Verapamil is a calcium channel blocker used to lower blood pressure, treat angina and control certain cardiac arrhythmias. It slows the heart rate and reduces the work of the heart.
Also known as: Verapamilo, Isoptin
Beta-blocker + calcium channel blocker: risk of severe AV block and cardiac arrest.
Propranolol (non-selective beta-1+beta-2) and verapamil profoundly depress AV conduction and contractility. Propranolol adds beta-2 blockade (bronchospasm) to verapamil's depressant effect. The combination can cause complete AV block, sinus arrest, cardiovascular collapse, and death. Absolutely CONTRAINDICATED — no safe dose exists for this combination.
Non-selective beta-blocker + non-dihydropyridine CCB: severe AV block and cardiac arrest. CONTRAINDICATED — risk of death.
Both depress AV conduction and contractility. The combination can cause high-grade AV block and cardiac arrest.
DailyMed/FDA (NIH/NLM) — approved Propranolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d5ac315-df2b-4b3a-bc7e-ad04752865c4
Beta-blocker + non-dihydropyridine CCB: risk of severe bradycardia.
Same mechanism as atenolol + verapamil. Both reduce AV conduction and contractility.
ECG, heart rate.
Severe bradycardia.
Avoid combination. If necessary, monitor ECG.
DailyMed/FDA; EMC-EMC PT
Beta-blocker + non-dihydropyridine calcium channel blocker: risk of bradycardia and AV block.
Both reduce AV conduction and contractility. The combination may cause severe bradycardia, AV block, and heart failure.
ECG, heart rate, blood pressure.
Severe bradycardia, AV block.
Avoid combination. If necessary, monitor ECG and vital signs.
DailyMed/FDA; EMC-EMC PT
Beta-blocker + non-dihydropyridine CCB: risk of AV block and heart failure.
Both reduce AV conduction and contractility. The combination can cause severe AV block, bradycardia, and heart failure.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Theophylline + verapamil: verapamil decreases theophylline metabolism, increasing its levels and the toxicity risk (QUADRO 2).
Verapamil inhibits CYP1A2, the main enzyme metabolising theophylline, potentially increasing theophylline concentrations by 20-25% or more. QUADRO 2 of Annex 7 lists theophylline among drugs interacting with calcium channel blockers. Theophylline toxicity presents with nausea, vomiting, tachycardia, tremors, insomnia and, at high levels, seizures and arrhythmias. The risk is higher in smokers who stop tobacco, the elderly or those with heart failure. When starting verapamil, consider reducing the theophylline dose and monitor serum levels and toxicity signs; prefer other calcium channel blockers when possible.
Theophylline + verapamil: verapamil inhibits theophylline metabolism — toxicity risk (nausea, tachycardia, seizures); reduce dose and monitor.
Verapamil (calcium channel blocker) inhibits theophylline hepatic metabolism — increased plasma levels (QUADRO 2, Theophylline: "Drugs that decrease theophylline metabolism: ... Verapamil").
Monitor theophylline toxicity symptoms (nausea, tachycardia, tremor).
Theophylline toxicity (tachycardia, tremor, seizures) after starting verapamil.
Monitor theophylline levels when starting verapamil; consider reducing the theophylline dose.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Theophylline)
Sirolimus + verapamil: verapamil reduces sirolimus metabolism, increasing its levels and the toxicity risk (QUADRO 2).
Verapamil inhibits CYP3A4 and P-glycoprotein, reducing sirolimus metabolism and efflux and increasing its plasma concentrations. QUADRO 2 of Annex 7 records this interaction in the calcium channel blocker section. The rise in levels can occur within the first days and present with nephrotoxicity, infections or anaemia. The risk is higher in transplant patients and the elderly. When starting verapamil, consider reducing the sirolimus dose and monitor serum levels and renal function; prefer other calcium channel blockers when possible.
Verapamil + sirolimus: CYP3A4 and P-gp inhibition — increased sirolimus; reduce dose and monitor levels.
Verapamil (CYP3A4/P-gp inhibitor) reduces sirolimus metabolism — increased concentrations (QUADRO 2, Calcium channel blockers: "Sirolimus: reduced sirolimus metabolism with diltiazem, nicardipine, verapamil").
Monitor renal function and signs of sirolimus toxicity.
Elevated sirolimus levels after starting verapamil.
Monitor sirolimus levels when starting verapamil; adjust the dose as needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Calcium channel blockers)
Verapamil is a CYP3A4 substrate; grapefruit juice inhibits this enzyme in the gut and may raise verapamil plasma concentrations, with risk of hypotension and bradycardia.
Avoid grapefruit juice during treatment with verapamil.
DailyMed/FDA (NIH/NLM) — approved Verapamil Hydrochloride tablet label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed1e0c14-3571-43f9-88fc-5a4d2b598263
VERAPAMIL ER label (CONTRAINDICATIONS): verapamil slows AV conduction — contraindicated in severe AV block and sick sinus syndrome; caution in first-degree AV block.
Contraindicated in severe AV block and sick sinus syndrome.
DailyMed/FDA (NIH/NLM) — Verapamil (NIVAGEN), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e36e485f-fbed-4e30-9a63-984931f2e54e
VERAPAMIL ER label (CONTRAINDICATIONS): contraindicated in patients with severe heart failure or severe left ventricular dysfunction (the negative inotropic effect may worsen heart failure).
Contraindicated in severe heart failure; use with caution in ventricular dysfunction.
DailyMed/FDA (NIH/NLM) — Verapamil (NIVAGEN), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e36e485f-fbed-4e30-9a63-984931f2e54e
VERAPAMIL ER label (Pregnancy): reproduction studies in rabbits and rats (up to 1.5× and 6× the human oral daily dose) with no evidence of teratogenicity; in rats, the dose was embryocidal and retarded fetal growth; no adequate studies in pregnant women — use only if clearly needed.
Use only if clearly needed (no teratogenicity in animals, but embryocidal effects in rats).
No specific breastfeeding data in the label; assess risk/benefit.
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Verapamil label (NIVAGEN), Pregnancy section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e36e485f-fbed-4e30-9a63-984931f2e54e
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Calcium channel blocker (phenylalkylamine): negative chronotropic and dromotropic effects (slows AV conduction) and arterial vasodilation — antihypertensive, antianginal and class IV antiarrhythmic (VERAPAMIL ER label).
L-type calcium channel blockade; CYP3A4 substrate and P-gp inhibitor.
Oral absorption; bioavailability is limited by first-pass effect (ER forms).
Extensive first-pass hepatic metabolism (CYP3A4); rifampin markedly reduces oral bioavailability and phenobarbital increases clearance (Drug Interactions).
Elimination half-life variable (approx. 2.8-7.4 h for oral forms, depending on formulation).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.