SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ranitidine 150mg Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

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

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet

Round, white, film-coated, biconvex tablets engraved 5C1

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Ranitidine tablets are indicated for the treatment of duodenal ulcers (including those associated with Helicobacter pylori infection) and for the treatment of benign gastric ulcers, including those associated with non-steroidal antiinflammatory agents (NSAIDs).

Ranitidine tablets are also indicated for the prevention of duodenal ulcers associated with NSAIDs.

In addition, ranitidine tablets are indicated for the treatment of post-operative ulcers, Zollinger-Ellison syndrome, and oesophageal reflux disease including the long-term management of healed oesophagitis. Ranitidine treatment may also be beneficial in patients with chronic episodic dyspepsia, characterised by epigastric or retrosternal pain related to meals, or disturbed sleep, but which is not associated with the above conditions.

Ranitidine tablets are also indicated in the following conditions where reduction of gastric secretion and acid output is required: the prevention of recurrent haemorrhage in patients with bleeding peptic ulcers and before administration of a general anaesthetic to patients considered to be at risk of acid aspiration (Mendelson’s syndrome), particularly obstetric patients during labour; and the prevention of gastrointestinal haemorrhage from stress ulceration in seriously ill patients.

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 a day, taken in the morning and evening. Duodenal or gastric ulcer

Patients with duodenal ulceration or gastric ulceration may be treated with 150 mg twice daily or a single dose of 300 mg at bedtime.

The tablets do not have to be taken in relation to the time of meals. Cases of duodenal ulcer, benign gastric ulcer and post-operative ulcer usually heal in four weeks. In patients whose ulcer has not healed after this initial period of treatment, healing usually occurs after a further four weeks of therapy.

Ulcers associated with NSAIDs

Eight weeks of treatment may be required for ulcers associated with NSAIDs.

The healing rates of patients with duodenal ulcers treated with 300 mg twice a day for 4 weeks is higher than those after 4 weeks treatment with 150 mg twice a day or 300 mg at night. The higher dose has not been associated with increased incidence of side effects.

Duodenal ulcers associated with H. pylori infection

Patients with duodenal ulcers associated with Helicobacter pylori infection may be given 150 mg twice a day or 300 mg at bedtime concurrently with 750 mg oral amoxycillin three times a day and 500 mg metronidazole three times a day for two weeks. The ranitidine therapy should then continue for a further two weeks. This regimen significantly reduces the frequency of recurrence of duodenal ulcers.

A maintenance dose of 150 mg at bedtime is recommended for patients who have responded to short-term therapy, particularly those with a history of recurring ulcers.

Prevention of NSAID associated duodenal ulcers

The usual dosage for the prevention of NSAID associated duodenal ulcers is 150 mg twice a day given concurrently with NSAID therapy.

Zollinger-Ellison syndrome

The usual starting dose for patients with Zollinger-Ellison syndrome is 150 mg three times a day, which can be increased as necessary. Doses up to 6 g per day to treat this syndrome have been well tolerated.

Gastro-oesophageal reflux disease

Relief of symptoms in patients with gastro-oesophageal reflux disease. A dose regimen of 150 mg twice a day for 2 weeks is recommended. This can be repeated in patients in whom the initial symptomatic response is inadequate.

Oesophageal reflux disease

The recommended dose for the management of oesophageal reflux disease is 150 mg twice a day or 300 mg at bedtime for up to 8 weeks, extending to 12 weeks if necessary. For patients with moderate to severe oesophagitis the dosage can be increased to 150 mg four times a day for up to 12 weeks. The higher dose has not been associated with increased incidence of side effects.

Healed oesophagitis

The recommended dose for the long-term treatment of healed oesophagitis is 150 mg twice a day. Long term treatment is not indicated in the management of unhealed oesophagitis, with or without Barrett’s epithelium.

Chronic episodic dyspepsia

The recommended dosage for treatment of chronic episodic dyspepsia is 150 mg twice a day for up to six weeks. Patients who do not respond or relapse shortly after treatment should be investigated.

Haemorrhage from stress ulceration or recurrent haemorrhage from peptic ulcers

The usual dosage for the prevention of haemorrhage from stress ulceration in seriously ill patients, or the prevention of recurring haemorrhage in patients bleeding from peptic ulceration, is 150 mg twice a day.

Acid aspiration

A dose of 150 mg can be given to patients considered to be at risk of acid aspiration 2 hours before administration of a general anaesthetic, and preferably also 150 mg the evening before.

