SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Ranitidine 75mg film coated tablets Lloydspharmacy Heartburn & Indigestion Relief Tablets RaniCalm 75mg film coated tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains ranitidine 75 mg (as the hydrochloride).

For full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Film coated tablets.

White to almost white, circular, biconvex, film coated tablets embossed with “BL” on one side and “75” on the other.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Short term relief of heartburn, indigestion, acid indigestion and hyperacidity.

For prevention of acid indigestion, indigestion, hyperacidity and heartburn associated with consuming food and drink.

4.2 Posology and method of administration

Route of administration Oral

Dosage

The tablets have to be swallowed whole.

Adults (Including the Elderly) and children 16 years of age and older:

Swallow one Ranitidine Film Coated tablet whole, with a drink of water, as soon as you have symptoms. If symptoms persist for more than one hour or return, take another tablet. Do not take more than four tablets in 24 hours.

For prevention of acid indigestion, indigestion, hyperacidity and heartburn associated with consuming food and drink, swallow one tablet with water, half to one hour beforehand.

Patients will be advised not to take the tablets for more than 2 weeks continuously and to consult their doctor if symptoms get worse or persist after 2 weeks treatment.

Children under 16 years

Not recommended for children under 16 years of age.

4.3 Contraindications

Ranitidine is contraindicated for people known to be hypersensitive to the drug or any of the ingredients of Ranitidine Film Coated tablets.

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 if indications include dyspepsia; patients of middle age and over with new or recently changed dyspeptic symptoms must be included] as treatment with ranitidine may mask 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 in renal impairment.

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

Regular supervision of patients who are taking non-steroidal anti0inflammatory drugs concomitantly with ranitidine is recommended, especially in elderly and in those with a history of peptic ulcer.

The Patient Information Leaflet and Label advises the patient not to take the maximum daily dose for more than 14 consecutive days unless advised by their doctor. The product is not indicated in the following patients without seeking their doctor's or pharmacist’s advice:

•    Patients with renal and/or hepatic impairment. Patients under regular medical supervision for other reasons.

•    Patients suffering from any other illness or taking medications either physician prescribed or self prescribed.

•    Patients of middle-aged or older with new or recently changed symptoms of indigestion.

•    Patients with unintended weight loss in association with symptoms of indigestion.

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 levels 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).

Oral Formulations:

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.

4.6    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. Like other over the counter drugs, Ranitidine Film Coated Tablets should not be taken during pregnancy without consulting a doctor. Ranitidine is also excreted in human breast milk and women who are breast-feeding will be advised to speak to their doctor before taking Ranitidine Film Coated Tablets.

4.7    Effects on ability to drive and use machines

No known effect.

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, ,/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.

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: Depression, reversible mental confusion, 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.

Very Rare: Vasculitis.

Gastrointestinal Disorders

Very Rare: Acute pancreatitis.

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

Rare: elevation of plasma creatinine (usually slight; normalised during continued treatment)

Reproductive System and Breast Disorders

Very Rare: Reversible impotence, breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea) in men.

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.

4.9 Overdose

Ranitidine 75 mg film coated tablets 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

Pharmacotherapeutic group: Drugs for Acid Related Disorders ,

ATC Code:A02BA02

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 long duration of action and a single 75mg dose suppresses gastric acid secretion for up to twelve hours.

Clinical studies have shown that Ranitidine 75 mg can relieve the symptoms of excess acid production for up to 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 half-life of ranitidine is 2-3 hours. In balance studies with 150mg 3H-ranitidine 60-70% of an oral dose 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.

5.3 Preclinical safety data

Extensive studies have been carried out in animals. The pharmacology of ranitidine hydrochloride shows it to be a surmountable H2 receptor antagonist which produces an inhibition of gastro acid secretion. Extensive toxicological investigators have been conducted which predicted a very safe profile for clinical use. This safety has been confirmed by extensive use in patients for many years.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose Magnesium Stearate Hypromellose Titanium Dioxide (E171)

6.2 Incompatibilities

Not applicable

6.3    Shelf life

3 years

6.4    Special precautions for storage

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

6.5 Nature and contents of container

Polyamide/ Aluminium/PVC/Aluminium blisters containing 6 tablets. Blisters packaged into outer container to give total of 24 tablets.

6.6 Special precautions for disposal

No special requirements

7 MARKETING AUTHORISATION HOLDER

Bristol Laboratories Limited Unit 3, Canalside, Northbridge Road,

Berkhamsted, Herts, HP4 1EG UK.

8    MARKETING AUTHORISATION NUMBER(S)

PL 17907/0247

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/08/2009

10 DATE OF REVISION OF THE TEXT

28/10/2011