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CIMETIDINE TABLETS BP 200MG

Active substance(s): CIMETIDINE

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT
Cimetidine Tablets BP 200mg.
Zabcid 200mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 200mg cimetidine BP.

3

PHARMACEUTICAL FORM
Pale green, circular, biconvex, film coated tablets, embossed with C1 on one
side.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications
Cimetidine/Zabcid Tablets are indicated for the
following.
a)
The treatment of duodenal and benign gastric ulceration, and
oesophageal reflux disease.
b)
The treatment of persistent dyspeptic symptoms with or without
ulceration, particularly meal-related upper abdominal pain.
c)
The prophylaxis of gastro-intestinal haemorrhage from stress
ulceration in seriously ill patients.
d)
Before general anaesthesia in patients thought to be at risk of acid
aspiration (Mendelson’s) syndrome, particularly obstetric patients during labour.
e)

To reduce malabsorption and fluid loss in short bowel syndrome.

f)
To reduce degradation of enzyme supplements in pancreatic
insufficiency.

g)

4.2

In the management of Zollinger-Ellison syndrome.

Posology and method of administration
The total daily dose should not normally exceed 2.4g. Dosage should be
reduced in patients with impaired renal function.
Adults: the usual dosage is 400mg twice a day with breakfast and at bedtime.
For patients with duodenal or benign gastric ulceration, a single daily dose of
800mg at bedtime is recommended. Other effective regimens are 200mg, 3
times a day with meals and 400mg at bedtime (1g/day) and, if inadequate,
400mg, 4 times a day (1.6g/day), also with meals and at bedtime.
Symptomatic relief is usually rapid.
Treatment should be given initially for at least 4 weeks (6 weeks 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 400mg at bedtime or 400mg in the morning and at bedtime. In patients with
benign peptic ulcer disease, relapse may be prevented by continued treatment,
usually with 400mg at bedtime; 400mg in the morning and at bedtime has also
been used.
In oesophageal reflux disease, 400mg, 4 times a day, with meals and at
bedtime, for 4 to 8 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
400mg, 4 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 200mg-400mg can be given every 4 to 6 hours. In patients
thought to be at risk of acid aspiration syndrome an oral dose of 400mg can be
given 90-120 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
400mg may be repeated at 4 hourly intervals, as required, up to the usual daily
maximum of 2.4g. The usual precautions to avoid acid aspiration should be
taken. In short bowel syndrome, e.g. following substantial resection for
Crohn’s disease, the usual dosage range can be used according to individual
response.
To reduce degradation of pancreatic enzyme supplements, 800mg-1,600mg a
day may be given according to response in 4 divided doses, 1 to 1½ hours
before meals.
Elderly: the normal adult dosage may be used unless renal function is
markedly impaired.

Children: experience in children is less than that in adults. In children more
than one year old, cimetidine 25mg-30mg/kg body weight per day in divided
doses may be administered. The use of cimetidine in infants under one year
old has not yet been fully evaluated; 20mg/kg body weight per day in divided
doses has been used.
Patients with impaired renal function: dosage should be reduced in patients
with impaired renal function according to creatinine clearance. The following
dosages are suggested:
Creatinine clearance
0 to 15ml per minute
15ml to 30ml per minute
30ml to 50ml per minute
over 50ml per minute

Cimetidine dosage
200mg, twice a day
200mg, 3 times a day
200mg, 4 times a day
normal dosage.

Method of administration: oral.

4.3

Contraindications
Hypersensitivity to cimetidine.

4.4

Special warnings and precautions for use
Patients with renal impairment require a lower dose of cimetidine than normal.
Dosage should be reduced in patients with impaired renal function according to
creatinine clearance (see dosage schedule in 4.2 above). The following dosages are
suggested: creatinine clearance of 0-15ml per minute, 200mg twice a day; 15 to 30ml
per minute, 200mg three times a day; 30 to 50ml per minute, 200mg four times a day;
over 50ml per minute, normal dosage.
Cimetidine is removed by haemodialysis, but not to any significant extent by
peritoneal dialysis.

Clinical trials of over six years' continuous treatment and more than 15 years'
widespread use have not revealed unexpected adverse reactions related to long-term
therapy.
Cimetidine can prolong the elimination of drugs metabolised by oxidation in the liver.
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 anti-inflammatory 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 tablets
can relieve the symptoms and help the superficial healing of the gastric cancer. The
consequences of potential delay in diagnosis should be borne in mind, especially in
middle aged patients or 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.
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).