Obstetric patients at the start of labour may be given a dose of 150 mg followed by further doses of 150 mg every six hours. Since gastric emptying and drug absorption are delayed during labour, it is recommended that any patient requiring emergency general anaesthesia should also be given a nonparticulate antacid such as sodium citrate, prior to administration of the anaesthetic. Normal precautions to avoid acid aspiration should also be taken.

Renal impairment

As ranitidine is excreted via the kidney, plasma levels are increased in patients with severe renal impairment. Therefore a lower dosage regimen of 150 mg at night for 4 to 8 weeks is recommended for such patients. The same regimen should be used if maintenance therapy is required. If an ulcer has not healed after treatment following this regimen, the dose should be increased to 150 mg twice a day followed by maintenance therapy of 150 mg at night if required.

Paediatric population:

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.

Older people:

The recommended adult dosage is appropriate. Rates of healing of ulcers and the incidence of side effects do not differ from younger patients.

4.3 Contraindications

Ranitidine products are contraindicated in patients known to have hypersensitivity to ranitidine or any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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

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 above under Dosage and Administration in Section 4.2 under Renal Impairment.

Regular supervision of patients who are taking non-steroidal antiinflammatory 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 NS AID associated ulceration of the duodenum but not of the stomach

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

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 ranitidine alone H2 receptor antagonists versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.82 (95% CI, 1.26-2.64).

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, 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.

2)    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.

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, amoxicillin and metronidazole. If high doses (2g) of sucralfate are co-administered with ranitidine the absorption of the latter may be reduced. This effect is not seen if sucralfate is taken after an interval of 2 h.

4.6 Fertility, pregnancy and lactation Fertility

There are no data on the effects of ranitidine on human fertility. There were no effects

on male and female fertility in animal studies (see section 5.3).

Pregnancy

Ranitidine crosses the placenta. Like other drugs ranitidine should only be used during pregnancy if considered essential.

Breast-feeding

Ranitidine is excreted in human breast milk. Like other drugs ranitidine should only be used during breast-feeding if considered essential.

4.7 Effects on ability to drive and use machines

None reported

4.8 Undesirable effects

List of adverse reactions

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; including isolated reports), not known (frequency cannot be estimated from the available data).

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.

Unknown: Dyspnoea

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, in elderly and in nephropatic 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 and tachycardia.

Vascular Disorders

Very rare: Vasculitis.

Gastrointestinal Disorders

Uncommon: Abdominal pain, constipation, nausea (these symptoms mostly improved during continued treatment).

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

Rare: Elevation of plasma creatinine (usually slight; normalised during continued 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).

Paediatric population

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.

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 no particular problems are expected following overdosage with ranitidine formulations.

Treatment

Symptomatic and supportive therapy should be given as appropriate.

5.1 Pharmacodynamic properties

ATC Code: A02B A02 (drugs for treatment of peptic ulcer, H2-receptor antagonists).

Ranitidine is a specific, rapidly acting histamine H2-antagonist which inhibits basal and stimulated secretion of gastric acid. It reduces the volume and the acid and pepsin content of the secretion. A single dose of 150mg suppresses gastric acid secretion for 12 hours.

5.2    Pharmacokinetic properties

Ranitidine is readily absorbed from the gastro-intestinal tract with peak plasma concentrations reached within 2-3 hours. The bioavailability of ranitidine is about 50% and the elimination half-life from plasma is 2-3 hours. A small proportion of ranitidine is metabolised in the liver and excreted as the N-oxide, the S-oxide, desmethyl ranitidine and as the furonic acid analogue. About 35% is eliminated unchanged.

Special Patient Populations

Paediatric population (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

Preclinical information has not been included because the safety profile of ranitidine has been established after many years of clinical use. Please refer to section 4.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Microcrystalline cellulose (E460)

Croscarmellose sodium Magnesium stearate Colloidal silicon dioxide

The coating contains:

Polyethylene glycol Hypromellose (E464)

Polydextrose (E1200) Vanillin

Titanium dioxide (E171) Carnauba wax (E903)

6.2    Incompatibilities

Not applicable

6.3    Shelf life

24 months

6.4    Special precautions for storage

Do not store above 25°C Store in the original container

6.5    Nature and contents of container

Blister strips in packs of 28, 30, 56, 60, 84, 112 and 120 tablets. HDPE tablet containers in pack sizes of 100, 250, 500 & 1000 tablets. Not all pack sizes may be marketed.

6.6    Special precautions for disposal

Not applicable

7    MARKETING AUTHORISATION HOLDER

Teva UK Limited Brampton Road Hampden Park Eastbourne East Sussex BN22 9AG UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 00289/0315

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

26/06/1997

10 DATE OF REVISION OF THE TEXT

13/04/2015