Drugs List

Therapeutic Indications

Uses

Acid aspiration during labour: prophylaxis
Before general anaesthesia in patients at risk of acid aspiration
Duodenal ulcer
Gastric ulcer
Gastro-oesophageal reflux disease
Prophylaxis of recurrent haemorrhage in bleeding peptic ulcers
Prophylaxis of stress induced GI haemorrhage in the seriously ill
Reflux oesophagitis
Zollinger-Ellison syndrome (and other hypersecretory conditions)

Administration

For slow intravenous injection or infusion, and intramuscular administration.

Contraindications

None known

Precautions and Warnings

Children under 6 months
Immunosuppression
Patients over 50 years
Acute porphyria
Breastfeeding
Chronic respiratory impairment
Diabetes mellitus
Pregnancy
Renal impairment - creatinine clearance below 50ml/minute

May mask symptoms of serious disease of the stomach and delay diagnosis
Reduce dose in patients with severe renal impairment
Exclude gastric cancer before commencing treatment
Monitor for signs/symptoms of pneumonia in patients at risk
Not licensed for all indications in all age groups
Avoid long term use

In patients with factors predisposing to cardiac rhythm disturbances, bradycardia has rarely been reported when ranitidine injection has been rapidly administered. Recommended rates of administration should not be exceeded.

In patients over 50 years of age, half-life is prolonged and renal clearance is reduced, which is consistent with age declining renal function. However, systemic exposure and accumulation of the drug are 50% higher. This indicates increased bioavailability in older patients which exceeds the effect of declining renal function.

The manufacturer advises to avoid in patients with a history of acute porphyria. Rare clinical reports suggest ranitidine may precipitate acute porphyric attacks. However, the Welsh Medicines Information Centre considers the drug to be safe in acute porphyria. NAPOS website classifies the drug as probably not porphyrinogenic, to be used as a first hand choice with no precautions needed. This is based on uneventful clinical experiences which points to non-porphyrinogenicity. They question the causality of the few case reports which pointed the drug as porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Ranitidine should be used with caution in pregnancy.

There is consensus that ranitidine may be used during pregnancy and Schaefer concludes that it may be prescribed where antacids have failed.

Animal studies have shown no evidence of teratogenicity or impairment of fertility. Available data on human pregnancies suggests that ranitidine is not a major teratogen. Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labour or undergoing caesarean section have been used without any adverse effect on labour, delivery or subsequent neonatal progress

Current practice guidelines also state that ranitidine is considered safe for use during pregnancy on the basis of several years of use without incidence and supporting evidence from observational studies.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ranitidine should be used with caution in breastfeeding.

Ranitidine is excreted in breast milk although the amount present in breast milk is lower than the paediatric dose. Since ranitidine has been widely used in paediatrics without significant side effects and exposure levels via breast milk are sub-therapeutic, there is consensus that ranitidine may be used during breastfeeding. Schaefer concludes that ranitidine may be used during lactation but other drugs of the same class that are excreted into breast milk at lower levels should be preferred. LactMed (via Toxnet) concludes that maternal ranitidine would not be expected to cause any adverse effects in breastfed infants.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute pancreatitis
Agranulocytosis
Alopecia
Altered liver function tests
Anaphylactic shock
Angioneurotic oedema
Arthralgia
Asystole
Atrioventricular block
Blurred vision
Bone marrow aplasia
Bone marrow hypoplasia
Bradycardia
Breast symptoms in men
Bronchospasm
Chest pain
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Dyspnoea
Erythema multiforme
Fever
Galactorrhoea
Gynaecomastia
Hallucinations
Headache
Hepatitis
Hypersensitivity reactions
Hypotension
Impotence
Interstitial nephritis
Involuntary movement disorders
Jaundice
Leucopenia
Myalgia
Nausea
Pancytopenia
Rash
Serum creatinine increased
Tachycardia
Thrombocytopenia
Urticaria
Vasculitis

Presentation

Solution for injection containing ranitidine (as the hydrochloride).

Drugs List

Therapeutic Indications

Uses

Acid aspiration during labour: prophylaxis
Before general anaesthesia in patients at risk of acid aspiration
Duodenal ulcer
Gastric ulcer
Gastro-oesophageal reflux disease
Prophylaxis of recurrent haemorrhage in bleeding peptic ulcers
Prophylaxis of stress induced GI haemorrhage in the seriously ill
Reflux oesophagitis
Zollinger-Ellison syndrome (and other hypersecretory conditions)

Dosage

Adults

Elderly

Children

Neonates

Patients with Renal Impairment

Administration

For slow intravenous injection or infusion, and intramuscular administration.

