Nizatidine Capsules 300mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Axid 300mg Capsules Nizatidine 300mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 300 mg of Nizatidine
3 PHARMACEUTICAL FORM
Size 1 capsule with an opaque brown cap and opaque pale yellow body, imprinted with ‘Flynn 3145’ in black ink.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of the following diseases where reduction of gastric acid is indicated:
1) Duodenal ulcer
2) Benign gastric ulcer
3) Prevention of duodenal or benign gastric ulcer recurrence
4) Gastric oesophageal reflux disease (including erosions, ulcerations and associated heartburn)
5) Gastric and/or duodenal ulcer associated with concomitant use of non-steroidal anti-inflammatory drugs
4.2 Posology and method of administration
Posology
Adults:
1) 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.
2) 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.
3) For the prevention of duodenal or benign gastric ulcer recurrence (prophylactic maintenance therapy): the recommended daily dose is 150 mg in the evening.
4) 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.
5) 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).
Paediatric population
The safety and efficacy of nizatidine in children has not been established. No data are
available.
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:
|
DOSAGE RECOMMENDED | ||
|
Indications |
Moderate Renal |
Severe Renal |
|
Impairment |
Impairment | |
|
Duodenal ulcer |
150 mg in the evening |
150 mg on alternate days |
|
Benign gastric ulcer |
150 mg in the evening |
150 mg on alternate days |
|
Prevention of duodenal or benign gastric |
150 mg in the evening on |
150 mg in the evening every |
|
ulcer recurrence |
alternate days |
third day |
|
Gastric oesophageal reflux disease |
From 150mg daily, up to 150mg twice daily |
From 150 mg on alternate days, up to 150mg daily |
|
Gastric and/or duodenal ulcer associated with concomitant use of non-steroidal anti-inflammatory drugs |
150 mg in the evening |
150 mg on alternate days |
Method of administration
For oral administration.
4.3 Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
Known hypersensitivity to H2-receptor antagonists.
4.4 Special warnings and precautions for use
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.
4.5 Interaction with other medicinal products and other forms of interaction
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.
4.6 Fertility, pregnancy and lactation
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.
Breast-feeding
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, the product should be administered to nursing mothers only if considered absolutely necessary.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website:
4.9 Overdose
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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: H2-receptor antagonists, ATC code: A02BA04
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.
5.2 Pharmacokinetic properties
Absorption: 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%.
Biotransformation: Metabolites include desmethyl nizatidine (7%), sulfoxide (6%), and N-oxide (5%). Desmethyl nizatidine is an active metabolite of limited potency.
Elimination: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. More than 90% of an oral dose of nizatidine (including metabolites) is excreted in the urine within 12 hours.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber in addition to that summarised in other sections of the Summary of Product Characteristics.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Starch flowable powder Starch
Silicone fluid 350 cs Povidone
Carboxymethyl cellulose sodium cross-linked Talc
Capsule shell:
Yellow iron oxide Red iron oxide Titanium dioxide Gelatin
Black ink (including Shellac, Black iron oxide, Propylene glycol)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 25 °C.
6.5
Nature and contents of container
Opaque or transparent PVC/aluminium foil blisters.
Packs contain 28 or 30 capsules.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Flynn Pharma Limited Alton House 4 Herbert Street Dublin 2 Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 13621/0028
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 11 August 1987 Date of latest renewal: 17 August 2005
10 DATE OF REVISION OF THE TEXT
13/11/2015