Description

Simple

A medication used to treat chest pain, abnormal heart rhythms, and high blood pressure.

Clinical

A non-dihydropyridine calcium channel blocker used in the treatment of angina, arrhythmia, and hypertension.

Overview

Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina,[16] and was the first calcium channel antagonist to be introduced into therapy in the early 1960s.[13] It is a member of the non-dihydropyridine class of calcium channel blockers, which includes drugs like [diltiazem] and [flunarizine], but is chemically unrelated to other cardioactive medications.[16] Verapamil is administered as a racemic mixture containing equal amounts of the S- and R-enantiomer, each of which is pharmacologically distinct - the S-enantiomer carries approximately 20-fold greater potency than the R-enantiomer, but is metabolized at a higher rate.[5]

Pharmacology

Indication

Verapamil is indicated in the treatment of vasopastic (i.e. Prinzmetal's) angina, unstable angina, and chronic stable angina. It is also indicated to treat hypertension, for the prophylaxis of repetitive paroxysmal supraventricular tachycardia, and in combination with digoxin to control ventricular... Read more

Pharmacodynamic

Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity.[16] Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times da... Read more

Mechanism of action

Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha-1 subunit,[14]Cav1.2, which is highly expressed on L-type calcium channels in vascul... Read more

Absorption

More than 90% of orally administered verapamil is absorbed - despite this, bioavailability ranges only from 20% to 30% due to rapid biotransformation following first-pass metabolism in the portal circulation.[16] Absorp... Read more

Protein binding

Verapamil is extensively protein-bound in plasma. R-verapamil is 94% bound to serum albumin while S-verapamil is 88% bound. Additionally, R-verapamil is 92% bound to alpha-1 acid glycoprotein and S-verapamil is 86% bound.[1... Read more

Volume of distribution

Verapamil has a steady-state volume of distribution of approximately 300L for its R-enantiomer and 500L for its S-enantiomer.[ Read more

Clearance

Systemic clearance following 3 weeks of continuous treatment was approximately 340 mL/min for R-verapamil and 664 mL/min for S-verapamil.[ Read more

Half life

Single-dose studies of immediate-release verapamil have demonstrated an elimination half-life of 2.8 to 7.4 hours, which increases to 4.5 to 12.0 hours following repetitive dosing.[16] The elimination half-life is also... Read more

Route of elimination

Approximately 70% of an administered dose is excreted as metabolites in the urine and ≥16% in the feces within 5 days. Approximately 3% - 4% is excreted in the urine as unchanged drug.[16]

Toxicity

Verapamil's reported oral TDLo is 14.4 mg/kg in women and 3.429 mg/kg in men.[18] The oral LD50 is 150 mg/kg in rats and 163 mg/kg in mice.[ Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Infection US
  • Kind: experimental
    • Percent: 12.1
  • Kind: placebo
    • Percent: 6.9
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 12.1
  • Kind: placebo
    • Percent: 11.2
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 8.8
  • Kind: placebo
    • Percent: 0.9
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 7.3
  • Clinical Trial
    Peripheral Edema US
  • Kind: experimental
    • Percent: 3.7
  • Kind: placebo
    • Percent: 0.9
  • Clinical Trial
    Flu syndrome US
  • Kind: experimental
    • Percent: 3.7
  • Kind: placebo
    • Percent: 2.6
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 3.3
  • Clinical Trial
    Sinusitis US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 2.6
  • Clinical Trial
    Pharyngitis US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 2.6
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 0.9
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 2.7
  • Clinical Trial
    Rhinitis US
  • Kind: experimental
    • Percent: 2.7
  • Kind: placebo
    • Percent: 2.6
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 2.7
  • Kind: placebo
    • Percent: 1.7
  • Clinical Trial
    Hypotension US
  • Kind: experimental
    • Percent: 2.5
  • Clinical Trial
    Pain US
  • Kind: experimental
    • Percent: 2.4
  • Kind: placebo
    • Percent: 1.7
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 2.4
  • Kind: placebo
    • Percent: 1.7
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 2.2
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 1.9
  • Clinical Trial
    Congestive Heart Failure US
  • Kind: experimental
    • Percent: 1.8
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 1.7
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 1.7
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 1.7
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Symptomatic hypotension US
  • Kind: experimental
    • Percent: 1.5
  • Clinical Trial
    Accidental injury US
  • Kind: experimental
    • Percent: 1.5
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Bradycardia US
  • Kind: experimental
    • Percent: 1.4
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 1.2
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 1.2
  • Clinical Trial
    Bradycardia US
  • Kind: experimental
    • Percent: 1.2
  • Clinical Trial
    Complete Heart Block US
  • Kind: experimental
    • Percent: 1.2
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 1.2
  • Clinical Trial
    Severe tachycardia US
  • Kind: experimental
    • Percent: 1
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 0.9
  • Clinical Trial
    Second or third degree AV block US
  • Kind: experimental
    • Percent: 0.8
  • Clinical Trial
    Abdominal Discomfort US
  • Kind: experimental
    • Percent: 0.6
  • Clinical Trial
    Flushing US
  • Kind: experimental
    • Percent: 0.6
  • Clinical Trial
    Diaphoresis US
    Varying Reports
    Muscle Fatigue US
    Varying Reports
    Vertigo US
    Varying Reports
    Sleepiness US
    Varying Reports
    Rotary nystagmus US
    Varying Reports
    Depressed mood US
    Varying Reports
    Asthenia US
    Varying Reports
    Aggravated allergy US
    Varying Reports
    Spotty menstruation US
    Varying Reports
    Increased urination US
    Varying Reports
    Impotence US
    Varying Reports
    Hyperprolactinemia US
    Varying Reports
    Galactorrhea US
    Varying Reports
    Gynecomastia US
    Varying Reports
    Tinnitus US
    Varying Reports

