CHAPTER 01 GASTRO-INTESTINAL SYSTEM

01.01 DYSPEPSIA AND GASTRO-OESOPHAGEAL REFLUX DISEASE

Dyspepsia
Pain or discomfort (including fullness, early satiety, bloating or nausea) centered in the upper abdomen. Functional (non-ulcer) dyspepsia is a condition where investigation of dyspepsia has not identified an underlying organic disease.

Before starting treatment
Consider stopping, replacing or adjusting regimen of causative drug, e.g. NSAIDs, bisphosphonates, tetracycline's, calcium channel blockers, if possible.

Refer patients >50 years with new-onset symptoms, and all patients with alarm symptoms (e.g. anaemia, dysphagia, evidence of bleeding, weight loss, recurrent vomiting) for endoscopy.
Distinguish
gastro-oesophageal reflux disease from other causes of dyspepsia.
Avoiding specific foods and changing lifestyle (e.g. low fat diet, avoidance of coffee and alcohol, weight loss and stopping smoking) may help.

Drug choice

Drug treatment has a low success rate; reassurance and explanation are the keys to management. If acid suppression is required, avoid long term continuous treatment; use intermittent short courses of treatment as needed.
Antacids
'When required' use may be appropriate in some patients with dyspepsia but antacids appear to be no better than placebo in functional dyspepsia (where placebo response is 20–60%).

H. pylori eradication
Dyspepsia: consider the 'test and treat' strategy: perform a non-invasive H. pylori test, eradicate the infection in those testing positive and give symptomatic treatment to those testing negative.

Functional dyspepsia: eradication cures symptoms in a minority of cases (similar to any other treatment for functional dyspepsia) and appears to be cost effective. See Table 01.01 Recommended H. pylori eradication regimens.

Acid suppression

Dyspepsia: PPIs are more effective than antacids or H2 antagonists at reducing symptoms; try full dose PPI for 4 weeks.
Functional dyspepsia: try either a H2 antagonist or PPI for 4 weeks (approximately 10% of patients benefit over placebo). As there is no evidence of any difference in effectiveness between the 2 classes, consider an H2 antagonist as it is less expensive.

Other drug treatment

At present, there is insufficient evidence regarding the value of domperidone and metoclopramide in functional dyspepsia. Other options include low dose TCAs, antispasmodic agents, sucralfate, behavioural therapy or psychotherapy, but none is of proven benefit.

Length of treatment

If the patient fails to respond after 4 weeks of acid suppression, consider increasing the dose of acid suppressant or switching drug classes for a further 4 weeks.

Refer to a specialist people whose symptoms persist after:

·         confirmed eradication of H. pylori

·         8 weeks of acid suppressant treatment.

 

Gastro-oesophageal reflux disease

A chronic and relapsing condition where exposure of the oesophagus to refluxed gastric contents causes symptoms (such as heartburn and acid regurgitation) or mucosal damage (oesophagitis). Symptom severity correlates poorly with the degree of mucosal damage.

Rationale for drug use:
Relieve symptoms and improve quality of life, Heal oesophagitis. Reduce risk of complications.
Before starting treatment

Lifestyle changes (see Dyspepsia) may be useful and should be recommended, although evidence for their effectiveness in GORD is limited.

Other suggestions include eating smaller meals, not eating before bed, raising the head of the bed and avoiding tight clothing.

Where possible stop drugs (e.g. NSAIDs, calcium channel blockers, nitrates and theophylline) known to cause or worsen reflux.

Endoscopy is indicated for:

·         Alarm symptoms (including dysphagia, weight loss, bleeding, abdominal mass, anaemia).

·         symptoms which are atypical or refractory to initial treatment

·         Longstanding symptoms in those >45–55 years who may be at risk of complications.

Treatment is often empiric as most patients with GORD have no endoscopic evidence of the disease.
Drug choice
Antacids: more effective than placebo in the relief of daytime symptoms. Use often limited by their short duration of action.
H2 antagonists: provide adequate symptom relief and healing for many patients with mild-to-moderate GORD.
PPIs: faster and more effective than H2 antagonists in controlling symptoms and healing inflammation, regardless of disease severity. All PPIs are clinically equivalent for most patients.
Metoclopramide and domperidone: may be useful in some patients with dyspeptic symptoms (e.g. bloating or early satiety) as well as reflux. They are as effective as H2 antagonists in relieving symptoms, but do not heal oesophagitis.
Treatment regimens
Use a graduated approach, depending on symptom severity.
Mild, intermittent symptoms
Patient or pharmacist directed therapy: lifestyle measures and antacids (short intermittent courses of H2 antagonist may be considered).
Mild-to-moderate symptoms
Prescriber directed therapy: depending on symptom severity choose
'Step-down: start with a PPI, then use minimum dose of PPI required to control symptoms or a less potent agent once symptoms are controlled.
'Step-up': lifestyle measures and antacids, then H2 antagonists, followed by PPIs if necessary.
Moderate-to-severe symptoms
Use the 'step-down' approach for rapid control of symptoms, confirmation of diagnosis and healing of oesophagitis.
Refer those with refractory or complicated disease to a specialist.
Length of treatment
For endoscopically-determined severe oesophagitis or complicated disease (e.g. stricture formation, Barrett's oesophagus) continue regular PPI long term.
In other people with symptomatic improvement, continue treatment for 4 weeks at the same dose. Consider stopping treatment after the initial course; a significant minority will not relapse.

In those who relapse consider endoscopy (if not done earlier) or repeat the course of previously successful drug, followed by 'step-down' to intermittent, symptom-driven treatment with the least costly but effective regimen.

Treatment endpoints
For people with complications, such as stricture or bleeding from oesophagitis, confirmation of healing is required; otherwise it is unnecessary.
H. pylori and GORD
There is no consistent evidence of an association between H. pylori and GORD.
However, it is recommended that H. pylori is tested for and eradicated in patients with GORD who require long term PPI treatment. This is because profound acid suppression may accelerate the progression of H. pylori-induced atrophic gastritis, increasing the potential risk of cancer.
Infant GORD
Common, but does not usually require treatment as it resolves with increasing age. If severe, thickening oral fluids may help. H2 antagonists or PPIs are also used but drug treatment should be avoided if possible; consider referral to a specialist.
Practice points

·         doubling dose of H2 antagonist does not increase efficacy and is not appropriate.

·         intermittent use of PPIs may be more cost-effective than continuous use of H2 antagonists

·         in most cases combination treatment is less effective than increasing the dose of PPI

·         evidence suggests that control of symptoms equates with healing of oesophagitis in patients maintained on PPIs.

Helicobacter pylori-related ulcers
H. pylori infection is the most common cause of peptic ulcer disease (PUD); most other cases are associated with the use of NSAIDs, see
NSAID-related ulcers.
Eradication of H. pylori is considered first line treatment for PUD; see
Recommended H. pylori eradication regimens (Table01.01). This confers long term cure in most of those affected by PUD. Other treatments that do not eradicate H. pylori may heal ulcers and prevent relapse, but only while continued.
Delay eradication of H. pylori in acute severe complications of PUD until the person is stabilized.
Rationale for drug use
Heal and reduce relapse rate of duodenal and gastric ulcers caused by H. pylori.
Reduce risk of PUD in patients who are H. pylori positive and at increased risk of NSAID-induced ulcer complications before starting long term NSAID.
Symptomatic relief in functional (non-ulcer)
dyspepsia.
Before starting treatment
Confirm the presence of H. pylori by urea breath test, faecal antigen test, laboratory-based serology or biopsy-based methods.
When to start treatment
Confirmed H. pylori infection and:

·         acute, recurrent or chronic gastric or duodenal ulcer

·         gastric mucosa-associated lymphoid tissue (MALT) lymphoma

·         following gastric cancer resection.

Consider eradicating H. pylori in atrophic gastritis, first degree relatives of gastric cancer patients and when treating uncomplicated non-ulcer dyspepsia.
Treatment regimens

Regimens with eradication rates of >80% are recommended. The most consistently effective combination is a PPI with clarithromycin and amoxicillin (see Table 01.01 Recommended H. pylori eradication regimens). Dual therapy and other ad hoc regimens are not recommended because of unsatisfactory eradication rates and the risk of developing drug resistance. True reinfection is uncommon after successful eradication. In patients with refractory infection or who undergo reinfection after therapy, H. pylori is usually antibiotic-resistant.

Factors influencing drug selection
Using at least 2 antibacterials improves eradication rates and reduces the subsequent acquired resistance (especially with metronidazole) associated with partial treatment.
Compliance is influenced by:

·         adverse effect profile; all regimens cause nausea, diarrhoea and taste disturbance; adverse effects are more common with metronidazole

·         cost to patient (only some available on the PBS)

·         duration of treatment (7-day treatments have the lowest rate of treatment withdrawal)

·         number of tablets required each day.

The optimal second line regimen when treatment fails is unclear. Ideally, treatment should be guided by sensitivity testing. If this is unavailable, use quadruple therapy (see Table 01.01 Recommended H. pylori eradication regimens) or PPI-based triple therapy using different antibacterial combination to initial regimen.
Microbiological culture and antibiotic sensitivity tests are indicated when 2 courses fail.
Treatment endpoints
Eradication is defined as testing negative for the organism 4 weeks or longer after eradication therapy, and at least 2–4 weeks after stopping acid suppressant treatment to avoid a false-negative result.
Confirmation of H. pylori eradication is generally advisable but not always necessary (varies according to factors such as initial indication and availability of investigations).
If indicated, use either the urea breath test or endoscopy (particularly for gastric ulcers and complicated duodenal ulcers, e.g. bleeding or perforation).
Serology is not a valid method for confirming eradication as antibody levels can take up to a year to fall.
Continue maintenance acid suppressant treatment in those with gastric ulcers, large ulcers (>1 cm diameter) or complicated ulcer disease until healing has been confirmed by endoscopy. Confirm bacterial eradication after stopping acid suppressant treatment.
Long term maintenance acid suppressant treatment may be necessary if eradication treatment fails or is contraindicated and if peptic ulcer recurs even in the absence of reinfection.
Gastric cancer

H. pylori is a recognized risk factor for gastric cancer. Eradication may reduce the risk of cancer at least in the short term; there is not enough evidence to recommend screening and treating the asymptomatic general population for infection (other than in areas of high gastric cancer prevalence).
Practice points

·         antacids may provide rapid symptomatic relief, but healing is limited

·         asymptomatic H. pylori infection does not require treatment

·         poor compliance and antibiotic resistance are major causes of failure to eradicate H. pylori; inform patients about possible unpleasant (but not serious) adverse effects, the need for compliance and the possibility of a cure without the need for long term medication.

NSAID-related ulcers
Most peptic ulcers induced by NSAIDs (including aspirin) are gastric; they are often silent and present with a complication. H. pylori infection and NSAIDs appear to be independent risk factors for peptic ulcer and peptic ulcer bleeding, see
Helicobacter pylori-related ulcers.
Rationale for drug use
Heal ulcer to provide symptom control and to reduce risk of complications (e.g. bleeding, perforation, obstruction).
Before starting treatment
Test for H. pylori using urea breath test, faecal antigen test, laboratory-based serology or biopsy-based methods.
Treatment
Stop the NSAID if possible and substitute simple analgesics (see
Paracetamol) and non-drug treatment. Then use H2 antagonist or PPI for 4–8 weeks.
If the NSAID cannot be stopped, healing is slower and recurrence more likely. Use PPI or misoprostol (although misoprostol is not always well tolerated).
After treatment, follow-up endoscopy to confirm healing is advisable.
Eradication of H. pylori infection is recommended after the ulcer has healed; see
Recommended H. pylori eradication regimens (Table 01.01).
Prevention
PPI, double dose H2 antagonist and misoprostol are all effective for primary and secondary prevention. Continue for duration of NSAID treatment.
PPIs at standard doses are cheaper and more convenient (once daily dosing) than double dose H2 antagonist. Misoprostol 400 micrograms daily has fewer adverse effects than 800 micrograms daily but is less effective in preventing gastric ulcers.
Practice points

·         in patients who continue to take NSAIDs, H. pylori eradication followed by acid suppression does not enhance ulcer healing compared with acid suppression alone; however, its eradication is recommended to eliminate it as a potential cause of ulcers.

