Verapamil, sold under various trade names,[1] is a medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia.[2] It may also be used for the prevention of migraines and cluster headaches.[3][4] It is given by mouth or by injection into a vein.[2]

Verapamil structure.svg
Clinical data
Trade namesVarious[1]
License data
  • US: C (Risk not ruled out)
Routes of
by mouth, intravenous
Drug classCalcium channel blocker
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life2.8–7.4 hours
Excretionkidney: 11%
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.000.133 Edit this at Wikidata
Chemical and physical data
Molar mass454.602 g/mol g·mol−1
3D model (JSmol)
ChiralityRacemic mixture

Common side effects include headache, low blood pressure, nausea, and constipation.[2] Other side effects include allergic reactions and muscle pains.[5] It is not recommended in people with a slow heart rate or heart failure.[5] It is believed to cause problems for the baby if used during pregnancy.[6] It is in the non–dihydropyridine calcium channel blocker family of medications.[2]

Verapamil was approved for medical use in the United States in 1981.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] Verapamil is available as a generic medication.[2] The wholesale cost in the developing world is about US$1.71–2.70 per month.[8] In the United States a month of treatment costs $25–50.[9] Long acting formulations exist.[5] In 2016 it was the 130th most prescribed medication in the United States with more than 5 million prescriptions.[10]

Medical usesEdit

Verapamil is used for controlling ventricular rate in supraventricular tachycardia and migraine headache prevention.[11] It is a class-IV antiarrhythmic and more effective than digoxin in controlling ventricular rate.[12] Verapamil is not listed as a first line agent by the guidelines provided by JAMA in JNC-8.[13] However, it may be used to treat hypertension if patient has co-morbid atrial fibrillation or other types of arrhythmia.[14][15]

Verapamil is also used intra-arterially to treat cerebral vasospasm.[16] Verapamil is used to treat the condition cluster headache.[17]


Use of verapamil is generally avoided in people with severe left ventricular dysfunction, hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, and hypersensitivity to verapamil.[18] It is also contraindicated in people with atrial flutter or fibrillation.[19]

Side effectsEdit

The most common side effect of Verapamil is constipation (7.3%). Other side effects include: dizziness (3.3%), nausea (2.7%), low blood pressure (2.5%), and headache 2.2%. Other side effects seen in less than 2% of the population include: edema, congestive heart failure, pulmonary edema, fatigue, elevated liver enzymes, shortness of breath, low heart rate, atrioventricular block, rash and flushing.[20]

Verelan 300-mg extended-release capsule

Along with other calcium channel blockers, verapamil is known to induce gingival enlargement.[21]


Acute overdose is often manifested by nausea, weakness, slow heart rate, dizziness, low blood pressure, and abnormal heart rhythms. Plasma, serum, or blood concentrations of verapamil and norverapamil, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Blood or plasma verapamil concentrations are usually in a range of 50–500 μg/l in persons on therapy with the drug, but may rise to 1–4 mg/l in acute overdose patients and are often at levels of 5–10 mg/l in fatal poisonings.[22][23]

Mechanism of actionEdit

Verapamil's mechanism in all cases is to block voltage-dependent calcium channels.[18] In cardiac pharmacology, calcium channel blockers are considered class-IV antiarrhythmic agents. Since calcium channels are especially concentrated in the sinoatrial and atrioventricular nodes, these agents can be used to decrease impulse conduction through the AV node, thus protecting the ventricles from atrial tachyarrhythmias.

Calcium channels are also present in the smooth muscle lining blood vessels. By relaxing the tone of this smooth muscle, calcium channel blockers dilate the blood vessels. This has led to their use in treating high blood pressure and angina pectoris. The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like verapamil dilate blood vessels, which increases the supply of blood and oxygen to the heart.[24] This controls chest pain, but only when used regularly. It does not stop chest pain once it starts. A more powerful vasodilator such as nitroglycerin may be needed to control pain once it starts.

Verapamil is also a Kv voltage gated potassium channel blocker.[25]

Pharmacokinetic detailsEdit

More than 90% of verapamil is absorbed when given orally,[18] but due to high first-pass metabolism, bioavailability is much lower (10–35%). It is 90% bound to plasma proteins and has a volume of distribution of 3–5 l/kg. It takes 1 to 2 hours to reach peak plasma concentration after oral administration.[18] It is metabolized in the liver to at least 12 inactive metabolites (though one metabolite, norverapamil, retains 20% of the vasodilating activity of the parent drug). As its metabolites, 70% is excreted in the urine and 16% in feces; 3–4% is excreted unchanged in urine. This is a nonlinear dependence between plasma concentration and dosage. Onset of action is 1–2 hours after oral dosage. Half-life is 5–12 hours (with chronic dosages). It is not cleared by hemodialysis. It is excreted in human milk. Because of the potential for adverse reaction in nursing infants, nursing should be discontinued while verapamil is administered.

