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Drug Reference

verapamil

Calcium channel blocker (non-dihydropyridine)· Brands: Isoptin, Calan, Verelan, Covera-HS, Securon, CordiloxIVPO

Mechanism of action
Verapamil is a phenylalkylamine, non-dihydropyridine calcium channel blocker. It blocks L-type voltage-gated calcium channels, with greater selectivity for cardiac conduction tissue and vascular smooth muscle than the dihydropyridines. In the sinoatrial and atrioventricular nodes it reduces the inward calcium current, slowing conduction and prolonging AV nodal refractoriness, which terminates re-entrant supraventricular tachycardias and slows the ventricular rate in atrial fibrillation or flutter. It also has negative inotropic and chronotropic effects and dilates arterioles, reducing afterload and myocardial oxygen demand. Verapamil has some alpha-adrenergic blocking activity, but this is not its main clinical action. Because it slows AV nodal conduction, it is hazardous in atrial fibrillation or flutter with pre-excitation, where it can increase the ventricular rate.
Pharmacokinetics
After oral administration verapamil undergoes extensive first-pass metabolism, giving a bioavailability of about 20 to 35 per cent and wide interindividual variation. Peak plasma concentrations occur around 1 to 2 hours after immediate-release doses; sustained-release formulations have a delayed and flatter profile. It is about 90 per cent protein bound and is metabolised mainly by CYP3A4 to norverapamil, which has some activity. The elimination half-life is typically 3 to 12 hours, prolonged in hepatic impairment, in older adults, and after chronic dosing. Metabolites are excreted mainly in urine, with some in bile and faeces. IV verapamil acts within minutes and has a short duration, so it requires monitored administration. Grapefruit juice and CYP3A4 inhibitors increase plasma concentrations; enzyme inducers such as rifampicin reduce them.
Indications & dosing

Hypertension

Immediate-release tablets are usually given three times daily; modified-release preparations are often given once daily. Avoid combining with a beta-blocker because of the risk of bradycardia and AV block.

  • adult · PO: 80–160 mg TID · Immediate-release tablets are usually given three times daily; modified-release preparations are often given once daily. Avoid combining with a beta-blocker because of the risk of bradycardia and AV block.

Chronic stable angina prophylaxis

Used when beta-blockers are unsuitable or insufficient. Constipation and ankle oedema are common. Do not stop suddenly, as rebound angina may occur.

  • adult · PO: 80–160 mg TID · Used when beta-blockers are unsuitable or insufficient. Constipation and ankle oedema are common. Do not stop suddenly, as rebound angina may occur.

Supraventricular tachycardia, termination of an acute episode

Give as a slow bolus over at least 2 minutes with continuous ECG and blood pressure monitoring. Avoid in wide-complex tachycardia and in suspected accessory pathway conduction. A second dose may be given if there is no response.

  • adult · IV: 5–10 mg single dose · Give as a slow bolus over at least 2 minutes with continuous ECG and blood pressure monitoring. Avoid in wide-complex tachycardia and in suspected accessory pathway conduction. A second dose may be given if there is no response.

Atrial fibrillation or flutter, acute rate control

For haemodynamically stable patients only. Verapamil is generally a second-line rate control agent. Avoid in heart failure with reduced ejection fraction.

  • adult · IV: 5–10 mg single dose · For haemodynamically stable patients only. Verapamil is generally a second-line rate control agent. Avoid in heart failure with reduced ejection fraction.

Hypertrophic cardiomyopathy, symptom controloff-label

Off-label. Often used when beta-blockers are not tolerated or not effective. Titrate against symptoms, heart rate and blood pressure; specialist follow-up is usual.

  • adult · PO: 80–160 mg TID · Off-label. Often used when beta-blockers are not tolerated or not effective. Titrate against symptoms, heart rate and blood pressure; specialist follow-up is usual.

Supraventricular tachycardia in children

Give under ECG monitoring. Infants under 1 year are more sensitive to hypotension and bradycardia and need specialist supervision. Maximum single dose is usually capped at the adult dose.

  • pediatric · IV: 0.1–0.3 mg/kg single dose · Give under ECG monitoring. Infants under 1 year are more sensitive to hypotension and bradycardia and need specialist supervision. Maximum single dose is usually capped at the adult dose.

