipotriol for breastfeeding, to avoid possible transfer to infant.
Adverse effects
Common: skin irritation (usually mild burning or stinging).
Infrequent: erythema and scaling.
Rare: allergic contact dermatitis, hypercalcaemia, photosensitivity, changes in pigmentation.
Dosage
Apply to affected area twice a day. Less frequent application may be adequate after initial period. Stop treatment after satisfactory improvement; reinstate if disease recurs.
Maximum
Adult
Cream or ointment, 5 mg calcipotriol (100 g) each week.

Liquid, 3 mg calcipotriol (60 mL) each week. >1 formulation, 5 mg calcipotriol each week.
Child
6–12 years, ointment, 50 g each week for up to 8 weeks.

>12 years, ointment, 75 g each week for up to 8 weeks.
Combination with betamethasone
For additional information see BETAMETHASONE (skin)
Adult, apply to the affected area once daily. Maximum of 100 g each week. Do not apply to >30% of body surface.
Patient counselling
Do not mix with other preparations unless instructed; mixing can destroy the calcipotriol.
Wash hands thoroughly after applying to avoid unintentional transfer to other body areas.
Do not apply to face; itch and redness occurs.
Protect treated areas from sunlight with protective clothing or sunscreen. Broad spectrum sunscreen, at least factor 15+, containing a physical agent (eg titanium dioxide) is recommended. Avoid sunlamps and tanning beds.
Practice points

·         calcipotriol is unstable in the presence of salicylic acid or UVA; to avoid loss of efficacy:

·         apply salicylic acid at a different time of day

·         apply calcipotriol after UVA treatment

·         may need to use calcipotriol for 4–6 weeks for maximum improvement

·         avoid use on skin folds, face and scalp, which are especially susceptible to irritation

·         avoid use with calcium or vitamin D supplements or drugs that increase the systemic availability of calcium (eg calcium-containing antacids, thiazide diuretics)

·         monitor plasma calcium and renal function every 3 months; if calcium is elevated, stop treatment and monitor calcium level each week until normal; may continue treatment with regular monitoring if the elevation is marginal

·         plasma calcium monitoring may not be required if patients are applying <30 g each week

·         to minimise risk of hypercalcaemia, use <100 g each week

·         calcipotriol may be used with UVB, PUVA, retinoids and immunosuppressants, allowing less frequent and lower dosing of these agents, thus minimising their adverse effects

·         there are limited data on the use of calcipotriol with betamethasone beyond a month; change to a single ingredient product after 4 weeks of treatment

Products

CALCIPOTRIOL CREAM 50 MCG   30 GM TUBE (DAIVONEX®)

CALCIPOTRIOL OINTMENT 50 MCG   30 GM TUBE (DAIVONEX®)

CALCIPOTRIOL OINTMENT 50 MCG + BETAMETHASONE   30 GM TUBE (DAIVOBET®)

CALCIPOTRIOL SCALP SOLUTION 50 MCG/ML   30 ML BOTTLE (DAIVONEX®)

 

HYDROQUINONE

Adverse Effects, Treatment, and Precautions

Topical hydroquinone may cause transient erythema and a mild burning sensation. High concentrations or prolonged use may produce hyperpigmentation especially on areas of skin exposed to sunlight. Occasionally hypersensitivity has occurred and some recommend skin testing before use. Hydroquinone should not be applied to abraded or sunburnt skin. It should not be used to bleach eyelashes or eyebrows and contact with the eyes should be avoided as it may produce staining and corneal opacities. The systemic effects of hydroquinone and their treatment are similar to those of phenol but tremors and convulsions may also occur.

