Ranitidine 150mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 150 mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ranitidine Hydrochloride equivalent to 150 mg ranitidine. For excipients see 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablets.
Appearance: White to yellowish, circular, convex, film-coated tablets, diameter 10 mm marked with letters “R” and “I” either side of the scoreline on one face.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
For the treatment of duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal anti-inflammatory agents.
For the prevention of NSAID associated duodenal ulcers.
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.
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
For oral 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.
Duodenal ulcers associated with Helicobacter pylori infection:
For duodenal ulcers associated with Helicobacter pylori infection ranitidine 300mg at bedtime or 150mg twice daily may be given with oral amoxicillin 750mg three times daily and metronidazole 500mg three times daily for two weeks. Therapy with ranitidine should continue for a further 2 weeks. This dose regimen significantly reduces the frequency of duodenal ulcer recurrence.
Maintenance treatment at a reduced dosage of 150mg at bedtime is recommended for patients who have responded to short-term therapy, particularly those with a history of recurrent ulcer.
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. Longterm treatment is not indicated in the management of patients with unheated 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 6 g 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 also150 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.
In patients with Renal Impairment accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with severe renal impairment (creatinine clearance less than 50ml/min). Accordingly, it is recommended that the daily dose of ranitidine in such patients should be 150mg at night for 4-8 weeks. The same dose should be used for maintenance treatment, if necessary. If an ulcer has not healed after treatment, 150mg twice daily dosage should be instituted followed, if need be, by maintenance treatment of 150mg at night.
Children 12 years and over
For children 12 years and over the adult dosage is given.
Children from 3 to 11 years and over 30kg of weight
See Section 5.2 Pharmacokinetic Properties (Special Patient Populations)
Peptic Ulcer Acute Treatment
The recommended oral dose for treatment of peptic ulcer in children is 4mg/kg/day to 8mg/kg/day administered as two divided doses to a maximum of 300mg ranitidine per day 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 5mg/kg/day to 10mg/kg/day administered as two divided doses to a maximum of 600mg (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.
4.3 Contraindications
Known hypersensitivity to ranitidine or any other ingredients in the product.
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. The dose should be adjusted as detailed under Dosage in Renal Impairment. See section 4.2.
Regular supervision of patients who are taking non-steroidal anti-inflammatory drugs concomitantly with ranitidine is recommended especially in the elderly and in those with a history of peptic ulcer. Current evidence shows that ranitidine protects against NSAID associated ulceration in the duodenum and not in the stomach.
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.
Use in elderly patients:
Rates of healing 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.
In patients such as the elderly, persons with chronic lung disease, diabetes or the immunocompromised, there may be an increased risk of developing community acquired pneumonia. A large epidemiological study showed n increased risk of developing community acquired pneumonia in current users of H2 receptor antagonists versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.63 (95%)
4.5 Interactions with other medicinal products and other forms of interaction
Ranitidine has the potential to affect the absorption, metabolism or renal excretion of other drugs. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment.
Interactions occur by several mechanisms including:
Inhibition of cytochrome P450-linked mixed function oxygenase system. Accordingly, ranitidine at therapeutic doses does not potentiate the actions of drugs which are inactivated by this enzyme; these include diazepam, lignocaine, phenytoin, propranolol and theophylline.
There have been reports of altered prothrombin time with coumarin anticoagulants (e.g. warfarin). Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine
Competition for renal tubular secretion
Since Ranitidine is partially eliminated by the cationic system, it may affect the clearance
of other drugs eliminated by this route. High doses of ranitidine (e.g such as those used in
the treatment of Zollinger-Ellison syndrome) may reduce the excretion of procainamide
and N-acetylprocainamide resulting in increased plasma level of these drugs. Alteration of gastric Ph
The bioavailability of certain drugs may be affected. This can result in either an increase
in absorption (e.g triazolam, midazolam, glipizide) or a decrease in absorption (e.g ketoconzaole, atazanavir, delaviridine, gefitnib).
There is no evidence of an interaction between ranitidine and amoxicillin or metronidazole.
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.
There are no data on the effects of ranitidine on human fertility. There were no effects on male and female fertility in animal studies.
4.7 Effects on ability to drive and use machines
None known.
4.8 Undesirable effects
The following convention has been utilized for the classification of undesirable effects:
Very common (> 1/10), common (> 1/100, <1/10), uncommon > 1/1000, < 1/100), rare (>1/10,000, < 1/1000), very rare (< 1/10,000).
Hepatobiliary Disorders
Rare: Transient and reversible changes in liver function tests.
Very rare: hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice. These were usually reversible.
Blood and lymphatic System Disorders
Very rare: 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.
Immune System Disorders
Uncommon: Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension, and chest pain
Very rare: anaphylactic shock.
These reactions have occasionally occurred after a single dose.
Cardiac Disorders
Very rare: As with other H 2 - receptor antagonists, bradycardia and A-V block. Nervous system Disorders
Common: Headache, sometimes severe, and dizziness.
Very rare: reversible involuntary movement disorders
Psychiatric Disorders
Very Rare: Depression
Very rare: reversible mental confusion, and hallucinations. These are predominantly reported in severely ill and elderly patients.
Skin and subcutaneous Tissue Disorders
Uncommon: Skin rash
Very rare: erythema multiforme, alopecia
Musculoskeletal and Connective Tissue Disorders
Vascular Disorders
Very rare: vasculitis
Renal and Urinary Disorders
Rare: Elevation of plasma creatinine (usually slight; normalised during continue treatment)
Very rare: acute interstitial nephritis Reproductive System and Breast disorders
Very rare: Reversible impotence, breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea)
Gastrointestinal Disorders
Uncommon:
Abdominal pain, constipation, nausea (these symptoms mostly improved during continued treatment).
Very rare: Acute pancreatitis, diarrhoea
Eye disorders
Uncommon: reversible blurred vision
There have been reports of blurred vision, which is suggestive of a change in accommodation.
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 data available in particular regarding growth and development.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued 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 at: www.mhra.gov.uk/yellowcard
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.
5.1. Pharmacodynamic properties
ATC Code: A02B A02 - Drugs for peptic ulcers and gastro-oesophageal reflux disease (GORD); H2-receptor antagonists
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-
basic butylated methacrylate copolymer hypromellose,
Macrogol 6000 purified talc titanium dioxide
6.2 Incompatibilities
Not applicable.
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
AL/PVC Blister packs.
Pack sizes: 28, 30, 56, 60, 84, 90, 100, 112, 120, 168, 180 (not all pack sizes may be marketed)
6.6 Special precautions for disposal
No special instructions.
7. MARKETING AUTHORISATION HOLDER
Relonchem Limited,
Cheshire House,
Gorsey Lane, Wides, Cheshire,
WA8 0RP,
United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 20395/0007
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25th January 2005
10 DATE OF REVISION OF THE TEXT
03/09/2015