Drugs List

Therapeutic Indications

Uses

Treatment of mild to moderate hypertension and renal hypertension.
Treatment and prophylaxis of chronic stable angina, vasospastic angina and unstable angina.
Treatment and prophylaxis of paroxysmal supraventricular tachycardia and the reduction of ventricular rate in atrial flutter/fibrillation.

Unlicensed Uses

Prophylaxis of cluster headache

Administration

For oral administration.

Contraindications

Porphyria
Hypotension (systolic pressure less than 90mm Hg)
Cardiogenic shock
Bradycardia (pulse rate at rest less than 50 beats per minute) except in patients with a functioning pacemaker.
Second or third degree AV block with no pacemaker
Sick sinus syndrome, including sino-atrial block
Uncompensated heart failure

History of cardiac failure or significantly reduced left ventricular function - verapamil may affect left ventricular contractility, this effect may cause cardiac failure to be precipitated or aggravated.
Atrial flutter/fibrillation associated with an accessory pathway (Wolff-Parkinson syndrome, Lown-ganong syndrome)
Acute myocardial infarction complicated by significant bradycardia, hypotension or left ventricular failure.

Concurrent ingestion of grapefruit juice

Precautions and Warnings

Hepatic impairment - See Dosage:Hepatic Impairment .
Renal impairment - See Dosage:Renal Impairment.

Verapamil may affect impulse conduction and should be used with caution in patients with first degree AV block or bradycardia.

Verapamil may affect left ventricular contractility; this effect is small but cardiac failure may be precipitated or aggravated. Therefore patients with incipient cardiac failure should only be given verapamil after such cardiac failure has been controlled with appropriate therapy.

Ventricular tachycardia may be precipitated in patients with atrial flutter or fibrillation in association with an accessory pathway (e.g. WPW syndrome).

When treating hypertension, monitoring of the patient's blood pressure at regular intervals is required.

Verapamil should be discontinued slowly after long term treatment.
There is some evidence that sudden withdrawal of calcium channel blockers may be associated with exacerbation of angina.

Use with caution in patients with diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).

Caution during the acute stage of myocardial infarction. Calcium channel blockers do not reduce the risk of myocardial infarction in unstable angina. The use of verapamil should be reversed for patients resistant to treatment with beta-blockers.

Use with caution in children under 18 years as a paradoxical increase in the rate of arrhythmias has been noted. To be used only under specialist advice.

Pregnancy (see 'Pregnancy' section). May inhibit labour.
Breastfeeding (see 'Lactation' section)

The ability to drive or operate machinery may be impaired. This is particularly true in the initial stages of treatment, or when changing over from another medication.

Verapamil may increase the blood levels of alcohol and slow its elimination. Therefore the effects of alcohol may be exaggerated.
St John's Wort may reduce the plasma concentration of verapamil.
Advise patient not to take aspirin, simvastatin or St. John's Wort unless under the advice of a physician.

The liquid formulation contains maltitol. Patients with rare hereditary problems of fructose metabolism should not take this medicine.

Some formulations contain lactose - use with caution or avoid in patients with galactosaemia, lactose intolerance, or glucose-galactose malabsorption syndrome should be treated with caution.

Use in Porphyria

Contraindicated. The Norwegian Porphyria Centre (NAPOS) classifies verapamil as being 'probably porphrinogenic'.

Pregnancy and Lactation

Pregnancy

Use during pregnancy only if essential and the benefits to the mother outweigh the potential risks to the foetus.

Animal studies in rabbits and rats have not shown any teratogenic effects at oral doses of between 15 mg/kg/day and 60mg/kg/day respectively. However, in rats this dose was embryocidal and retarded foetal growth and development (probably due to maternal toxicity). There is limited information to concerning the use of calcium blockers in human pregnancy. Verapamil crosses the placenta. No congenital anomalies were reported in infants whose mothers took verapamil in the first trimester. Furthermore, no adverse effects were observed in infants whose mothers took verapamil in late pregnancy. Verapamil may inhibit labour and in some cases it has been associated with maternal hyperprolactinaemia and galactorrhoea. It is possible that verapamil could cause relaxation of the uterine muscles or reduce uterine blood flow.

