Ranitidine Indigestion Relief Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 75mg Tablets BP
Ranitidine Indigestion Relief Tablets (GSL use only)
Ranitidine Indigestion Relief & Prevention Tablets (P use only)
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ranitidine Hydrochloride 84mg*
*equivalent to ranitidine base 75mg
for excipients, see 6.1
3 PHARMACEUTICAL FORM
Film-coated Tablet
A peach, round, biconvex, film-coated, tablet, marked “75” on one side and “G” on the reverse
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ranitidine 75mg Tablets BP are indicated as a “Pharmacy Medicine” as follows:-
Ranitidine 75mg Tablets BP are indicated for the symptomatic relief of heartburn indigestion, acid indigestion and hyperacidity. In addition they may also be used for prevention of acid indigestion, indigestion, hyperacidity and heartburn associated with consuming food and drink.
Ranitidine 75mg Tablets BP are not indicated in the following patients without seeking a doctor's or pharmacist's advice:
• Patients with renal and/or hepatic impairment.
Patients suffering from any other illness or taking medications either self prescribed or prescribed by a physician.
Patients with new or recently changed symptoms of indigestion, who are middle aged or over.
Patients with symptoms of indigestion who have experienced unintended weight loss.
Women who are breast feeding, since ranitidine is excreted in human breast milk.
Patients under regular medical supervision for other reasons.
Ranitidine 75mg Tablets BP are indicated as a “General Sales List Medicine” as follows:-
Rantidine 75mg Tablets BP are indicated for the symptomatic relief of heartburn indigestion, acid indigestion.
Ranitidine 75mg Tablets BP are not indicated in the following patients without seeking a doctor’s or pharmacist’s advice.
Patients with renal and/or hepatic impairment.
Patients suffering from any other illness or taking medications either self prescribed or prescribed by a physician.
Patients with new or recently changed symptoms of indigestion, who are middle aged or over.
Patients with symptoms of indigestion who have experienced unintended weight loss.
Women who are breast feeding, since ranitidine is excreted in human breast milk.
Patients under regular medical supervision for other reasons.
4.2 Posology and method of administration
Route of Administration: Oral
Dosage for the “Pharmacy Medicine”
Adults (Including The Elderly) and children 16 years of age and older:
One Ranitidine 75mg tablet taken whole, with a drink of water, as soon as symptoms occur. If symptoms persist for more than one hour or return, one more tablet may be administered. There is a maximum dosage of four tablets in a period of 24 hours.
For prevention of acid indigestion, indigestion, hyperacidity and heartburn associated with consuming food and drink, one tablet with water, should be administered, half to one hour before eating or drinking.
Patients should not take the tablets continuously for more than 2 weeks and should consult their doctor if symptoms get worse or persist after such treatment.
Children under 16 years
Not recommended for children under 16 years of age.
Dosage for the “General Sales List Medicine”
Adults (Including The Elderly) and children 16 years of age and older:
One Ranitidine 75mg tablet taken whole, with a drink of water, as soon as symptoms occur. If symptoms persist for more than one hour or return, one more tablet may be administered. There is a maximum dosage of two tablets in a period of 24 hours.
Patients should not take the tablets continuously for more than 6 days and should consult their pharmacist or doctor if symptoms get worse or persist after such treatment.
Children under 16 years
Not recommended for children under 16 years of age.
4.3 Contraindications
Ranitidine products are contraindicated in patients known to have hypersensitivity to any component of the preparation.
4.4 Special warnings and precautions for use
The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer, dyspepsia; patients of middle age and over with new or recently changed dyspeptic symptoms as treatment with ranitidine may mask symptoms of gastric carcinoma.
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment.
The dosage should be adjusted as detailed above under Dosage and Administrationin Section 4.2 in renal impairment.
Rare clinical reports suggest that ranitidine may precipitate acute porphyric attacks. Ranitidine should therefore be avoided in patients with a history of acute porphyria.
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 H2 receptor antagonists versus those who had stopped treatment, with an observed adjusted relative risk increase of 1,82 (95% CI 1,26-2,64). [7, 8]
The product contains the colouring agent E110 (Sunset Yellow). This can cause allergic type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.
