ZANTAC TABLETS 150MG

Active substance: RANITIDINE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Zantac Tablets 150mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains ranitidine 150mg (as the hydrochloride).

3

PHARMACEUTICAL FORM
Tablet.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adults
Duodenal ulcer and benign gastric ulcer, including that associated with nonsteroidal anti-inflammatory agents.
Prevention of non-steroidal anti-inflammatory drug associated duodenal
ulcers.
Treatment of duodenal ulcers associated with Helicobacter pylori infection.
Post-operative ulcer.
Oesophageal reflux disease including long term management of healed
oesophagitis.
Symptomatic relief in gastro-oesophageal reflux disease.
Zollinger-Ellison Syndrome.
Chronic episodic dyspepsia, characterised by pain (epigastric or retrosternal)
which is related to meals or disturbs sleep but not associated with the above
conditions.
Prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously
ill patients
Prophylaxis of recurrent haemorrhage with bleeding peptic ulcers.
Before general anaesthesia in patients at risk of acid aspiration (Mendelson's
syndrome), particularly obstetric patients during labour.

For appropriate cases, Zantac injection is also available (see separate SPC).
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 (including the elderly) / Adolescents (12 years and over)
Usual dosage is 150 mg twice daily, taken in the morning and evening.
Duodenal ulcer, gastric ulcer:
The standard dosage regimen is 150 mg twice daily or 300 mg at night. It is
not necessary to time the dose in relation to meals.
In most cases of duodenal ulcer, benign gastric ulcer and post-operative ulcer,
healing occurs within 4 weeks. Healing usually occurs after a further 4 weeks
of treatment in those not fully healed after the initial course of therapy.
Ulcers following NSAID therapy or associated with continued NSAIDs:
8 weeks treatment may be necessary
Prevention of NSAID associated duodenal ulcers:
150 mg twice daily may be given concomitantly with NSAID therapy.
In duodenal ulcer, 300 mg twice daily for 4 weeks results in healing rates
which are higher than those at 4 weeks with ranitidine 150 mg twice daily or
300 mg at night. The increased dose has not been associated with an increased
incidence of unwanted effects.
Duodenal ulcers associated with Helicobacter pylori infection:
For duodenal ulcers associated with Helicobacter pylori infection, ranitidine
300 mg at bedtime or 150 mg twice daily may be given with oral amoxicillin
750 mg three times daily and metronidazole 500 mg three times daily for two
weeks. Therapy with ranitidine should continue for a further two weeks. This
dose regimen significantly reduces the frequency of duodenal ulcer recurrence.
Maintenance treatment at a reduced dosage of 150 mg at bedtime is
recommended for patients who have responded to short term therapy,
particularly those with a history of recurrent ulcer.
Gastro-oesophageal reflux disease:
Symptom relief in gastro-oesophageal reflux disease. In patients with gastrooesophageal reflux disease, a dose regimen of 150 mg twice daily for 2 weeks