Cluster headache prophylaxisoff-label

Off-label. Usually started at a lower divided dose and titrated upwards. ECG monitoring is advised at higher doses. Practice varies widely by centre and formulary.

  • adult · PO: 240–480 mg daily · Off-label. Usually started at a lower divided dose and titrated upwards. ECG monitoring is advised at higher doses. Practice varies widely by centre and formulary.
Contraindications & precautions
  • Cardiogenic shock or severe hypotension (systolic blood pressure below 90 mmHg) · Verapamil causes vasodilatation and negative inotropy, which can worsen shock.
  • Severe left ventricular systolic dysfunction (heart failure with reduced ejection fraction) · Negative inotropic effect may precipitate decompensation.
  • Sick sinus syndrome, sinoatrial block, or second- or third-degree AV block without a functioning pacemaker · Verapamil slows AV nodal conduction and can cause severe bradycardia or asystole.
  • Atrial fibrillation or flutter complicating Wolff-Parkinson-White syndrome or another accessory pathway · AV nodal blockade can accelerate conduction down the accessory pathway, risking ventricular fibrillation.
  • Concomitant intravenous beta-blocker · Additive negative chronotropic and inotropic effects can cause profound bradycardia, hypotension, or asystole.
  • Concomitant ivabradine · Both drugs reduce heart rate; combination increases risk of severe bradycardia.
  • Hypersensitivity to verapamil or other components of the formulation · Avoid further exposure.
  • Monitor heart rate and blood pressure on initiation and during dose titration, especially in patients with conduction disease or those taking other rate-limiting drugs.
  • Use with caution in hepatic impairment: verapamil is extensively metabolised by CYP3A4, so reduce the dose and monitor for toxicity.
  • Check for interactions with CYP3A4 inhibitors and inducers (for example, macrolides, azole antifungals, rifampicin, carbamazepine, St John's wort) and with digoxin, simvastatin, beta-blockers and ivabradine.
  • Do not use immediate-release verapamil to control rapid ventricular rate in atrial fibrillation or flutter unless an accessory pathway has been excluded.
  • In heart failure, use only if systolic function is preserved and the patient is clinically stable; avoid in heart failure with reduced ejection fraction.
  • Advise on managing constipation with dietary fibre, adequate fluids and laxatives if needed, and taper gradually when stopping to avoid rebound angina.
Adverse effects
  • Constipation
  • Dizziness
  • Headache
  • Flushing
  • Peripheral oedema
  • Symptomatic bradycardiaserious
  • Hypotensionserious
  • Second- or third-degree AV blockserious
  • Heart failure exacerbationserious
  • Gingival hyperplasia
Interactions
  • digoxinmajorMonitor digoxin plasma concentrations before and after starting verapamil, and adjust the digoxin dose downwards (often by 25-50%) as guided by levels. Monitor ECG and heart rate. Consider using a different calcium channel blocker (e.g., amlodipine) if appropriate, and avoid combination in patients with significant conduction abnormalities or heart block.
  • metoprololmajorAvoid concomitant use. If unavoidable, monitor heart rate, blood pressure and ECG closely, and consider reducing the dose of metoprolol. Alternative calcium channel blockers such as amlodipine may be safer.
  • simvastatinmajorAvoid co-prescribing verapamil with simvastatin doses above 10 mg daily. If combination is necessary, limit simvastatin to 10 mg/day and monitor for muscle symptoms and creatine kinase levels.
  • bisoprololmajorAvoid co-prescription where possible. If combination is necessary, use cautiously with lower doses of both agents. Monitor heart rate, blood pressure and ECG at baseline and after any dose change. Consider switching to a dihydropyridine calcium channel blocker if rate control is not the primary goal. Intravenous verapamil should be avoided in patients taking bisoprolol.
  • carvedilolmajorAvoid coadministration, particularly in patients with heart failure or conduction abnormalities. If necessary, use cautiously with baseline ECG and monitoring of heart rate, blood pressure, and signs of heart failure. Reduce doses as needed.
  • dabigatranmajorAvoid the combination unless clearly necessary. If co-prescribed, reduce dabigatran dose to the lower approved regimen (e.g., 110 mg twice daily) when indicated, and monitor closely for bleeding signs and symptoms. Check renal function before and during therapy. Consider an alternative anticoagulant with a more predictable profile, e.g., apixaban or edoxaban, or an alternative antiarrhythmic agent.