Patients who are taking non-steroidal anti-inflammatory drugs especially the elderly should be referred to their doctor before taking Ranitidine 75mg Tablets BP.
For the Pharmacy Medicine, patients are advised not to take the maximum daily dose for more than 14 consecutive days, unless advised by their doctor.
For the General Sales List Medicine, patients will be advised not to purchase a second pack of tablets without the advice of a pharmacist or doctor.
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) 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-acetylprocainamide 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, delaviridine, gefitnib).
There is no evidence of an interaction between ranitidine and amoxicillin and metronidazole. If high doses (2 g) of sucralfate are co-administered with ranitidine the absorption of the latter may be reduced. This effect is not seen if sucralfate is taken after an interval of 2 h.
4.6 Pregnancy and lactation
Pregnancy
Ranitidine crosses the placenta. Like other drugs ranitidine should only be used during pregnancy if considered essential.
Lactation
Ranitidine is excreted in human breast milk. Like other drugs ranitidine should only be used during nursing if considered essential.
4.7 Effects on ability to drive and use machines
None reported.
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.
Vascular Disorders
Very Rare: Vasculitis.
Gastrointestinal Disorders
Very Rare: Acute pancreatitis
Uncommon: abdominal pain, diarrhoea, 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, Steve-Johnson Syndrome.
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[6]. Rare: elevation of plasma creatinine (usually slight; normalised during continued treatment)
Reproductive System and Breast Disorders
Very Rare: Reversible impotence [3], breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea)
Paediatric population
The safety of ranitidine has been assessed in children aged 0 to 16 years with acid-related disease and was generally well tolerated with an adverse event profile resembling that in adults. There are limited long term safety data available, in particular regarding growth and development.
Antibiotic-associated diarrhoea may occur when amoxycillin and metronidazole are taken with ranitidine.
Overdose
4.9
Symptoms and Signs
Ranitidine is very specific in action and no particular problems are expected following overdosage with ranitidine formulations.
Treatment
Symptomatic and supportive therapy should be given as appropriate.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
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 so a single 75mg dose suppresses gastric acid secretion for ten to twelve hours.
5.2 Pharmacokinetic properties
The bioavailability of ranitidine is consistently about 50%. Absorption of ranitidine after oral administration is rapid and peak plasma concentrations are usually achieved 2-3 hours after administration. Absorption is not significantly impaired by food or antacids. Ranitidine is not extensively metabolised. Elimination of the drug is primarily by tubular secretion. The elimination half-life for ranitidine is 2-3 hours. In balance studies with 150mg 3H-Ranitidine 60-70% of an oral dose was excreted in urine and 26% in faeces. Analysis of urine excreted in the first 24 hours after dosing showed that 35% of the oral dose was eliminated unchanged. About 6% of the dose is excreted as the N-oxide, 2% as the S-oxide, 2% as desmethyl ranitidine and 12% as the furoic acid analogue.
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 gastric acid secretion. Extensive toxicological investigations have been conducted which predict a 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
Hydroxypropylmethylcellulose
Titanium Dioxide
Triethyl Citrate
Polydextrose
Polyethylene Glycol
Sunset Yellow FCF Aluminium LakeE110
Iron Oxide Yellow E172
6.2 Incompatibilities
Not applicable
6.3 Shelf life
36 months
6.4 Special precautions for storage
Do not store above 25° C. Store in the original package.
6.5 Nature and contents of container
For the “Pharmacy Medicine”
Aluminium foil strip blister packaging, containing 6, 12, 24 or 48 tablets. (not all pack sizes are marketed)
For the “General Sales List Medicine”
Aluminium foil strip blister packaging, containing 6 or 12 tablets. (not all pack sizes are marketed)
6.6 Special precautions for disposal
No special instructions
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd t/a Mylan
Station Close
Potters Bar
Herts
EN6 1TL
8 MARKETING AUTHORISATION NUMBER(S)
PL 04569/0431
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/01/2010
10 DATE OF REVISION OF THE TEXT
20/02/2012