Cimetidine Tablets 800 Mg
SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT
Cimetidine Tablets 800 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Cimetidine 200 mg
Also contains 61.48 mg lactose per tablet, for a full list of excipients see section 6.1
3. PHARMACEUTICAL FORM
Film-coated tablet
Oblong, pale green film-coated tablet with a logo on one side and ‘CIMET 800’ imprinted on the other
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cimetidine is indicated in the treatment of duodenal and benign gastric ulceration, recurrent and stomal ulceration, oesophageal reflux disease and other conditions where reduction of gastric acid by Cimetidine has been shown to be beneficial: persistent dyspeptic symptoms with or without ulceration, particularly meal related upper abdominal pain; the prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients; before general anesthesia in patients thought to be at risk of acid aspiration (Mendelson’s Syndrome), particularly obstetric patients during labour; to reduce malabsorption and fluid loss in the short bowel syndrome; and in pancreatic insufficiency to reduce degradation of enzyme supplements. Cimetidine is also recommended in the management of the Zollinger-Ellison syndrome.
4.2 Posology and method of administration
For oral administration
The total daily dose by any route should not normally exceed 2.4 g. Dosage should be reduced in patients with impaired renal function
The usual dosage is 400 mg twice a day, with breakfast and at bedtime. For patients with duodenal or benign gastric ulceration, a single daily dose of 800 mg at bedtime is recommended. Other effective regimes are 200 mg three times a day with meals and 400 mg at bedtime, and, if inadequate, 400 mg four times a day, also with meals and at bedtime.
Symptomatic relief is usually rapid. Treatment should be given initially for at least four weeks (six week in benign gastric ulcer. Most ulcers will have healed by that stage, but those which have not will usually do so after a further course of treatment.
Treatment may be continued for longer periods in those patients who may benefit from reduction of gastric secretion and the dosage may be reduced as appropriate to 400 mg at bedtime or 400 mg in the morning and at bedtime.
In patients with benign peptic ulcer disease, relapse may be prevented by continued treatment, usually with 400 mg at bedtime; 400 mg in the morning and at bedtime has also been used.
In oesophageal reflux disease, 400 mg four times a day, with meals and at bedtime, for four to eight weeks is recommended to heal oesophagitis and relieve associated symptoms. In patients with very high gastric acid secretion (e.g. Zollinger Ellison syndrome) it may be necessary to increase the dose to 400 mg four times a day, or in occasional cases further.
Antacids can be made available to all patients until symptoms disappear.
In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients, doses of 200 to 400 mg can be given every four to six hours by the oral route.
In patients thought to be at risk of acid aspiration syndrome, an oral dose of 400 mg can be given 90 to 120 minutes before induction of general anaesthesia or, in obstetric practice, at the start of labour. While such a risk persists, a dose of up to 400 mg may be repeated (parentally if appropriate) at four hourly intervals as required up to the usual daily maximum of 2.4 g. Cimetidine syrup should not be used. The usual precautions to avoid acid aspiration should be taken.
In the short bowel syndrome, e.g. following substantial resection for Crohn’s disease, the usual dosage range (see above) can be used according to individual response.
To reduce degradation of pancreatic enzyme supplements, 800 to 1600 mg a day may be given, according to response, in four divided doses, one to one and a half hours before meals.
Elderly:
The normal adult dosage may be used unless renal function to markedly impaired Children:
Experience in children is less than that in adults. In children more than one year old, Cimetidine 25 to 30 mg/kg body weight per day in divided doses may be administrated by oral route.
The use of Cimetidine in infants under one year old is not fully evaluated; 20 mg/kg body weight per day in divided doses has been used.
4.3. Contra-indications
Hypersensitivity to Cimetidine or to any other of the tablet ingredients.
4.4. Special warnings and precautions for use
Dosage should be reduced in patients with impaired renal function according to creatinine clearance. The following doses are suggested:
Creatinine clearance of 0 to 15 ml per minute, 200 mg twice a day;
15 to 30 ml per minute 200 mg three times a day;
30 to 50 ml per minute, 200 mg four times a day; over 50 ml per minute, normal dosage.