 

01.01.01 Anti-acids and simeticone
Other agents such as alginic acid and simethicone are often included in antacid preparations. Claims are made that these agents help relieve symptoms of reflux or excess gas, but there is limited evidence to support this.
Mode of action

Neutralize hydrochloric acid secreted by gastric parietal cells.
Indications:

Symptomatic relief of: dyspepsia ; peptic ulcer disease (PUD); gastro-oesophageal reflux disease (GORD).

Specific considerations
Constipation exacerbated by antacids containing aluminium and calcium.
Diarrhoea exacerbated by laxative effect of antacids containing magnesium.
Heart failure, chronic renal failure, cirrhosis, and oedema avoid antacids containing sodium; may increase fluid retention.
Renal impairment: Antacids containing aluminium and/or magnesium should not be used as in severe impairment; as accumulation may occur.
Pregnancy: Safe to use as antacids; ADEC category A.

Patient counselling
Take between meals or at bedtime when symptoms occur or you expect they might occur.
Tablets should be chewed or sucked before swallowing for the best effect.
Antacids can reduce the effect of a number of other medicines taken by mouth. The best way to avoid a problem is to separate taking antacids and other medicines by at least 2 hours.
Practice points

·         optimum antacid effect is achieved if taken 1–3 hours after meals

·         liquid preparations are more effective, but less convenient, than solid preparations

 

ALUMINIUM HYDROXIDE

Mode of action

Neutralize hydrochloric acid secreted by gastric parietal cells.
Indications
Symptomatic relief of dyspepsia, peptic ulcer disease and GORD; Phosphate binder in chronic renal failure.

Specific considerations

Constipation: exacerbated by antacids containing aluminium and calcium.
Diarrhoea: exacerbated by laxative effect of antacids containing magnesium.
Heart failure, chronic renal failure, cirrhosis, oedema: avoid antacids containing sodium; may increase fluid retention.
Renal impairment: Aluminium accumulation may result in bone disease and encephalopathy; in severe impairment do not use as an antacid and minimize use as a phosphate binder.
Surgery: if using as a phosphate binder in renal impairment continue treatment preoperatively.
Pregnancy: safe to use as an antacid; contraindicated as a phosphate binder.
Adverse effects
Common: constipation.
Infrequent: hypophosphataemia.
Rare: intestinal obstruction, osteomalacia, proximal myopathy, encephalopathy, anaemia.
Dosage
Antacid, dose according to label.
Phosphate binding in renal impairment, 600–1200 mg with food, usually up to 3600 mg (6 tablets) daily.
Patient counselling
Phosphate binder: if you skip a meal save your dose and take it when you next eat.

Practice points

·         relatively slow onset of action as an antacid

·         commonly combined with magnesium to prevent constipating effects

·         in moderate-to-severe renal impairment monitor plasma aluminium concentrations at baseline and every 3 months

·         optimum antacid effect is achieved if taken 1–3 hours after meals

·         liquid preparations are more effective, but less convenient, than solid preparations

Products

Multi combination products

 

MAGNESIUM ANTACIDS
Agents include magnesium carbonate, magnesium hydroxide and magnesium trisilicate; usually used with aluminium hydroxide. Magnesium hydroxide is the most potent and fastest acting.

Mode of action
Neutralize hydrochloric acid secreted by gastric parietal cells.
Indications
Symptomatic treatment of dyspepsia, peptic ulcer disease and GORD.
Adverse effects
Common: diarrhoea, belching (magnesium carbonate).
Rare: hypermagnesaemia.
Dosage: Dose according to label.

Products
ALUMINIUM + MAGNESIUM COMPLEXES SUSP. (ALKACID
®, ALOXAL®, ALUMAG®, HYDROGEL®, MAALOX PLUS®, MAALOX®, MOXAL PLUS®, MOXAL®, NEUTRACID®, NOVAGEL PLUS®, NOVAGEL® )

ALUMINIUM + MAGNESIUM COMPLEXES TABS (ACENIL®, ALUMAG®, MALUGEL®, MAALOX PLUS®, MAALOX®, MOXAL PLUS®, MOXAL®, NOVAGEL PLUS®, NOVAGEL®, RAMCID®)

 

SIMETICONE (activated DIMETICONE)

Mode of action

Simeticone is a mixture of liquid dimeticones containing finely divided silicon dioxide to enhance the defoaming properties of the silicone. It lowers surface tension and when administered by mouth causes bubbles of gas in the gastrointestinal tract to coalesce, thus aiding their dispersion.

Indication

Simeticone is used for the relief of flatulence and abdominal discomfort due to excess gastrointestinal gas in disorders such as dyspepsia and gastro-oesophageal reflux disease.

Simeticone is also used as a defoaming agent in radiography or endoscopy of the gastrointestinal tract.

Dosage

Doses of 100 to 250 mg three or four times daily have been given. For many gastrointestinal disorders, it is given with an antacid.

Doses of 20 to 40 mg of simeticone have been given with feeds to relieve colic in infants.

Practical points

A brief review of the use of simeticone for gastrointestinal symptoms concluded that although it was commonly prescribed in combination with an antacid, there was no good evidence that it provided additional benefit. When used alone it probably helps to relieve minor postoperative and postprandial symptoms and it was a useful aid in upper gastrointestinal endoscopy.  However, some considered there was no convincing evidence that it was effective for the treatment of eructation, flatulence, or other signs or symptoms of excess gastrointestinal gas.  

Products:

SIMETICONE TABS 120-125 MG (CHEWABLE) (DEFLAT®, GAZIX®)

 

01.02 ANTISPASMODICS AND OTHER DRUGS ALTERING GUT MOTILITY

Nausea and vomiting
Rationale for drug use:
Prevent or relieve symptoms.
Prevent complications (dehydration, electrolyte disturbance).
Before starting treatment
Identify, treat or remove cause if possible.
Ensure adequate hydration.
Drug choice
Dopamine antagonists
All except domperidone have central dopamine antagonist activity and may cause EPSE.
Domperidone and metoclopramide are widely used to treat nausea and vomiting. They also have prokinetic activity which may be useful in nausea and vomiting due to gastroparesis.
Prochlorperazine is widely used in the prevention and treatment of nausea and vomiting. It is available as tablets, suppositories or injection.
Droperidol is used for postoperative nausea and vomiting (PONV). It has a long duration of action and counteracts adverse opioid effects; however, the risk of sedation and EPSE limit its use. Although it has been associated with prolongation of QT interval this does not appear clinically important with antiemetic doses.
Haloperidol is used to treat nausea and vomiting following cancer chemotherapy when other agents are ineffective and the risk of adverse CNS effects is considered acceptable.
Sedating antihistamines
Dimenhydrinate, pheniramine and promethazine are mainly used to prevent motion sickness and for nausea and vomiting associated with other vestibular disorders. They have additional sedative and anticholinergic properties.
Anticholinergics
Hyoscine hydrobromide is used to prevent motion sickness but may be poorly tolerated due to anticholinergic adverse effects.
5HT3 antagonists
Dolasetron, granisetron, ondansetron and tropisetron are mainly used to prevent or treat nausea and vomiting following cancer chemotherapy, radiotherapy or surgery. They appear to have similar efficacy.
Substance P antagonists
Aprepitant is used with a 5HT3 antagonist and dexamethasone to prevent nausea and vomiting associated with highly emetogenic chemotherapy.
Corticosteroids
Dexamethasone is used for prevention of PONV and as adjunctive treatment in chemotherapy-induced nausea and vomiting.
Benzodiazepines
Lorazepam may be used as adjunctive treatment in chemotherapy-induced nausea and vomiting, particularly for anticipatory nausea and vomiting. Efficacy may be related to anxiolytic and sedative effects.
Factors influencing drug selection
The main factor influencing drug selection is the cause of nausea and vomiting. Other factors include:
Age: the EPSE of dopamine antagonists are more common in children and young adults (usually as acute dystonic reactions) and in the elderly. Age can also influence the risk and severity of nausea and vomiting (e.g. postoperative vomiting is twice as common in children compared to adults).
Gender: females are more susceptible to nausea and vomiting following cancer chemotherapy, radiotherapy or surgery.
Route of administration: drugs in rectal or parenteral form are necessary where oral medication is not tolerated or is contraindicated (e.g. after major surgery).
Severity: in prolonged severe vomiting, high dose combination antiemetic treatment is often needed (seek specialist advice).
Special cases
Cancer chemotherapy
Nausea and vomiting due to chemotherapy can affect quality of life and may result in dehydration, weight loss and malnutrition.
Radiotherapy:

Consider need for prophylaxis with a 5HT3 antagonist and/or dexamethasone. Risk of radiotherapy-induced nausea and vomiting is influenced by the site and dose of radiation as well as individual patient factors.
Pregnancy:

Nausea and vomiting are common during the first trimester. Avoid drug treatment if possible. Emphasize the importance of adequate hydration (e.g. using ice chips if necessary).
Dietary modification may help. Symptoms may also improve with ginger (up to 1 g daily) or pyridoxine (vitamin B6, up to 50 mg twice daily). If these are not effective consider using metoclopramide, promethazine or prochlorperazine orally, if tolerated. Prochlorperazine suppositories are useful if nausea and vomiting are severe.
Hyperemesis gravidarum: IV rehydration is the main treatment. Metoclopramide, prochlorperazine or ondansetron are used if symptoms are prolonged and intractable.
Postoperative
Prophylaxis is important and provides the greatest benefit for patients at higher risk of PONV. There is no one treatment of choice; 5HT3 antagonists, droperidol, dexamethasone, prochlorperazine and dimenhydrinate have all been shown to be effective. Combination treatment may be more effective than a single agent especially in moderate-to-high risk patients.
Antiemetic prophylaxis is most effective when given at the end of surgery except for dexamethasone which should be given before induction of anaesthesia.
Metoclopramide in standard doses (10 mg IV) is not effective for prevention of PONV.
Motion sickness
Hyoscine hydrobromide and some of the sedating antihistamines are used. They are more effective if given before motion sickness develops (the first dose is usually given before travel). Hyoscine hydrobromide may be slightly more effective than the sedating antihistamines but may not be as well tolerated.


01.02.01 Antispasmodics

CHLORDIAZEPOXIDE+CLNIDINIUM BROMIDE

 

CHLORDIAZEPOXIDe 

Mode of action

Chlordiazepoxide causes depressant effects on the sub cortical levels of the CNS and calming effects due to actions on the limbic system and reticular formation.

Indications

Chlordiazepoxide is a benzodiazepine with general properties similar to those of diazepam. It is used in the short-term treatment of anxiety disorders and insomnia. Chlordiazepoxide is also used in muscle spasm, in alcohol withdrawal syndrome, and for premedication.

Contraindications

As for Diazepam.

Adverse effect

As for Diazepam.

Hepatic impairment: progressive drowsiness began after 20 days of treatment with chlordiazepoxide in a woman with cirrhosis and hepatitis.  One week after stopping the drug the patient could not be roused and full consciousness was not regained for another week. Accumulation of active metabolites of chlordiazepoxide may have been responsible for the prolonged stupor.

Chlordiazepoxide has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Dosage

Chlordiazepoxide is given by mouth as the hydrochloride or the base; the doses given refer equally to both. It may also be administered by deep intramuscular or slow intravenous injection as the hydrochloride. Preparations formulated for intramuscular use are stated to be unsuitable for intravenous administration due to the formation of air bubbles in the solvent.

Elderly and debilitated patients should be given one-half or less of the usual adult dose.

The usual dose by mouth for the treatment of anxiety is up to 30 mg daily in divided doses; in severe conditions up to 100 mg daily has been given. For acute or severe anxiety an initial dose of 50 to 100 mg of the hydrochloride has been given by injection, followed if necessary by 25 to 50 mg three or four times daily.

For relief of muscle spasm a dose of 10 to 30 mg daily by mouth in divided doses is recommended, and 10 to 30 mg by mouth may be given before retiring for insomnia associated with anxiety.

For the control of the acute symptoms of alcohol withdrawal chlordiazepoxide or chlordiazepoxide hydrochloride may be given by mouth in a dose of 25 to 100 mg repeated as needed up to a maximum of 300 mg daily. For severe symptoms treatment may be initiated by injection of 50 to 100 mg, repeated if necessary after 2 to 4 hours.

