Ranitidine 75mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 75mg 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 tablets
Pink, round, biconvex, film-coated tablets with embossment “75” on one side. 4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Ranitidine Tablets are indicated for the short-term symptomatic relief
heartburn.
4.2 Posology and method of administration
Adults (including the elderly) and adolescents of 16 years of age and older.
One Ranitidine 75mg tablet should be taken when symptoms occur, day or night. Do not take more than two tablets in 24 hours.
Patients will be instructed not to take the tablets for more than 2 weeks continuously. They must consult their doctor if symptoms deteriorate or persist after 2 weeks treatment.
Children under 16 years.
The tablets are not recommended for children under 16 years of age.
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Ranitidine tablets should not be given to children under 16 years of age.
4.4 Special warnings and precautions for use
The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer 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 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 versus those who had stopped treatment, with an observed adjusted relative risk increase of 1,82 (95% CI 1,26-2,64).
The product is not indicated if patients present with any of the following without first seeking their doctor’s advice:
• Patients who have unintended weight loss associated with their indigestion symptoms.
• Patients with renal and/or hepatic impairment or patients under regular medical supervision for any reason.
• Patients suffering from any other illness or taking self-prescribed or physician-prescribed medicines.
• Patients of middle age or older with new or recently changed symptoms of indigestion.
• Patients taking NSAID’s, especially the elderly, should seek their doctor’s advice before taking ranitidine.
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, gefitinib).
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.
Ranitidine may increase the effects of alcohol.
4.6 Fertility, pregnancy and lactation
Pregnancy
Ranitidine crosses the placenta. Like other drugs ranitidine should only be used during pregnancy if considered essential.
As with other self-prescribed drugs, ranitidine should not be taken during pregnancy without first consulting a doctor.
Lactation
Ranitidine is excreted in human breast milk. Like other drugs ranitidine should only be used during breast-feeding if considered essential.
Fertility
There are no data on the effects of ranitidine on human fertility. There were no effects on male and female fertility in animal studies (see section 5.3).
4.7 Effects On The Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed. According to the pharmacodynamic properties of ranitidine, no influence on the ability to drive or use machines is expected. However, rare side effects (see section 4.8 Undesirable effects) affecting the CNS and the eye, and an increase in the effects of alcohol with the intake of ranitidine (see section 4.5 Interactions with other medicinal products and other forms of interaction) might adversely affect these abilities.
4.8 Undesirable effects
The following convention has been utilised for the classification of undesirable effects: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)
Adverse event frequencies have been estimated from spontaneous reports from postmarketing data.
Blood and 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
Not known Dyspnoea
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 patients, in elderly patients and in nephropatic patients.
Nervous system disorders
Common
Fatigue
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 tachycardia, bradycardia and A-V block
Vascular disorders Very Rare Vasculitis
Gastrointestinal disorders
Uncommon
Abdominal pain, constipation, nausea (these symptoms mostly improved during continued treatment)
Very rare
Acute pancreatitis, diarrhoea
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, pruritus Very rare
Erythema multiforme, alopecia
Musculoskeletal and connective tissue disorders
Very rare
Musculoskeletal symptoms such as arthralgia and myalgia
Renal and urinary disorders
Rare
Elevation of plasma creatinine (usually slight; normalised during continued treatment)
Very rare
Acute interstitial nephritis
Reproductive system and breast disorders
Very rare
Reversible impotence, 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.
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
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 lidocaine (lignocaine). Ranitidine may be removed from plasma by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: H2 receptor antagonists ATC Code: A02B A02 Mode of action
Ranitidine is a specific, histamine H2 antagonist with a rapid onset of action. Both basal and stimulated gastric acid secretion are inhibited, reducing both the acid content and also to a smaller extent the pepsin content and volume of the gastric juice.
Ranitidine has a relatively long duration of action, a 75 mg dose of ranitidine effectively suppressing gastric acid secretion for up to 12 hours.
5.2 Pharmacokinetic Properties
Ranitidine has a bioavailability of approximately 50%. After oral administration, rapid absorption is followed by the attainment of peak plasma concentrations 2 - 3 hours later.
The pharmacokinetics of ranitidine are dose proportional in the dose range between 75mg and 300mg.
Ranitidine is metabolised in the liver to Ranitidine-N-oxide, N-Desmethylranitidine, Ranitidine-S-oxide and the furane acid analogue. After oral administration, ranitidine is excreted within 24 hours via the kidneys to approx. 30% as unchanged ranitidine, up to 6% as N-oxide, to a small degree in demethylised and in S-oxidised form, and as furane acid analogue. In patients with normal kidneys, renal excretion is effected predominantly by tubular secretion with a renal clearance of about 490-520 ml/min.
Additionally, ranitidine is excreted via the bile.
After oral intake, mean elimination half-life in patients with normal kidneys is 2.3-3 hours. In patients with renal insufficiency, the half-life is prolonged two-to threefold.
5.3 Pre-clinical Safety Data
The pharmacological and toxicological properties of ranitidine are well established. There are no additional data from preclinical studies of clinical concern.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose Croscarmellose sodium Colloidal anhydrous silica Magnesium stearate Talc
Film coating material Castor oil Hypromellose Talc
Titanium dioxide (E 171) Iron oxide red (E 172)
6.2
Incompatibilities
Not Applicable.
6.3 Shelf Life
3 years.
6.4. Special precautions for storage
Do not store above 25°C
6.5 Nature and Content 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 10 or 12 or 20 or 28 tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
ratiopharm GmbH Graf Arco Str. 3 89079 Ulm Germany
8. MARKETING AUTHORISATION NUMBER
PL 15773/0404
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
14/01/2007
10 DATE OF REVISION OF THE TEXT
15/11/2014