4.5

Interaction with other medicinal products and other forms of interaction
Cimetidine can prolong the elimination of drugs metabolised by oxidation in the liver.
Although pharmacological interactions between cimetidine and a number of drugs
have been demonstrated, eg diazepam and propranolol, only those with oral
anticoagulants, phenytoin and theophylline and intravenous lignocaine 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.
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.
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) of chemotherapeutic 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

Fertility, Pregnancy and lactation
Although tests in animals and clinical evidence reveal no hazards from the
administration of cimetidine during pregnancy or lactation, the drug does cross
the placental barrier and is excreted in breast milk. The use of this preparation

during pregnancy and lactation should be avoided unless considered essential
by the physician.

4.7

Effects on ability to drive and use machines
Patients should take care when driving, operating machinery or carrying out
other activities which require full alertness if they feel dizzy, very tired and/or
confused.

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 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).
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: Galactorrhoea
General disorders and administration site conditions
Common:
Tiredness
Very rare: Fever. Fever cleared on withdrawal of the
drug.
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
Overdosage of up to 20g has been reported 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, one of the H2 blockers, is a reversible, competitive antagonist of
the actions of histamine on H2 receptors. It is highly selective in its action and
is virtually without effect on H1 receptors or, indeed, on receptors for other
autacoids or drugs. The most prominent of the effects of histamine that are
mediated by H2 receptors is stimulation of gastric acid secretion and they
interfere remarkably little with physiological functions other than gastric
secretion.
Cimetidine inhibits gastric acid secretion elicited by histamine or other H2
agonists in a dose-dependent, competitive manner; the degree of inhibition
parallels the plasma concentration of the drug over a wide range. In addition,
the H2 blockers inhibit gastric secretion elicited by muscarinic agonists or by
gastrin, although this effect is not always complete. This breadth of inhibitory
effect is not due to non specific actions at the receptors for these other
secretagogues. Rather, this effect, which is non-competitive and indirect,
appears to indicate either that these 2 classes of secretagogues utilise histamine
as the final common mediator or, more probably, that ongoing histaminergic
stimulation of the parietal cell is important for amplification of the stimuli
provided by acetyl choline or gastrin when they act on their own discrete
receptors. Receptors for all 3 secretagogues are present on the parietal cell.
The ability of H2 blockers to suppress responses to all 3 physiological
secretagogues makes them potent inhibitors of all phases of gastric acid

secretion. Thus, these drugs will inhibit basal (fasting) secretion and nocturnal
secretion and also that stimulated by food, sham feeding, fundic distension,
insulin, or caffeine. The H2 blockers reduce both the volume of gastric juice
secreted and its hydrogen ion concentration. Output of pepsin, which is
secreted by the chief cells of the gastric glands (mainly under cholinergic
control), generally falls in parallel with the reduction in volume of the gastric
juice. Secretion of intrinsic factor is also reduced, but it is normally secreted
in great excess, and absorption of vitamin B12 is usually adequate even during
long-term therapy with H2 blockers.
Concentrations of gastrin in plasma are not significantly altered under fasting
conditions; however, the normal prandial elevation of gastrin concentration
may be augmented, apparently as a consequence of a reduction in the negative
feedback that is normally provided by acid.

5.2

Pharmacokinetic properties
Cimetidine is rapidly and virtually completely absorbed. Absorption is little
impaired by food or by antacids. Peak concentrations in plasma are attained in
about 1 to 2 hours. Hepatic first-class metabolism results in a bioavailability
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 as oxidation products. Small
amounts are recovered in the stool.

5.3

Preclinical safety data
None stated.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Microcrystalline cellulose, povidone 30, sodium starch glycollate, sodium
lauryl sulphate, colloidal silicon dioxide and magnesium stearate.
Film coating: hydroxypropyl methylcellulose (E464), polyethylene glycol,
and colours: quinoline yellow aluminium lake (E104), indigo carmine
aluminium lake (E132), titanium dioxide (E171) and iron oxide yellow
(E172).

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 25°C. Protect from light.

6.5

Nature and contents of container
1)
Polypropylene tubes with low density polyethylene caps.
density polyethylene film may be used as packing material.

High

Pack sizes: 100, 250, 500 and 1,000 tablets.
2)

Blister packs consisting of clear
aluminium foil, contained in a carton.

PVC

and

hard

temper

Pack sizes: 12, 24, 48, 60 and 120 tablets.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited
Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford
DA1 5BS
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 40147/0013

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/06/2010

10

DATE OF REVISION OF THE TEXT
07/08/2014

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Source: Medicines and Healthcare Products Regulatory Agency

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