Chlordiazepoxide hydrochloride has also been given for anaesthetic premedication in a dose of 50 to 100 mg intramuscularly one hour before surgery.

 

CLIDINIUM BROMIDE

Mode of action

Clidinium bromide is a quaternary ammonium antimuscarinic with peripheral effects similar to those of atropine. It inhibits gastric secretion of HCL and Gastro intestinal motility by competitive antagonism of acetylcholine at postganglionic parasympathetic receptor sites in smooth muscle and secretary glands.

Indications

Adjunct therapy for peptic ulcer.; Irritable Bowel Syndrome (irritable colon, spastic colon); Non-ulcer dyspepsia.

Contraindications

 Glaucoma; Prostatic hypertrophy; Benign bladder neck obstruction; Hypersensitivity to clidinium bromide.

Adverse effect

Cardiovascular: palpitations, bradycardia, tachycardia.

Central nervous system: drowsiness, flushing, headache, nervousness.

Dermatologic: urticaria, anaphylaxis, increased body temperature due to decreased sweating.

Gastro intestinal: altered taste perception, nausea, vomiting, dysphagia, heartburn, constipation, bloated feeling, paralytic ileus, gastroesophageal reflux.

Genitourinary: urinary hesitancy, retention, impotence, dizziness, insomnia, fever.

Ocular: blurred vision, mydriasis, photophobia, cycloplegia, increased intraocular pressure.

Products

CHLORDIAZEPOXIDE+CLNIDINIUM BROMIDE TABS 5+2.5MG (APO-CHLORAX®, LIBRAX®, POXIDIUM®)

 

OTILONIUM BROMIDE

Mode of action

Otilonium bromide is endowed with a marked spasmolytic action on the smooth

muscle of the digestive tract.

Indications
Treatment of irritable bowel, pain and spasm of the distal enteric tract.

Contraindications

Known hypersensitivity to the product.

Adverse Effects

At the therapeutic doses, the product does not cause atropine-like effects. Headache and dizziness are reported occasionally following oral otilonium bromide 40 mg three times daily. Gastrointestinal effects such as nausea, vomiting, epigastric pain and abdominal discomfort have occurred occasionally in patients receiving oral otilonium bromide 40 mg three times daily.

Specific considerations
To be used with caution in subjects with glaucoma, prostatic hypertrophy, pyloric stenosis.

Pregnancy and lactation: Although no hembryotoxic, teratogenic or mutagenic effects on animals have been

reported, like for all drug products during pregnancy and lactation, it should be administered only in cases of need and under medical supervision.

Overdose: In the animal, otilonium bromide was proven practically devoid of toxicity. Consequently also in the

human, no particular over dosage-related problems should appear. In case of overdose a possible symptomatic

and support therapy is recommended.

Dosage
1 Tablet 2-3 times a day, according the physician’s judgment. If otherwise not specified, treatment duration should be 5-7 days and up to 4 weeks, depending on severity of condition. Longer treatments of up to 1-2 years have been done if needed.

Products

OTILONIUM BROMIDE TABS 40 MG (SPASMOMEN®)

 

01.02.02 Antimuscarinics 

HYOSCYAMINE (HYOSCINE BUTYL BROMIDE)

Mode of action

Hyoscyamine is a tertiary amine antimuscarinic agent with central and peripheral actions. It is a more powerful suppressant of salivation than atropine and usually slows rather than increases the heart rate, especially in low doses. Its central action differs than that of Atropine in that it depresses the cerebral cortex, especially the motor areas, and produces drowsiness and amnesia.

Indications
Irritable bowel syndrome (IBS) ; Renal and biliary colic; Aid in GI radiology or endoscopy.

Contraindications

There are no contraindications for orally administered Hyoscine; however it should not be administered parenterally in the following conditions:

·         Glaucoma.

·         hypertrophy of prostate.

·         Mechanical stenosis of the gastrointestinal tract.

·         Megacolon.

·         Tachycardia.

Drug Interaction

On parenteral administration of Hyoscine Tricyclic antidepressants, Quinidine, and Amantadine can potentiate the anticholinergic effect of Hyoscine.

Adverse Effects

No Atropine-like adverse effects are observed on the salivary glands or sweat secretion when Hyoscine is administered in the usual dose. A slight increase in the pulse rate may occur when it is administered IV, parenteral administration may cause transient disturbances in accommodation.
Specific considerations
Children: use with caution in children <6 years.
Dosage
IBS, renal and biliary colic
Adult: Oral, 20 mg 4 times daily. IV/IM, 20–40 mg, repeated after 30 minutes if needed. Maximum, 100 mg/day.
Child 6–12 years: Oral, 10 mg 3 times daily. IV/IM, 0.5 mg/kg every 6–8 hours.
Aid in GI radiology: Adult, IV 20 mg as a single dose.

Products

HYOSCYAMINE (HYOSCINE BUTYL BROMIDE) AMPS 20MG/AMPS (BUSCOPAN®, SPASMOPAN®, SPASMOCIN®, SCOBUTYL®)

HYOSCYAMINE (HYOSCINE BUTYL BROMIDE) ORAL DROPS 0.125 MG/ML 15 ML BOTTLE (NEO-ALLOSPASMIN®)

HYOSCYAMINE (HYOSCINE BUTYL BROMIDE) TABS 10 MG (BUSCOPAN®, DIVIDOL®,   SCOPINAL®, SPASMONORE®, SPASMOPAN®)


01.02.03  Dopamine Antagonists ( Antiemetics)

DOMPERIDONE
Mode of Action:

Enhance gastric emptying and intestinal motility.

Indications
Marketed: Nausea and vomiting, Gastroparesis (idiopathic or diabetic).
Accepted: Stimulation of lactation.
Contraindications
Concurrent administration with ketoconazole.
Specific considerations
Children: avoid use unless indicated for cancer chemotherapy. Some practitioners may prefer domperidone to metoclopramide.
Pregnancy: safe to use; ADEC category B2.
Breastfeeding: used during first months of breastfeeding to stimulate lactation; mother may be less drowsy than with metoclopramide.
Adverse effects
Common: dry mouth, headache.
Infrequent: hyperprolactinaemia leading to galactorrhoea and gynaecomastia; rash, insomnia.
Rare: extra pyramidal effects.
Dosage
Nausea and vomiting
Adult, 10–20 mg every 6–8 hours; maximum continuous treatment 12 weeks.
Child, 200–400 micrograms/kg every 4–8 hours.
Gastroparesis: 10–20 mg 3–4 times daily for up to 6 months.
Lactation stimulation: 10 mg 3 times daily, taper dose over 7–10 days before stopping.
Maximum: 80 mg daily.
Administration instructions
Give at least half an hour before meals.
Practice points

·         does not usually cross the blood–brain barrier significantly so extra pyramidal reactions are rare; may be an alternative to metoclopramide.

Products
DOMPERIDONE SUPP. 10 MG (AS MALEATE) (MOTILAT®
)

DOMPERIDONE SUPP. 60 MG (AS MALEATE) (MOTILIUM®, VOMIVER®)

DOMPERIDONE SUSP.  5 MG/5ML (AS MALEATE) (MOTILAT®, MOTILIUM®)

DOMPERIDONE TABS 10 MG (AS MALEATE) (COSTI®, DOMPERIDE®, MOTILAT®, MOTILIUM®, PERIDON®)

 

METOCLOPRAMIDE

Mode of action

Has central dopamine antagonist activity and may cause extra pyramidal adverse effects (more likely in people <20 years). Metoclopramide enhances gastric emptying and intestinal motility.

Metoclopramide stimulates motility of the upper gastro intestinal tract without stimulating gastric, biliary, or pancreatic secretions. It increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum, resulting in accelerated gastric emptying and intestinal transit.
Indications
Marketed: Nausea and vomiting, Gastric stasis (e.g. after gastric surgery, diabetic gastroparesis), Aid in GI radiology (increases transit in barium studies), Difficult small intestinal intubation.
Accepted: Gastro-oesophageal reflux disease (GORD), Stimulation of lactation.

Combination with paracetamol: relief of migraine.
Contraindications
Phaeochromocytoma.
Specific considerations
Parkinson's disease use with caution as may worsen symptoms; domperidone is preferred.
Depression, avoid long term use as may worsen mental state.
Renal impairment: reduce dose in moderate and severe impairment.
Elderly: use lower doses; elderly people are more sensitive to adverse effects.

Children: avoid use; increased risk of extra pyramidal adverse effects.
Pregnancy: safe to use; ADEC category A.

Young adults <20 years: use low doses, increased risk of extra pyramidal adverse effects.
Breastfeeding: used during first months of breastfeeding to stimulate lactation.
Adverse effects
Common: restlessness, drowsiness, dizziness, headache.
Infrequent: extra pyramidal adverse effects, hypertension, hypotension, hyperprolactinaemia leading to galactorrhoea, diarrhoea, constipation, depression.
Rare: agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, tardive dyskinesia.
Dosage
Nausea and vomiting
Adult, oral/IV/IM 10 mg every 6–8 hours as needed.
Child, oral/IV/IM 0.15 mg/kg every 6–8 hours as needed.
Cancer chemotherapy
Adult, IV 10–40 mg every 4 hours; or IV infusion 1–3 mg/kg over 15 minutes; or SC infusion 40–120 mg over 24 hours.
Child, IV 1–2 mg/kg every 4 hours, maximum daily total of 10 mg/kg.
GORD, gastric stasis: Adult, oral 10 mg 4 times daily.
GI radiology, intubation of intestine: Adult, IV 10 mg as a single dose.
Renal impairment: Moderate impairment, reduce dose by one-quarter. Severe impairment, halve dose.
Lactation stimulation: 10 mg 3 times daily, taper dose over 7–10 days before stopping.

Counselling
This medicine may make you feel drowsy or dizzy; do not drive or operate machinery until you know how metoclopramide affects you.
Practice points

·         acute dystonic reactions are best treated by IM/IV benztropine

·         choose domperidone for stimulating lactation; drowsiness is common with metoclopramide.

Products
METOCLOPRAMIDE AMPS 10 MG/AMP (AS HCL)  (ANTIVOT®, CLOPRAM®, PRIMPERAN®)

METOCLOPRAMIDE TABS 10 MG (CLOPRAM®,  ELITAN®, PRIMPERAN®, PYLOMID®)

 

01.02.04   5HT3 Antagonists

ONDANSETRON
Mode of action

Central and peripheral 5HT3 receptor blockade.
Indications
Prevention and treatment of nausea and vomiting following cancer chemotherapy; Postoperative radiotherapy-induced where conventional antiemetics are not tolerated.

Specific considerations
Hepatic impairment: reduce dose in severe impairment.
Children: seek specialist advice about use in children <2 years.
Pregnancy: limited data available; ADEC category B1.
Breastfeeding: no data available, although 1 or 2 doses after delivery should not be a concern.
Adverse effects
Common: constipation, headache, transient rise in hepatic transaminases.
Rare: hypersensitivity reactions (including anaphylaxis), arrhythmias, ECG changes, transient visual disturbances, e.g. blurred vision, (rapid IV administration), extra pyramidal effects, seizures.
Dosage
Cancer chemotherapy
Adult: Highly emetogenic, first dose, IV 8 mg or oral 24 mg 30 minutes before chemotherapy. Maintenance, oral 4–8 mg every 12 hours for the first 24–48 hours. Moderately emetogenic, first dose, oral/IV 8 mg 1–2 hours before treatment. Maintenance, 4–8 mg every 12 hours for the first 24–48 hours.
Child >2 years: Oral/IV 0.15 mg/kg 30 minutes before treatment and then every 6–12 hours for up to 48 hours.
Postoperative nausea and vomiting
Adult: Prevention, IV 4 mg at induction. Treatment, IV 4–8 mg may be given if needed.
Child >2 years: Prevention, IV 0.1 mg/kg up to 4 mg at induction.
Radiotherapy: Adult, oral 8 mg every 8–12 hours for up to 5 days.
Severe hepatic impairment: Do not exceed 8 mg daily.
Administration instructions
Give IV injection over at least 5 minutes (or infuse over 15 minutes) as there have been reports of transient adverse effects if given more rapidly; may be given IM if dose volume is suitable.
Practice points

·         more effective for acute than delayed symptoms of cancer chemotherapy-induced nausea and vomiting

Products

ONDANSETRON AMPS 4 MG/AMP (AS HCL  (ONDANSETRON®, SETRON®, ZOFRAN®)

ONDANSETRON AMPS 8 MG/AMP (AS HCL)   (ONDANSETRON®, SETRON®, ZOFRAN®)

ONDANSETRON TABS 4 MG (AS HCL) (ZEMITRON®, ZOFRAN®)

ONDANSETRON TABS 8 MG (AS HCL) (SETRON®, ZEMITRON®, ZOFRAN®)

 

TROPISETRON

Mode of action
Central and peripheral 5HT3 receptor blockade.
Indications

Nausea and vomiting associated with cancer chemotherapy, postoperative,  radiotherapy-induced,

where conventional antiemetics are not tolerated.

