Ranitidine 300mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 300 mg Tablets BP
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ranitidine Hydrochloride equivalent to 300 mg ranitidine. For excipients see 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablets.
Appearance: White to yellowish, oblong, convex, film-coated tablets, size 8.2 x 17 mm, impressed with the Greek letter Delta (A)on one face and a central division line on the other face.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
1. For the treatment of duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal anti-inflammatory agents.
2. For the prevention of NSAID associated duodenal ulcers.
3. For the treatment of post-operative ulcer, Zollinger-Ellison syndrome and oesophageal reflux disease including the long term management of healed oesophagitis. Other patients with chronic episodic dyspepsia, characterised by pain (epigastric or retrosternal) which is related to meals or disturbs sleep but is not associated with the preceding conditions may benefit from ranitidine treatment.
4. Ranitidine Tablets are indicated for the following conditions where reduction of gastric secretion and acid output is desirable: the prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients; the prophylaxis of recurrent haemorrhage in patients with bleeding peptic ulcers and before general anaesthesia in patients considered to be at risk of acid aspiration (Mendelson’s syndrome), particularly obstetric patients during labour.
Children (3 to 18 years)
- Short term treatment of peptic ulcer
- Treatment of gastro-oesophageal reflux, including reflux oesophagitis and
symptomatic relief of gastro-oesophageal reflux disease.
4.2 Posology and method of administration
Adults: The usual dosage is 150 mg twice daily, taken in the morning and evening.
Alternatively, patients with duodenal ulceration, gastric ulceration or oesophageal reflux disease may be treated with a single bedtime dose of 300 mg. It is not necessary to time the dose in relation to meals. In most cases of duodenal ulcer, benign gastric ulcer and post operative ulcer, healing occurs in 4 weeks. Healing usually occurs after a further 4 weeks of treatment in those patients whose ulcers have not fully healed after the initial course of therapy.
In ulcers following NSAID therapy or associated with continued NSAIDs, 8 weeks’ treatment may be necessary.
For the prevention of NSAID associated duodenal ulcers ranitidine 150 mg twice daily may be given concomitantly with NSAID therapy. In duodenal ulcer 300 mg twice daily for 4 weeks results in healing rates which are higher than those at 4 weeks with ranitidine 150 mg twice daily or 300 mg at night. The increased dose has not been associated with an increased incidence of unwanted effects.
Maintenance treatment at a reduced dosage of 150 mg at bedtime is recommended for patients who have responded to short-term therapy, particularly those with a history of recurrent ulcer. In the management of oesophageal reflux disease, the recommended course of treatment is either 150 mg twice daily or 300 mg at bedtime for up to 8 weeks or if necessary 12 weeks.
In patients with moderate to severe oesophagitis, the dosage of ranitidine may be increased to 150 mg four times daily for up to 12 weeks. The increased dose has not been associated with an increased incidence of unwanted effects. For the long-term treatment of healed oesophagitis, the recommended adult oral dose is 150 mg twice daily. Long-term treatment is not indicated in the management of patients with unhealed oesophagitis, with or without Barrett’s epithelium.
In patients with Zollinger-Ellison syndrome, the starting dose is 150 mg three times daily and this may be increased as necessary. Patients with this syndrome have been given increasing doses up to 6g daily and these doses have been well tolerated.
For patients with chronic episodic dyspepsia the recommended course of treatment is 150 mg twice daily for up to 6 weeks. Anyone not responding or relapsing shortly afterwards should be investigated.
In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, treatment with 150 mg twice daily may be substituted for ranitidine injection once oral feeding commences in patients considered to be still at risk from these conditions.
In patients thought to be at risk of acid aspiration syndrome an oral dose of 150 mg can be given 2 hours before induction of general anaesthesia, and preferably also 150 mg the previous evening.