Uses and Administration

Hydroquinone increases melanin excretion from melanocytes and may also prevent its production. Hydroquinone is used topically as a depigmenting agent for the skin in hyperpigmentation conditions such as chloasma (melasma), freckles, and lentigines (small macules that resemble freckles). Concentrations of 2 to 4% are commonly used; higher concentrations may be very irritant and increase the risk of ochronosis. It may be several weeks before any effect is apparent but depigmentation may last for 2 to 6 months after discontinuation. Application of hydroquinone should be discontinued if there is no improvement after 2 months. Hydroquinone should be applied twice daily only to intact skin which should be protected from sunlight to reduce repigmentation. Hydroquinone preparations often include a sunscreen or a sunblocking basis.

Hydroquinone is also used as an antoxidant for ether and in photographic developers.

Products

HYDROQUINONE CREAM 4 %   30 GM TUBE (ECLADERM®, ELDOQUIN®, FEDIQUIN®, PHILAQUIN®)

 

METHOXSALEN
Psoralens
Mode of action
The therapeutic effect of UVA-activated psoralens for psoriasis probably involves binding to DNA and inhibition of DNA synthesis, resulting in decreased cell proliferation. In the absence of UV light, psoralens are inert.
Indications
Photosensitizers before UVA phototherapy in the following conditions:
Marketed: Vitiligo
Accepted: Psoriasis, severe, refractory, disabling
Atopic eczema: Polymorphic light eruption
T cell lymphomas, e.g. mycosis fungoides
Contraindications
Conditions associated with photosensitivity, eg porphyria, xeroderma pigmentosum, lupus erythematosus; Aphakia (increased risk of retinal damage due to lack of lenses); Cataracts; Melanoma, invasive squamous cell carcinoma.
Specific considerations
Treatment with photosensitising medications: increases risk of phototoxic and photoallergic reactions; avoid combination.
Hepatic impairment: Use cautiously.
Children: Should not be used in children; safety not established.
Pregnancy: Avoid use; ADEC category B2.
Lactation: Avoid use; safety not established.
Adverse effects
Common: Oral psoralens, itch, nausea, erythema.
Infrequent: Oral, CNS effects (including nervousness, insomnia, depression).
Topical, contact allergy.
PUVA therapy
itch, mild transient erythema, oedema, vesiculation, bullae formation, onycholysis, acneiform eruptions, hypertrichosis, pigmentation alterations, exacerbation of systemic lupus erythematosus
Long term effects, premature skin ageing, cutaneous carcinogenesis, cataract formation
Severe burns may result from overexposure to sunlight or UVA radiation.
Dosage
Oral, 0.6 mg/kg taken with milk or after food, 2 hours before UV light exposure.

Lotion, apply a 1:10 dilution of the 1% lotion (resulting in a 0.1% preparation) to affected areas 30 minutes before UV light exposure.
Patient counselling
Do not sunbathe for 24 hours before and 48 hours after, PUVA therapy.
Most people have 20–30 PUVA treatments.
After taking methoxsalen, avoid exposure to sunlight, even through glass and cloud cover, for at least 8 hours. After application to the skin, exposure to sunlight should be avoided for at least 12–48 hours. If exposure to sunlight cannot be avoided, protective clothing should be worn and sunscreens applied to all areas that may be exposed, including lips.
Wear wrap-around sunglasses with 100% UVA-absorbing properties during daylight for 24 hours after taking methoxsalen, and after methoxsalen with UVA treatment, to avoid cataracts.
Certain foods contain natural photosensitisers, eg limes, figs, parsley, parsnips, mustard, carrots and celery; these must be eaten sparingly, or avoided, while taking methoxsalen.
Practice points

·         PUVA treatments may be given 2 or 3 times a week, but must be at least 48 hours apart

·         never dispense the lotion for home use

·         if nausea occurs divide the oral dose in two and give 15 minutes apart

·         cataracts may occur in patients who fail to wear suitable eye protection for 24 hours after oral treatment

·         overexposure to sunlight or artificial UV emission after taking methoxsalen may result in serious burning

·         ophthalmic examination, measurement of antinuclear antibody titre and hepatic function should be performed before and every 12 months after, beginning of treatment

·         examine skin for malignancy every 6 months, depending on dose and duration of treatment

