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 Ranitidine 150 mg. For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated Tablet (tablet).
Creamish-yellow, round, biconvex, film-coated tablets marked with “MR 150” on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ranitidine tablets are indicated for the treatment of benign gastric ulcers and duodenal ulcers.
Ranitidine Tablets are also indicated for Zollinger-Ellison Syndrome and for the treatment of reflux oesophagitis.
Ranitidine tablets are indicated for the long-term treatment of duodenal and benign gastric ulcers to prevent their recurrence. Long-term treatment is indicated in patients with a history of recurrent ulcers.
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 dose is 150 mg twice daily, taken in the morning and evening. A single bedtime dose of 300 mg may be given to patients with duodenal or gastric ulcers. Treatment may be continued for 4-8 weeks. For maintenance, the usual dose is 150 mg at bedtime.
For the management of reflux oesophagitis, the recommended dose is 150 mg twice daily or 300 mg at bedtime, usually for up to 8 weeks, this may be extended to a maximum of 12 weeks if necessary.
Severe Oesophagitis:
The dose is 150 mg, four times a day for up to a maximum of 12 weeks. This raised level of dosing has not been associated with a raised level of side effects. Long-term treatment in patients with unhealed oesophagitis is not indicated, either in the presence of Barrett’s epithelium or its absence.
Zollinger-Ellison Syndrome :
An initial dose of 150 mg, three times a day, may be increased up to 300 mg three times a day. Daily divided doses of up to 6g have been used and found to be well tolerated.
Elderly Patients:
In patients with normal renal function, the doses of Ranitidine Tablets are the same as for younger adults.
Children :
The experience of ranitidine treatment in children is limited.
The recommended dose for treating active peptic ulcer is 2-4 mg/kg, twice daily, up to a maximum daily dose of 300 mg ranitidine, given in divided doses.
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).
Safety and efficacy in new-born patients has not been established.
Renal Impairment:
In patients with severe renal impairment, plasma levels of the drug are increased. The dose in such patients is 150 mg at night for 4-8 weeks. The same dose is used for maintenance. If healing has not occurred, 150 mg twice daily should be used, followed by 150 mg at night for maintenance.
|
Creatinine clearance mL/min. |
Dose of ranitidine |
|
<50 |
150 mg |
|
>50 |
300 mg |
Ranitidine is removed by hemodialysis. Dialysis patients should therefore take Ranitidine after each dialysis occasion.
Method of Administration
Route of administration: Oral
The tablet should be swallowed whole with a sufficient amount of fluid. In children the tablets may be dissolved in water or crushed. The application of a more convenient dosage form may be considered.
4.3 Contraindications
Hypersensitivity to ranitidine or any component of Ranitidine Tablets.
4.4 Special warnings and precautions for use
Treatment with histamine H2receptor antagonists may mask symptoms of stomach carcinoma and therefore delay its 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 above under Dosage in Renal Impairment.
Regular supervision of patients who are taking non-steroidal anti-inflammatory drugs 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.
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 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.
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 an 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% CI, 1.07-2.48).
4.5 Interaction 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:
1) Inhibition of cytochrome P450-linked mixed function oxygenase system:
Ranitidine at usual therapeutic doses does not potentiate the actions of drugs which are inactivated by this enzyme system such as diazepam, lidocaine, phenytoin, propanolol 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.
2) Competition for renal tubular secrection:
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.
3) 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. ketoconazole, atazanavir, delaviridine, gefitnib).
There is no evidence of an interaction between ranitidine and -amoxicillin or metronidazole
4.6 Fertility, pregnancy and lactation
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. It is excreted in human breast milk.
Like other drugs it should only be used during pregnancy and nursing if considered essential.
4.7 Effects on ability to drive and use machines
Not applicable
4.8 Undesirable effects
The following convention has been utilised 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).
Adverse event frequencies have been estimated from spontaneous reports from postmarketing data.
Blood & lymphatic system Disorders
Very Rare:
Blood count changes (leucopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.
Immune System Disorders
Rare:
Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain).
Very Rare:
Anaphylactic shock
These events have been reported after a single dose.
Psychiatric Disorders
Very Rare:
Reversible mental confusion, depression and hallucinations.
These have been reported predominantly in severely ill and elderly patients.
Nervous System Disorders Very Rare:
Headache (sometimes severe), dizziness and reversible involuntary movement disorders.
Eye Disorders
Very Rare:
Reversible blurred vision.
There have been reports of blurred vision, which is suggestive of a change in accommodation.
Cardiac Disorders
Very Rare:
As with other H2 receptor antagonists bradycardia and A-V Block.
Vascular Disorders Very Rare:
Vasculitis.
Gastrointestinal Disorders
Very Rare:
Acute pancreatitis. Diarrhoea.
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.
Skin and Subcutaneous Tissue Disorders
Rare:
Skin Rash.
Very Rare:
Erythema multiforme, alopecia.
Musculoskeletal and Connective Tissue Disorders
Very Rare:
Musculoskeletal symptoms such as arthralgia and myalgia.
Renal and Urinary Disorders
Very rare:
Acute interstitial nephritis.
Reproductive System and Breast Disorders
Very Rare:
Reversible impotence. Breast symptoms in men.
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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: H2-Receptor Antagonists-ATC Code: A02BA02
Ranitidine is a specific rapidly acting histamine H2-receptor antagonist. It 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 150mg dose effectively suppressing gastric acid secretion for 12 hours.
5.2 Pharmacokinetic properties
The bioavailabililty of ranitidine is consistently about 50%. Absorption of ranitidine after oral administration is rapid and peak plasma concentrations are usually achieved within 2-3 hours of 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 balanced studies with 150 mg 3H-Ranitidine 60-70% of an oral dose was excreted in
urine and 25% in faeces. Analysis of urine excretion 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.
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
No additional data of relevance.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose (E460),
Hypromellose (E464),
Croscarmellose sodium (E468),
Castor oil,
Colloidal anhydrous silica,
Purified talc (E553b),
Magnesium stearate,
Ferric oxide yellow (E172),
Titanium dioxide (E171).
6.2 Incompatibilities
None reported
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in the original packaging.
6.5 Nature and contents of container
Ranitidine Tablets are packed in cold-form blister sheets (structure from outer to inner side: oriented polyamide/aluminium foil/hard PVC film with a backing of aluminium foil coated with heat seal lacquer) in the following pack sizes:-
Blister sheets of five tablets each, in boxes of 5 tablets per carton.
Blister sheets of seven tablets each, in boxes of 7, 14, 28, 56, 98 and 112 tablets per carton.
Blister sheets of eight tablets each, in boxes of 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88 and 96 tablets per carton.
Blister sheets of ten tablets each, in boxes of 10, 20, 30, 50, 60, 80, 100 and 120 tablets per carton.
Blister sheets of fifteen tablets each, in boxes of 15, 30, 45, 60, 75, 90, 105 and 120 tablets per carton.
Blister sheets of thirty tablets each, in boxes of 30, 60, 90, 120 and 150 tablets per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Activase Pharmaceuticals Limited, 11 Boumpoulinas, 3rd floor,
PC. 1060 Nicosia.
Cyprus
8 MARKETING AUTHORISATION NUMBER(S)
PL 28444/0102
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
09/01/2013
10 DATE OF REVISION OF THE TEXT
09/01/2013