In obstetric patients at commencement of labour, an oral dose of 150 mg may be given followed by 150 mg at 6 hourly intervals. It is recommended that since gastric emptying and drug absorption are delayed during labour, any patient requiring emergency general anaesthesia should be given, in addition, a non-particulate antacid (eg sodium citrate) prior to induction of anaesthesia. The usual precautions to avoid acid aspiration should also be taken.
Children:
Children 12 years and over
For children over 12 years the adult dosage is given.
Children from 3 to 11 years and over 30 kg of weight
See Section 5.2 Pharmacokinetic Properties - Special Patient Populations.
Peptic Ulcer Acute Treatment
The recommended oral dose for the treatment of peptic ulcer in children is 4 mg/kg/day to 8 mg/kg/day administered as two divided doses to a maximum of 300 mg ranitidine per day for a duration of 4 weeks. For those patients with incomplete healing, another 4 weeks of therapy is indicated, as healing usually occurs after eight weeks of treatment.
Gastro-Oesophageal Reflux
The recommended oral dose for the treatment of gastro-oesophageal reflux in children is 5 mg/kg/day to 10 mg/kg/day administered as two divided doses in a maximum dose of 600 mg (the maximum dose is likely to apply to heavier children or adolescents with severe symptoms).
Neonates
Safety and efficacy in new-born patients has not been established.
Use in elderly patients: Rates of healing of ulcers in clinical trial patients aged 65 and over have not been found to differ from those in younger patients. Additionally, there was no difference in the incidence of adverse effects.
For oral use.
4.3 Contraindications
Known hypersensitivity to ranitidine or any other ingredients in the product.
Although clinical reports of acute intermittent porphyria associated with ranitidine administration have been rare and inconclusive, ranitidine should be avoided in patients with a history of this condition.
4.4 Special warnings and precautions for use
Treatment with a histamine H2-antagonist may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition. Accordingly, where gastric ulcer has been diagnosed or in patients of middle age and over with new or recently changed dyspeptic symptoms the possibility of malignancy should be excluded before therapy with Ranitidine Tablets is instituted.
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment. Accordingly, it is recommended that the therapeutic regimen for ranitidine in such patients be 150 mg at night for 4-8 weeks. The same dose should be used for maintenance treatment should this be deemed necessary. If an ulcer has not healed after treatment the standard dosage regimen of 150 mg twice daily should be instituted, followed, if need be, by maintenance treatment of 150 mg at night.
4.5 Interaction with other medicinal products and other forms of interaction
Regular supervision of patients who are taking NSAIDs concomitantly with ranitidine is recommended, especially in the elderly. Current evidence shows that ranitidine protects against NSAID associated ulceration in the duodenum and not in the stomach.
Ranitidine does not inhibit the hepatic cytochrome P450-linked mixed function oxygenase system. Accordingly, ranitidine does not potentiate the actions of drugs which are inactivated by this enzyme; these include diazepam, lignocaine, phenytoin, propranolol, theophylline and warfarin.
4.6 Fertility, Pregnancy and lactation
Like other drugs, ranitidine should only be used during pregnancy and nursing if considered essential.
Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labour or undergoing caesarean section have been without any adverse effect on labour, delivery or subsequent neonatal progress. Ranitidine is also excreted in human breast milk.
4.7 Effects on ability to drive and use machines
None known.
4.8 Undesirable effects
Transient and reversible changes in liver function tests can occur. There have been occasional reports of hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice. These were usually reversible. Acute pancreatitis has been reported rarely.
Leucopenia and thrombocytopenia have occurred rarely in patients. These are usually reversible. Rare cases of agranulocytosis or of pancytopenia, sometimes with marrow hypoplasia, or aplasia have been reported.
Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension, anaphylactic shock) have been seen rarely following the parenteral and oral administration of ranitidine. These reactions have occasionally occurred after a single dose.
As with other H2-receptor antagonists, there have been rare reports of bradycardia and A-V block.
