H2 -antagonists (H2 -receptor antagonists / H 2 -blockers).

Nizatidine

Axid 150mg capsules: Each capsule contains 150mg of nizatidine. Axid 300mg capsules: Each capsule contains 300mg of nizatidine.

Hard capsule. Axid 150mg capsules: Size 2 capsule with an opaque dark yellow cap and opaque pale yellow body, imprinted with 'Flynn 3144' in black ink. Axid 300mg capsules: Size 1 capsule with an opaque brown cap and opaque pale yellow body, imprinted with 'Flynn 3145' in black ink.

For the treatment of the following diseases where reduction of gastric acid is indicated: Duodenal ulcer Benign gastric ulcer Prevention of duodenal or benign gastric ulcer recurrence Gastric oesophageal reflux disease (including erosions, ulcerations and associated heartburn) Gastric and/or duodenal ulcer associated with concomitant use of non-steroidal anti-inflammatory drugs

For oral administration.

Adults: For treatment of duodenal ulcer, the recommended daily dose is 300mg in the evening. Treatment should continue for four weeks, although this period may be reduced if healing is confirmed earlier by endoscopy. Most ulcers will heal within four weeks, but if complete ulcer healing has not occurred after four weeks therapy, patients should continue therapy for a further four weeks.

For the treatment of benign gastric ulcer, the recommended daily dose is 300mg in the evening for four or, if necessary, eight weeks. Prior to treatment with nizatidine, care should be taken to exclude the possibility of gastric cancer.

If preferred, the 300mg daily dose for the treatment of duodenal or benign gastric ulcer may be given as two divided doses of 150mg in the morning and evening.

For the prevention of duodenal or benign gastric ulcer recurrence (prophylactic maintenance therapy), the recommended daily dose is 150mg in the evening.

For the treatment of gastric oesophageal reflux disease, the recommended dosage is from 150mg twice daily, up to 300mg twice daily. Therapy for up to 12 weeks is indicated for erosions and ulcerations, and associated heartburn.

For the treatment of gastric and/or duodenal ulcer associated with concomitant use of non-steroidal anti-inflammatory drugs, the recommended daily dose is 300mg daily (either 300mg at bedtime or 150mg twice daily, in the morning and in the evening) for up to 8 weeks. In most patients, the ulcers will heal within 4 weeks. During treatment, the use of non-steroidal anti-inflammatory drugs may continue.

Patients with impaired renal function: For patients who have moderate renal impairment (creatinine clearance less than 50ml/min) or patients who have severe renal impairment (creatinine clearance less than 20ml/min), the dosage should be reduced as follows:

Dosage Recommended

Not recommended, as safety and efficacy have not been established

Age does not significantly influence efficacy or safety. Normally dosage modification is not required, except in patients who have moderate to severe renal impairment (creatinine clearance less than 50ml/min).

Known hypersensitivity to H₂-receptor antagonists.

As nizatidine is partially metabolised by the liver and principally excreted by the kidneys, patients with impaired liver or kidney function should be treated with caution.

Symptomatic response to nizatidine therapy does not preclude the presence of gastric malignancy.

There is evidence that oral nizatidine does not affect the serum levels of concomitantly administered aminophylline, theophylline, chlordiazepoxide, diazepam, lignocaine, phenytoin, ibuprofen, metoprolol, warfarin, or lorazepam. Nizatidine does not inhibit the hepatic cytochrome P450-linked drug metabolising enzyme system, but may increase absorption of salicylates when they are used in very high dosage. However, nizatidine and other histamine H₂-receptor antagonists can reduce the gastric absorption of drugs whose absorption is dependent on an acidic gastric pH. Approximately 35% of nizatidine is bound to plasma protein. Warfarin, diazepam, paracetamol, propantheline, phenobarbitone, and propranolol did not affect plasma protein binding of nizatidine in vitro.

Absorption of nizatidine is not clinically significantly affected by food intake, anticholinergic agents, or antacids.

In large scale clinical trials, sweating and urticaria were significantly more common in patients treated with oral nizatidine when compared with placebo. In these trials, 1.9% of treated patients experienced somnolence, compared to 1.6% of placebo patients (non-significant).

In the same trials, patients treated with both nizatidine and placebo had mild, transient, asymptomatic elevations of transaminases or alkaline phosphatase; rare instances of marked elevations (>500iu/l) occurred in nizatidine-treated patients. The overall rate of occurrences of elevated liver enzymes and elevations to 3-times the upper limit of normal, however, did not differ significantly from placebo. All abnormalities were reversible after discontinuation of nizatidine. Since introduction, hepatitis and jaundice have been reported. Rare cases of cholestatic or mixed hepatocellular and cholestatic injury with jaundice have been reported, with reversal of the abnormalities after discontinuation.

The following effects have also been rarely reported, although a causal relationship has not always been established: thrombocytopenic purpura, fatal thrombocytopenia, exfoliative dermatitis, vasculitis, arthralgia, myalgia, gynaecomastia, impotence, hyperuricaemia, fever, nausea, and reversible mental confusion.

Rare episodes of hypersensitivity reactions (eg, bronchospasm, laryngeal oedema, rash, pruritus, and eosinophilia), serum sickness, and anaphylaxis have been reported.

Flynn Pharma Ltd

(POM)

30 March 2009