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Ranitidine 75mg Film-Coated Tablets

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Document: spc-doc_PL 17907-0028 change

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 the 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

Symptomatic relief of heartburn, indigestion, acid indigestion and hyperacidity.

4.2    Posology and method of administration

Posology

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 two tablets in 24 hours.

Do not take the tablets for more than 6 days without the advice of a pharmacist or doctor.

Children under 16 years

Not recommended for children under 16 years of age.

Route of Administration Oral

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

4.4 Special warnings and precautions for use

Treatment with a histamine H2-antagonist such as Ranitidine film coated tablets may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition.

Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with renal impairment (creatinine clearance less than 50 ml/min). Ranitidine film coated tablets are not suitable for these patients without medical supervision.

People who are taking non-steroidal anti-inflammatory drugs especially those with a history of peptic ulcer and the elderly should not self-medicate with Ranitidine 75mg tablets but seek their doctor’s advice before use.

People with a history of porphyria should avoid use of the product.

Consumers will be advised not to purchase a second pack of tablets without the advice of a pharmacist of doctor.

The product is not indicated in the following people without seeking their doctor's advice:

•    Patients with severe renal impairment (creatinine clearance less than 50ml/min) and/or hepatic impairment.

•    Patients under regular medical supervision for other reasons.

•    Patients taking medications either physician prescribed or self-prescribed.

•    Those with difficulty swallowing, persistent stomach pain or unintended weight loss in association with symptoms of indigestion.

•    Those who are middle-aged or elderly with new or recently changed 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 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) 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, itraconazole, posaconazole, atazanavir, delaviridine, gefitnib).

4.6 Fertility, pregnancy and lactation

Pregnancy

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 should not be taken during pregnancy without consulting a doctor or pharmacist.

Lactation

Ranitidine is also excreted in human breast milk and women who are breastfeeding will be advised to speak to their doctor before taking Ranitidine Film Coated Tablets.

Fertility

There are no human data on the effect of ranitidine on fertility. In animal studies, no effect on fertility was observed.

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, <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, 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. Vascular Disorders

Very Rare: Vasculitis.

Gastrointestinal Disorders

Very Rare: Acute pancreatitis, diarrhea.

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

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)

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

Symptoms and Signs

Ranitidine 75 mg film coated tablets are very specific in action and accordingly no particular problems are expected following over dosage with the drug.

Treatment

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: H2-receptor antagonist, 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

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 a plateau in the absorption phase result from reabsorption of drug excreted into the intestine. The absolute bioavailability of ranitidine is 5060%, and plasma concentrations increase proportionally with increasing dose up to 300 mg.

Absorption is not significantly impaired by food or antacids.

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 includes 6% of the dose in urine as the N-Oxide, 2% as the S-Oxide, 2% as desmethyl ranitidine and 1-2% 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

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mg H- ranitidine, 98% of the dose was recovered, including 5% in the faeces

and 93% in the urine, of which 70% was unchanged parent drug. After oral

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administration of 150 mg H-ranitidine, 96% of the dose was recovered, 26% in the 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 500mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.

Special Patient Populations

• 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.

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 6 or 12 tablets.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Bristol Laboratories Limited Unit 3, Canalside, Northbridge Road,

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Berkhamsted, Herts, HP4 1EG UK.


MARKETING AUTHORISATION NUMBER(S)

PL 17907/0028


DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/06/1993 / 06/03/2007


DATE OF REVISION OF THE TEXT

09/08/2016