Zantac Tablets 150 mg

Each tablet contains ranitidine 150 mg (as the hydrochloride).

Tablet.

Adults

Duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal anti-inflammatory agents.

Prevention of non-steroidal anti-inflammatory drug associated duodenal ulcers.

Treatment of duodenal ulcers associated with Helicobacter pylori infection.

Post-operative ulcer.

Oesophageal reflux disease including long term management of healed oesophagitis.

Symptomatic relief in gastro-oesophageal reflux disease.

Zollinger-Ellison Syndrome.

Chronic episodic dyspepsia, characterised by pain (epigastric or retrosternal) which is related to meals or disturbs sleep but not associated with the above conditions.

Prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients

Prophylaxis of recurrent haemorrhage with bleeding peptic ulcers.

Before general anaesthesia in patients at risk of acid aspiration (Mendelson's

syndrome), particularly obstetric patients during labour.

For appropriate cases, Zantac injection is also available (see separate SPC).

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.

Adults (including the elderly) / Adolescents (12 years and over)

Usual dosage is 150 mg twice daily, taken in the morning and evening.

Duodenal ulcer, gastric ulcer:

The standard dosage regimen is 150 mg twice daily or 300 mg at night. 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 within 4 weeks. Healing usually occurs after a further 4 weeks of treatment in those not fully healed after the initial course of therapy.

Ulcers following NSAID therapy or associated with continued NSAIDs:

8 weeks treatment may be necessary

Prevention of NSAID associated duodenal ulcers:

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 300 mg at bedtime or 150 mg twice daily may be given with oral amoxicillin 750 mg three times daily and metronidazole 500 mg three times daily for two weeks. Therapy with ranitidine should continue for a further two weeks. This dose regimen significantly reduces the frequency of duodenal ulcer recurrence.

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.

Gastro-oesophageal reflux disease:

Symptom relief in gastro-oesophageal reflux disease. In patients with gastro-oesophageal reflux disease, a dose regimen of 150 mg twice daily for 2 weeks is recommended and this can be repeated in patients in whom the initial symptomatic response is inadequate

Oesophageal reflux disease:

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 12 weeks if necessary.

In patients with moderate to severe oesophagitis, the dosage of ranitidine may be increased to 150 mg 4 times daily for up to 12 weeks. The increased dose has not been associated with an increased incidence of unwanted effects.

Healed oesophagitis:

For long term treatment, recommended adult dose is 150 mg twice daily. Long term treatment is not indicated in management of patients with unhealed oesophagitis with or without Barrett's epithelium.

Zollinger-Ellison syndrome:

The starting dose for Zollinger-Ellison syndrome is 150 mg three times daily, and this may be increased as necessary. Doses up to 6 grams per day have been well tolerated.

Chronic episodic dyspepsia:

The standard dosage regimen for patients with chronic episodic dyspepsia is 150 mg twice daily for up to 6 weeks. Anyone not responding or relapsing shortly afterwards should be investigated.

Prophylaxis of haemorrhage from stress ulceration in seriously ill patients or prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration:

150 mg twice daily may be substituted for the injection once oral feeding commences.

Prophylaxis of acid aspiration (Mendelson's) syndrome:

150 mg oral dose can be given 2 hours before anaesthesia, and preferably also 150 mg the previous evening. Alternatively, the injection is also available. In obstetric patients in labour 150 mg every 6 hours, but if general anaesthesia is required it is recommended that a non-particulate antacid (e.g. sodium citrate) be given in addition. The usual precautions to avoid acid aspiration should also be taken.

Children from 3 to 11 years and over 30 kg of weight

See Section 5.2 Pharmacokinetic Properties (Special Patient Population)

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 complete 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 to a maximum 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:

Accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with severe renal impairment (creatinine clearance less than 50 ml/min). Accordingly, it is recommended that the daily dose of ranitidine in such patients should be 150 mg 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, 150 mg twice daily dosage should be instituted followed, if need be, by maintenance treatment of 150 mg at night.

Ranitidine is contra-indicated in patients known to have hypersensitivity to any component of the preparation.

Malignancy:

The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer (and if indications include dyspepsia, patients of middle age and over with new or recently changed dyspeptic symptoms) as treatment with ranitidine may mask symptoms of gastric carcinoma.

Renal Disease:

Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment. The dosage should be adjusted as detailed 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 and in those with a history of peptic ulcer.

Rare clinical reports suggest that ranitidine may precipitate acute porphyric attacks. Ranitidine should therefore be avoided in patients with a history of acute porphyria.

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).

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

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.

Not applicable.

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), unknown (cannot be estimated from the available data).

Blood & Lymphatic System Disorders

Unknown:

Blood count changes (leucopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.

Immune System Disorders

Uncommon:

Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain).

Unknown:

Anaphylactic shock.

These events have been reported after a single dose.

Psychiatric Disorders

Very Rare:

Depression.

Unknown:

Reversible mental confusion and hallucinations.

These have been reported predominantly in severely ill and elderly patients.

Nervous System Disorders

Common:

Headache (sometimes severe) and dizziness.

Unknown:

Reversible involuntary movement disorders.

Eye Disorders

Uncommon:

Reversible blurred vision.

There have been reports of blurred vision, which is suggestive of a change in accommodation.

Cardiac Disorders

Unknown:

As with other H₂ receptor antagonists bradycardia and A-V Block.

Vascular Disorders

Unknown:

Vasculitis.

Gastrointestinal Disorders

Common:

Diarrhoea.

Unknown:

Acute pancreatitis.

Hepatobiliary Disorders

Very Rare:

Transient and reversible changes in liver function tests.

Unknown:

Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice, these were usually reversible.

Skin and Subcutaneous Tissue Disorders

Uncommon:

Skin Rash.

Unknown:

Erythema multiforme, alopecia.

Musculoskeletal and Connective Tissue Disorders

Unknown:

Musculoskeletal symptoms such as arthralgia and myalgia.

Renal and Urinary Disorders

Unknown:

Acute interstitial nephritis.

Reproductive System and Breast Disorders

Unknown:

Reversible impotence, breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea).

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.

Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage. Symptomatic and supportive therapy should be given as appropriate.

Ranitidine is a specific rapidly acting histamine H₂-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 150 mg dose effectively suppresses gastric acid secretion for twelve hours.

Absorption of ranitidine after oral administration is rapid and peak plasma concentrations are usually achieved within two hours of administration. Absorption is not significantly impaired by food or antacids. The elimination half-life of ranitidine is approximately 2 hours. Ranitidine is excreted via the kidneys mainly as the free drug and in minor amounts as metabolites Its major metabolite is an N-oxide and there are smaller quantities of S-oxide and desmethyl ranitidine. The 24 hour urinary recovery of free ranitidine and its metabolites is about 40% with orally administered drug.

Special Patient Populations

Children (3 years and above)

Limited pharmacokinetic data show 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.

No additional data of relevance.

Tablet core:

Microcrystalline cellulose NF

Magnesium stearate EP

Methylhydroxypropyl cellulose (E464) EP

Film coat:

Titanium Dioxide E171 EP

Triacetin NF

None.

60 months.

None necessary.

Cartons of 30, 60 or 90 tablets, in aluminium foil strips or push through double foil blister packs.

No special instructions.

Glaxo Wellcome UK Limited

Trading as GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

PL 10949/0042

27 March 2002

10 March 2009

POM