ZANTAC 75 TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Zantac 75

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet containsjanitidine hydrochloride 84mg (equivalent to ranitidine 75mg)

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Pink, five-sided, biconvex, film-coated tablet.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic 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

Posology

Adults (including the elderly) and children 16 years of age and older:

Swallow one Zantac 75 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

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 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). Zantac 75 is not suitable for these patients without medical supervision.

Patients who are taking non-steroidal anti-inflammatory drugs especially in those with a history of peptic ulcer and the elderly should be referred to their doctor before taking Zantac 75. Current evidence shows that ranitidine protects against NSAID associated ulceration in the duodenum and not in the stomach.

Although clinical reports of acute intermittent porphyria associated with ranitidine administration have been rare and inconclusive, ranitidine should be avoided in patients with a history of this condition.

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 impairment (creatinine clearance less than 50 ml/min) 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 age 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 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 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, delavirdine, gefitnib).

Erlotinib and medicinal products altering pH

Concomitant administration of 300 mg ranitidine and erlotinib decreased erlotinib exposure [AUC] and maximum concentrations [Cmax] by 33% and 54%, respectively.

However, when erlotinib was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b.i.d., erlotinib exposure [AUC] and maximum concentrations [Cmax] decreased only by 15% and 17%, respectively.

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, Zantac 75 should not be taken during pregnancy without consulting a doctor.

Breastfeeding

Ranitidine is also excreted in human breast milk and women who are breast feeding will be advised to speak to their doctor before taking Zantac 75 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 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

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, constipation, nausea. (these symtoms 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

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 galactorrhea).

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Ranitidine 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. Drugs For Peptic Ulcer

And Gastro-Oesophageal Reflux Disease (Gord). 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 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 mg 3H-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 administration of 150 mg 3H-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 since been confirmed by extensive use in patients for many years.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet Core

Microcrystalline Cellulose

Magnesium Stearate

Film-coat

Methylhydroxy­propylcellulo­se (E464)

Titanium Dioxide (E171)

Synthetic red iron oxide (E172)

Triacetin

* As Opadry Pink YS-1–1441-G

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25 °C. Tablets should not be removed from blisters until immediately prior to use.

6.5 Nature and contents of container

Push through double foil blisters of 2, 5, 6, 10, 12, 14, 18, 20, 24, 30, 36 or 48 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Omega Pharma Ltd.

1st Floor

32 Vauxhall Bridge Road LONDON, SW1V 2SA United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 02855/0082

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

Date of first authorisation: 27/09/1994

Date of latest renewal: 15/08/2007