Ranitidine 75 Mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 75 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 83.75 mg of Ranitidine Hydrochloride equivalent to 75 mg of Ranitidine.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet
Light pink, round, biconvex film-coated tablets printed with ‘75’ in black ink on one side.
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
Dosage
Adults (including the elderly) and children of 16 years of age and older:
Swallow one Ranitidine 75mg 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
The tablets are not recommended for children under 16 years of age.
4.3 Contraindications
Ranitidine is contraindicated in patients known to be hypersensitive to the active substance or to any of the excipients of the medicinal product.
4.4 Special warnings and precautions for use
Treatment with histamine (H2) antagonists 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 then 50 ml/min). Ranitidine 75 mg Film-coated Tablets is not suitable for these patients without medical supervision.
Patients, who are taking non-steroidal anti-inflammatory drugs (NSAID’s), especially in those with a history of peptic ulcer and the elderly, should be referred to their doctor before taking Ranitidine 75mg Film-coated Tablets. 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 1,262,64).
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 or a decrease in absorption.
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 75 Film-coated Tablets 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 Ranitidine 75mg 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, <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 of 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 symtoms 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)
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: H2 - receptor antagonists ATC Code: A02B A02
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 12 hours.
Clinical studies have shown that Ranitidine 75mg Film-coated Tablets 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 50-60%, 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 142L.
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
Microcrystalline cellulose Croscarmellose sodium Colloidal anhydrous silica Magnesium stearate Talc
Film coating material Castor oil
Opadry OY-S-54902 Pink containing:
Hypromellose
Talc
Titanium dioxide Red ferric oxide
Printing ink
Opacode S-1-17823 containing: Shellac
Isopropyl alcohol Iron oxide black [E172]
N-Butyl alcohol Propylene glycol Ammonium hydroxide 28%
6.2. Incompatibilities
Not applicable.
6.3. Shelf-Life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
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 7 or 10 or 12 or 14 or 20 or 28 tablets.
Not all pack sizes may be marketed
6.6. Instructions for Use, Handling and Disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Ranbaxy (UK) Limited Building 4, Chiswick Park 566 Chiswick High Road London, W4 5YE United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 14894/0012
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
26/08/2008
10 DATE OF REVISION OF THE TEXT
08/02/2013