Ranitidine 300mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 300mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Ranitidine Hydrochloride equivalent to Ranitidine 300 mg.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated Tablet
Creamish-yellow, round, biconvex, film-coated tablets marked with “MR 300” on one side.
4 CLINICAL PARTICULARS
4.1. Therapeutic Indications
Ranitidine tablets are indicated for the treatment of benign gastric ulcers and duodenal ulcers.
Ranitidine Tablets are also indicated for Zollinger-Ellison Syndrome and for the treatment of reflux oesophagitis.
Ranitidine tablets are indicated for the long-term treatment of duodenal and benign gastric ulcers to prevent their recurrence. Long-term treatment is indicated in patients with a history of recurrent ulcers
Children (3 to 18 years)
• Short term treatment of peptic ulcer
• Treatment of gastro-oesophageal reflux, including reflux oesophagitis and
symptomatic relief of gastro-oesophageal reflux disease.
4.2. Posology and Method of Administration
Adults
The usual dose is 150 mg twice daily, taken in the morning and evening. A single bedtime dose of 300 mg may be given to patients with duodenal or gastric ulcers. Treatment may be continued for 4-8 weeks. For maintenance, the usual dose is 150 mg at bedtime.
For the management of reflux oesophagitis, the recommended dose is 150 mg twice daily or 300 mg at bedtime, usually for up to 8 weeks, this may be extended to a maximum of 12 weeks if necessary.
Severe Oesophagitis:
The dose is 150 mg, four times a day for up to a maximum of 12 weeks. This raised level of dosing has not been associated with a raised level of side effects. Long-term treatment in patients with unhealed oesophagitis is not indicated, either in the presence of Barrett’s epithelium or its absence.
Zollinger-Ellison Syndrome :
An initial dose of 150 mg, three times a day, may be increased up to 300 mg three times a day. Daily divided doses of up to 6g have been used and found to be well tolerated.
Elderly Patients:
In patients with normal renal function, the doses of Ranitidine Tablets are the same as for younger adults.
Children:
The experience of ranitidine treatment in children is limited.
The recommended dose for treating active peptic ulcer is 2-4 mg/kg, twice daily, up to a maximum daily dose of 300 mg ranitidine, given in divided doses.
Children 12years and over
For children 12years and over the adult dosage is given Children from 3 to 11 years and over 30 kg of weight
See section 5.2 Pharmacokinetic properties - Special Patient Populations. Peptic Ulcer Acute Treatment
The recommended oral dose for the treatment of peptic ulcer in children is 4 mg/kg/day to 8 mg/kg/day administered as two divided doses to a maximum of 300 mg ranitidine per day for a duration of 4 weeks. For those patients with incomplete healing, another 4 weeks of therapy is indicated, as healing usually occurs after eight weeks of treatment.
Gastro-Oesophageal Reflux
The recommended oral dose for the treatment of gastro-oesophageal reflux in children is 5 mg/kg/day to 10 mg/kg/day administered as two divided doses in a maximum dose of 600 mg (the maximum dose is likely to apply to heavier children or adolescents with severe symptoms).
Neonates
Safety and efficacy in new-born patients has not been established.
Renal Impairment:
In patients with severe renal impairment, plasma levels of the drug are increased. The dose in such patients is 150 mg at night for 4-8 weeks. The same dose is used for maintenance. If healing has not occurred, 150 mg twice daily should be used, followed by 150 mg at night for maintenance.
|
Creatinine clearance mL/min. |
Dose of ranitidine |
|
<50 |
150 mg |
|
>50 |
300 mg |
Ranitidine is removed by hemodialysis. Dialysis patients should therefore take Ranitidine Ranbaxy after each dialysis occasion.
Method of Administration
The tablet should be swallowed whole with a sufficient amount of fluid. In children the tablets may be dissolved in water or crushed. The application of a more convenient dosage form may be considered.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4. Special Warnings and Precautions for Use
Malignancy
The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer and in patients of middle age and over with new or recently changed dyspeptic symptoms) as treatment with ranitidine may mask symptoms of gastric carcinoma.
Renal Disease
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with renal impairment. The dose should be adjusted as detailed in section 4.2 Patients with Renal Impairment.
Regular supervision of patients who are taking non-steroidal anti-inflammatory drugs concomitantly with ranitidine is recommended, especially in the elderly and in those with a history of peptic ulcer.
Rare clinical reports suggest that ranitidine may precipitate acute porphyria 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 versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.82 (95% CI, 1.26-2.64).
