Nizatidine 300mg Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nizatidine 300mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 300mg of nizatidine For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Hard capsule.
No. 1 white / caramel hard gelatine capsule imprinted axial “NTD” on the cap and “300” on the body with black ink.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
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 antiinflammatory drugs
4.2 Posology and method of administration
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.
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 50ml/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 50ml/min) or patients who have severe renal impairment (creatinine clearance less than 20ml/min), the dosage should be reduced as follows:
DOSAGE RECOMMENDED
|
No Renal Impairment |
Moderate Renal Impairment |
Severe Renal Impairment |
|
600mg |
150mg twice daily |
150mg daily |
|
300mg |
150mg in the evening |
150mg on alternate days |
|
150mg |
150mg on alternate days |
150mg every third day |
4.3 Contraindications
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 ‘Posology and method of administration' section.)
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 nizatidine does not affect the serum levels of concomitantly administered aminophylline, theophylline, chlordiazepoxide, diazepam, lidocaine, 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. Approximately 35 per cent of nizatidine is bound to plasma protein. Warfarin, diazepam, paracetamol, propantheline, phenobarbital 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 Pregnancy and lactation
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, nizatidine 150mg and 300mg capsules should be administered to nursing mothers only if considered absolutely necessary.
4.7 Effects on ability to drive and use machines
There is no influence of nizatidine on the ability to drive or use machines.
4.8 Undesirable effects
In large scale clinical trials, sweating and urticaria were significantly more common in nizatidine treated patients when compared with placebo. In these trials, 1.9 per cent of treated patients experienced somnolence, compared to 1.6 per cent 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 (e.g., bronchospasm, laryngeal oedema, rash, pruritus and eosinophilia), serum sickness and anaphylaxis have been reported.
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
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 of nizatidine after oral administration is rapid and peak plasma concentrations (700 - 1800ng/ml after 150mg; 1400 - 3600ng/ml after 300mg 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.
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
Capsule contents: Pregelatinised starch Dimeticone Povidone
Magnesium stearate
Capsule shell Gelatin
Red iron oxide E172 Titanium dioxide E171 Yellow iron oxide E172 Black iron oxide E172
Printing ink:
Denatured alcohol Shellac
«-butyl alcohol Black iron oxide (E172)
6.2
Incompatibilities
Not applicable.
Shelf life
6.3
3 years.
6.4 Special precautions for storage
Store in the original package.
6.5 Nature and contents of container
Aluminium foil, PVC/PVdC heat sealable 31.5pm thick (aluminium 20.0pm thick), PVC/PVdC transparent foil (PVC: 250pm thick, PVdC coating: 60g/m2)
Aluminium foil, PVC/PVdC heat sealable 31.5pm thick (aluminium 20.0pm thick), PVC/PVdC white opaque foil (PVC: 250pm thick, PVdC coating: 60g/m2)
Aluminium foil, PVC/PVdC heat sealable 31.5pm thick (aluminium 20.0pm thick), PVC/PVdC white opaque foil (PVC: 250pm thick, PVdC coating: 40g/m2)
Blister packs containing 10, 15, 20, 28, 30, 50, 100 capsules.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
Not applicable.
7. Marketing Authorisation Holder
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0101
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18/05/2010
10 DATE OF REVISION OF THE TEXT
25/06/2013