Summary of Product Characteristics Updated 07-Feb-2020 | GlaxoSmithKline UK
A clear, pale yellow, mint flavoured liquid.
AdultsZantac syrup is indicated for the treatment of duodenal ulcer and benign gastric ulcer, including that associated with non-steroidal anti-inflammatory agents. In addition, Zantac syrup is indicated for the prevention of NSAID associated duodenal ulcers. Zantac syrup is also indicated for the treatment of post-operative ulcer, Zollinger-Ellison Syndrome and oesophageal reflux disease including long term management of healed oesophagitis. Other patients with chronic episodic dyspepsia, characterised by pain (epigastric or retrosternal) which is related to meals or disturbs sleep but is not associated with the preceding conditions may benefit from ranitidine treatment. Zantac syrup is indicated for the following conditions where reduction of gastric secretion and acid output is desirable; the prophylaxis of gastro-intestinal haemorrhage from stress ulceration in seriously ill patients, the prophylaxis of recurrent haemorrhage in patients with bleeding peptic ulcers and before general anaesthesia in patients considered to be 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.See section 4.4 Special warnings and precautions for use.
Adults (including the elderly)The usual dosage is 150 mg twice daily, taken in the morning and evening. Alternatively, patients with duodenal ulceration, gastric ulceration or oesophageal reflux disease may be treated with a single bedtime dose of 300 mg. It is not necessary to time the dose in relation to meals.Duodenal ulcer, benign gastric ulcer and post-operative ulcer:In most cases of duodenal ulcer, benign gastric ulcer and post operative ulcer, healing occurs in four weeks. Healing usually occurs after a further 4 weeks of treatment in those patients whose ulcers have not fully healed after the initial course of therapy.NSAID associated peptic ulceration, including prophylaxis of duodenal ulcers:In ulcers following non-steroidal anti-inflammatory drug therapy or associated with continued non-steroidal anti-inflammatory drugs, 8 weeks treatment may be necessary.For the prevention of non-steroidal anti-inflammatory drug associated duodenal ulcers ranitidine 150 mg twice daily may be given concomitantly with non-steroidal anti-inflammatory drug 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 nocte. The increased dose has not been associated with an increased incidence of unwanted effects.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: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 if necessary 12 weeks.In patients with moderate to severe oesophagitis, the dosage of ranitidine may be increased to 150 mg four times daily for up to twelve weeks. The increased dose has not been associated with an incidence of unwanted effects.For the long-term management of oesophagitis the recommended adult oral dose is 150 mg twice daily. Long-term treatment is not indicated in the management of patients with unhealed oesophagitis with or without Barrett's epithelium.Zollinger-Ellison syndrome:In patients with Zollinger-Ellison Syndrome, the starting dose is 150 mg three times daily and this may be increased as necessary. Patients with this syndrome have been given increasing doses up to 6 g per day and these doses have been well tolerated.Chronic episodic dyspepsia:For patients with chronic episodic dyspepsia the recommended course of treatment is 150 mg twice daily for up to six weeks. Anyone not responding or relapsing shortly afterwards should be investigated.Prophylaxis of haemorrhage from stress ulceration or recurrent haemorrhage:In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or in the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, treatment with Zantac tablets 150 mgs twice daily may be substituted for Zantac injection once oral feeding commences in patients considered to be still at risk from these conditions.Prophylaxis of Mendelson's syndrome:In patients thought to be at risk of acid aspiration syndrome an oral dose of 150 mg can be given 2 hours before induction of general anaesthesia, and preferably also 150 mg the previous evening. In obstetric patients at commencement of labour, an oral dose of 150 mg may be given followed by 150 mg at six hourly intervals. It is recommended that since gastric emptying and drug absorption are delayed during labour, any patient requiring emergency general anaesthesia should be given, in addition, a non-particulate antacid (eg sodium citrate) prior to induction of anaesthesia. The usual precautions to avoid acid aspiration should also be taken.
Children 12 years and overFor children 12 years and over the adult dosage is given.
Children (3 to 11 years)See Section 5.2 Pharmacokinetic properties (Other special populations)Zantac syrup contains approximately 7.5%w/v ethanol. Therefore an alternative formulation of ranitidine may be considered necessary for at-risk groups, including children (see section 4.4 Special warnings and precautions for use).
Patients over 50 years of ageSee Section 5.2 Pharmacokinetic Properties (Other special populations)
Peptic Ulcer Acute TreatmentThe 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 RefluxThe 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).
NeonatesSafety and efficacy in new-born patients has not been established.
Patients with renal impairmentAccumulation 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 be 150 mg at night for 4 to 8 weeks. The same dose should be used for maintenance treatment if necessary. If an ulcer has not healed after treatment, the standard dosage regimen of 150 mg twice daily should be instituted, followed, if need be, by maintenance treatment at 150 mg at night.
Method of administrationFor oral administration.
MalignancyThe 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 DiseaseRanitidine 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 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. Current evidence shows that ranitidine protects against NSAID associated ulceration in the duodenum and not in the stomach.Rare clinical reports suggest that ranitidine may precipitate acute porphyric attacks. Ranitidine should therefore be avoided in patients with a history of acute porphyria.Rates of healing of ulcers in clinical trial patients aged 65 and over have not been found to differ from those in younger patients. Additionally, there was no difference in the incidence of adverse effects.Zantac syrup contains approximately 7.5% w/v ethanol (alcohol), i.e. up to 405 mg per 5 ml spoonful which is equivalent to about 11 ml of beer or 5 ml of wine. It is harmful for those suffering from alcoholism. It should be taken into account in pregnant or lactating women, high-risk groups (those suffering from alcoholism, liver disease, epilepsy, brain injury or disease) and children (see section 4.2). It may modify or increase the effects of other medicines.Zantac Syrup contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.Alternative formulation of Zantac may be considered preferential in these populations.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 alone 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).
Concomitant administration of 300 mg ranitidine and erlotinib decreased erlotinib exposure (AUC) and maximum concentrations (Cmax) by 33% and 54%, respectively. However, when erlotinib was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b.i.d., erlotinib exposure (AUC) and maximum concentrations (Cmax) decreased only by 15% and 17%, respectively.
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.
PregnancyRanitidine 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, ranitidine should only be used during pregnancy if considered essential.
Breast-feedingRanitidine is excreted in human breast milk. Like other drugs, ranitidine should only be used during breast-feeding if considered essential.
FertilityThere 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).
|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 patients, in elderly and in nephropatic patients. Nervous System Disorders|
|Very Rare:||Headache (sometimes severe), dizziness and reversible involuntary movement 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, A-V block and tachycardia.|
|Uncommon:||Abdominal pain, constipation, nausea (these symptoms mostly improved during continued treatment).|
|Very Rare:||Acute pancreatitis, diarrhoea|
|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|
|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).|
Paediatric populationThe 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 available, in particular regarding growth and development.
Reporting of suspected adverse reactionsReporting 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
Symptoms and signsRanitidine is very specific in action and accordingly no particular problems are expected following overdosage with the drug.
TreatmentSymptomatic and supportive therapy should be given as appropriate.
Mechanism of actionRanitidine is a specific, rapidly acting H2-antagonist. It inhibits basal and stimulated secretion of gastric acid, reducing both the volume of the acid and pepsin content of the secretion. Ranitidine has a relatively long duration of action and a single 150 mg dose effectively suppresses gastric acid secretion for twelve hours.
DistributionRanitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.
MetabolismRanitidine 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.
EliminationPlasma 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 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 ageIn 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.
Date of Authorisation: 01 November 1993
Date of renewal: 13 April 2010
3rd February 2020