Specific considerations
Children: limited data available. Seek specialist advice about use in children <2 years.
Pregnancy: limited data available; ADEC category B3.
Breastfeeding: no data available, although 1 or 2 doses after delivery should not be a concern.
Adverse effects
Common: constipation, headache, transient rise in hepatic transaminases, abdominal pain, diarrhoea, dizziness, fatigue.
Infrequent: hypertension.
Rare: hypersensitivity reactions (including anaphylaxis), arrhythmias, ECG changes, extra pyramidal effects.
Dosage
Cancer chemotherapy
Adult
Initially, IV 5 mg 15 minutes before chemotherapy.
Maintenance, oral 5 mg daily for 5 days.
Child >2 years
Initially, IV 0.2 mg/kg (up to 5 mg) before chemotherapy.
Maintenance, oral/IV 0.2 mg/kg once daily (up to 5 mg) for up to 5 days each cycle.
Postoperative nausea and vomiting
Adult: Prevention and treatment, IV 2 mg daily.
Child >2 years: Prevention and treatment, IV/oral, 0.05–0.2 mg/kg (up to 2 mg) once or twice daily.
Administration instructions
Do not give IM. Give IV injection over at least 1 minute or infuse over 15 minutes.
Counselling
Take capsules with water at least 1 hour before food.
This medicine may cause dizziness or fatigue in some people. Be careful driving or operating machinery until you know how tropisetron affects you.

Practice points
More effective for acute than delayed symptoms of cancer chemotherapy-induced nausea and vomiting.

Products

TROPISETRON AMPS 5 MG/AMPS (AS HCL)   (NAVOBAN®)

TROPISETRON CAPS 5 MG (AS HCL) (NAVOBAN®)

 

01.02.05  Other Antispasmodics

MEBEVERINE
Mode of action
Direct acting smooth muscle relaxant; reduces GI motility and spasm.
Indications
Irritable bowel syndrome; GI disorders associated with smooth muscle spasm.
Specific considerations
Pregnancy: No data; ADEC category B2.
Breastfeeding: No data available.

Contraindications

Paralytic ileus.
Adverse effects
dyspepsia, anorexia, constipation, dizziness, insomnia, headache, decreased pulse rate, malaise.
Dosage

135 mg 2 times daily.
Products

MEBEVERINE TABS 135 MG (AS HCL) (BEVACOL®, BEVETALIN®, DUSPATALIN®, MEBETALIN®)

MEBEVERINE TABS 200 MG (AS HCL) (DUSPATALIN®)

 

01.03 ULCER HEALING DRUGS

01.03.01  H2 Receptor Antagonists

FAMOTIDINE

Mode of action
Competitively block H2 receptors on parietal cells, reducing gastric acid secretion.
Indications
Peptic ulcer disease (PUD); Gastro-oesophageal reflux disease (GORD); Dyspepsia.

Specific considerations

Phenylketonuria: effervescent tablets contain aspartame.
Renal impairment: Although renally cleared, dosage reduction is rarely required in renal impairment.

Surgery: Continue treatment throughout perioperative period.
Pregnancy: Safe to use; ADEC category B1.
Breastfeeding: No adverse effects reported.

Adverse effects

Infrequent: hypotension.
Rare: headache, tiredness, dizziness, confusion (especially in elderly people), diarrhoea, constipation, rash; thrombocytopenia, agranulocytosis, hepatitis, vasculitis, interstitial nephritis.

Dosage
PUD: Initially, 40 mg once daily in the evening for 4–8 weeks. Maintenance 20 mg once daily in the evening.
GORD: 20 mg twice daily.
Dyspepsia: 20 mg once or twice daily for 4–8 weeks.
Practice points

·         in maintenance treatment of PUD and GORD, some specialists use larger doses (up to double those quoted); however there is no evidence of increased benefit and cost advantages over PPIs may be lost

·         the efficacy of H2 antagonists for stress ulcer prophylaxis is controversial; meta-analysis indicates some benefit over placebo in reducing clinically significant bleeding but cost efficacy is questioned; stop prophylaxis when stressors are removed.

Products

FAMOTIDINE TABS 10 MG (ACIFAM®, FAMODINE®, GASTRIFAM®)

FAMOTIDINE TABS 20 MG (ACIFAM®, AMODINE®, FAMODAR®, FAMODINE®, GASTRIFAM®, PEPCIDIN®)

FAMOTIDINE TABS 40 MG (ACIFAM®, AMODINE®, FAMODAR®, FAMODINE®, GASTRIFAM®, PEPCIDIN®)

 

RANITIDINE
For additional information see 12.1.3 H2 antagonists.
Mode of action
competitively block H2 receptors on parietal cells, reducing gastric acid secretion.
Indications
Marketed: Peptic ulcer disease (PUD); Gastro-oesophageal reflux disease (GORD); Dyspepsia.
Accepted: Stress ulcer prophylaxis.

Contraindications
Acute porphyria.

Specific considerations
Phenylketonuria: effervescent tablets contain aspartame.
Renal impairment: Although renally cleared, dosage reduction is rarely required in renal impairment.

Surgery: Continue treatment throughout perioperative period.
Pregnancy: Safe to use; ADEC category B1.
Breastfeeding: No adverse effects reported.
Adverse effects
Infrequent: Brady arrhythmia (following rapid IV administration), hypotension.
Rare: interstitial nephritis, involuntary movement disorder (reversible), headache, tiredness, dizziness, confusion (especially in elderly people), diarrhoea, constipation, rash (all common with cimetidine); thrombocytopenia, agranulocytosis, hepatitis, vasculitis.
Dosage
PUD
Oral, initially 300 mg daily as a single evening dose (or 2 divided doses) for 4–8 weeks or
IV/IM, 50 mg every 6–8 hours.
Maintenance, oral 150–300 mg daily as a single evening dose.
GORD
Oral, 300 mg daily as a single evening dose, or 2 divided doses.
Stress ulcer prophylaxis:

Oral, 150 mg twice daily until risk factors removed.
IV, 50 mg every 6–8 hours; or 50 mg initially, then IV infusion 125–250 micrograms/kg/hour until risk factors removed.
Dyspepsia: Oral, 150 mg twice daily for 4–8 weeks.
Child: Oral, 2–4 mg/kg twice daily (maximum 300 mg daily). IV, 1 mg/kg (up to 50 mg) every 6–8 hours.
Administration instructions
IV, dilute in sodium chloride 0.9% and give over not less than 5 minutes or infuse at 25 mg/hour over 2 hours.

Products

RANITIDINE AMPS 50 MG/AMPS (EPADOREN®, RANIDINE®, ROLAN®, TUPAST®, ZANTAC®, ZYDAC®)

RANITIDINE SYRUP 75 MG/5ML (EPADOREN®, RANIDINE®)

RANITIDINE TABS 75 MG (NADINE®, PEPTACID®, RANACID®, RANIDINE®, ZANTAC®)

RANITIDINE TABS 150 MG (ANTAGONIN®, HISTAC®, NADINE®, PEPTAC®, PEPTACID®, RANID®, RANIDINE®, ROLAN®, ZANTAC®)

RANITIDINE TABS 300 MG (ANTAGONIN®, HISTAC®, NADINE®, PEPTAC®, RANID®, RANIDINE®, ROLAN®, ZANTAC®)


01.03.02 Chelates and Complexes (Cytoprotective Agents)

BISMUTH SUBCITRATE
See also Helicobacter pylori-related ulcers.
Mode of action
Forms an acid- and pepsin-resistant protective coating at the ulcer site. May also have antibacterial effects against H. pylori.
Indications
H. pylori eradication (with other agents) after failure of first line treatments.
Contraindications
Severe renal impairment.
Specific considerations
Pregnancy: Avoid use; bismuth is a heavy metal that crosses the placenta; ADEC category B2.
Breastfeeding: Avoid use; excreted in breast milk.
Adverse effects
Common: blackening of faeces, darkening of teeth and tongue.
Infrequent: nausea, vomiting, dizziness, headache, diarrhea.
Dosage
H. pylori eradication: 1 tablet 4 times daily for 10–14 days.
Administration instructions
Take on an empty stomach; chew tablets before swallowing.
Food or milk may bind with bismuth subcitrate and reduce its efficacy.
Practice points

·         if a further course is required for ulcer healing, repeat treatment after a 4–8-week interval.

Products

BISMUTH SUBCITRATE, COLLOIDAL TABS 120 MG (AS BISMUTH III OXIDE) (DE-NOL®)

 

01.03.03 Proton Pump Inhibitors

ESOMEPRAZOLE

Mode of action
Irreversibly inactivate the hydrogen/potassium ATPase enzyme system (proton pump), suppressing both stimulated and basal acid secretion. When PPIs are stopped, acid secretion is restored by synthesis of new hydrogen/potassium ATPase.
Indications
Gastro-oesophageal reflux disease (GORD); H. pylori eradication, as part of an effective regimen treatment of gastric ulcer; prevention of peptic ulcer and short term treatment of upper GI symptoms associated with NSAIDs; Dyspepsia; Zollinger–Ellison syndrome; Scleroderma oesophagus.

Specific considerations
Gastric carcinoma: exclude before starting treatment for gastric ulcers; PPIs may mask symptoms and delay diagnosis.
Hepatic impairment: Risk of accumulation when higher doses are used; monitor for adverse effects; dosage adjustment not usually required.
Surgery: Continue treatment perioperatively.
Pregnancy: Avoid use, ranitidine preferred; ADEC category B3.
Breastfeeding: Safe to use; all are acid labile; small amount in milk is likely to be destroyed by acid in infant's stomach.
Adverse effects
Common: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness.
Infrequent: rash, itch, flatulence, constipation, decreased absorption of cyanocobalamin (vitamin B12) may occur with long term use.
Rare: confusion, agitation, aggression, arthralgia, agranulocytosis, PPIs are generally well tolerated.
gynaecomastia, myalgia, interstitial nephritis, raised liver enzymes, hepatitis, jaundice, thrombocytopenia, leucopenia, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reactions.

Dosage
GORD
Initially, oral/IV 20–40 mg once daily; change from IV to oral treatment as soon as possible.
Maintenance, reduce to minimum required.
H. pylori eradication
See also
Table 01–01 Recommended H. pylori eradication regimens
Oral, 20 mg twice daily for 1 week, with 2 antibiotics.
NSAID-associated upper GI symptoms
Oral, 20 mg once daily for 4 weeks.

Prevention of NSAID-associated peptic ulcer
Oral, 20 mg once daily.
Patient counselling
Swallow tablet whole; do not crush or chew. Alternatively, the tablet may be dispersed in water and taken within 30 minutes.
Tell your doctor if you develop symptoms such as black stools or coffee-coloured vomit.

Practice points

·         esomeprazole is the S-isomer of omeprazole

·         esomeprazole tablets may be dispersed in water and taken within 30 minutes.