    Contraindications

    • Route:
      • Intravenous
    • Time Period: Only applies to concomitant use of intravenous verapamil and intravenous beta-adrenergic blockers.
    • Regions: US
    • With Categories:
        • Name: Adrenergic beta-Antagonists
        • Drugbank Id: DBCAT000456
        • Mesh Id: D000319
    • Route:
      • Oral
    • Dose Form:
      • Tablet, extended release
    • Time Period: Do not administer verapamil/trandolapril within 2 days of flibanserin. Discontinue verapamil/trandalopril at least 2 weeks prior to starting flibanserin.
    • Regions: US
    • With Drugs:
        • Name: Trandolapril
        • Drugbank Id: DB00519
    • With Drugs Coadmin:
        • Name: Flibanserin
        • Drugbank Id: DB04908
    • Route:
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Ventricular Tachycardia (VT)
        • Drugbank Id: DBCOND0085135
    • Hypersensitivity:
      • true
    • Regions: US
    • Regions: US
    • Patient Conditions:
        • Name: Accessory bypass tract
        • Drugbank Id: DBCOND0107652
        • Name: Atrial Fibrillation (AF)
        • Drugbank Id: DBCOND0047324
    • Regions: US
    • Patient Conditions:
        • Name: Accessory bypass tract
        • Drugbank Id: DBCOND0107652
        • Name: Atrial Flutter
        • Drugbank Id: DBCOND0000496
    • Regions: US
    • Patient Conditions:
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
        • Name: Third degree AV block
        • Drugbank Id: DBCOND0107810
    • Regions: US
    • Patient Conditions:
        • Name: Atrioventricular block second degree
        • Drugbank Id: DBCOND0007764
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
    • Regions: US
    • Patient Conditions:
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
        • Name: Sick Sinus Syndrome
        • Drugbank Id: DBCOND0000493
    • Regions: US
    • Patient Conditions:
        • Name: Shock, Cardiogenic
        • Drugbank Id: DBCOND0000550
    • Regions: US
    • Patient Conditions:
        • Name: Severe hypotension
        • Drugbank Id: DBCOND0095479
        • Modification Of:
          • Base:
            • Name: Hypotension
            • Drugbank Id: DBCOND0020133
          • Severity:
            • Includes:
              • severe
    • Regions: US
    • Patient Conditions:
        • Name: Severe Left Ventricular Dysfunction
        • Drugbank Id: DBCOND0124564
        • Modification Of:
          • Base:
            • Name: Left Ventricular Dysfunction
            • Drugbank Id: DBCOND0031407
          • Severity:
            • Includes:
              • severe

    Food Interactions

    Avoid alcohol. Verapamil significantly inhibits the elimination of alcohol, leading to elevated blood alcohol levels.

    Avoid grapefruit products. Co-administration with grapefruit may significantly increase serum concentrations.

    Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.