·         topical treatment results in more prolonged photosensitivity, greater incidence of adverse effects and is less cosmetically acceptable than systemic treatment

·         use of topical methoxsalen in psoriasis has largely been abandoned, except for psoriasis of the hands and feet or localised chronic plaques

Products

METHOXSALEN CAPS 10 MG (OXSORALEN®)

METHOXSALEN PAINT  0.03G/15ML (ULTRAMELADININE®)

13.07 DRUGS FOR WARTS AND CALLUSES

Warts
Warts are caused by human papilloma virus (HPV). Different HPV genotypes infect particular locations and only some are associated with neoplasia. Warts are commonly classified according to location and morphology. Cutaneous warts include common, flat, mosaic, plantar and palmar warts. Anogenital warts involve the vulva, vagina, cervix, penis, scrotum, urethra and rectum. Extracutaneous warts include oral and laryngeal lesions.
Rationale for drug use
Eradicate warts.
Stop spread to other sites or people.
Reduce unwanted local effects.
Before starting treatment
Discuss the need to remove cutaneous warts only when they are a cosmetic problem or causing unwanted effects as treatments are destructive and an immune response usually will remove the wart (30% disappear within 6 months and most disappear within 3 years without treatment in immunocompetent individuals).
Note current and past treatments, both successful and unsuccessful, and complications including pain, scarring, changes in pigmentation and extension of warts.
Consider possibility of adjacent mucous membrane involvement in patients with external anogenital warts; specialist referral for anoscopy or colposcopy may be indicated.
Consider factors that may predispose to HPV infection, eg immunosuppression.
Assess pregnancy status; podophyllotoxin and podophyllum resin are contraindicated in pregnancy and imiquimod should be avoided.
Encourage patients with anogenital warts to tell sexual partners and suggest they seek medical advice. Screening for other STIs may also be appropriate.
When to start treatment
Unwanted local effects, eg itch, burning, bleeding or painful coitus associated with genital warts; tenderness precluding weight bearing with plantar warts.
Cosmetic and psychosocial considerations.
Numerous and/or large warts.
Warts in immunocompromised patients, as may develop into squamous cell carcinomas.
Drug choice
There is no specific HPV antiviral and treatment relies on local tissue destruction or immune modification.
Cutaneous warts
Salicylic acid: treatment of choice; inexpensive and may be used at home; relatively safe with few complications. It is irritant and not suitable for application to the face or broken skin; reduce frequency of application if discomfort occurs. Use caution in diabetes and peripheral vascular disease.
Also available in combination with trichloracetic acid (Upton's paste) and lactic acid. The combination with lactic acid has not been shown to be more effective than salicylic acid alone.
Glutaraldehyde: reserve for plantar warts; irritant and not suitable for application to face or broken skin; stains skin brown; rarely used.
Podophyllum resin: available alone or in combination with salicylic acid; may cause severe systemic toxicity; use under close supervision.
Anogenital warts
Podophyllotoxin: treatment of choice; available as a paint for self-treatment of external genital warts; irritant but low systemic toxicity; compliance is important.
Imiquimod: modifies immune response; use for self-treatment of external genital warts; has the advantage of less frequent application and few adverse effects; clearance rates similar to established treatments.
Other drug treatment
Monochloroacetic acid, formaldehyde, nitric acid and silver nitrate are rarely used for cutaneous warts. Retinoids, intralesional bleomycin, interferon alfa or beta, contact immunotherapy, oral colchicine and cimetidine have been used in the treatment of cutaneous and anogenital warts but there is insufficient evidence of efficacy. There is some evidence of efficacy for topical fluorouracil but it is not superior to simpler treatments.
Non-drug treatment
Cryotherapy may be used for cutaneous and anogenital warts; multiple treatments required; painful (essentially preventing use in children); contraindicated in patients with cold intolerance; may cause scarring, dyspigmentation, infection and rarely, damage to underlying nerves.
Electrosurgery and curettage, blunt dissection, carbon dioxide laser are costly options for cutaneous and anogenital warts without distinct advantages; may be tried if topical agents or cryotherapy fail.
Practice points