Products

ESOMEPRAZOLE TABS 20 MG (NEXIUM®)

ESOMEPRAZOLE TABS 40 MG (NEXIUM®, PUMPINOX®)

ESOMEPRAZOLE VIAL 40 MG (NEXIUM®)

 

LANSOPRAZOLE

Mode of action

Irreversibly inactivate the hydrogen/potassium ATPase enzyme system (proton pump), suppressing both stimulated and basal acid secretion. When PPIs are stopped, acid secretion is restored by synthesis of new hydrogen/potassium ATPase.
Indications
Marketed: Peptic ulcer disease (PUD); Gastro-oesophageal reflux disease (GORD); H. pylori eradication, as part of effective eradication regimen, Dyspepsia.
Accepted: Zollinger–Ellison syndrome; Scleroderma oesophagus; In selected patients for stress ulcer prophylaxis; Acute upper GI bleeding; prevention of acid aspiration.

Specific considerations

Same as esomeprazole

Adverse effects

PPIs are generally well tolerated.

Common: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness
Infrequent: pharyngitis, rhinitis, cough, rash, itch, flatulence, constipation.

Rare: agranulocytosis, gynaecomastia, myalgia, interstitial nephritis, raised liver enzymes, hepatitis, jaundice, thrombocytopenia, leucopenia, Stevens–Johnson syndrome, toxic epidermal necrolysis..

Dosage
PUD: Initially, 30 mg once daily for 4–8 weeks. Maintenance, 15–30 mg once daily.
GORD: Adult, initially, 30 mg once or twice daily. Maintenance, reduce to minimum required.

Child >1 year
<30 kg, 15 mg once daily for 8–12 weeks (maximum 30 mg twice daily).
>30 kg, 30 mg once daily for 8–12 weeks (maximum 30 mg twice daily).
Dyspepsia: Initially, 15–30 mg daily for 4–8 weeks.
Zollinger–Ellison syndrome: Adjust dose according to gastric acid output. Initially, 60 mg once daily. Maintenance, 30–180 mg daily (give doses >120 mg daily as 2 divided doses).
H. pylori eradication: 30 mg twice daily for 1 week, with 2 antibiotics.
Severe hepatic impairment: Maximum recommended dose 30 mg daily.
Patient counselling
Swallow capsule whole; do not crush or chew. Alternatively, the capsule may be opened and the contents dispersed in apple, orange or tomato juice, yoghurt or apple sauce; take immediately.
Add the granules to 30 mL of water, stir well and drink immediately.
Tell your doctor if you develop symptoms such as black stools or coffee-coloured vomit.

Products

LANSOPRAZOLE CAPS/TABS 15 MG (LANSAZOL®, LANSOMID®, LANZOTEC®,  LANZOPRAL®, LANZOR®, LAZAL®, PEPTAZOLE®, TAKEPRON®, ULTRAZOLE®)

LANSOPRAZOLE CAPS/TABS 30 MG (LANSAZOL®, LANSOMID®, LANZOTEC®,  LANZOPRAL®, LANZOR®, LAZAL®, PEPTAZOLE®, TAKEPRON®, ULTRAZOLE®)

 

OMEPRAZOLE

Mode of action

Irreversibly inactivate the hydrogen/potassium ATPase enzyme system (proton pump), suppressing both stimulated and basal acid secretion. When PPIs are stopped, acid secretion is restored by synthesis of new hydrogen/potassium ATPase.
Indications
Marketed: Peptic ulcer disease (PUD); Gastro-oesophageal reflux disease (GORD); Zollinger–Ellison syndrome;
H. pylori eradication as part of effective eradication regimen; Treatment and prevention of peptic ulcer and erosion associated with NSAIDs.
Accepted: Scleroderma oesophagus; In selected patients for stress ulcer prophylaxis; acute upper GI bleeding; Prevention of acid aspiration.

Specific considerations

Same as esomeprazole

Adverse effects

PPIs are generally well tolerated.

Common: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness
Infrequent: decreased absorption of cyanocobalamin (vitamin B12) may occur with long term use rash, itch, flatulence, constipation.
Rare: paraesthesia, confusion, arthralgia, haemolytic anaemia, agranulocytosis, photosensitivity.
gynaecomastia, myalgia, interstitial nephritis, raised liver enzymes, hepatitis, jaundice, thrombocytopenia, leucopenia, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis.

Dosage
PUD: Initially, oral 20–40 mg once daily for 4–8 weeks (gastric ulcer). Maintenance, oral 20 mg once daily.
GORD: Initially, oral 20–40 mg once daily (up to 80 mg daily can be used). Maintenance, reduce to minimum required.
Zollinger–Ellison syndrome: Adjust dose according to gastric acid output. Initially, 60 mg once daily.. Maintenance, oral 20–120 mg daily (give doses >80 mg daily as 2 divided doses).
H. pylori eradication: Oral, 20 mg twice daily for 1 week, with 2 antibiotics.
NSAID-associated PUD or erosion: Treatment, oral 20–40 mg once daily for 4–8 weeks. Prophylaxis, oral 20 mg once daily.
Child: <10 kg, 5 mg once daily.
10–20 kg, 10 mg once daily (maximum 20 mg/day).
>20 kg, 20 mg once daily (maximum 40 mg/day).
Patient counselling
Swallow tablet or capsule whole; do not crush or chew. Alternatively, omeprazole tablets may be dispersed in water, orange juice or yoghurt; take within 30 minutes.
Tell your doctor if you develop symptoms such as black stools or coffee-coloured vomit.

Practice points

·         omeprazole tablets may be dispersed in water, orange juice or yogurt; give within 30 minutes

·         continuous IV administration for 72 hours following endoscopic therapy for bleeding ulcers has been used; seek specialist advice.

Products

OMEPRAZOLE TABS OR CAPS 20 MG (LOSEC®, OMEDAR®, OPRAZOLE®)

OMEPRAZOLE TABS OR CAPS 10 MG (HYPOSEC®, GASEC®, LOPRAZ®, LOSEC®, ODASOL®,OMEDAR®, OMEPREX®,OMISEC®, OPRAZOLE®, RISEK®, RYTHMOGASTRY® OMEPREX®)

OMEPRAZOLE VIAL 40 MG (IPROTON®, LORDIN®, LOSEC®, ODASOL®, OPRAZOLE®, RISEC®)

 

PANTOPRAZOLE

Mode of action

Irreversibly inactivate the hydrogen/potassium ATPase enzyme system (proton pump), suppressing both stimulated and basal acid secretion. When PPIs are stopped, acid secretion is restored by synthesis of new hydrogen/potassium ATPase.
Indications
Marketed: Peptic ulcer disease (PUD); Gastro-oesophageal reflux disease (GORD); Zollinger–Ellison syndrome;
H. pylori eradication as part of effective eradication regimen; Treatment and prevention of peptic ulcer and erosion associated with NSAIDs.
Accepted: Scleroderma oesophagus; In selected patients for stress ulcer prophylaxis; acute upper GI bleeding; Prevention of acid aspiration.
Specific considerations

Same as esomeprazole

Adverse effects

PPIs are generally well tolerated.

Common: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness.
Infrequent: dry mouth, increased sweating , rash, itch, flatulence, constipation, decreased absorption of cyanocobalamin (vitamin B12) may occur with long term use
Rare: gynaecomastia, myalgia, interstitial nephritis, raised liver enzymes, hepatitis, jaundice, thrombocytopenia, leucopenia, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reactions.
Dosage
PUD: Initially, oral/IV 40 mg once daily for 4–8 weeks; change from IV to oral treatment as soon as possible.
GORD: Initially, oral 40 mg once or twice daily; IV 20–40 mg daily (change to oral treatment as soon as possible). Maintenance, reduce to minimum required.
Prevention of NSAID-associated dyspepsia, PUD or erosion: Oral, 20 mg once daily.
Zollinger–Ellison syndrome: Adjust dose according to gastric acid output. Usually 80–120 mg oral twice daily or 80 mg 3 times daily.
H. pylori eradication:
Oral, 40 mg twice daily for 1 week, with 2 antibiotics.
Patient counselling
Swallow tablet whole; do not crush or chew.

Tell your doctor if you develop symptoms such as black stools or coffee-coloured vomit.
Products

PANTOPRAZOLE TABS 40 MG (CONTROLOC®, PANTODAR®, PANTOLOC®, PANTOVER®, PROTON®, RAZON®)

01.03.04 Other Ulcer Healing Drugs (Gastrointestinal Haemorrhage)

SOMATOSTATIN

Mode of action
Inhibit release of growth hormone and of various peptides of the gastroenteropancreatic endocrine system.
Indications
Marketed: Acromegaly where surgery or radiotherapy are contraindicated or have failed to control disease, or until radiotherapy becomes fully effective; Relief of symptoms associated with gastroenteropancreatic tumours, e.g. carcinoid tumours, VIPomas; Prevention of complications following pancreatic surgery (SC octreotide).
Accepted: Glucagonomas (octreotide).
Specific considerations
Insulinoma: possible increase in severity and duration of hypoglycaemia.
Diabetes: variable effect on blood glucose; adjust dose of insulin and oral antidiabetic drugs.
Gastroenteropancreatic endocrine tumours: occasional sudden escape from symptomatic control with rapid recurrence of severe symptoms.
Pregnancy: avoid use; may produce fetal growth retardation, probably due to suppression of growth hormone; ADEC category C.
Breastfeeding: avoid use.
Adverse effects

Common: abdominal pain, flatulence, nausea, vomiting, diarrhoea, gallstones, fatigue, hyperglycaemia, hypoglycaemia, hair loss, transient local reaction at injection site.
Rare: hypothyroidism, pancreatitis, hepatic dysfunction.
Comparative information
There are no direct comparative data between long acting lanreotide and long acting octreotide. They seem to have similar efficacy and safety.
Practice points

·         monitor thyroid function during long term treatment

·         ultrasound of the gall bladder before, and every 6–12 months during, treatment is recommended by the manufacturers.

Products

SOMATOSTATIN (ACETATE HYDRATE) VIALS 0.25 MG/VIAL (SOMATOSTATIN®)

SOMATOSTATIN (ACETATE HYDRATE) VIALS 3 MG/VIAL (SOMATOSTATIN®)

 

TERLIPRESSIN

Mode of action
Vasoconstrictor.
Indications
Bleeding oesophageal varices; Hepatorenal syndrome.
Specific considerations
Hypertension, atherosclerosis, cardiac disease: caution required due to vasoconstriction and fluid retention caused by terlipressin.
Pregnancy: contraindicated; may stimulate uterine contraction.
Breastfeeding: safe to use.
Adverse effects
abdominal cramps, headache, increased BP, pallor
Dosage
Bleeding oesophageal varices, IV, 2 mg, followed by 1–2 mg every 4–6 hours until bleeding controlled. Maximum duration of treatment 72 hours.

Practice points

·         monitor BP, fluid balance, and sodium and potassium concentrations

·         terlipressin is a pro-drug of vasopressin

Products

TERLIPRESSIN AMPS 1MG/ AMP (GLYPRESSIN®)

 

01.04 ACUTE DIARRHOEA

01.04.01 Antimotility Drugs

LOPERAMIDE

Mode of action
Activate opioid receptors in the gut wall, decreasing bowel motility and increasing fluid absorption.
Indications
Diarrhoea, usually short term treatment in adults, Intestinal stoma (to reduce frequency and fluidity of motions).

Combination with simethicone
Diarrhoea with associated gas-related abdominal discomfort, short term treatment in adults.
Contraindications
Intestinal obstruction, Children <2 years.
Specific considerations
Pregnancy: 1 or 2 doses safe to use; ADEC category B3.
Breastfeeding: 1 or 2 doses safe to use.
Severe ulcerative colitis: may precipitate toxic megacolon.
Hepatic impairment: avoid use in severe impairment; may precipitate hepatic encephalopathy.
Children: avoid use in children <6 years (contraindicated in children <2 years).
Adverse effects
Common: abdominal pain and bloating, nausea, vomiting, constipation.
Rare: paralytic ileus, dizziness, rash.
Dosage
Adult
Acute diarrhoea: Initially, 4 mg, then 2 mg after each loose bowel action.
Intestinal stoma: 4–8 mg daily in 2–3 divided doses. Maximum dose 16 mg daily.
Short gut syndrome diarrhoea: Child, up to 1.25 mg/kg/day in 2–3 doses has been used.