Verapamil has been reported to be effective in both short-term[26] and long-term treatment of mania and hypomania.[27] Addition of magnesium oxide to the verapamil treatment protocol enhances the antimanic effect.[28] It has on occasion been used to control mania in pregnant patients, especially in the first three months. It does not appear to be significantly teratogenic. For this reason, when one wants to avoid taking valproic acid (which is high in teratogenicity) or lithium (which has a small but significant incidence of causing cardiac malformation), verapamil is usable as an alternative, albeit presumably a less effective one.

Veterinary useEdit

Intra-abdominal adhesions are common in rabbits following surgery. Verapamil can be given postoperatively in rabbits which have suffered trauma to abdominal organs to prevent formation of these adhesions.[29][30][31] Such effect was not documented in another study with ponies.[32]

Uses in cell biologyEdit

Verapamil is also used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein.[33] This is useful, as many tumor cell lines overexpress drug efflux pumps, limiting the effectiveness of cytotoxic drugs or fluorescent tags. It is also used in fluorescent cell sorting for DNA content, as it blocks efflux of a variety of DNA-binding fluorophores such as Hoechst 33342. Radioactively labelled verapamil and positron emission tomography can be used with to measure P-glycoprotein function.[34]

See alsoEdit


  1. ^ a b "Verapamil". Archived from the original on 1 August 2017. Retrieved 14 December 2016.
  2. ^ a b c d e f "Verapamil Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  3. ^ Tfelt-Hansen, PC; Jensen, RH (1 July 2012). "Management of cluster headache". CNS Drugs. 26 (7): 571–80. doi:10.2165/11632850-000000000-00000. PMID 22650381.
  4. ^ Merison, K; Jacobs, H (November 2016). "Diagnosis and Treatment of Childhood Migraine". Current Treatment Options in Neurology. 18 (11): 48. doi:10.1007/s11940-016-0431-4. PMID 27704257.
  5. ^ a b c WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 267. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  6. ^ "Verapamil Use During Pregnancy |". Archived from the original on 21 December 2016. Retrieved 14 December 2016.
  7. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  8. ^ "Verapamil HCL". International Drug Price Indicator Guide. Retrieved 8 December 2016.
  9. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 156. ISBN 9781284057560.
  10. ^ "The Top 300 of 2019". Retrieved 22 December 2018.
  11. ^ Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs 10th edition. USA: LWW. 2012. pp. 497, 1349. ISBN 978-1609137137.
  12. ^ Srinivasan, Viswanathan; Sivaramakrishnan, H; Karthikeyan, B (2011). "Detection, Isolation and Characterization of Principal Synthetic Route Indicative Impurities in Verapamil Hydrochloride". Scientia Pharmaceutica. 79 (3): 555–68. doi:10.3797/scipharm.1101-19. PMC 3163365. PMID 21886903.
  13. ^ James, PA; Oparil, S; Carter, BL; Cushman, WC; Dennison-Himmelfarb, C; Handler, J; Lackland, DT; LeFevre, ML; MacKenzie, TD; Ogedegbe, O; Smith, SC Jr; Svetkey, LP; Taler, SJ; Townsend, RR; Wright, JT Jr; Narva, AS; Ortiz, E (5 February 2014). "2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee (jnc 8)". JAMA. 311 (5): 507–20. doi:10.1001/jama.2013.284427. ISSN 0098-7484. PMID 24352797.
  14. ^ Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs. LWW; Tenth, North American edition. 2012. pp. 320–22. ISBN 978-1609137137.
  15. ^ Trejo, Raul; Sieber, William; Beck, Ellen (15 February 2005). "Management of Cluster Headache". American Family Physician. 71 (4): 717–724. Archived from the original on 13 November 2015. Retrieved 4 November 2015.