Apart from the treatment of maternal hypertension, verapamil has also been used to treat foetal supraventricular tachycardia. However Schaefer concludes that other agents should be used in preference to verapamil for this indication. Schaefer comments that verapamil is amongst one of the best studied calcium antagonists during pregnancy and is one of the preferred first-line calcium channel blockers for the treatment of hypertension in the second or third trimesters. In the first trimester, calcium antagonists are considered to be second-line therapy.

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 14-17 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 ).

Recommended for use in pregnancy, 1st trimester? - as a second-line agent.

Recommended for use in pregnancy, 2nd and 3rd trimester? - is a preferred first-line calcium channel blocker for hypertension.

Known human teratogen? - No

Pregnancy-specific adverse effects on the mother - may inhibit labour.

Animal data: - Animal studies have reported the following effects; embryocidal and retarded foetal growth and development

Crosses the placenta? - Yes

Lactation

Verapamil should only be given during breast-feeding if essential.

Verapamil is excreted in breast milk in small amounts and is unlikely to be harmful. One study reported that no verapamil was detected in infant's plasma following a maternal dose of 80mg three times daily. Rare hypersensitivity reactions have been reported though, which should be taken into consideration. Verapamil can cause hyperprolactinaemia and galactorrhoea however the clinical relevance on nursing mothers is unknown. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Information published on LactMed states that verapamil would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.

Hale states the infant should be observed for hypotension, bradycardia or weakness. Schaefer concluded that verapamil is one of the calcium antagonists of choice during breastfeeding.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - Yes.

Side Effects

Sinus bradycardia
Sinus arrest
Sinus arrest with asystole
Second and third degree AV block
Bradyarrhythmia in atrial fibrillation
Hypotension
Aggravation of cardiac failure
Cardiac failure
Constipation
Flushing
Headache
Nausea
Vomiting
Dizziness
Fatigue
Ankle oedema
Allergic reaction
Erythema
Pruritus
Liver function disturbances
Increase in serum transaminases
Increase in alkaline phosphatase
Gynaecomastia in older men
Gingival hyperplasia
Increased prolactin
Quincke's oedema
Stevens-Johnson syndrome
Erythromelalgia
Paraesthesia
Myalgia
Arthralgia
Alopecia
Urticaria
Impotence
Abdominal pain
Ileus
Peripheral oedema
Purpura
Tremor
Extrapyramidal effects
Vertigo
Tinnitus
Palpitations
Tachycardia
Galactorrhoea
Dystonia
Muscle weakness
Aggravation of angina
Bradycardia
Angioedema
Asystole
Erythema multiforme

Presentation

Tablets containing 40mg verapamil hydrochloride
Tablets containing 80mg verapamil hydrochloride
Tablets containing 120mg verapamil hydrochloride
Tablets containing 160mg verapamil hydrochloride

Sugar free oral solution containing 40mg/5ml verapamil hydrochloride

Drugs List

Therapeutic Indications

Uses

Treatment of mild to moderate hypertension and renal hypertension.
Treatment and prophylaxis of chronic stable angina, vasospastic angina and unstable angina.
Treatment and prophylaxis of paroxysmal supraventricular tachycardia and the reduction of ventricular rate in atrial flutter/fibrillation.

Unlicensed Uses

Prophylaxis of cluster headache

Dosage

Not all products are licensed in all age groups.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Contraindications

Porphyria
Hypotension (systolic pressure less than 90mm Hg)
Cardiogenic shock
Bradycardia (pulse rate at rest less than 50 beats per minute) except in patients with a functioning pacemaker.
Second or third degree AV block with no pacemaker
Sick sinus syndrome, including sino-atrial block
Uncompensated heart failure

History of cardiac failure or significantly reduced left ventricular function - verapamil may affect left ventricular contractility, this effect may cause cardiac failure to be precipitated or aggravated.
Atrial flutter/fibrillation associated with an accessory pathway (Wolff-Parkinson syndrome, Lown-ganong syndrome)
Acute myocardial infarction complicated by significant bradycardia, hypotension or left ventricular failure.

