Document: spc-doc_PL 02855-0081 change

• spc-doc_PL 02855-0081
• spc-doc_PL 02855-0085

---

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Zantac 75 Relief

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Quantities per tablet Active Ingredient:

Ranitidine Hydrochloride 84mg (equivalent to ranitidine 75mg)

3    PHARMACEUTICAL FORM

Tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

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

4.2 Posology and method of administration

Route of Administration

Oral

Dosage

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

Swallow one Zantac 75 Relief 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.

4.3 Contraindications

Ranitidine is contraindicated for people known to be hypersensitive to the drug or any of the ingredients of Zantac 75 Relief tablets.

4.4 Special warnings and precautions for use

Treatment with a histamine ^-antagonist such as Zantac 75 Relief 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 Relief is not suitable for these patients without medical supervision.

People taking non-steroidal anti-inflammatory drugs, especially those with a history of peptic ulcer and the elderly, should not self-medicate with Zantac 75 Relief 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 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 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).

4.6    Pregnancy and lactation

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

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: 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

Very Rare: Acute pancreatitis. Diarrhoea.

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 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.

Overdose

Symptoms and Signs

Ranitidine is very specific in action and no particular problems are expected following overdose with the drug. Up to 6g per day has been administered without untoward effect.

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 ATC Code

Pharmacotherapeutic group: H2-receptor antagonist, ATC code: A02BA02

Pharmacotherapeutic group

H2-receptor antagonists, ATC code: A02BA02

Mechanism of Action

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

Pharmacodynamic Effects

Ranitidine has a long duration of action and a single 75 mg dose effectively suppresses gastric acid secretion for at least 12 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 50-60%, and plasma concentrations increase proportionally with increasing dose up to 300 mg.

Absorption is not significantly impaired by food or antacids.

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 been confirmed by extensive use in patients for many years.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet Core

Microcrystalline Cellulose NF Magnesium Stearate

Filmcoat (Aqueous)

Hypromellose (E464)*

Titanium Dioxide (E171)*

Synthetic red iron oxide (E172)*

Triacetin*

Purified Water (Not detected in final formulation) *As Opadry Pink YS-1-1441-G

6.2 Incompatibilities

None known

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, 6, and 12 tablets

6.6 Special precautions for disposal

No special instructions

7 MARKETING AUTHORISATION HOLDER

Omega Pharma Ltd.

1^st Floor

32 Vauxhall Bridge Road LONDON, SW1V 2SA