Headache, sometimes severe, and dizziness have been reported in a very small proportion of patients. Rare cases of reversible mental confusion, depression and hallucinations have been reported, predominantly in severely ill and elderly patients.
Skin rash has been reported, including rare cases of mild erythema multiforme. Musculoskeletal symptoms such as arthralgia and myalgia have been reported rarely.
No clinically significant interference with endocrine or gonadal function has been reported. There have been a few reports of breast symptoms (swelling and/or discomfort) in men taking ranitidine; some cases have resolved on continued ranitidine treatment. Discontinuation of therapy may be necessary in order to establish the underlying cause.
The safety of ranitidine has been assessed in children aged 0 to 16 years with acid-related disease and was generally well tolerated with an adverse event profile resembling that in adults. There are limited long term safety data available, in particular regarding growth and development.
4.9 Overdose
Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage.
Symptomatic and supportive therapy should be given as appropriate. If need be, the drug maybe be removed from the plasma by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: A02B A02
Ranitidine is a specific, rapidly acting histamine H2-antagonist.
Ranitidine inhibits basal and stimulated secretion of gastric acid, reducing both the volume and the acid and pepsin content of the secretion. Ranitidine has a relatively long duration of action and so a single 150 mg dose effectively suppresses gastric acid secretion for 12 hours.
5.2 Pharmacokinetic properties
The bioavailability of ranitidine is consistently about 50%. Absorption of ranitidine after oral administration is rapid and peak plasma concentrations are usually achieved 2-3 hours after administration. Absorption is not significantly impaired by food or antacids. Ranitidine is not extensively metabolised. Elimination of the drug is primarily by tubular secretion. The elimination half-life of ranitidine is 2-3 hours. In balance studies with 150 mg 3H-ranitidine 60-70% of an oral dose was excreted in urine and 26% in faeces. Analysis of urine excreted in the first 24 hours after dosing showed that 35% of the oral dose was eliminated unchanged. About 6% of the dose is excreted as the N-oxide, 2% as the S-oxide, 2% as desmethyl ranitidine and 1-2% as the furoic acid analogue.
Use in renal transplants: ranitidine has been used in patients with renal transplants. Special Patient Populations
Children (3 years and above)
Limited pharmacokinetic data have shown that there are no significant differences in half-life (range for children 3 years and above: 1.7 - 2.2 h) and plasma clearance (range for children 3 years and above: 9 - 22 ml/min/kg) between children and healthy adults receiving oral ranitidine when correction is made for body weight.
5.3 Preclinical safety data
Extensive studies in animals have not revealed any significant toxicological abnormalities nor any mutagenic potential of ranitidine. Chronic high dose tests in rodents have not demonstrated carcinogenicity.
Reproductive toxicological studies in rodents have not revealed any teratological or toxicological effects of ranitidine.
In standard bacterial tests for mutagenicity (Salmonella, E. Coli) at concentrations up to the maximum recommended for these assays ranitidine was not found to be mutagenic.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
tablet core
croscarmellose sodium magnesium stearate microcrystalline cellulose
tablet coat polymethacrylate hydroxypropylmethylcellulose polyethylene glycol 6000 purified talc titanium dioxide
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 25 °C. Store in the original package.
6.5 Nature and contents of container
Carton: Printed carton manufactured from white folding box board.
Blister packs (al/al).
Push-through foil for PVC blister. Aluminium foil, 20 pm, one side bright, hard, plain, dull side lacquered (suitable for subsequent printing), bright side heatseal lacquered suitable for sealing against PVC.
Formpacking bottom strip. Aluminium strip, 45 pm, one side bright, soft, plain, dull side lacquer-laminated to OPA film, 25 pm, bright side lacquer-laminated to hard PVC film, 60 pm.
Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Medley Pharma Limited Unit 2A,
Olympic Way Sefton Business Park Liverpool L30 1RD UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 43870/0027
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
7 January 2003
10 DATE OF REVISION OF THE TEXT
18/12/2014