Cimetidine is removed by haemodialysis, but not to any significant extent by peritoneal dialysis.
The safety of prolonged use is not fully established and care should be taken to observe periodically patients given prolonged treatment.
Care should be taken that patients with a history of peptic ulcer, particularly the elderly, being treated with cimetidine and a non-steroidal antiinflammatory agent are observed regularly.
Before initiating therapy with this preparation for any gastric ulceration, malignancy should be excluded by endoscopy and biopsy, if possible, because Cimetidine treatment can mask symptoms and allow transient healing of gastric cancer. The potential delay in diagnosis should particularly be borne in mind in patients of middle age and over, with new or recently changed dyspeptic symptoms.
Due to possible interaction with coumarins, close monitoring of prothrombin time is recommended when cimetidine is concurrently used.
In patients on drug treatment or with illnesses that could cause falls in blood cell count, the possibility that H2-receptor antagonism could potentiate this effect should be borne in mind. Co-administration of therapeutic agents with a narrow therapeutic index, such as phenytoin or theophylline, may require dosage adjustment when starting or stopping concomitantly administered cimetidine (see section 4.5).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine
4.5. Interaction with other medicinal products and other forms of interaction
Cimetidine can prolong the elimination of drugs metabolized by oxidation in the liver. Although pharmacological interactions with a number of drugs, e.g.
diazepam, propronalol, have been demonstrated, only those with oral anticoagulants, phenytoin, theophylline, and intravenous lidocaine appear, to date, to be of clinical significance. Close monitoring of patients on Cimetidine receiving oral anticoagulants or phenytoin is recommended and a reduction in the dosage of these drugs may be necessary.
Cimetidine has the potential to affect the absorption, metabolism or renal excretion of other drugs which is particularly important when drugs with a narrow therapeutic index are administered concurrently. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment (see Section 4.4).
Interactions may occur by several mechanisms including:
1. Inhibition of certain cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6 and CYP3A3/A4, and CYP2C18); Inhibition of these enzymes may result in increased plasma levels of certain drugs including warfarin-type coumarin anticoagulants (e.g. warfarin), tricyclic antidepressants (e.g. amitriptyline), class I antiarrhythmics (e.g. lidocaine), calcium channel blockers (e.g. nifedipine, diltiazem), oral sulfonylureas (e.g. glipizide), phenytoin, theophylline and metoprolol.
2. Competition for renal tubular secretion; This may result in increased plasma levels of certain drugs including procainamide, metformin, ciclosporin and tacrolimus.
3. Alteration of gastric pH; the bioavailability of certain drugs may be affected. This can result in either an increase in absorption (e.g. atazanavir) or a decrease in absorption (e.g. some azole antifungals such as ketoconazole, itraconazole or posaconazole).
4. Unknown mechanisms; Cimetidine may potentiate the myelosuppressive effects (e.g. neutropenia, agranulocytosis) ofchemotherapeutic agents such as carmustine, fluorouracil, epirubicin, or therapies such as radiation. Isolated cases of clinically relevant interactions have been documented with narcotic analgesics (e.g. morphine).
4.6. Pregnancy and Lactation
Although tests in animals and clinical evidence have not revealed any hazards from the administration of Cimetidine during pregnancy or lactation, both animal and human studies have shown that it does cross the placental barrier and is excreted in milk. As with most drugs, the use of Cimetidine should be avoided during pregnancy and lactation unless essential.
4.7. Effects on ability to drive and use machines
None known
4.8. Undesirable effects
Adverse experiences with cimetidine are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000).
Blood and lymphatic system disorders Uncommon: Leukopenia
Rare: Thrombocytopenia, aplastic anaemia
Very rare: Pancytopenia, agranulocytosis
Immune system disorders
Very rare: Anaphylaxis. Anaphylaxis is usually cleared on withdrawal of
the drug.
Psychiatric disorders
Uncommon: Depression, confusional states, hallucinations.
Confusional states, reversible within a few days of withdrawing cimetidine, have been reported, usually in elderly or ill patients.