Contraindications

None known

Precautions and Warnings

Children under 6 months
Immunosuppression
Patients over 50 years
Acute porphyria
Breastfeeding
Chronic respiratory impairment
Diabetes mellitus
Pregnancy
Renal impairment - creatinine clearance below 50ml/minute

May mask symptoms of serious disease of the stomach and delay diagnosis
Reduce dose in patients with severe renal impairment
Exclude gastric cancer before commencing treatment
Monitor for signs/symptoms of pneumonia in patients at risk
Not licensed for all indications in all age groups
Avoid long term use

In patients with factors predisposing to cardiac rhythm disturbances, bradycardia has rarely been reported when ranitidine injection has been rapidly administered. Recommended rates of administration should not be exceeded.

In patients over 50 years of age, half-life is prolonged and renal clearance is reduced, which is consistent with age declining renal function. However, systemic exposure and accumulation of the drug are 50% higher. This indicates increased bioavailability in older patients which exceeds the effect of declining renal function.

The manufacturer advises to avoid in patients with a history of acute porphyria. Rare clinical reports suggest ranitidine may precipitate acute porphyric attacks. However, the Welsh Medicines Information Centre considers the drug to be safe in acute porphyria. NAPOS website classifies the drug as probably not porphyrinogenic, to be used as a first hand choice with no precautions needed. This is based on uneventful clinical experiences which points to non-porphyrinogenicity. They question the causality of the few case reports which pointed the drug as porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Ranitidine should be used with caution in pregnancy.

There is consensus that ranitidine may be used during pregnancy and Schaefer concludes that it may be prescribed where antacids have failed.

Animal studies have shown no evidence of teratogenicity or impairment of fertility. Available data on human pregnancies suggests that ranitidine is not a major teratogen. Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labour or undergoing caesarean section have been used without any adverse effect on labour, delivery or subsequent neonatal progress

Current practice guidelines also state that ranitidine is considered safe for use during pregnancy on the basis of several years of use without incidence and supporting evidence from observational studies.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ranitidine should be used with caution in breastfeeding.

Ranitidine is excreted in breast milk although the amount present in breast milk is lower than the paediatric dose. Since ranitidine has been widely used in paediatrics without significant side effects and exposure levels via breast milk are sub-therapeutic, there is consensus that ranitidine may be used during breastfeeding. Schaefer concludes that ranitidine may be used during lactation but other drugs of the same class that are excreted into breast milk at lower levels should be preferred. LactMed (via Toxnet) concludes that maternal ranitidine would not be expected to cause any adverse effects in breastfed infants.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute pancreatitis
Agranulocytosis
Alopecia
Altered liver function tests
Anaphylactic shock
Angioneurotic oedema
Arthralgia
Asystole
Atrioventricular block
Blurred vision
Bone marrow aplasia
Bone marrow hypoplasia
Bradycardia
Breast symptoms in men
Bronchospasm
Chest pain
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Dyspnoea
Erythema multiforme
Fever
Galactorrhoea
Gynaecomastia
Hallucinations
Headache
Hepatitis
Hypersensitivity reactions
Hypotension
Impotence
Interstitial nephritis
Involuntary movement disorders
Jaundice
Leucopenia
Myalgia
Nausea
Pancytopenia
Rash
Serum creatinine increased
Tachycardia
Thrombocytopenia
Urticaria
Vasculitis

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: January 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Ranitidine 50mg/2ml Solution for Injection and Infusion. Alliance Pharmaceuticals. Revised February 2015

Summary of Product Characteristics: Ranitidine Injection 25mg/ml Solution for Injection. Amdipharm Mercury Company Limited. Revised November 2015

Summary of Product Characteristics: Zantac Injection 50mg/2ml. GlaxoSmithKline UK. Revised October 2015

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 September 2017

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: March 10, 2015
Last accessed: January 14, 2016

The Welsh Medicines Information Centre (WMIC) - Porphyria Information Service.
Available at: https://www.wmic.wales.nhs.uk/porphyria_info.php
Last revised: May, 2016
Last accessed: January 14, 2016

The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Last revised: January 11, 2012
Last accessed: January 14, 2016