Combination with simethicone
Initially, 2 tablets, then 1 tablet after each loose bowel action. Maximum 4 tablets daily
Practice points

·         do not use loperamide as an antidiarrhoeal in children, especially in those <6 years, except under specialist supervision for diarrhoea associated with short gut syndrome

·         use as symptomatic treatment only in adults with acute diarrhoea

·         some people with chronic diarrhoea may require long term opioids; this should be a specialist decision.

Products

LOPERAMIDE CAPS/TABS 2 MG (AS HCL) (DIAPEN®, IMODIUM®, IMOTRIL®, LOPERIUM®, VACONTIL®)

 

01.05 CHRONIC BOWEL DISORDERS

Inflammatory bowel disease
A relapsing and remitting disorder characterised by chronic non-specific inflammation of the GIT. It can also be associated with extra-intestinal symptoms (e.g. fever, skin lesions, eye or joint manifestations). The 2 main forms, Crohn's disease and ulcerative colitis, differ in presentation, site, progression of disease and treatment. Choice of treatment is guided by location, extent, severity and complications of disease as well as response to current or previous treatment.
Rationale for drug use
Relieve symptoms.
Induce and maintain remission.
Prevent complications.
Correct and/or prevent nutritional deficiencies.
Before starting treatment
Stopping smoking is probably the most important factor in maintaining remission of Crohn's disease. Smoking is associated with a 3–4-fold increased risk of developing Crohn's disease and may also worsen its clinical course.
Use NSAIDs with caution in Crohn's disease and ulcerative colitis as they may exacerbate active disease or precipitate a relapse.
Drug choice
Includes drugs that control symptoms and those that modify the disease by inducing and maintaining long term bowel healing.
Symptomatic treatment
5-Aminosalicylates
Sulfasalazine, mesalazine, olsalazine, balsalazide; used to treat mild-to-moderate inflammatory bowel disease (IBD). There is conflicting evidence regarding their role in maintaining remission in Crohn's disease, but they can be effective maintenance treatment in ulcerative colitis.
The 5-aminosalicylates are equally effective; the choice of agent depends mainly on the disease location, dosage forms and adverse effects, e.g. sulfasalazine often causes reversible male infertility.
Corticosteroids
Continue corticosteroids only for as long as needed to control acute inflammation, since they are ineffective for maintaining remissions. Patients who require chronic corticosteroid therapy are candidates for immunosuppressants.
Topical preparations are effective in left-sided or distal ulcerative colitis.
Budesonide is effective in mild-to-moderate ileal or right ileocolonic Crohn's disease; may be better tolerated than other corticosteroids; not used widely due to cost.
Disease modifying treatment
Drugs that target the inflammatory processes are usually effective in controlling active disease and may sustain symptomatic remission for prolonged periods.
Immunosuppressants
Azathioprine, mercaptopurine, methotrexate and cyclosporine (see
Immunosuppressants). Since the onset of action takes 3–6 months, they are not useful for acute disease; use only when prolonged treatment is planned. Consider their use if it has not been possible to wean the patient from corticosteroids after 6 weeks.
Crohn's disease: azathioprine and mercaptopurine are effective in treating and maintaining remission in chronically active Crohn's disease which is refractory to, or dependent on, corticosteroids. Methotrexate is also useful for treating this group of patients, and appears promising as maintenance treatment.
It is not yet clear how long immunosuppressive agents should be used; benefit of treatment up to 4 years has been shown.
Ulcerative colitis: the role of azathioprine and mercaptopurine in ulcerative colitis is less well defined, but they appear effective in inducing and maintaining remission. There is insufficient evidence for the use of methotrexate in this disease.
Cyclosporine can induce remission in severe ulcerative colitis refractory to standard treatment with corticosteroids.
Infliximab
Infliximab is generally used in severe Crohn's disease unresponsive to conventional therapy; rapidly induces clinical and endoscopic remission and may provide useful maintenance therapy. Its use is currently limited by uncertainties regarding safety and cost-benefit ratio.
Other drug treatment
Metronidazole, alone or with ciprofloxacin, given for up to 3 months may be effective in mild-to-moderate active Crohn's disease. High doses are usually necessary and the adverse effects (especially neurotoxicity) may be limiting. Other antibiotics including clarithromycin, rifabutin and clofazimine, singly or in combination, may be useful.
Antidiarrhoeals, such as codeine and loperamide, remain useful in Crohn's disease but are contraindicated in severe ulcerative colitis because of the risk of toxic megacolon.
Cholestyramine can reduce diarrhoea due to terminal ileal disease or resection in Crohn's disease. Parenteral vitamin B12 supplements may also be necessary in these patients.
Antispasmodics should not be used for IBD.
Several other agents have been trialled in IBD although no firm recommendations can be made about their use in routine practice. Thalidomide and immunosuppressants, such as tacrolimus and mycophenolate mofetil, may be of benefit. Nicotine, topical anaesthetic, clonidine, heparin, fish oil and cytokine antibodies, other than infliximab, are among a variety of agents being evaluated.
Non-drug treatment
Dietary treatment: the role of enteral nutrition in Crohn's disease is controversial. It may induce remission of active disease if taken for 4–6 weeks as the sole nutritional source, but its use is limited by cost, compliance and a high relapse rate when stopped. It is a valuable option in children and is effective in inducing and maintaining remission while promoting linear growth.
There is no evidence that dietary intervention has any specific therapeutic effect in ulcerative colitis.
Probiotics: live bacteria that benefit health by altering the microbial environment. They may be useful in maintaining remission in ulcerative colitis and in the treatment of Crohn's disease.
Other measures: adequate nutrition (including replacing specific deficiencies such as iron, calcium, fat-soluble vitamins) and attention to related secondary complications (such as osteoporosis resulting from malabsorption, corticosteroid therapy or both) are also important. Psychological support is often required.
Treatment regimens
Crohn's disease

In active disease oral corticosteroids still provide the quickest and most reliable response; about 70% of patients improve within 4 weeks.
Acute, mild-to-moderate: limited course of oral corticosteroid or 5-aminosalicylate or antibiotic (e.g. metronidazole, ciprofloxacin).
Acute, severe: hospital admission; short course of high dose oral or IV corticosteroid. Consider
infliximab if response is inadequate.
Maintenance of remission: immunosuppressant (e.g. azathioprine, mercaptopurine, methotrexate). Conventional corticosteroids have no role. Budesonide may prolong time to relapse but does not alter remission rate at 12 months. Despite conflicting evidence regarding their efficacy in sustaining remission, 5-aminosalicylates are commonly used.
Chronic active or refractory disease: immunosuppressant such as azathioprine, mercaptopurine or methotrexate with or without low dose corticosteroid.
Ulcerative colitis

Acute, mild-to-moderate: a 5-aminosalicylate with or without a short course of oral corticosteroid; use rectal preparations for distal disease.
Acute, severe: hospital admission; short course of high dose oral or IV corticosteroid (usually with 5-aminosalicylate), with or without immunosuppressive agent such as azathioprine. Cyclosporine is used in disease refractory to corticosteroid treatment.
Maintenance of remission: 5-aminosalicylate or immunosuppressant (e.g. azathioprine, mercaptopurine). Corticosteroids are ineffective in maintaining remission.
Chronic active: immunosuppressant (e.g. azathioprine, mercaptopurine) and/or low dose corticosteroid.
Special cases
Pregnancy: Seek specialist advice. In pregnant patients it is important to maintain or start treatment to keep inflammatory bowel disease quiescent as uncontrolled disease is a threat to the pregnancy. Give folic acid supplementation.
Breastfeeding: Treatment should be maintained to prevent relapse.
Practice points

·         infliximab with azathioprine or mercaptopurine may provide long term benefit in Crohn's disease; combination therapy of methotrexate and infliximab is currently under investigation

·         using oral and rectal mesalazine is more effective than either alone and is useful in refractory ulcerative colitis.

 

01.05.01  Aminosalicylates

MESALAZINE
Mode of action

Exact mechanism unknown but exert local anti-inflammatory action in the bowel wall.

Indications

Inflammatory large bowel disease, acute and maintenance; Ulcerative colitis, rectal Ulcerative colitis, rectal (suppository) and rectosigmoidal (enema) disease.

Contraindications

Allergy to salicylates.

Specific considerations

Renal impairment: use with caution; monitor regularly, especially in severe impairment; possible risk of worsening renal impairment.
Hepatic impairment: use with caution in severe impairment as hepatically cleared.

Children: not marketed for use in children <12 years but dose below has been used
Surgery: continue treatment throughout perioperative period.

Pregnancy: safe to use; ADEC category C.

Breastfeeding: safe to use.
Adverse effects

More common with higher doses
Common: nausea, rash, headache, diarrhea.
Infrequent: interstitial nephritis.

Rare: neuropathy,. blood dyscrasias, pancreatitis (reversible), hepatitis.
Dosage

Ulcerative colitis
enema, rectal foam, 2–4 g once daily, enema, suppository, 1 g once daily.
Acute: tablet, 500 mg 3 times daily,  tablet, granule, 500 mg – 1 g 3 times daily.
Maintenance: tablet, 250 mg 3 times daily, tablet, granule, 500 mg 3 times daily.
Crohn's disease
Acute: tablet, 500 mg 3 times daily, tablet, 1–1.5 g 3 times daily.
Maintenance: tablet, 250 mg 3 times daily, tablet, 500 mg – 1 g 3 times daily.
Child: tablet, initially, 15–20 mg/kg 3 times daily; maintenance, 10 mg/kg 2–3 times daily.
Counselling
Swallow tablets or granules whole without chewing or crushing them.
Take tablets at least half an hour before food.
Practice points

·         the value of mesalazine in small bowel Crohn's disease is controversial

Products

MESALAZINE ENEMA 1 GM (PENTASA®)

MESALAZINE POWDER 1 GM SACHET (PENTASA®)

MESALAZINE SUPP. 1 GM (PENTASA®)

MESALAZINE TABS 400 MG (ASACOL®, MEZACOL®)

MESALAZINE TABS 500 MG (PENTASA®)

 

SULFASALAZINE

Mode of action

Exact mechanism unknown but exert local anti-inflammatory action in the bowel wall.
Indications
Ulcerative colitis; acute and remission maintenance; rheumatoid arthritis; Crohn's disease (limited role in colonic disease; much less effective than in ulcerative colitis).
Contraindications
Allergy to sulfonamide or salicylate.

Specific considerations
Blood dyscrasias, increased risk of myelosuppression.
Asthma, severe allergy may be exacerbated.
Renal impairment: use with caution; monitor regularly, especially in severe impairment; possible risk of worsening renal impairment.
Hepatic impairment: use with caution in severe impairment as hepatically cleared.
Surgery: continue treatment throughout perioperative period.

Pregnancy: safe to use; give a folic acid supplement daily (0.5–5 mg); ADEC category A.
Breastfeeding: Safe to use.
Adverse effects

More common with higher doses.
Common: vomiting, reversible male infertility (oligospermia), haemolysis (not usually severe) nausea, rash, headache, diarrhea.
Infrequent: yellow–orange discolouration of urine or skin interstitial nephritis.
Rare: toxic epidermal necrolysis, fibrosing alveolitis, meningitis, hypersensitivity including serum sickness, anaphylactoid reactions, arthralgia, itch., blood dyscrasias, pancreatitis (reversible), hepatitis.
Dosage

Ulcerative colitis
Adult: Acute, oral 2–4 g daily in 3–4 doses. Higher doses (up to 8 g daily) are sometimes used but risk of toxicity is increased. Maintenance, oral 500 mg 4 times daily.
Localised rectal, 1–2 suppositories morning and night after defecation.
Child >2 years: Acute, oral 40–60 mg/kg daily in 3–4 doses. Maintenance, oral 20–30 mg/kg daily in divided doses.
Colonic Crohn's disease, mild active: Adult, oral 3–6 g daily in divided doses.
Counselling
Take tablets with food to reduce stomach upset.
Practice points

·         sulfasalazine's role in Crohn's disease is limited to active disease in patients with colonic involvement

·          obtain urinalysis, liver function tests and complete blood examination at baseline and every 2 weeks for the first 3 months of treatment, then at least every 6 months

·         soft (hydrogel) lenses may be stained by sulfasalazine use; disposable lenses may still be used

·         sulfasalazine impairs absorption of folic acid; consider supplementation, especially before and during pregnancy.