·         as some warts may regress spontaneously, no treatment may be an option

·         HPV persists after treatment and a degree of infectivity may remain even in the absence of clinical lesions

·         patients with cutaneous warts should be advised about ways to reduce the chance of spreading the infection (individual towels and avoiding skin maceration)

·         plantar warts at pressure points should be treated with non-surgical methods to reduce risk of painful scarring

·         in patients with diabetes, lesions may be best left untreated since poor circulation may result in infection

·         specialist referral is required for oral, laryngeal, urethral, anorectal, vaginal and cervical (especially if cervical dysplasia present on Pap smear) warts

Anogenital warts

·         patients with warts should use condoms particularly with new sexual partners as they protect against other STIs; however, condoms may only reduce the risk of HPV transmission

·         HPV types that cause external visible warts are rarely associated with cervical abnormalities that can cause cancer; women should have regular cervical smears as part of the usual cervical screening program

 

SALICYLIC ACID

Mode of action
Keratolytic, weak antifungal and antibacterial actions.

Indications
Dandruff; Dermatitis; seborrhoeic; Ichthyosis; Psoriasis, Acne; Warts (cutaneous), corns and calluses; Fungal infections.

Contraindications
Allergy to salicylic acid; Use on facial and anogenital warts, moles, birthmarks; Use on inflamed, broken or infected skin; Use in intertriginous areas.
Specific considerations
Diabetes, peripheral vascular disease: acute inflammation or ulceration may occur, especially on feet.
Elderly: Age-related peripheral vascular disease makes acute inflammation and ulceration of the extremities more likely.
Children: At increased risk of toxicity because of increased absorption and increased ratio of treated area to total body surface area; lower threshold for skin irritation; do not use in neonates.
Pregnancy: Safe to use for warts; for other uses, contact specialised information service

Lactation: Safe to use for warts.
Adverse effects
Salicylate intoxication and death have resulted from the topical use of salicylic acid.
Factors that increase the risk of salicylate intoxication include age of patient, amount applied, frequency of application and occlusion (either naturally in skin folds or as occlusive dressings).
Infrequent: skin irritation.
Rare: skin ulceration, erosion, salicylism (intoxication due to absorption; symptoms include confusion, dizziness, headaches, rapid breathing, tinnitus).
Dosage
Psoriasis, seborrhoeic dermatitis affecting body: Apply cream or lotion in a thin layer to affected areas 2–3 times a day.
Scalp psoriasis, dandruff, seborrhoeic dermatitis: Apply shampoo to wet hair and massage vigorously into scalp and leave for at least 3–5 minutes; rinse hair thoroughly after shampooing; repeat twice a week.
Warts, corns, calluses: Before application, clean affected area, soak wart in warm water for 5 minutes, remove loose tissue with a blade, pumice stone, cloth or emery board and dry thoroughly. Apply preparation to lesion only; contact with adjacent tissue may be reduced by encircling lesion with soft paraffin or a bandage.
Apply solution or cream 1–2 times a day.
Acne: Cleansing bar, lotion, lather with warm water and rinse off 2–3 times a day.
Wipes, wipe pad over affected area 2–3 times a day; do not rinse after treatment.
Patient counselling
Avoid contact with eyes, mouth and other mucous membranes.

