Ranitidine 75mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 75mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains 84.00mg Ranitidine Hydrochloride (equivalent to 75.00mg Ranitidine).
3 PHARMACEUTICAL FORM
Coated tablet.
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
Dose
Adults:
One Ranitidine 75mg Tablets 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 tablets should be swallowed whole with fluid.
4.3 Contraindications
Ranitidine Tablets should not be given to patients known to have hypersensitivity to ranitidine or any component of the tablet.
Ranitidine tablets should not be given to children under 16 years because safety and efficacy have not been established in this patient group.
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). Ranitidine 75 mg is not suitable for these patients without medical supervision.
Patients taking NSAIDs, especially in those with a history of peptic ulcer and the elderly, should seek their doctor’s advice before using this product. Current evidence shows that ranitidine protects against NSAID associated ulceration in the duodenum and not in the stomach.
Isolated reports suggest a relationship between the intake of ranitidine and the occurrence of acute porphyria. Administration of ranitidine to patients with a history of acute porphyria should therefore be avoided.
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 with unintended weight loss in association with symptoms of indigestion.
- Patients of middle age or older 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 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. 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.
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 have been 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 (uticaria, 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 predominately 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 Disorder
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 arthragalia and myalgia
Renal and Urinary Disorders Very rare: Acute interstitial nephritis.
Rare: Elevation of plasma creatinine (usually slight; normalized 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.
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, unabsorbed tablets should be removed by gastric lavage.
Haemodialysis can be used to remove drug from the plasma Symptomatic and supportive
treatment should be given as required.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ranitidine is a competitive inhibitor of the action of histamine at the histamine H2-receptors. It inhibits basal gastric acid secretion as well as gastric acid secretion stimulated by e.g. histamine, pentagastrin or food. Ranitidine reduces gastric acid secretion as well as to a limited degree total pepsin output and total gastric juice volume.
Studies showed that therapeutic doses of 150 mg ranitidine twice a day, on average, inhibit gastric acid secretion by more than 60% for 24 hours. At night these doses were sufficient to inhibit gastric acid secretion by 70 - 90%. Doses of 150 mg in the evening were shown to inhibit gastric acid secretion by 40 - 70% for 24 hours on average.
Therapeutic doses necessary to inhibit gastric acid secretion by 50-60% for 24 hours were 300 mg ranitidine. Nocturnal gastric acid secretion was reduced by almost 90%.
5.2 Pharmacokinetic properties
Ranitidine is rapidly absorbed after oral administration with mean peak levels occurring at 1.25 to 3 hours. Bioavailability of ranitidine tablets is 50% on average with an inter-individual variability of 28 - 76%.
After oral administration of 150 mg ranitidine mean peak plasma levels were about 400 ng/ml.
Inter-individual variability was observed. After 12 hours, mean plasma levels were 40 ng/ml. After oral administration of 300 mg ranitidine mean peak plasma levels were 700 to 800 ng/ml.
In several studies, the plasma concentration necessary to inhibit 50% of gastric acid secretion in adults was between 73 and 165 ng/ml.
Plasma-protein binding is approximately 15%. The volume of distribution is 1.2 - 1.8 l/kg in adults and 2.5 l/kg in children. Mean total clearance is 570 - 710 ml/min in adults and about 800 ml/min in children and young persons.
In the liver ranitidine is metabolised to ranitidine-N-oxide, N-desmethylranitidine, ranitidine-Soxide and a furan acid analogue. About 35 % of the orally administered dose is excreted
unchanged in the urine within 24 hours, 6% of the dose is excreted as the N-oxide, 2% as the S-oxide, 2% as desmethyl ranitidine and 1-2% as the furoic acid analogue.
In persons with normal renal functions the elimination half-life after oral administration is 2.3 to 3 hours. In patients with impaired renal function elimination half-life maybe 2 to 3 times longer than this. Only small amounts of ranitidine are found in cerebrospinal fluid.
Ranitidine passes the placental barrier. Following intravenous and oral administration of ranitidine during parturition, ranitidine concentrations corresponding to those in the mother's serum have been found in umbilical cord blood of the new-born. Twelve hours later only very small amounts were present.
Ranitidine is found in human breast milk, the ratio milk/plasma concentration being
1.9 (range:
0.6 to 20.9) two hours after administration.
Unless otherwise stated, the pharmacokinetics of ranitidine in children is the same as for adults.
5.3 Preclinical safety data
Ranitidine has a high safety margin. In dogs oral doses of ranitidine of up to 400mg/kg/day for
54 weeks resulted in dose related occasional cases of mild diarrhoea, increased salivation and
vomiting. Rapid respiration and muscular tremors with one fatality occurred in dogs receiving
450mg/kg ranitidine. Rats tolerated daily doses of 2,000mg/kg for 78 weeks well.
In animal tests ranitidine has shown no mutagenic, carcinogenic or teratogenic potential and does not impair fertility.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline Cellulose Ph Eur, Polyvidone Ph Eur, Magnesium Stearate Ph Eur, Methylhydroxypropylcellulose Ph Eur, Titanium dioxide Ph Eur (E171), Talc Ph Eur, Macrogol 6000 Ph Eur and Methacrylic acid copolymer USNF.
6.2 Incompatibilities
None known.
6.3
Shelf life
The shelf-life is three years.
6.4 Special precautions for storage
No special precautions are required
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
M & A Pharmachem Ltd Wigan Road, Westhoughton Bolton, Lancashire BL5 2AL
8 MARKETING AUTHORISATION NUMBER(S)
PL 04077/0228
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
09/01/2004
10 DATE OF REVISION OF THE TEXT
08/06/2015