is recommended and this can be repeated in patients in whom the initial
symptomatic response is inadequate
Oesophageal reflux disease:
In the management of oesophageal reflux disease, the recommended course of
treatment is either 150 mg twice daily or 300 mg at bedtime for up to 8 weeks
or 12 weeks if necessary.
In patients with moderate to severe oesophagitis, the dosage of ranitidine may
be increased to 150 mg 4 times daily for up to 12 weeks. The increased dose
has not been associated with an increased incidence of unwanted effects.
Healed oesophagitis:
For long term treatment, recommended adult dose is 150 mg twice daily.
Long term treatment is not indicated in management of patients with unhealed
oesophagitis with or without Barrett's epithelium.
Zollinger-Ellison syndrome:
The starting dose for Zollinger-Ellison syndrome is 150 mg three times daily,
and this may be increased as necessary. Doses up to 6 grams per day have
been well tolerated.
Chronic episodic dyspepsia:
The standard dosage regimen for patients with chronic episodic dyspepsia is
150 mg twice daily for up to 6 weeks. Anyone not responding or relapsing
shortly afterwards should be investigated.
Prophylaxis of haemorrhage from stress ulceration in seriously ill patients or
prophylaxis of recurrent haemorrhage in patients bleeding from peptic
ulceration:
150 mg twice daily may be substituted for the injection once oral feeding
commences.
Prophylaxis of acid aspiration (Mendelson's) syndrome:
150 mg oral dose can be given 2 hours before anaesthesia, and preferably also
150 mg the previous evening. Alternatively, the injection is also available. In
obstetric patients in labour 150 mg every 6 hours, but if general anaesthesia is
required it is recommended that a non-particulate antacid (e.g. sodium citrate)
be given in addition. The usual precautions to avoid acid aspiration should
also be taken.
Children from 3 to 11 years and over 30 kg of weight
See Section 5.2 Pharmacokinetic Properties (Special Patient Population)
Patients over 50 years of age
See Section 5.2 Pharmacokinetic Properties (Special Patient Populations,
Patients over 50 years of age)
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
complete 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 to
a maximum of 600 mg (the maximum dose is likely to apply to heavier
children or adolescents with severe symptoms).
Safety and efficacy in new-born patients has not been established.
Renal Impairment:
Accumulation of ranitidine with resulting elevated plasma concentrations will
occur in patients with renal impairment (creatinine clearance less than 50
ml/min). Accordingly, it is recommended that the daily dose of ranitidine in
such patients should be 150 mg at night for 4-8 weeks. The same dose should
be used for maintenance treatment, if necessary. If an ulcer has not healed
after treatment, 150 mg twice daily dosage should be instituted followed, if
need be, by maintenance treatment of 150 mg at night.
4.3

Contraindications
Ranitidine is contra-indicated in patients known to have hypersensitivity to
any component of the preparation.

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 if indications include dyspepsia, 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 dosage should be adjusted as detailed under
Dosage in 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 porphyric attacks.
Ranitidine should therefore be avoided in patients with a history of acute porphyria.
Use in elderly patients:
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 H2 receptor
antagonists versus those who had stopped treatment, with an observed adjusted
relative risk increase of 1.63 (95% CI, 1.07–2.48). Postmarketing 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 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 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 randitidine and amoxycillin
and metronidazole.

4.6

Fertility, pregnancy and lactation
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. It is
excreted in human breast milk.
Like other drugs it should only be used during pregnancy and nursing if
considered essential.
There are no data on the effects of ranitidine on human fertility. There were no
effects on male and female fertility in animal studies.

4.7

Effects on ability to drive and use machines
None applicable.

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 post-marketing data.

Blood & 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.

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 and elderly patients.
Nervous System Disorders

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 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.
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).
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
Ranitidine is very specific in action and accordingly no particular problems are
expected following overdosage. Symptomatic and supportive therapy should
be given as appropriate.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: H2-receptor antagonists
ATC code: A02BA02
Ranitidine is a specific rapidly acting histamine H2-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 150 mg dose effectively suppresses gastric
acid secretion for twelve 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 5060% 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 demthylranitidine
and 1 to 2% as the furoic acid analogue.
Elimination
Plasma concentrations decline bi-exponentially, with a terminal half-life of 23 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.
Special Patient Populations
Children (3 years and above)
Limited pharmacokinetic data show 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
Non-clinical data revealed no special hazard for humans based on conventional
studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic
potential and toxicity to reproduction and development.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Tablet core:
Microcrystalline cellulose NF
Magnesium stearate EP
Methylhydroxypropyl cellulose (E464) EP
Film coat:
Titanium Dioxide E171 EP
Triacetin NF

6.2

Incompatibilities
None.

6.3

Shelf life
60 months.

6.4

Special precautions for storage
None necessary.

6.5

Nature and contents of container
Cartons of 30, 60 or 90 tablets, in aluminium foil strips or push through double
foil blister packs.

6.6

Special precautions for disposal
No special instructions.

7

MARKETING AUTHORISATION HOLDER
Glaxo Wellcome UK Limited
Trading as Glaxo Laboratories and/or GlaxoSmithKline UK
Stockley Park West
Uxbridge
Middlesex
UB11 1BT

8

MARKETING AUTHORISATION NUMBER(S)
PL 10949/0042

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
01 March 1993 / 27 March 1997.

10

DATE OF REVISION OF THE TEXT
05/12/2012

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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