  • tacrolimusmajorAvoid co-prescription if possible. If combination is considered necessary, measure tacrolimus trough levels before and after starting verapamil, and at intervals thereafter. Reduce the tacrolimus dose as needed to maintain therapeutic trough concentrations. Monitor renal function and watch for signs of tacrolimus toxicity.
Renal & hepatic adjustment
  • Hepatic impairment (mild): Consider a lower starting dose and titrate slowly according to blood pressure, heart rate and tolerability. Monitor for signs of accumulation.
  • Hepatic impairment (moderate): Reduce the starting dose by approximately 30 to 50% and titrate cautiously. Monitor blood pressure, heart rate and ECG closely.
  • Hepatic impairment (severe): Avoid unless the benefit clearly outweighs the risk. If used, give a substantially reduced dose under specialist supervision and monitor closely. (avoid)
Monitoring, pregnancy & toxicity
  • Blood pressure and heart rate · Baseline, during dose titration, after any dose change, and throughout intravenous administration.
  • ECG (PR interval, bradycardia, AV block) · Baseline, during intravenous use, and periodically during oral therapy, especially in the elderly or those with conduction disease.
  • Signs of heart failure (dyspnoea, oedema, weight gain) · Before starting and regularly during therapy, particularly in patients with left ventricular dysfunction.
  • Liver function tests · Baseline and periodically in patients with hepatic impairment or those on long-term therapy.
  • Concomitant drugs and grapefruit intake (CYP3A4 interactions) · Review at initiation and whenever medicines change; advise patients to avoid grapefruit juice.
  • Pregnancy: Use in pregnancy only when clearly indicated, for example for supraventricular arrhythmias or severe hypertension when safer alternatives are unsuitable. Verapamil crosses the placenta; monitor maternal blood pressure, heart rate and fetal wellbeing. For hypertension in pregnancy, labetalol or nifedipine are usually preferred.
  • Toxicity: Cardiovascular depression: severe hypotension, bradycardia, shock, and reduced cardiac output. · Stop verapamil. Give IV fluids, atropine for bradycardia, calcium chloride or gluconate, and vasopressors (for example noradrenaline) as needed. Consider glucagon and high-dose insulin euglycaemia in refractory cases.
  • Toxicity: Conduction disturbances: PR prolongation, higher-degree AV block, junctional rhythms, asystole. · Continuous ECG monitoring and immediate cardiology support. Use calcium salts, glucagon, transcutaneous or transvenous pacing, and vasopressors. Refractory cases may need extracorporeal support.
  • Toxicity: Metabolic and neurological toxicity: hyperglycaemia, metabolic acidosis, confusion, seizures, coma. · Supportive care in an intensive care setting. Treat seizures with benzodiazepines, monitor and correct glucose and acid-base status, and provide ventilatory support if required.
  • Toxicity: Non-cardiogenic pulmonary oedema and respiratory depression. · Give oxygen, consider non-invasive or invasive ventilation, and manage in a critical care setting. Treat hypotension and cardiac dysfunction as above.
Antidotes & reversal
  • Calcium gluconate (IV) · IV calcium, glucagon and high-dose insulin-euglycaemia; SR preparations cause prolonged toxicity.
Clinical notes
Verapamil is used orally for hypertension, angina and some supraventricular arrhythmias, and intravenously for rapid termination of AV nodal re-entrant tachycardia and for rate control in selected supraventricular tachycardias. It is not suitable for broad-complex tachycardia unless a supraventricular origin is certain. Common adverse effects include constipation, bradycardia, AV block, hypotension, flushing, headache, dizziness and worsening heart failure. It is contraindicated in cardiogenic shock, severe hypotension, severe left ventricular dysfunction, sick sinus syndrome, second- or third-degree AV block without a pacemaker, and atrial fibrillation or flutter with pre-excitation. Avoid concurrent IV beta-blockers and use oral beta-blockers only with caution because of additive bradycardia and AV block. It raises digoxin and simvastatin concentrations; review interacting drugs and grapefruit juice. Doses and formulations vary by indication and region, so confirm against the local formulary and product information. Monitor blood pressure, heart rate and ECG during initiation or IV use.

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BNF; local formulary; summary of product characteristics; local protocols