Concurrent ingestion of grapefruit juice

Precautions and Warnings

Hepatic impairment - See Dosage:Hepatic Impairment .
Renal impairment - See Dosage:Renal Impairment.

Verapamil may affect impulse conduction and should be used with caution in patients with first degree AV block or bradycardia.

Verapamil may affect left ventricular contractility; this effect is small but cardiac failure may be precipitated or aggravated. Therefore patients with incipient cardiac failure should only be given verapamil after such cardiac failure has been controlled with appropriate therapy.

Ventricular tachycardia may be precipitated in patients with atrial flutter or fibrillation in association with an accessory pathway (e.g. WPW syndrome).

When treating hypertension, monitoring of the patient's blood pressure at regular intervals is required.

Verapamil should be discontinued slowly after long term treatment.
There is some evidence that sudden withdrawal of calcium channel blockers may be associated with exacerbation of angina.

Use with caution in patients with diseases in which neuromuscular transmission is affected (myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy).

Caution during the acute stage of myocardial infarction. Calcium channel blockers do not reduce the risk of myocardial infarction in unstable angina. The use of verapamil should be reversed for patients resistant to treatment with beta-blockers.

Use with caution in children under 18 years as a paradoxical increase in the rate of arrhythmias has been noted. To be used only under specialist advice.

Pregnancy (see 'Pregnancy' section). May inhibit labour.
Breastfeeding (see 'Lactation' section)

The ability to drive or operate machinery may be impaired. This is particularly true in the initial stages of treatment, or when changing over from another medication.

Verapamil may increase the blood levels of alcohol and slow its elimination. Therefore the effects of alcohol may be exaggerated.
St John's Wort may reduce the plasma concentration of verapamil.
Advise patient not to take aspirin, simvastatin or St. John's Wort unless under the advice of a physician.

The liquid formulation contains maltitol. Patients with rare hereditary problems of fructose metabolism should not take this medicine.

Some formulations contain lactose - use with caution or avoid in patients with galactosaemia, lactose intolerance, or glucose-galactose malabsorption syndrome should be treated with caution.

Use in Porphyria

Contraindicated. The Norwegian Porphyria Centre (NAPOS) classifies verapamil as being 'probably porphrinogenic'.

Pregnancy and Lactation

Pregnancy

Use during pregnancy only if essential and the benefits to the mother outweigh the potential risks to the foetus.

Animal studies in rabbits and rats have not shown any teratogenic effects at oral doses of between 15 mg/kg/day and 60mg/kg/day respectively. However, in rats this dose was embryocidal and retarded foetal growth and development (probably due to maternal toxicity). There is limited information to concerning the use of calcium blockers in human pregnancy. Verapamil crosses the placenta. No congenital anomalies were reported in infants whose mothers took verapamil in the first trimester. Furthermore, no adverse effects were observed in infants whose mothers took verapamil in late pregnancy. Verapamil may inhibit labour and in some cases it has been associated with maternal hyperprolactinaemia and galactorrhoea. It is possible that verapamil could cause relaxation of the uterine muscles or reduce uterine blood flow.

Apart from the treatment of maternal hypertension, verapamil has also been used to treat foetal supraventricular tachycardia. However Schaefer concludes that other agents should be used in preference to verapamil for this indication. Schaefer comments that verapamil is amongst one of the best studied calcium antagonists during pregnancy and is one of the preferred first-line calcium channel blockers for the treatment of hypertension in the second or third trimesters. In the first trimester, calcium antagonists are considered to be second-line therapy.

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 14-17 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 ).

Recommended for use in pregnancy, 1st trimester? - as a second-line agent.

Recommended for use in pregnancy, 2nd and 3rd trimester? - is a preferred first-line calcium channel blocker for hypertension.