Nervous system disorders Common: Headache, dizziness
Cardiac disorders Uncommon: Tachycardia
Rare: Sinus bradycardia
Very rare: Heart block
Gastrointestinal disorders Common: Diarrhoea
Very rare: Pancreatitis. Pancreatitis cleared on withdrawal of the drug.
Hepatobiliary disorders Uncommon: Hepatitis
Rare: Increased serum transaminase levels. Hepatitis and increased serum transaminase levels cleared on withdrawal of the drug.
Skin and subcutaneous tissue disorders Common: Skin rashes
Very rare: Reversible alopecia and hypersensitivity vasculitis.
Hypersensitivity vasculitis usually cleared on withdrawal of the drug.
Musculoskeletal and connective tissue disorders Common: Myalgia
Very rare: Arthralgia
Renal and urinary disorders
Uncommon: Increases in plasma creatinine
Rare: Interstitial nephritis. Interstitial nephritis cleared on withdrawal of the drug. Small increases in plasma creatinine have been reported, unassociated
with changes in glomerular filtration rate. The increases do not progress with continued therapy and disappear at the end of therapy.
Reproductive system and breast disorders Uncommon: Gynaecomastia and reversible impotence.
Gynaecomastia is usually reversible upon discontinuation of cimetidine therapy. Reversible impotence has been reported particularly in patients receiving high doses (e.g. in Zollinger-Ellison Syndrome). However, at regular dosage, the incidence is similar to that in the general population.
Very rare: Gal actorrhoea
General disorders and administration site conditions
Common: Tiredness
Very rare: Fever. Fever cleared on withdrawal of the drug.
4.9. Overdose
Acute overdosage of up to 20 g has been reported several times with no significant ill effects. Induction of vomiting and/or gastric lavage may be employed together with symptomatic and supportive therapy.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Cimetidine is a histamine H2-receptor antagonist which rapidly inhibits both basal and stimulated gastric secretion of acid and reduces pepsin output. It is a reversible, competitive antagonist, and is used as an anti ulcer drug. It is highly selective in its action, is virtually without effect on the widespread distribution of H2-receptors in the body. Cimetidine interferes remarkably little with physiological functions other than gastric secretion, implying that extragastric Hi-receptors are of minor physiological importance.
However, H2 blockers like Cimetidine do inhibit those effects on the cardiovascular and other systems that are elicited through the corresponding receptors by exogenous or endogenous histamine.
5.2. Pharmacokinetic Properties
Cimetidine is absorbed from the gastro intestinal tract and peak plasma concentrations are obtained about an hour after administration on an empty stomach, and about 2 hours after administration with food. The duration of action is reported to be prolonged by administration with food.
Peak concentrations in plasma are attained in about 1 to 2 hours. Hepatic first pass metabolism results in bioavailabilities of about 60% for Cimetidine. The elimination half life is about 2 to 3 hours. Cimetidine is eliminated primarily by the kidneys, and 60% or more may appear in the urine unchanged; much of the rest is oxidation products. Small amounts are recovered in the stools.
Cimetidine crosses the placental barrier and is excreted in milk. It does not readily cross the blood brain barrier.
5.3. Preclinical Safety Data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Maize Starch Povidone K30 Magnesium Stearate Sodium Starch Glycollate Isopropyl Alcohol
Opadry OY 5912 (Hypromellose, E171, E104, E172 and E132)
6.2. Incompatibilities
Not applicable
6.3. Shelf Life
24 Months
6.4 Special precautions for storage
Containers: Do not store above 25°C. Keep the container tightly closed. Store in
the original container.
Blister Packs: Do not store above 25°C. Store in the original package. Keep container in the outer carton
6.5. Nature and Contents of Container
Polypropylene/polyethylene containers and closures: 100, 250, 500, and 1000 tablets
PVC/ Aluminium foil blister packs: 30 tablets
6.6 Instruction for Use/Handling
Not applicable
7 MARKETING AUTHORISATION HOLDER
Cheliona Healthcare Limited
Boumpoulinas 11, 3 rd floor
Nicosia
Cyprus
P C 1060
Cyprus
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0025
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17/03/2009
10 DATE OF REVISION OF THE TEXT
23/09/2011