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Ranitidine 75mg Tablets

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Document: spc-doc_PL 16028-0123 change

SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ranitidine 75mg Tablets

Kirkland Signature Indigestion Relief 75mg Tablets Galpharm Indigestion Relief 75mg Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 83.75 mg of Ranitidine Hydrochloride equivalent to 75 mg of Ranitidine.

For excipients see 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet (tablet)

Light pink, round, biconvex, film-coated tablets debossed with “75” on one side.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Ranitidine 75mg Tablets are indicated for the short-term symptomatic relief of acid indigestion and heartburn

4.2    Posology and method of administration

Adults (including the elderly) and adolescents of 16 years of age and older.

One Ranitidine 75mg tablet should be taken when symptoms occur, day or night. Do not take more than two tablets in 24 hours.

Patients will be instructed not to take the tablets for more than 2 weeks continuously. They must consult their doctor if symptoms deteriorate or persist after 2 weeks treatment.

Children under 16 years.

The tablets are not recommended for children under 16 years of age.

4.3 Contraindications

•    Hypersensitivity to ranitidine or any of its components.

•    Ranitidine tablets should not be given to children under 16 years of age.

4.4 Special warnings and precautions for use

The product is not indicated if the patient presents with any of the following without first seeking their doctor’s advice:

•    Treatment with histamine (H2) antagonists may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition. If the patient has been diagnosed as having a gastric ulcer or in middle aged or older patients who have experienced new or recently changed dyspeptic symptoms the possibility of malignancy must be excluded before commencing ranitidine.

•    Patients who have unintended weight loss associated with their indigestion symptoms.

•    Patients with renal and/or hepatic impairment or patients under regular medical supervision for any reason.

•    Patients suffering from any other illness or taking self-prescribed or physician-prescribed medicines.

•    Patients taking NSAID’s, especially the elderly, should seek their doctor’s advice before taking ranitidine.

•    Ranitidine Tablets should be avoided in patients with a history of acute intermittent porphyria.

•    Patients with a history of peptic ulcer or at risk of developing peptic ulcer should seek their doctor’s advice before taking tablets containing 75 mg ranitidine.

•    Those with difficulty swallowing or persistent stomach pain.

4.5 Interaction with other medicinal products and other forms of interactions

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 mechanism 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.

However, there are isolated reports of patients, in whom elevations of theophylline plasma levels and signs and symptoms of theophylline overdosage were observed under concurrent treatment with ranitidine, and theophylline. Therefore, during concurrent treatment with ranitidine, the theophylline plasma concentrations should be controlled and the theophylline dosage adjusted if necessary.

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-acetlyprocainamide 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, delavirdine, gefitinib).

There is no evidence of an interaction between ranitidine and 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 taken after an interval of 2 h.

As ranitidine absorption from the gastro-intestinal tract may be reduced by the concurrent use of antacids, ranitidine should be taken about 2 hours before such agents.

The effects of alcohol may be increased by taking ranitidine.

4.6 Pregnancy and lactation

There are no adequate or well controlled studies in man. A dose equivalent to 160 times the normal human dose showed no adverse effects on the foetus when given to pregnant rats and rabbits.

Ranitidine is excreted in breast-milk, and women who are breast-feeding must be advised to take the advice of their doctor before commencing ranitidine. It also crosses the placenta; but therapeutic doses given to obstetric patients in labour or undergoing caesarean section have not been observed to cause adverse effects on labour, delivery or subsequent neonatal progress. Ranitidine, as other self prescribed drugs, should not be taken during pregnancy without first consulting a doctor.

No effects on ability to drive and use machines have been observed.

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 postmarketing data. Blood & Lymphatic System Disorders

Very Rare: Blood count changes (leucopenia, thrombocytopenia, neutropenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.

Immune System Disorders

Rare: Hypersensitivity reactions (urticaria, angioneurotic oedema, pyrexia, bronchospasm, eosinophilia, hypotension and chest pain).

Very Rare: Anaphylactic shock.

These events have been reported after a single dose.

Psychiatric Disorders

Very Rare: Reversible confusional state, depression, insomnia, nightmares and hallucinations.

These have been reported predominantly in severely ill and elderly patients.

Unknown: Agitation, loss of libido

Nervous System Disorders

Very Rare: Headache (sometimes severe), dizziness, ataxia, lethargy, somnolence, syncope, migraine, paraesthesia, convulsion, tremor and reversible involuntary movement disorders.

Eye Disorders

Very Rare: Conjunctivitis, eyelid oedema, eye pain, eye swelling, diplopia and reversible vision blurred.

There have been reports of vision blurred, which is suggestive of a change in accommodation.

