SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Ranitidine Tablets BP 300 mg

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Ranitidine Hydrochloride 336mg*

*equivalent to Ranitidine 300mg

3. PHARMACEUTICAL FORM

Coated Tablet

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

Ranitidine Tablets BP are indicated for the treatment of duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal antiinflammatory agents. In addition, Ranitidine Tablets BP are indicated for the prevention of NSAID-associated duodenal ulcers. Ranitidine Tablets BP are indicated for the treatment of duodenal ulcers associated with Helicobacter Pylori. Ranitidine Tablets BP are also indicated for the treatment of postoperative ulcer, Zollinger-Ellison syndrome and oesophageal reflux disease including 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 gastro-intestinal 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 (including the elderly): The usual dosage is 150mg twice daily, taken orally 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 300mg. 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 four 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 non-steroidal anti-inflammatory drug therapy or associated with continued non-steroidal anti-inflammatory drugs, 8 weeks treatment may be necessary.

For the prevention of non-steroidal anti-inflammatory drug-associated duodenal ulcers Ranitidine Tablets BP 150mg twice daily may be given concomitantly with nonsteroidal anti-inflammatory drug therapy.

In duodenal ulcer, 300mg twice daily for 4 weeks results in healing rates which are higher than those at 4 weeks with ranitidine 150mg twice daily or 300mg at night. The increased dose has not been associated with an increased incidence of unwanted effects.

For duodenal ulcers associated with Helicobacter Pylori ranitidine 300mg at bedtime or ranitidine 150mg twice daily may be given with oral amoxycillin 750mg three times daily and metronidazole 500mg 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 150mg 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 150mg twice daily or 300mg 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 150mg four times daily for up to twelve weeks. The increased dose has not been associated with an increased incidence of unwanted effects.

For the long-term management of oesophagitis the recommended adult oral dose is 150mg 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 150mg three times daily and this may be increased as necessary. Patients with this syndrome have been given increasing doses up to 6 g per day and these doses have been well tolerated.

For patients with chronic episodic dyspepsia the recommended course of treatment is 150mg twice daily for up to six weeks. Anyone not responding or relapsing shortly afterwards should be investigated.

In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or in the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, treatment with ranitidine tablets 150mg twice daily may be substituted for parenteral ranitidine 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 150mg can be given 2 hours before induction of general anaesthesia, and preferably also 150mg the previous evening.

In obstetric patients at commencement of labour, an oral dose of 150mg may be given followed by 150mg at six 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 (e.g. sodium citrate) prior to induction of anaesthesia. The usual precautions to avoid acid aspiration should also be taken.

Children 12 years and over

For children 12 years and over 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.

4.3 Contra-Indications

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

4.4. Special Warnings and Special 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 BP 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 150mg at night for 4 to 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 150mg twice daily should be instituted, followed, if need be, by maintenance treatment of 150mg at night.

Regular supervision of patients who are taking non-steroidal antiinflammatory 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.

Rates of healing of ulcers in patients aged 65 and over have not been found to differ from those in younger patients. Additionally, there is no difference in the incidence of adverse effects.

4.5. Interaction with other Medicinal Products and other Forms of Interaction

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. There is no evidence of an interaction between ranitidine and amoxycillin 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. Ranitidine is also excreted in human breast milk. Like other drugs, ranitidine should only be used during pregnancy and nursing if considered essential.

4.7. Effects on Ability to Drive and Use Machines

No adverse effects known.

4.8. Undesirable Effects

The following have been reported in patients treated with ranitidine. The relationship to ranitidine therapy has not been established in many cases.

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, A-V block and asystole.

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 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.

Antibiotic-associated diarrhoea may occur when amoxycillin and metronidazole are taken with ranitidine.

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 with the drug. Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

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 150mg dose effectively suppresses gastric acid secretion for twelve 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 halflife of ranitidine is 2-3 hours. In balance studies, 60-70% of an oral dose of radio-labelled ranitidine 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.

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. Pre-clinical Safety Data

There are no additional data of relevance to the prescriber.

6. PHARMACEUTICAL PARTICULARS 6.1. List of Excipients

Tablet Core

Microcrystalline cellulose    Ph.    Eur.

Magnesium stearate    Ph.    Eur.

Croscarmellose sodium    USNF

Purified water    Ph.    Eur.

Film Coat

Methylhydroxypropyl cellulose (E464) Ph.    Eur.

Titanium Dioxide (E171)    Ph.    Eur.

Polydextrose    FCC

Triethyl Citrate    FCC

Polyetheylene Glycol    USNF

6.2. Incompatibilities

None known.

6.3.    Shelf life

4 years (Al/Al blisters)

4 years (HDPE containers)

6.4.    Special Precautions for Storage

Store below 25°C in a dry place; protect from heat and moisture.

HDPE containers with child resistant polypropylene caps, with heat induction

seal and pulp board liner

and

Aluminium strip blister packaging.

6.6. Instructions for Use/Handling

No special instructions.

7    MARKETING AUTHORISATION HOLDER

Generics [UK] Ltd t/a Mylan

Station Close

Potters Bar

Herts

EN6 1TL

8. MARKETING AUTHORISATION NUMBER(S)

PL 4569/0290

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

06 February 1998

10 DATE OF REVISION OF THE TEXT

29/01/2010