Axid.

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

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

For the treatment of gastric oesophageal reflux disease, the recommended dosage is from 150 mg twice daily, up to 300 mg 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 300 mg daily (either 300 mg at bedtime or 150 mg 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.

The elderly: 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 50 ml/min).

Children: Not recommended, as safety and efficacy have not been established.

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

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. (See section 4.2.)

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.

Usage in pregnancy: The safety of nizatidine for use during pregnancy has not been established. Animal studies have shown no evidence of impaired fertility or teratogenicity attributable to nizatidine. Nizatidine should only be used in pregnant women, or in those planning pregnancy, if considered absolutely necessary, and then with caution.

Usage in lactation: Studies conducted in lactating women have shown that 0.1% of the administered oral dose of nizatidine is secreted in human milk in proportion to plasma concentrations. Because of the growth depression in pups reared by lactating rats treated with nizatidine, Axid should be administered to nursing mothers only if considered absolutely necessary.

None stated.

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: thrombocytopenic purpura, fatal thrombocytopenia, leucopenia, agranulocytosis, anaemia, 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.

There is little experience of overdose in humans. Tested at very high doses in animals, nizatidine has been shown to be relatively non-toxic. Animal studies suggest that cholinergic-type effects, including lacrimation, salivation, emesis, miosis, and diarrhoea, may occur following very large oral doses.

Treatment: Symptomatic and supportive therapy is recommended. Activated charcoal, emesis, or lavage may reduce nizatidine absorption. The ability of haemodialysis to remove nizatidine from the body has not been conclusively demonstrated. However, this method is not expected to be efficient, since nizatidine has a large volume of distribution.

Nizatidine is a potent, selective, competitive and fully reversible histamine H₂-receptor antagonist. Nizatidine significantly decreased basal and stimulated gastric acid and pepsin concentration, in addition to the volume of gastric secretion.

In various clinical trials, nizatidine, administered as either a single daily dose (at bedtime) or in two divided doses (morning and evening), significantly inhibited gastric acid secretion, and ulcer pain was usually rapidly abolished.

Nizatidine has no significant effect on the serum concentrations of gastrin, gonadotrophins, prolactin, growth hormone, antidiuretic hormone, cortisol, testosterone, 5-alpha-dihydrotestosterone, or oestradiol.

Nizatidine has no antiandrogenic action.

Absorption of nizatidine after oral administration is rapid and peak plasma concentrations (700-1800 ng/ml after 150 mg; 1400-3600 ng/ml after 300 mg dose) are usually achieved within two hours of administration (range 0.5-3 hours). Oral bioavailability exceeds 70%, and the elimination half-life is approximately 1.6 hours. Minor (6%) first pass hepatic metabolism occurs, but nizatidine is principally excreted via the kidneys, about 60% as unchanged drug, renal clearance is about 500ml/min. Metabolites include desmethyl nizatidine (7%), sulphoxide (6%), and N-oxide (5%). Desmethyl nizatidine is an active metabolite of limited potency. More than 90% of an oral dose of nizatidine (including metabolites) is excreted in the urine within 12 hours.

There are no preclinical data of relevance to the prescriber in addition to that summarised in other sections of the Summary of Product Characteristics.

Starch flowable powder

Starch

Silicone fluid 350 cs

Magnesium stearate (Axid 150mg)

Povidone (Axid 300mg)

Carboxymethyl cellulose sodium cross-linked (Axid 300mg)

Talc (Axid 300mg)

Capsules shell:

Yellow iron oxide

Red iron oxide (Axid 300mg)

Titanium dioxide

Gelatin

Black ink (SW-9008)

Shellac

Black iron oxide

Propylene glycol

None known.

24 months unopened.

Do not store above 25°C.

Opaque or transparent PVC/aluminium foil blisters.

Packs contain 28 or 30 capsules.

None.

Flynn Pharma Limited

Alton House

4 Herbert Street

Dublin

Ireland

PL 13621/0027

PL 13621/0028

Date of first authorisation: 11 August 1987

Date of last renewal of authorisation: June 2005

October 2008