Post-marketing data indicate reversible mental confusion, depression, and hallucinations have been reported most frequently in severely ill and elderly patients (see section 4.8).
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, propanolol 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 secrection:
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 level 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 or 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 hours.
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 drugs it should only be used during pregnancy if considered essential.
Breast-feeding
Ranitidine is excreted in human breast milk. Like other drugs it 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 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 postmarketing data.
|
Uncommon |
Rare: |
Very Rare: |
Not known | |
|
Blood & lymphatic system Disorders |
Blood count changes (leucopenia, thrombocytopenia) . These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia. | |||
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Immune System Disorders |
Hypersensitivit y reactions (urticaria, angioneurotic |
Anaphylactic shock |
Dyspnoe a These events have |
|
oedema, fever, bronchospasm, hypotension and chest pain). |
been reported after a single dose. | |||
|
Psychiatric Disorders |
Reversible mental confusion, depression and hallucinations. These have been reported predominantly in severely ill patients, in elderly and in nephropatic patients. | |||
|
Nervous System Disorders |
Headache (sometimes severe), dizziness and reversible involuntary movement disorders. | |||
|
Eye Disorders |
Reversible blurred vision. There have been reports of blurred vision, which is suggestive of a change in accommodation. | |||
|
Cardiac Disorders |
As with other H2 receptor antagonists bradycardia , A-V Block and tachycardia. | |||
|
Vascular Disorders |
Vasculitis | |||
|
Gastrointestina l Disorders |
Abdominal pain, constipation , nausea (these symptoms mostly improved during continued treatment). |
Acute pancreatitis. Diarrhoea. | ||
|
Hepatobiliary Disorders |
Transient and reversible |
Hepatitis (hepatocellular, |
|
changes in liver function tests. |
hepatocanalicular or mixed) with or without jaundice, these were usually reversible. | |||
|
Skin and Subcutaneous Tissue Disorders |
Skin Rash. |
Erythema multiforme, alopecia | ||
|
Musculoskeleta l and Connective Tissue Disorders |
Musculoskeletal symptoms such as arthralgia and myalgia. | |||
|
Renal and Urinary Disorders |
Elevation of plasma creatinine usually slight; normalised during continued .reatment) |
Acute interstitial nephritis | ||
|
Reproductive System and Breast Disorders |
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
Symptoms and signs
Ranitidine is very specific in action and accordingly no particular problems are expected following overdosage.
Treatment
Symptomatic and supportive therapy should be given as appropriate
5.1 Pharmacodynamic Properties
Pharmacotherapeutic Group: H2-Receptor Antagonists-ATC Code: A02BA02
Mechanism of action
Ranitidine is a specific rapidly acting histamine H2-receptor 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 relatively long duration of action and so a single 150mg dose effectively suppressing gastric acid secretion for 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 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.
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 is similar after both oral and i.v. dosing; and includes 6% of the dose in urine as the N-oxide, 2% as the S-oxide, 2% as desmethylranitidine and 1 to 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 faeces and 93% in urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in 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 500 mL/min, which exceeds glomerular filtration indicating
net renal tubular secretion.
Other Special Populations Children (3 years and above)
Limited pharmacokinetic data have shown that there are no significant differences in half-life (range for children 3 years and above: 1.7 - 2.2 h) and plasma clearance (range for children 3 years and above: 9 - 22 ml/min/kg) between children and healthy adults receiving oral ranitidine when correction is made for body weight.
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
No additional data of relevance
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose; hypromellose; croscarmellose sodium; castor oil; colloidal anhydrous silica; purified talc; magnesium stearate; ferric oxide yellow (E172) ; titanium dioxide (E171).
6.2 Incompatibilities
None reported
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in the original container
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) in the following pack sizes:-
Blister sheets of five tablets each, in boxes of 5 tablets per carton.
Blister sheets of seven tablets each, in boxes of 7, 14, 28, 56, 98 and 112 tablets per carton.
Blister sheets of eight tablets each, in boxes of 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88 and 96 tablets per carton.
Blister sheets of ten tablets each, in boxes of 10, 20, 30, 50, 60, 80, 100 and 120 tablets per carton.
Blister sheets of fifteen tablets each, in boxes of 15, 30, 45, 60, 75, 90, 105 and 120 tablets per carton.
Blister sheets of thirty tablets each, in boxes of 30, 60, 90, 120 and 150 tablets per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
None.
7. Marketing Authorisation Holder
Medreich Plc Warwick House Plane Tree Crescent Feltham TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0092
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/12/2010
10 DATE OF REVISION OF THE TEXT
26/08/2016