Wash hands immediately after applying medication, unless hands are being treated.
Solutions for the removal of warts should not be used near heat or open flame or while smoking; avoid inhalation of vapours.
Practice points

·         keratolytic activity of salicylic acid potentiates effects of topical corticosteroids, dithranol and tar by increasing their dermal penetration

·         cumulative irritant or drying effect with abrasive or medicated soaps or cleansers, acne products, alcohol-containing preparations and medicated cosmetics; avoid combinations if possible

·         to minimise systemic absorption following application, do not use for prolonged periods, in high concentrations, on large areas of the body, or on inflamed or broken skin

·         to remove thick, adherent scales in psoriasis, creams or lotions may be used under occlusion overnight, eg using a plastic shower cap

·         to avoid excessive drying, begin acne treatment with a single application daily and then, if necessary, increase frequency gradually; use cautiously with other topical acne preparations

·         may be used with other agents such as coal tar (in eczema and psoriasis), dithranol (in psoriasis), lactic acid, trichloracetic acid and podophyllum resin (removal of warts)

·         there is a lack of substantial evidence that the combination of lactic acid and salicylic acid is any more effective than salicylic acid alone in treating warts

Products

SALICYLIC ACID 20 % + LACTIC ACID 5 % + POLIDOCANOL 2 % TOPICAL LOTION  10 ML (COLLOMACK®)

 

13.08 MISCELLANEOUS

B-SITOSTEROL

Indications
burns; chronic wounds (bed ulcers, diabetic foot, leg ulcers), surgical wounds; cracked heels, cracked nipples.

Products

B-SITOSTEROLE CREAM (30-75) GM TUBE (AVOMEB®, MEBO®)

 
CALAMINE

Calamine has mild astringent and antipruritic actions and is used as a dusting powder, cream, lotion, or ointment in a variety of skin conditions although its value is uncertain.

Products

CALAMINE 15 %+ZINC OXIDE 5 % CREAM (VASOGEN®)

CALAMINE 15 %+ZINC OXIDE 5 % LOTION   200 ML BOTTLE (AL RAZI CALAMIN®)

 

DEPROTEINIZED DYALICATE

Mode of action
concentrated deproteinized calf blood extract with trophic and healing action. Containes nucleotides, nucleozides, glycolipides, oligopeptides, aminoacids, essential microelements, electrolits and intermediar glucidic and lipidic metabolism products. Stimulates ATP synthesis through the glucose and oxygen caption growth by special cells in conditions of tissular hypoxia, accelerates regeneration of cut tissues, angiogenesis, revascularisation of ischemizated tissues, colagen synthesis and plagues reepitelization.
Indications
atherosclerotic or diabetic angiopathy; cerebral, ischemic or haemorrhagic ictus, myocardium infarct, trophic ulcers, decubitus, spread chemical and termic burns.

For ointment and gel - treatment of trenant plagues, burns, ulcers and venous insufficiency. It is applied around the plague and on the newly formed epithelium at its boundaries. If the plague doesn’t ooze anymore it is totally covered with the ointment. On the ozeing part gel is applied.

For dental forms – for topical treatment of mucosal lesions and denture pressure sores.
Contraindications

Hyper sensibility to the drug. Congestive cardiac insufficiency, lung edema, oliguria, anuria or hyper hydration.

Side effects

Allergic reaction (rash, pruritus, anaphylactic shock).

Dosage
250-500 ml i.v. or i.a. dayly or several times per week with the speed of 20-40 drops/min, in sum  10-20 perfusions.

For skin gel or ointment – it is applied in a thin layer 2-3 times per day.

Patient counselling
In cases of bedsores apply gel until a scab emerges and then use ointment until the new skin surface appears. For burns use either gel or ointment. Normal course of treatment depends on the body's healing process, but usually lasts from 4 to 8 weeks. Use of the gel may irritate or burn the skin, but these side effects do not require interruption of therapy.

Products

DEPROTEINIZED DYALICATE AMP 2-10 ML (SOLCOSERYL®)

DEPROTEINIZED DYALICATE DENTAL PASTE  5 GM (SOLCOSERYL®)

DEPROTEINIZED DYALICATE GEL (20-30) GM (SOLCOSERYL®)

DEPROTEINIZED DYALICATE OINTMENT (20-30) GM (SOLCOSERYL®)

 

EMOLLIENT CREAM AND OINTMENT

Products

EMOLLIENT CREAM

EMOLLIENT OINTMENT

 

HEPARIN + CEPAE EXTRACT + ALLENTOIN

Heparin: loosens the tissue structure. It has an anti-inflammatory effect and helps to bind water to the scar tissue.