Products

SULFASALAZINE TABS 500 MG (SALAZOPYRIN®)

01.05.02  Corticosteroids

BUDESONIDE

Mode of action

Anti-inflammatory. Formulation delivers budesonide predominantly to the ileum and ascending colon. Systemic absorption is reduced by high first-pass metabolism, producing mainly local effects in the gut. However, some systemic effects occur.
Indications
Induction of remission in mild-to-moderate Crohn's disease affecting the ileum and/or the ascending colon.
Delay relapse during maintenance therapy for Crohn's disease.
Specific considerations
Surgery: continue treatment throughout perioperative period. Depending on the type of surgery additional corticosteroid coverage may be needed to avoid adrenal crisis.
Children: not recommended.
Pregnancy: use if indicated; ADEC category B3.
Breastfeeding: limited data; appears safe.
Adverse effects
Infrequent and usually of mild-to-moderate severity. However, adrenal suppression may occur even with short courses of therapy. Despite limited data on prolonged therapy, the possibility of long term glucocorticoid adverse effects should be considered.
Dosage

9 mg once daily in the morning just before food.

Patient counseling

Swallow the capsules whole, do not crush or chew them.

Do not stop taking this medication suddenly.

Therapeutic effects may take 2–4 weeks to become apparent.

Avoid grapefruit as it may increase the risk of side effects with budesonide.

Practice points

·         budesonide has a favourable topical activity/systemic effects ratio which may offer benefit over conventional corticosteroids

·         high cost limits use

·         transfer from a corticosteroid with significant systemic effects to budesonide requires cautious tailoring of dose to avoid adrenal crisis

·         wean budesonide slowly as for other corticosteroids.

Products
BUDESONIDE ENEMA 2 MG (ENTOCORT®, ENEMACORT®
)

BUDESONIDE TABS 3 MG (ENTOCORT®)

 

01.06 LAXATIVE DRUGS

01.06.01  Bulk Forming Laxatives

BULKING AGENTS
Agents include ispaghula husk, psyllium and sterculia.
Mode of action
Absorb water in the colon to increase faecal bulk which stimulates peristaltic activity.
Indications
Constipation, to improve stool consistency; Colostomy and ileostomy, to regulate faecal consistency.
Contraindications
Intestinal obstruction, partial or complete; Colonic atony.

Specific considerations
Renal impairment: potassium content of products and fluid volume required may be unacceptable in moderate-to-severe impairment.
Adverse effects
Common: flatulence, bloating, abdominal discomfort.
Rare: allergic reaction (e.g. wheeze, chest tightness, urticaria) with ispaghula, intestinal obstruction, oesophageal obstruction.
Dosage
Dose according to product label.
Practice points

·         use in acute constipation when dietary modification is inadequate

·         give with extra fluid to ensure laxative effect, or with minimal fluid to harden stool

·         full effect may take several days

·         use cost and patient preference to guide choice between agents

·         should not be taken immediately before going to bed.

·         some products contain frangula (buckthorn) bark which is a stimulant laxative.

Products

STERCULIA+FRANGULA GRANULES COMBINATION 62 % + 8 % 200 GM (NORMACOL PLUS®)

 

01.06.02  Stimulant laxatives

BISACODYL

Mode of action

Act by direct stimulation of nerve endings in colonic mucosa to increase intestinal motility. May cause accumulation of water and electrolytes in the colonic lumen.
Indications
Constipation; Bowel preparation before diagnostic or surgical procedures requiring bowel emptying.
Contraindications
Intestinal obstruction, partial or complete; Acute abdominal conditions, e.g. appendicitis; Inflammatory bowel condition.
Specific considerations
Elderly: increased risk of faecal incontinence.
Pregnancy: avoid direct stimulants except for occasional doses; ADEC category A.
Lactation: m

ay be used.
Adverse effects
Infrequent: rectal irritation, proctitis (with rectal administration), abdominal cramps, fluid and electrolyte imbalance (especially hypokalaemia).
Dosage
Constipation
Adult: Oral, 5–15 mg as a single dose at night. Rectal, 10 mg once daily when required.
Child: >3 years, oral 5–10 mg as a single dose at night; rectal 5–10 mg once daily as required. <3 years, rectal 5 mg once daily as required.

Bowel preparation: Adult, up to 30 mg orally on the night before the procedure (or 10 mg on each of the 2 nights before the procedure), usually followed by 10 mg rectally on the morning of the procedure.

Practice points

·         onset of action is 6–12 hours (oral); 15–60 minutes (suppository); 5–15 minutes (enema)

·         may be used long term for constipation in spinal damage, chronic neuromuscular disease and in people taking opioids; often used with other laxatives

·         stimlants are the laxative group most often associated with laxative misuse.

Products

BISACODYL SUPP. 10 MG (DULCOLAX®, LAXADYL®, SACOLUX®)

BISACODYL TABS 5 MG (BICODYL®, DULCOLAX®, LAXADYL®)

 

CASTOR OIL

The fatty oil obtained by cold expression from the seeds of Ricinus communis. It is a clear, almost colourless or slightly yellow, viscous, hygroscopic liquid. Miscible with alcohol and with glacial acetic acid; slightly soluble in petroleum spirit.

Indications

Castor oil is used externally for its emollient effect. It has also been used topically to allay irritation due to foreign bodies in the eye. Castor oil may be employed as the solvent in some injections.

Castor oil is used for bowel evacuation before radiological procedures, endoscopy, surgery, it has been used as a laxative, but such use is obsolete.

Contraindications

Intestinal obstruction.

Adverse Effects and Precautions

Oral administration of castor oil, particularly in large doses, may produce nausea, vomiting, colic, and severe purgation. Castor oil should be used with caution in pregnancy and menstruation..

The seeds of Ricinus communis contain a toxic protein, ricin. Allergic reactions have been reported in subjects handling the seeds.

Products

CASTOR OIL, AROMATIC 60-100ML/BOTTLE

 

GLYCEROL
Also known as glycerin.
Mode of action
Non-absorbable sugar. Osmotic laxative; it draws water into the faeces, has lubricating properties and may also act as a stimulant by its local irritant effects.
Indications

Constipation.
Adverse effects
Infrequent: rectal discomfort.
Rare: rectal mucosal erosion.
Dosage

1 suppository once daily when required.
Practice points

Onset of action is 5–30 minutes

Products

GLYCERIN SUPP. (ADULT) (JOCERIN®, GLYCERIN®,)

GLYCERIN SUPP. (CHILD) (JOCERIN®, GLYCERIN®,)

SENNA
Mode of action

Act by direct stimulation of nerve endings in colonic mucosa to increase intestinal motility. May cause accumulation of water and electrolytes in the colonic lumen.
Indications
Constipation.

Contraindications
Intestinal obstruction, partial or complete, Acute abdominal conditions, e.g. appendicitis, Inflammatory bowel condition.
Specific considerations
Elderly: Increased risk of faecal incontinence.
Pregnancy: Avoid direct stimulants except for occasional doses; ADEC category A.
Lactation: May be used.
Adverse effects
Infrequent: discolouration of urine (yellowish brown or red)
Rare: nephritis (with large doses), hepatitis, melanosis coli (chronic use)

Dosage
Adult: 7.5–30 mg at bedtime.
Child
6–12 years, 7.5–15 mg at bedtime.
2–6 years, 3.75–7.5 mg at bedtime.

Practice points

·         onset of action is 6–12 hours

Products

SENNA TABS (LAXAL®, SENNOKET®, SENNA LAX®)

 

01.06.04  Osmotic laxatives

LACTULOSE
Mode of action

Poorly absorbed, metabolized by colonic bacteria; it exerts an osmotic effect in the colon. Increase in intraluminal pressure stimulates peristalsis.
Beneficial effects in hepatic encephalopathy are thought to result from prevention of absorption of ammonia by lowering faecal pH as well as its laxative effect.

Indications
Constipation; Hepatic encephalopathy.
Contraindications

Intestinal obstruction, partial or complete, Galactose or lactose intolerance (products contain galactose <1.65 g/15 mL and lactose <0.9 g/15 mL).

Specific considerations
Pregnancy: Safe to use.
Breastfeeding: Safe to use.
Adverse effects

Common: flatulence, abdominal discomfort.

Infrequent: diarrhoea, electrolyte imbalances.

Dosage

Constipation
Adult: Initially 15–30 mL daily in 1 or 2 doses. Doses up to 90 mL daily may be used if necessary. Maintenance, 10–25 mL daily.
Child: 6–12 years, 15 mL daily. 1–5 years, 5–10 mL daily. <12 months, 3–5 mL daily.
Hepatic encephalopathy
Adult: Oral/nasogastric tube, 30–45 mL every 1–2 hours to induce rapid laxative effect. Reduce to 30–45 mL 3–4 times daily when laxative effect has been achieved. The dose is subsequently adjusted to produce 2–3 soft stools per day.

Rectal (if the oral route is unavailable), dilute 300 mL of lactulose oral liquid with 700 mL water or sodium chloride 0.9%; retain enema for 30–60 minutes and repeat every 4–6 hours until the person is able to take orally.
Child: Oral/nasogastric tube, 1 mL/kg (up to adult dose) every 1–2 hours until desired response, then every 6 hours.

Counselling

This medicine tastes very sweet, it may help to mix it with fruit juice, water or milk

Practice points

·         onset of action is 1–3 days

·         a systematic review concluded there was not enough evidence to determine whether lactulose benefited patients with hepatic encephalopathy

 

Products
LACTULOSE SYRUP 10 GM/15ML 100-300 ML BOTTLE (EZILAX®
, LACTULOSE®, LACTUVER®, LAXODAD®, RAMLAC®, RIALAC®)

 

PHOSPHATE ENEMA
Mode of action
Non-absorbable salts retain fluid in the colon by osmotic effect and stimulate peristalsis.
Indications
Bowel preparation, for GI endoscopic or surgical procedures; Chronic constipation.
Contraindications

Intestinal obstruction, partial or complete, Severe colitis, especially toxic megacolon, Phenylketonuria, Heart failure (products containing sodium phosphate), Renal impairment (products containing sodium phosphate; leads to hyperphosphataemia).

Specific considerations

Cardiovascular disease (e.g. heart failure) avoid use of sodium salts; use with caution as fluid and electrolyte disturbances can occur. Electrolyte disturbance may be worsened, avoid use.
Renal impairment: Avoid use of magnesium or sodium salts; significant fluid and electrolyte disturbance may occur, Elderly: Use with caution; risk of electrolyte disturbance and dehydration.
Children: Use of sodium phosphate in children <2 years may cause hypocalcaemia.
Small volume preparations may cause dehydration and electrolyte disturbance if not used with adequate hydration.
Pregnancy: Other sodium/magnesium laxatives: limited data available; safe to use short term if other agents ineffective.
Breastfeeding: Safe to use.

Adverse effects

Small volume products that contain sodium phosphate used for bowel preparation can cause serious fluid and electrolyte disturbance, including hypocalcaemia, hyperphosphataemia and hyperkalaemia. Acute renal failure has also been reported.
All sodium or magnesium laxatives may cause nausea, bloating, fluid and electrolyte depletion and rectal irritation.

Rectal gangrene has been associated with the use of phosphate enemas in elderly patients and was believed to be due to a direct necrotizing effect of the phosphate on the rectum.

Dosage

See directions on label.

Patient counselling

Bowel preparation, do not eat from 1–2 hours before starting preparation until after procedure performed; clear fluids are permitted; expect diarrhoea usually after about 1 hour and a clear water-like discharge by 4 hours.

Practice points

·         onset of action is 30 minutes – 3 hours

·         oral medication taken during or within the hour before sodium or magnesium laxative may be flushed from the GIT without absorption

·         avoid laxatives containing sodium phosphate in renal impairment

·         sodium or magnesium laxatives may be given orally or rectally; they are poorly and slowly absorbed.

