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, the predominant L-type calcium channel in the cardiovascular... 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

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.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Verapamil.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Verapamil.
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Verapamil is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
The therapeutic efficacy of Verapamil can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The therapeutic efficacy of Verapamil can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The therapeutic efficacy of Verapamil can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamine
The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Verapamil.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Verapamil.
4-Methoxyamphetamine
The therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Verapamil.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Verapamil.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Verapamil.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Verapamil.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Verapamil.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Verapamil.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Verapamil.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be decreased when combined with Verapamil.
9-Methylguanine
The metabolism of 9-Methylguanine can be decreased when combined with Verapamil.
Abacavir
Verapamil may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abafungin
The therapeutic efficacy of Abafungin can be increased when used in combination with Verapamil.
Abatacept
The metabolism of Verapamil can be increased when combined with Abatacept.
19 References
  1. 1 . Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83.PubMed: 8725386
  2. 2 . Ahmed JH, Meredith PA, Elliott HL: The influence of age on the pharmacokinetics of verapamil. Pharmacol Res. 1991 Oct;24(3):227-33. doi: 10.1016/1043-6618(91)90085-c.PubMed: 1956867
  3. 3 . Dadashzadeh S, Javadian B, Sadeghian S: The effect of gender on the pharmacokinetics of verapamil and norverapamil in human. Biopharm Drug Dispos. 2006 Oct;27(7):329-34. doi: 10.1002/bdd.512.PubMed: 16892180
  4. 4 . Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x.PubMed: 19125880
  5. 5 . Busse D, Fromm MF, Morike K, Drescher S, Kuhlkamp V, Eichelbaum M: Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing. Clin Pharmacol Ther. 2001 May;69(5):324-32. doi: 10.1067/mcp.2001.115125.PubMed: 11372000
  6. 6 . Ninomiya T, Takano M, Haruna T, Kono Y, Horie M: Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2). J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002.PubMed: 12883317
  7. 7 . Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA: Verapamil block of T-type calcium channels. Mol Pharmacol. 2011 Mar;79(3):411-9. doi: 10.1124/mol.110.069492. Epub 2010 Dec 13.PubMed: 21149638
  8. 8 . Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30.PubMed: 18974361
  9. 9 . Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1.PubMed: 19515014
  10. 10 . Striessnig J, Ortner NJ, Pinggera A: Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22.PubMed: 25966690
  11. 11 . Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30.PubMed: 9570190
  12. 12 . Motulsky HJ, Snavely MD, Hughes RJ, Insel PA: Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors. Circ Res. 1983 Feb;52(2):226-31.PubMed: 6297831
  13. 13 . Echizen H, Eichelbaum M: Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet. 1986 Nov-Dec;11(6):425-49. doi: 10.2165/00003088-198611060-00002.PubMed: 3542336
  14. 14 . FDA Approved Drug Products: Verelan® PM extended-release capsules Link
  15. 15 . FDA Approved Drug Products: Verapamil HCl for intravenous injection Link
  16. 16 . Verapamil FDA Label Link
  17. 17 . FDA Approved Drugs: Tarka® extended-release tablets Link
  18. 18 . CaymanChem: Verapamil MSDS Link
  19. 19 . FDA Approved Drug Products: Calan SR tablets Link