Cepae extract: is obtained from onions. It generates an anti-inflammatory, bactericidal effect. And it reduces swelling while preventing excessive growth of the connective tissue.

Allantoin: encourages wound healing and has a soothing effect. In older scars its most important effect is to replenish and regulate the extreme lack of water in the scar tissue – and to promote blood flow.

Indications
burns; chronic wounds, scars, surgical wounds.

Products

HEPARIN + CEPAE EXTRACT + ALLENTOIN GEL  50GM (CONTRATUBEX®)

 

SODIUM STIBOGLUCONATE

Pharmacokinetics

The pentavalent antimony compounds are poorly absorbed from the gastrointestinal tract. After intravenous doses an initial distribution phase is followed by biexponential elimination by the kidneys. The elimination half-life of the initial phase is about 1.7 hours and that of the slow terminal phase is about 33 hours. The corresponding half-lives after intramuscular doses are reported to be 2 hours and 766 hours respectively.Antimony has been detected in breast milk

Uses and Administration

Pentavalent antimony, as sodium stibogluconate or meglumine antimonate, is used as first-line treatment for all forms of leishmaniasis except Leishmania aethiopica infections.

For systemic use, sodium stibogluconate is given by intramuscular or intravenous injection as a solution containing the equivalent of 100 mg of pentavalent antimony per mL. Intramuscular injection is generally preferable. Intravenous injections must be administered very slowly (over at least 5 minutes) and preferably through a fine needle to avoid thrombophlebitis; as with trivalent antimony compounds, they should be stopped immediately if coughing, vomiting, or substernal pain occurs. Meglumine antimonate is given by deep intramuscular injection as a solution containing the equivalent of 85 mg of pentavalent antimony per mL. Doses are expressed in terms of the equivalent amount of pentavalent antimony.

Local variations exist in treatment schedules but WHO recommends the following regimens:

In visceral leishmaniasis, initial treatment is based on daily injection of pentavalent antimony 20 mg/kg to a maximum of 850 mg for at least 20 days. The length of treatment varies from one endemic area to another, but is continued until no parasites are detected in consecutive splenic aspirates taken at 14-day intervals. Patients who relapse are re-treated at the same dose

Early non-inflamed lesions of cutaneous leishmaniasis due to all forms of Leishmania except L. aethiopica, L. amazonensis, and L. braziliensis may be treated by infiltration with intralesional injections of 1 to 3 mL of sodium stibogluconate or meglumine antimonate (approximately 100 to 300 mg of pentavalent antimony), repeated once or twice if necessary at intervals of 1 to 2 days. Systemic therapy with pentavalent antimony 10 to 20 mg/kg daily is given if the lesions are more severe and continued until a few days after clinical and parasitological cure is achieved.

Cutaneous leishmaniasis due to L. aethiopica is not responsive to antimonials at conventional doses. In cutaneous leishmaniasis due to L. braziliensis, prolonged systemic treatment with pentavalent antimony 20 mg/kg daily for a minimum of 4 weeks is indicated. Similar doses are required for diffuse cutaneous leishmaniasis due to L. amazonensis and are continued for several months after clinical improvement occurs. Relapses should be expected until immunity develops.

In mucocutaneous leishmaniasis, daily doses of pentavalent antimony 20 mg/kg are given for a minimum of 4 weeks; if the response is poor, 10 to 15 mg/kg may be given every 12 hours. Relapses are well known and have generally been associated with inadequate or interrupted treatment; they are treated with the same drug given for at least twice as long as the original treatment. Only when that fails should alternative treatment be given.

