Ranitidine 150mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ranitidine 150mg Tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ranitidine 150mg (as hydrochloride)
3 PHARMACEUTICAL FORM
Coated tablet.
White to off-white, round, bi-convex.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ranitidine 150mg Tablets are indicated for the following:
- duodenal ulcer
- benign gastric ulcer
- maintenance treatment for patients who have responded to short term therapy especially those with a history of recurrent ulcer
- symptomatic relief of gastro-oesophageal reflux disease
- Zollinger-Ellison syndrome
Conditions in which a reduction in gastric secretion is required:
- prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients.
- the prophylaxis of recurrent haemorrhage from bleeding peptic ulcers.
- before general anaesthesia in patients thought to be at risk of acid aspiration (Mendelson’s Syndrome) particularly during labour.
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
Dose
Adults:
Duodenal ulcer and benign gastric ulcer:
The usual dose is 150mg Ranitidine tablets twice daily, taken in the morning and the evening, or 300mg as a single bed time dose. If healing has not occurred within four weeks, treatment should he continued for a further four weeks.
150mg at bedtime is recommended for patients who have responded to short term therapy, particularly those with a history of recurrent ulcer.
Gastroesophageal reflux disease
The usual dose is 150mg Ranitidine tablets twice daily, taken in the morning and the evening, or 300mg as a single bed time dose, for up to 8 or 12 weeks if necessary if necessary.
Patients with pathological hypersecretory conditions such as Zollinger-Ellison syndrome
The starting dose is 150mg Ranitidine tablets three times daily. The daily dose may be increased up to 6g Ranitidine per day, if necessary.
Prevention of acid aspiration during general anaesthesia 150mg Ranitidine the night before and 2 hours before the administration of a general anaesthetic. 150mg ranitidine at the beginning of labour followed by 150mg at 6 hourly intervals. Should emergency general anaesthesia be required a non-particulate antacid (sodium citrate) should be administered prior to induction.
Prophylaxis of haemorrhage from stress ulceration in seriously ill patients 150mg Ranitidine twice daily once the patient is able to eat, for as long as necessary.
Prophylaxis of recurrent haemorrhage in patients with bleeding duodenal or gastric ulcers 150mg Ranitidine twice daily once the patient is able to eat, for as long as necessary.
Children 12 years and over
For children 12 years 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.
Adults with Renal Impairment:
Ranitidine is excreted in the urine and therefore plasma levels of ranitidine are increased in patients with severe renal impairment.
The recommended dose in patients with severe impairment of renal function is 150 mg at night for 4 to 8 weeks.
Length of Treatment
The length of treatment depends on response. Healing of ulcers is normally observed after 4 to 8 weeks.
Method of administration
Ranitidine tablets should be swallowed whole with fluid and with or without food.
4.3 Contraindications
Ranitidine Tablets should not be given to patients known to have hypersensitivity to ranitidine or any component of the tablet.
4.4 Special warnings and precautions for use
Treatment with H2 antagonists may mask symptoms of gastric carcinoma and delay diagnosis. Therefore the possibility of malignancy should be excluded before starting treatment if gastric ulcer has been diagnosed or if there is a new or recently changed presentation of dyspeptic symptoms. 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.
Ranitidine is excreted in the urine and therefore plasma levels of ranitidine are increased in patients with severe renal impairment. The recommended dose in patients with severe impairment of renal function is l50mg at night.
Patients, particularly the elderly, who are also taking a non-steroidal antiinflammatory agent with ranitidine should be carefully monitored as Ranitidine may not protect them from gastric ulceration.
4.5 Interaction with other medicinal products and other forms of interaction
At normal dosage, ranitidine does not inhibit cytochrome P450; although some minor interactions have been seen with some products these have not been shown to be of clinical relevance.
4.6 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.
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
Ranitidine is well tolerated although as with all drugs, some patients occasionally experience side effects.
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.
Listed below are side effects which have been reported with the taking of various doses of ranitidine.
Frequency estimate: very common >10%; occasional >1 to 10%; uncommon >0.1 to 1%; rare >0.01% to 0.1%; very rare 0.001% to 0.01%; isolated cases <0.001%
Hypersensitivity reactions
Rare: Hypersensitivity reactions, including urticaria, fever, hypotension, angioneurotic oedema, bronchospasm
Very rare: Anaphylactic shock, vasculitis or vasculitic rash Isolated cases: Acute interstitial nephritis
Blood and lymphatic system disorders
Very rare: Leucopoenia, thrombocytopenia, agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or aplastic anaemia. These effects were usually reversible.
Cardiac disorders
Very rare: Arrhythmia, such as tachycardia or bradycardia, A-V conduction disturbance.
Gastrointestinal
Very rare: Nausea, diarrhoea, acute pancreatitis Hepatobiliary disorders
Rare: Transient and reversible changes in liver function test values Very rare: hepatitis and jaundice, usually reversible
Musculoskeletal disorders Very rare: Arthralgia, myalgia
Nervous system/psychiatric disorders Rare: Headache, dizziness
Very rare: Severe headache, confusion, hallucinations, involuntary movement disorders and depression. These have been reported, mainly in elderly or severely ill patients.
Skin and subcutaneous tissue disorders (see also hypersensitivity)
Rare: Skin rash
Very rare: Erythema multiforme, alopecia Other
Very rare: Gynaecomastia, erectile dysfunction, visual disturbances
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.
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 interindividual variability of 28 - 76%.
After oral administration of 150 mg ranitidine mean peak plasma levels were about 400 ng/ml.
Interindividual 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 1/kg in adults and 2.5 1/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.
Special Patient 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.
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, Polyvidone, Magnesium Stearate, Methylhydroxypropylcellulose, Titanium dioxide (E171), Talc, Macrogol 6000 and Methacrylic acid copolymer.
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months
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 60 tablets.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Founts (UK) Pharmacare Ltd First Floor,
2 Victoria Road,
Harpenden,
Hertfordshire,
AL5 4EA,
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
PL 39484/0045
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/03/2006
DATE OF REVISION OF THE TEXT
31/07/2011
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