Ranitidine 75mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 75mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
75mg Ranitidine (as hydrochloride)
3 PHARMACEUTICAL FORM
Coated tablet White to off-white, round biconvex film coated tablets with a break line on one side and the imprint "R75" on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ranitidine 75mg Tablets are indicated for the short term symptomatic relief of heartburn, indigestion, acid indigestion and hyperacidity.
4.2 Posology and method of administration
Adults: One Ranitidine 75mg Tablet should be taken as soon as symptoms appear. If symptoms persist for more than one hour, or return a second Ranitidine 75mg Tablet should be taken. The maximum daily dose is two Ranitidine 75mg Tablets.
Children: Ranitidine 75mg Tablets should not be taken by children under the age of 16 years.
Length of Treatment: Do not take the tablets for more than 6 days without the advice of a pharmacist or doctor. Medical attention should be sought if symptoms worsen.
Method of administration: Ranitidine 75mg tablets should be swallowed whole with fluid.
4.3
Contraindications
Ranitidine 75mg Tablets should not be given to patients known to have hypersensitivity to Ranitidine or any ingredients of the tablet.
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 than 50 ml/min). Ranitidine 75mg Tablets are not suitable for these patients without medical supervision.
Patients taking NSAIDS, especially those with a history of peptic ulcer and the elderly, should be referred to their doctor before taking Ranitidine 75mg 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 oxygenese 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. (e.g. ketoconazole, itraconazole, posaconazole, atazanavir, delavirdine, gefitnib).
4.6 Fertility, pregnancy and lactation
Pregnancy: There are no adequate studies on the effect of Ranitidine in pregnancy although animal studies have not produced evidence that it will harm the foetus. Like other medicines, Ranitidine should only be used during pregnancy if absolutely necessary following appropriate medical consultation.
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. Lactation: Ranitidine is found in human breast milk so nursing mothers should avoid taking ranitidine.
4.7 Effects on ability to drive and use machines
No effects known
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 (>1/1,000, <1/100); rare (>1/10,000, <1/1,000); very rare (<1/10,000).
Blood and lymphatic system disorders:
Very rare: Blood count changes (Leucopoenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.
Immune System Disorders:
Rare: Hypersensitivity reactions, (urticaria, fever, hypotension, angioneurotic oedema, bronchospasm, chest pain Very rare: Anaphylactic shock,
Psychiatric Disorders
Very Rare: Reversible mental confusion, depression and hallucinations.
These have been reported predominantly in severely ill and elderly patients.
Nervous system
Rare: Headache (sometimes severe), dizziness, 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:
Very rare: Diarrhoea, acute pancreatitis,
Uncommon: abdominal pain, constipation, nausea (these symptoms moistly improve during continued treatment)
Hepatobiliary disorders:
Rare: Transient and reversible changes in liver function test.
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
Musculoskeletal and Connective Tissue Disorders:
Very rare: Arthralgia, 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 gynecomastia 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
4.9 Overdose
Complications from overdose are not expected after oral administration. Daily doses of 6300mg of ranitidine administered orally for several months were well tolerated. Treatment for overdose: If there are signs of intoxication. 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. Haemodialysis can be used to remove drug from the plasma.
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
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 75 mg can relieve the symptoms of excess acid production for up to twelve hours.
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.
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 3Hranitidine, 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.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline Cellulose, Polyvidone, Magnesium Stearate, Methylhydroxypropylcellulose, Titanium dioxide (E171), Talc, Macrogol6000 and Methacrylic acid copolymer.
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months
6.4 Special precautions for storage
Store in the original package. Do not store above 25°C
6.5 Nature and contents of container
Blister strip comprising aluminium foil on both sides. The strips are packed in cartons to contain 5, 6, 10 or 12 tablets.
6.6 Special precautions for disposal
None
7 MARKETING AUTHORISATION HOLDER
Relonchem Limited Cheshire House
Gorsey Lane, Widnes, Cheshire WA8 0RP, UK
MARKETING AUTHORISATION NUMBER(S)
8
PL 20395/0079
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28/07/2011
10 DATE OF REVISION OF THE TEXT
24/05/2016