Cardiac Disorders

Very Rare: As with other H2 receptor antagonists palpitations, bradycardia, tachycardia, atrioventricular block and cardiac arrest.

Vascular Disorders

Very Rare: Flushing, hypertension and vasculitis.

Respiratory Thoracic and Mediastinal Disorders Very Rare: Dyspnoea, asthma and wheezing.

Unknown: Laryngospasm

Gastrointestinal Disorders

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

Very Rare: Pancreatitis acute, dyspepsia, flatulence, vomiting, dry mouth, lip swelling, mouth ulceration and stomatitis.

Hepatobiliary Disorders

Very Rare: Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice, usually reversible.

Skin and Subcutaneous Tissue Disorders Rare: Skin rash.

Very Rare: Erythema multiforme, alopecia, hyperhidrosis, angioedema, face swelling, eczema, rash erythematous, erythema, skin exfoliation, photosensitivity reaction, purpura, rash maculo-papular Unknown: Pruritus

Musculoskeletal and Connective Tissue Disorders Very Rare: Arthralgia and myalgia.

Renal and Urinary Disorders

Very rare: Tubulointerstitial nephritis, acute interstitial nephritis.

Reproductive System and Breast Disorders

Very Rare: Reversible erectile dysfunction, gynaecomastia and galactorrhoea (breast conditions).

General Disorders and Administration Site Conditions Very Rare: Asthenia, malaise, pyrexia and face oedema.

Unknown Fatigue

Investigations

Rare: liver function tests abnormal (transient and reversible), blood creatinine increased (usually slight; normalised during continued treatment).

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

Treatment should be supportive and symptomatic. Gastric lavage should be carried out and / or emesis induced. Seizures may be managed with diazepam, bradycardia with atropine and ventricular arrhythmias with lignocaine (also known as lidocaine). Ranitidine may be removed from plasma by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

ATC Code: A02B A (H2-receptor antagonist)

Mode of action

Ranitidine is specific, histamine H2 - antagonist with a rapid onset of action. Both basal and stimulated gastric acid secretion are inhibited, reducing both the acid content and also to a smaller extent the pepsin content and volume of the gastric juice.

Ranitidine has a relatively long duration of action, a 75 mg dose of ranitidine effectively suppressing gastric acid secretion for up to 12 hours.

5.2 Pharmacokinetic properties

Ranitidine has a bioavailability of approximately 50%. After oral administration, rapid absorption is followed by the attainment of peak plasma concentrations 2 - 3 hours later.

Ranitidine is metabolised in the liver to Ranitidine-N-oxide, N-Desmethylranitidine, Ranitidine-S-oxide and the furane acid analogue. After oral administration, ranitidine is excreted within 24 hours via the kidneys to approx. 30% as unchanged ranitidine, up to 6% as N-oxide, to a small degree in demethylised and in S-oxidised form, and as furane acid analogue. In patients with normal kidneys, renal excretion is effected predominantly by tubular secretion with a renal clearance of about 490-520 ml/min.

Additionally, ranitidine is excreted via the bile.

After oral intake, mean elimination half-life in patients with normal kidneys is 2.3-3 hours. In patients with renal insufficiency, the half-life is prolonged two-to threefold.

5.3 Preclinical safety data

The pharmacological and toxicological properties of ranitidine are well established. There are no additional data from preclinical studies of clinical concern.

6.    PHARMACEUTICAL PARTICULARS

6.1    List of Excipients

Microcrystalline cellulose; croscarmellose sodium; colloidal anhydrous silica; magnesium stearate; talc.

Film coating material: Castor oil and Opadry OY-S-54902 Pink containing hypromellose; talc; titanium dioxide (E171); red ferric oxide (E172).

6.2 Incompatibilities

Not Applicable.

6.3    Shelf life

3 years.

6.4    Special precautions for storage

Keep tablets in outer carton in order to protect from light. Do not store above 25°C.

6.5    Nature and contents of container

Ranitidine Tablets are packed in cold-form blister sheets (structure from outer to inner side: oriented polyamide/aluminium foil/hard PVC film with a backing of aluminium foil coated with heat seal lacquer), each containing 6 or 7 or 10 tablets.

Packs of 6 or 12 or 10 or 20 or 24 or 28 tablets. Pack of 6, 10 or 12 can be sold as GSL pack.

6.6    Special precautions for disposal

No special requirements.

7.    MARKETING AUTHORISATION HOLDER

Galpharm Healthcare Limited

Wrafton

Braunton

Devon

EX33 2DL

United Kingdom

8. MARKETING AUTHORISATION NUMBER

PL 16028/0123

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

05/04/2007 / 12/03/2009

10    DATE OF REVISION OF THE TEXT

06/10/2016