Contraindications

Allergy to sodium stibogluconate

Significant impairment of renal function

Adverse Effects, Treatment, and Precautions

Adverse effects are generally less frequent and less severe with the pentavalent antimony compounds sodium stibogluconate and meglumine antimonate than with trivalent compounds such as antimony sodium tartrate. Nevertheless, similar precautions should be observed, especially in patients on high-dose therapy.

Intramuscular injections of sodium stibogluconate can be painful and intravenous use has been associated with thrombophlebitis.

Common side-effects of pentavalent antimony are anorexia, vomiting, nausea, malaise, arthralgia and myalgia, headache, lethargy, and pancreatitis. ECG changes are dose-dependent and most commonly include T-wave inversion and prolonged QT interval. Renal damage is a rarely reported toxic effect. Pentavalent antimony is usually well tolerated. Serious side-effects when they occur usually involve the liver or the heart when it is prudent to interrupt the course temporarily.

Breast feeding: The amount of antimony distributed into the breast milk of a patient given sodium stibogluconate was considered not to constitute a hazard and oral absorption was not detected in an animal study.1 The American Academy of Pediatrics also considers that the use of antimony is usually compatible with breast feeding.2 Others, however, have felt that more safety evaluation was required before antimony could be considered completely safe during breast feeding


Table 13–01 Comparison of Vehicles

Vehicle

Effect

Indications

Comments

Examples

ointments

occlusive and lubricating

dry, scaly skin

better topical penetration of incorporated drugs than creams and lotions; greasy, difficult to wash off; may cause folliculitis

soft paraffin, lanolin

creams

cooling and lubricating

moist or dry skin; use where a washable (non-greasy) and cosmetically elegant vehicle is needed

preservatives can cause sensitisation

cetomacrogol cream, aqueous cream

lotions and solutions

drying and cooling

hairy and intertriginous regions; acute exudation

can be applied without friction

calamine lotion, potassium permanganate solution

pastes

drying and protective

psoriasis, warts

more occlusive and absorptive, less greasy than ointments, reducing spreading of active ingredient

Lassar's paste (zinc oxide and salicylic acid), Upton's paste (salicylic acid and trichloracetic acid)

aerosols and sprays

cooling

conditions in which direct application is difficult or painful

allow application without touching skin

antifungals, eg miconazole sprays, sunscreen spray for hairy areas

                                                                                                                                                                                   

Table 13–02 Suggested Weekly Quantities of Topical Preparations

Age

Face & neck

Arm & hand

Leg & foot

Trunk (front)

Trunk (back incl. buttocks)

3–6 months

7 g

7 g

10 g

7 g

10 g

1–2 years

10 g

10 g

15 g

15 g

20 g

3–5 years

10 g

15 g

20 g

20 g

25 g

6–10 years

15 g

20 g

30 g

25 g

35 g

Adult & child >10 years

20 g

30 g

55 g

50 g

50 g

Based on twice a day application for 1 week; for corticosteroids, calcipotriol and pimecrolimus do not exceed the suggestions without specialist recommendation

 

 

 

 

 

 

 

 

 

 

 

Table 13–03 Comparison Of Potency and Uses of Topical Corticosteroids

Corticosteroid

Examples of indications

mild

hydrocortisone (0.5–1%)

facial and flexural dermatitis and psoriasis; nappy dermatitis

hydrocortisone acetate (0.5–1%)

moderate

betamethasone valerate (0.02 & 0.05%)

mild-to-moderate atopic dermatitis, adjunctive treatment in extensive psoriasis

triamcinolone acetonide (0.02%)

desonide (0.05%)

potent

betamethasone dipropionate (0.05%)

short term use in severe inflammatory dermatoses

betamethasone valerate (0.1%)

mometasone furoate (0.1%)

more severe conditions, eg discoid eczema

methylprednisolone aceponate (0.1%)

very potent

betamethasone dipropionate in an optimised vehicle (0.05%)

severe eczema and psoriasis, eg refractory lichen simplex chronicus; also useful for eczema of hands and feet, occlusion may be used but atrophy may occur