Ranitidine 150mg Film-coated Tablets

Each tablet contains ranitidine hydrochloride equivalent to 150mg ranitidine.

For a full list of excipients, see section 6.1.

Film-coated tablets

Creamish yellow, round, biconvex, film-coated tablets with inscription “IL” on one side and plain on other side.

Adults

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

Prevention of NSAID 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 is 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.

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.

For oral administration.

Adults (including the elderly) / Adolescent (12 years and over):

The usual dosage is 150mg 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 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.

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 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.

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 150mg four 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, 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.

Zollinger-Ellison syndrome

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 daily and these doses have been well tolerated.

Chronic episodic dyspepsia:

For patients with chronic episodic dyspepsia the recommended course of treatment is 150mg 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.

Prophylaxis of acid aspiration (Mendelson's syndrome):

In patients thought to be at risk of acid aspiration (Mendelson's) 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 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.

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

See Section 5.2 Pharmacokinetic Properties - Special Patient Populations.

Patients over 50 years of age

See Section 5.2 Pharmacokinetic Properties (Special Patient Populations, Patients over 50 years of age)

Peptic Ulcer Acute Treatment

The recommended oral dose for the 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 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 dose of 600mg (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 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.

Known hypersensitivity to ranitidine or any other ingredients in the product.

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 renal impairment. The dosage should be adjusted as detailed in section 4.2 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:

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 versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.82 (95% CI 1.26-2.64). Postmarketing data indicate reversible mental confusion, depression, and hallucinations have been reported most frequently in severely ill and elderly patients (see section 4.8).

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; 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.

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 and metronidazole.

If high doses (2 g) 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.

Pregnancy

Like other drugs, ranitidine should only be used during pregnancy 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.

Lactation

Ranitidine is also excreted in human breast milk.

Like other drugs, ranitidine should only be used during nursing if considered essential.

None known

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 post-marketing data.

Blood & Lymphatic System Disorders

Very Rare:

Blood count changes (leucopenia and thrombocytopenia) have occurred in patients. These are usually reversible. Cases of agranulocytosis or of pancytopenia, sometimes with marrow hypoplasia, or marrow aplasia have been reported.

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

Uncommon:

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

Very Rare:

Acute pancreatitis

Hepatobiliary Disorders

Rare:

Transient and reversible changes in liver function tests can occur.

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.

Symptoms and Signs

Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage with Ranitidine formulations.

Treatment

Symptomatic and supportive therapy should be given as appropriate.

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 150mg dose effectively suppresses gastric acid secretion for 12 hours.

Absorption

Following oral administration of 150 mg ranitidine, maximum plasma concentrations (300 to 550 ng/mL) occurred after 1—3 hours. Two distinct peaks or plateau in the absorption phase result from reabsorption of drug excreted into the intestine. The absolute bioavailability of ranitidine is 50-60% and plasma concentrations increase proportionally with increasing dose up to 300 mg.

Distribution

Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.

Metabolism

Ranitidine is not extensively metabolised. The fraction of the dose recovered as metabolites is similar after both oral and i.v. dosing; and includes 6% of the dose in urine as the N-oxide, 2% as the S-oxide, 2% as desmethylranitidine and 1 to 2% as the furoic acid analogue.

Elimination

Plasma concentrations decline bi-exponentially, with a terminal half-life of 2-3 hours. The major route of elimination is renal. After IV administration of 150 mg 3H-ranitidine, 98% of the dose was recovered, including 5% in faeces and 93% in urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in faeces and 70% in urine of which 35% was unchanged parent drug. Less than 3% of the dose is excreted in bile. Renal clearance is approximately 500 mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.

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 - 22ml/min/kg) between children and healthy adults receiving oral ranitidine when correction is made for body weight.

Patients over 50 years of age

In patients over 50 years of age, half-life is prolonged (3-4 h) and clearance is reduced, consistent with the age-related decline of renal function. However, systemic exposure and accumulation are 50% higher. This difference exceeds the effect of declining renal function, and indicates increased bioavailability in older patients.

No additional data of relevance.

Core Tablet:

Microcrystalline Cellulose 112 (Flocel 112)

Magnesium Stearate

Cross carmellose Sodium

Colloidal Anhydrous silica

Purified Talc

Film Coat:

Hypromellose E 15

Purified Talc

Titanium Dioxide (E171)

Castor Oil

Ferric Oxide yellow

Not applicable

36 months

Do not store above 25°C. Store in the original package.

The immediate pack of Ranitidine film-coated tablets is Aluminium/ Aluminium blister.

The lidding foil is hard tampered aluminium foil (0.025mm) with HSL coating on bright side. Forming foil is cold formable alu-alu triple laminated film.

The blisters are packed in cartons along with pack insert.

Pack sizes: 28, 30, 56, 60, 84, 90, 100, 112, 120, 168, 180 tablets

Not all pack sizes are marketed

No special instructions

Accord Healthcare Limited

Sage House

319 Pinner Road

Harrow

Middlesex

HA1 4HF

United Kingdom

PL 20075/0063

29/06/2005

20-June-2011