Known human teratogen? - No

Pregnancy-specific adverse effects on the mother - may inhibit labour.

Animal data: - Animal studies have reported the following effects; embryocidal and retarded foetal growth and development

Crosses the placenta? - Yes

Lactation

Verapamil should only be given during breast-feeding if essential.

Verapamil is excreted in breast milk in small amounts and is unlikely to be harmful. One study reported that no verapamil was detected in infant's plasma following a maternal dose of 80mg three times daily. Rare hypersensitivity reactions have been reported though, which should be taken into consideration. Verapamil can cause hyperprolactinaemia and galactorrhoea however the clinical relevance on nursing mothers is unknown. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Information published on LactMed states that verapamil would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months.

Hale states the infant should be observed for hypotension, bradycardia or weakness. Schaefer concluded that verapamil is one of the calcium antagonists of choice during breastfeeding.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - Yes.

Effects on Ability to Drive and Operate Machinery

The ability to drive or operate machinery may be impaired due to drowsiness. This is particularly true in the initial stages of treatment, or when changing over from another medication.

Counselling

Advise the patient that the effects of alcohol may be exaggerated by verapamil.

The patient should be advised that their ability to drive or operate machinery may be impaired due to drowsiness. This is particularly true in the initial stages of treatment, or when changing over from another medication.

Advise patient to avoid all grapefruit products whilst taking verapamil.

Advise patient not to take aspirin, simvastatin or St. John's Wort unless under the advice of a physician.

Side Effects

Sinus bradycardia
Sinus arrest
Sinus arrest with asystole
Second and third degree AV block
Bradyarrhythmia in atrial fibrillation
Hypotension
Aggravation of cardiac failure
Cardiac failure
Constipation
Flushing
Headache
Nausea
Vomiting
Dizziness
Fatigue
Ankle oedema
Allergic reaction
Erythema
Pruritus
Liver function disturbances
Increase in serum transaminases
Increase in alkaline phosphatase
Gynaecomastia in older men
Gingival hyperplasia
Increased prolactin
Quincke's oedema
Stevens-Johnson syndrome
Erythromelalgia
Paraesthesia
Myalgia
Arthralgia
Alopecia
Urticaria
Impotence
Abdominal pain
Ileus
Peripheral oedema
Purpura
Tremor
Extrapyramidal effects
Vertigo
Tinnitus
Palpitations
Tachycardia
Galactorrhoea
Dystonia
Muscle weakness
Aggravation of angina
Bradycardia
Angioedema
Asystole
Erythema multiforme

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 ).

Shelf Life and Storage

Do not store above 25 degrees C.

Oral solution: Discard any remainder 3 months after first opening.

Further Information

Last Full Review Date: December 2012

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale,T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Verapamil tablets BP 40mg. Actavis UK Ltd. Revised January 2011.
Summary of Product Characteristics: Verapamil tablets BP 80mg. Actavis UK Ltd. Revised January 2011.
Summary of Product Characteristics: Verapamil tablets BP 120mg. Actavis UK Ltd. Revised January 2011.
Summary of Product Characteristics: Verapamil tablets BP 160mg. Actavis UK Ltd. Revised January 2011.

Summary of Product Characteristics: Verapamil 40mg tablets. Teva UK Limited. Revised August 2011.
Summary of Product Characteristics: Verapamil 80mg tablets. Teva UK Limited. Revised October 2011.
Summary of Product Characteristics: Verapamil 120mg tablets. Teva UK Limited. Revised October 2011.

Summary of Product Characteristics: Verapamil 40mg/5ml oral solution. Rosemont Pharmaceuticals Ltd. Revised February 2016.

NAPOS: The Norwegian Porphyria Centre
Available at: https://www.drugs-porphyria.org/languages/UnitedKingdom/selsearch.php?l=gbr
Drug: Verapamil. Last accessed: December 12, 2012

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
Verapamil. Last revised: January 04, 2011
Last accessed: December 12, 2012