Products

PHOSPHATE ENEMA (SODIUM ACID PHOSPHATE+SODIUM PHOSPHATE) 125-133 ML BOTTLE (PHOSPHATE ENEMA B®, FLETCHERS PHOSPHATE ENEMA®,  JO-ENEMA®,, KLYSMOL®)

 

01.06.05  Bowel cleansing solution

MACROGOL

Mode of action

so-osmotic solutions containing electrolytes and polyethylene glycol (PEG), which clean the bowel by causing diarrhoea.
Indications
Used before colonic surgery, colonoscopy, or radiological examination to ensure the bowel is free of solid contents.
Whole bowel irrigation for selected poisonings, including controlled release preparations, iron, lithium and potassium
Contraindications

Intestinal obstruction, gastric retention, gastro-intestinal ulceration, perforated bowel, congestive cardiac failure, toxic colitis, toxic megacolon or ileus.

Specific considerations
Pregnancy: Safe to use.
Breastfeeding: Safe to use.
Adverse effects

Common: nausea, bloating, vomiting.

Dosage

Bowel evacuation before surgery, colonoscopy, or radiological examination, adult over 18 years, 2 liters of reconstituted solution on the evening before procedure.

Counselling

This medicine tastes very sweet, it may help to mix it with fruit juice, water or milk.

Products
POLYETHYLENE GLYCOL 4000 10 GM/SACHET (FORLAX®
)

POLYETHYLENE GLYCOL 4000 64 GM/SACHET (FORTRANS®)

 

01.07 LOCAL PREPARATIONS FOR ANAL AND RECTAL DISORDERS

Perianal disorders
The most common perianal conditions treated with drugs are haemorrhoids, anal fissure and pruritus. Many perianal problems require surgical intervention.
Rationale for drug use
Symptom relief.
Before starting treatment
Attention to factors such as diet and hygiene is often an important first step in treating these conditions.
Give advice on avoiding prolonged straining. A high fibre diet, adequate fluid intake and bulking agents or stool softeners prevent straining and so may reduce pain associated with haemorrhoids and anal fissure.
Consider secondary causes of pruritus ani such as infections (e.g. worms) or skin conditions. To reduce irritation keep area clean and dry, avoid soap products, rough toilet paper and nylon clothing. Simple emollients (e.g. zinc and castor oil cream) applied after cleansing may also help.
Drug choice
Evidence for efficacy of topical anorectal medication is anecdotal.
Anorectal products often contain a corticosteroid and/or a local anaesthetic agent.
Topical glyceryl trinitrate (0.2%) is available for anal fissures; it provides modest efficacy by relaxing the internal anal sphincter but headache is a common adverse effect.
Practice points

·         limit use of topical products to maximum of 7 days as local anaesthetics may cause sensitisation of perianal skin and topical corticosteroids may exacerbate local infection and cause skin atrophy

·         topical corticosteroids and local anaesthetics are safe to use in pregnancy and breastfeeding.

 

01.07.01  Soothing Haemorrhoidal Preparations

ANORECTAL PRODUCTS

Mode of action

Plain anti-haemorrhoidal ointment and suppositories posses' emollient and soothing properties as well as astringent action thus relieving the pain and irritation associated with haemorrhoids.

Indications

Haemorrhoids; Anal fissure; Pruritus ani.

Contraindications

Hypersensitivity to any of the components, fungal infections, tuberculosis of the skin, vaccinia, varicella, herpes simplex, markedly impaired circulation.

Adverse effects

Dermatologic: local burning, itching, irritation, dryness, allergic contact dermatitis, secondary infection, hypo pigmentation, folliculitis.

Dosage

Use according to manufacturer's product information.

Products

HAEMORRHOIDAL OINTMENT PREPARATIONS, SOOTHING (PROCTOLAIN®)

HAEMORRHOIDAL SUPP. PREPARATIONS, SOOTHING (PROCTOLAIN®)


01.07.02   Compound Haemorrhoidal Preparations with Corticosteroids

Indications

Skin conditions, including internal haemorrhoids, and anal fissures.

Contraindications

Hypersensitivity to any of the components, fungal infections, tuberculosis of the skin, vaccinia, varicella, herpes simplex, markedly impaired circulation.

Adverse effects

Dermatologic: local burning, itching, irritation, dryness, allergic contact dermatitis, secondary infection, hypo pigmentation, folliculitis.

Products

HAEMORRHOIDAL+CORTICOSTEROIDS OINTMENT COMPOUND PREPARATIONS (PROCTOPROCTO-GLYVENOL®, PROCTOHEAL®, PROCTOSYNALAR®, PROCTOLAR CENTER®)

 

HAEMORRHOIDAL+CORTICOSTEROIDS SUPP.  COMPOUND PREPARATIONS (PROCTO-GLYVENOL®, PROCTOHEAL®, PROCTOSYNALAR®, PROCTOLAR CENTER®)

 

01.07.03  Rectal Sclerosants

ETHANOLAMINE OLEATE 

Indications

used as a sclerosant in the treatment of varicose veins and oesophageal varices.

Adverse effect

Monoethanolamine oleate is irritant to skin and mucous membranes. Local injection may cause sloughing, ulceration, and, in severe cases, necrosis. Pain may occur at the site of injection. Patients receiving treatment for oesophageal varices may develop pleural effusion or infiltration. Hypersensitivity reactions have been reported.

Sclerotherapy should not be used to treat varicose veins of the legs in patients with thrombosis or a tendency to thrombosis, or with acute phlebitis, marked arterial, cardiac, or renal disease, local or systemic infections, or uncontrolled metabolic disorders such as diabetes mellitus.

Effects on the kidneys: Acute renal failure, which clears spontaneously within 3 weeks

Dosage

sclerotherapy of varicose veins

2 to 5 mL of a 5% solution of monoethanolamine oleate is injected slowly into empty isolated sections of vein, divided between 3 or 4 sites. Injection into full veins is also possible.

sclerotherapy of oesophageal varices

1.5 to 5 mL of a 5% solution per varix to a maximum total dose of 20 mL per treatment session. Treatment may be given in the initial management of bleeding varices, then repeated at intervals until the varices are occluded.

Products

ETHANOLAMINE OLEATE AMPS 5 %   5 ML

 

01.09 DRUGS AFFECTING INTESTINAL SECRETIONS

01.09.01 Drugs Affecting Biliary Composition and Flow

URSODEOXYCHOLIC ACID
Mode of action
Unclear; alters bile acid composition resulting in greater concentration of ursodeoxycholic acid; increases bile acid output and bile flow. Some evidence for immunological mechanisms.
Indications
Chronic cholestatic liver diseases (e.g. primary biliary cirrhosis (PBC), primary sclerosing cholangitis, cholestasis related to cystic fibrosis).
Contraindications
Acute cholecystitis/cholangitis or bile duct obstruction.
Specific considerations
Children: Limited data; children with PBC may have an initial deterioration in symptoms which may be alleviated by dose reduction and slow titration of dose.
Pregnancy: Limited data; is used for cholestasis of pregnancy but information on efficacy is lacking; ADEC category B3.
Breastfeeding: Limited data; consult specialist advisory service.
Adverse effects
Common: diarrhoea
Infrequent: increased itch, increased cholestasis, nausea, vomiting, sleep disturbance.
Dosage

Adult: PBC and chronic cholestatic diseases other than cystic fibrosis, 10–15 mg/kg/day in 2–4 divided doses.
Cystic fibrosis, up to 20 mg/kg/day.
Child: 15–20 mg/kg/day in 2–3 divided doses.

Practice points

·         use in PBC improves liver function tests but effect on mortality is unclear; changes in liver function tests are not a clear measurement of efficacy; further studies are required to establish efficacy in PBC

·         use in primary sclerosing cholangitis improves liver function tests but does not significantly improve symptoms, histology or survival

·         little information available on efficacy in cystic fibrosis.

Products

URSODEOXYCHOLIC ACID TABS 100 MG (URSA®)

 

01.09.02 Pancreatic Enzymes

Mode of action

Pancreatic enzymes are essential for fat, protein and carbohydrate digestion. Supplements aim to correct enzymatic deficiency. All products are of porcine origin.

Indications

Cystic fibrosis; Chronic pancreatitis; After gastrectomy or pancreatic surgery.

Contraindications

Hypersensitivity to porcine products

Specific considerations

Pregnancy: Safety not established; seek specialist advice.

Breastfeeding: few data; appears safe

Drug interactions

Decreased effect: calcium carbonate, magnesium hydroxide.

Increased effect: H2 – antagonist (e.g. Famotidine, Cimetidine)

Adverse effects

Common: nausea, vomiting, abdominal pain.
Infrequent: irritation of skin around mouth and anus.
Rare:  hyperuricaemia, hyperuricuria, fibrinosing colonopathy (bowel stricture) in children with cystic fibrosis taking high doses.

Dosage:

Dose must be individualised and is guided by stool quality and quantity. Specialist supervision is recommended.

Cystic fibrosis: maximum dose 10 000 units of lipase/kg/day

Counselling

Take this medicine with meals and snacks.
Swallow the capsule whole. Alternatively, open the capsule and sprinkle the granules onto a small amount of soft food (e.g. apple sauce) and swallow immediately. Do not crush or chew the capsule or granules.
Avoid taking this medicine with hot liquid or food as heat can destroy it.

Practice points

·         patients who develop new GI symptoms should be reviewed to exclude fibrosing colonopathy

·          the use of pancreatic supplements may not relieve pain of chronic pancreatitis; analgesics may be required.

Products

PANCREATIN (AMYLASE 8,000 IU+LIPASE 10,000 IU+PROTEASE 600 IU) CAPS (MINIMICROSPHEERES) (CREON®)

(METHIXINE 1MG, DIMETHYL POLYSILOXANE 40 MG, GLUTAMIC ACID 100 MG, CELLULASE 300 IU, PEPSIN, PANCREATIN) (SPASMO-CANULASE®)


01.09.03 Treatment of Hepatic Encephalopathy

ORNITHINE ASPARTATE

Mode of action

Ornithine is an aliphatic amino acid. It is used as a dietary supplement.

Indications

It has been used in various indications including the treatment of hyperammonaemia and hepatic encephalopathy.

Products

ORNITHINE ASPARTATE AMPS 5GM/10ML (HEPA-MERZ®)

ORNITHINE ASPARTATE GRANULES 3GM/SACHET (HEPA-MERZ®)
Table 01.01 Recommended H. Pylori Eradication Regimens

 

Regimen

Dosage

Duration

Eradication rates1

Comments

First line

PPI

standard dose twice daily

7 days

>90%

available as 'single script' therapy via PBS-R;

clarithromycin

500 mg twice daily

amoxicillin

1 g twice daily

First line (consider when amoxicillin unsuitable)

PPI

standard dose twice daily

7 days

>80%

metronidazole has relatively high rates of pretreatment resistance and greater likelihood of treatment failure

clarithromycin

500 mg twice daily

metronidazole

400 mg twice daily

First line (consider when clarithromycin unsuitable)

PPI

standard dose twice daily

14 days

80–90%

metronidazole has relatively high rates of pretreatment resistance and greater likelihood of treatment failure

amoxicillin

500 mg 3 times daily

metronidazole

400 mg 3 times daily

Second line (failure of first line regimen)2

PPI

standard dose twice daily

10–14 days

75%

complicated regimen and poorly tolerated

bismuth subcitrate (SAS)

120 mg 4 times daily

metronidazole

400 mg 3 times daily

tetracycline

500 mg 4 times daily

 

1most studies quoting eradication rates used omeprazole; other PPIs are equally effective

 

2if sensitivity testing unavailable

                                                                         

Table 01.02 Comparison of Laxative Classes

 

Laxative class

Onset of action

Place in treatment

bulking agents

oral, 48–72 hours

acute and chronic constipation

stool softeners

oral, 24–72 hours; rectal, 5–20 minutes

prevention of straining after rectal surgery and in acute perianal disease; little data to support use in acute or chronic constipation

stimulant laxatives

oral, 6–12 hours; rectal, 5–60 minutes

short term treatment of moderate-to-severe constipation; regular use in chronic neuromuscular disease, opioid-induced constipation; bowel preparation

osmotic laxatives

glycerol, lactulose, sorbitol

oral, 24–72 hours; rectal, 5–30 minutes

chronic constipation; second line in acute constipation; opioid-induced constipation

iso-osmotic, sodium or magnesium salts, including sodium phosphate

oral, 0.5–3 hours; rectal, 2–30 minutes

short term treatment of moderate-to-severe constipation; chronic constipation; bowel preparation