  16. ^ Jun, P.; Ko, N. U.; English, J. D.; Dowd, C. F.; Halbach, V. V.; Higashida, R. T.; Lawton, M. T.; Hetts, S. W. (2010). "Endovascular Treatment of Medically Refractory Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage". American Journal of Neuroradiology. 31 (10): 1911–16. doi:10.3174/ajnr.A2183. PMC 4067264. PMID 20616179.
  17. ^ Drislane, Frank; Benatar, Michael; Chang, Bernard S.; Acosta, Juan; Tarulli, Andrew (1 January 2009). Blueprints Neurology. Lippincott Williams & Wilkins. pp. 71–. ISBN 978-0-7817-9685-9. Archived from the original on 8 June 2013. Retrieved 14 November 2010.
  18. ^ a b c d "CALAN (verapamil) Packet Insert" (PDF). Archived (PDF) from the original on 4 March 2016.
  19. ^ "BNF is only available in the UK". NICE. Retrieved 17 May 2019.
  20. ^ "G.D. Searle LLC Division of Pfizer Inc". CALAN – verapamil hydrochloride tablet, Package Insert. Pfizer. October 2013. Archived from the original on 7 September 2015. Retrieved 4 November 2015.
  21. ^ Steele, RM; Schuna, AA; Schreiber, RT (1994). "Calcium antagonist-induced gingival hyperplasia". Annals of Internal Medicine. 120 (8): 663–64. doi:10.7326/0003-4819-120-8-199404150-00006. PMID 8135450.
  22. ^ Wilimowska, Jolanta; Piekoszewski, Wojciech; Krzyanowska-Kierepka, Ewa; Florek, Ewa (2006). "Monitoring of Verapamil Enantiomers Concentration in Overdose". Clinical Toxicology. 44 (2): 169–71. doi:10.1080/15563650500514541. PMID 16615674.
  23. ^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, California: Biomedical Publications. pp. 1637–39.
  24. ^ "Verapamil hydrochloride tablet". DailyMed Archived from the original on 2 February 2016. Retrieved 9 November 2015.
  25. ^ Wang, Shao-Ping; Wang, Jian-An; Luo, Rong-Hua; Cui, Wen-Yu; Wang, Hai (September 2008). "Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation". Clinical and Experimental Pharmacology & Physiology. 35 (9): 1077–1084. doi:10.1111/j.1440-1681.2008.04964.x. ISSN 1440-1681. PMID 18505444.
  26. ^ Giannini, AJ; Houser Jr, WL; Loiselle, RH; Giannini, MC; Price, WA (1984). "Antimanic effects of verapamil". The American Journal of Psychiatry. 141 (12): 1602–03. doi:10.1176/ajp.141.12.1602. PMID 6439057.
  27. ^ Giannini, AJ; Taraszewski, R; Loiselle, RH (1987). "Verapamil and lithium in maintenance therapy of manic patients". Journal of Clinical Pharmacology. 27 (12): 980–82. doi:10.1002/j.1552-4604.1987.tb05600.x. PMID 3325531.
  28. ^ Giannini, A.James; Nakoneczie, Ann M.; Melemis, Stephen M.; Ventresco, James; Condon, Maggie (2000). "Magnesium oxide augmentation of verapamil maintenance therapy in mania". Psychiatry Research. 93 (1): 83–87. doi:10.1016/S0165-1781(99)00116-X. PMID 10699232.
  29. ^ Elferink, Jan G.R.; Deierkauf, Martha (1984). "The effect of verapamil and other calcium antagonists on chemotaxis of polymorphonuclear leukocytes". Biochemical Pharmacology. 33 (1): 35–39. doi:10.1016/0006-2952(84)90367-8. PMID 6704142.
  30. ^ Azzarone, Bruno; Krief, Patricia; Soria, Jeannette; Boucheix, Claude (1985). "Modulation of fibroblast-induced clot retraction by calcium channel blocking drugs and the monoclonal antibody ALB6". Journal of Cellular Physiology. 125 (3): 420–26. doi:10.1002/jcp.1041250309. PMID 3864783.
  31. ^ Steinleitner, Alex; Lambert, Hovey; Kazensky, Carol; Sanchez, Ignacio; Sueldo, Carlos (1990). "Reduction of primary postoperative adhesion formation under calcium channel blockade in the rabbit". Journal of Surgical Research. 48 (1): 42–45. doi:10.1016/0022-4804(90)90143-P. PMID 2296179.
  32. ^ Baxter, Gary M.; Jackman, Bradley R.; Eades, Susan C.; Tyler, David E. (1993). "Failure of Calcium Channel Blockade to Prevent Intra-abdominal Adhesions in Ponies". Veterinary Surgery. 22 (6): 496–500. doi:10.1111/j.1532-950X.1993.tb00427.x. PMID 8116206.
  33. ^ Bellamy, W T (1996). "P-Glycoproteins and Multidrug Resistance". Annual Review of Pharmacology and Toxicology. 36: 161–83. doi:10.1146/ PMID 8725386.
  34. ^ Luurtsema, Gert; Windhorst, Albert D.; Mooijer, Martien P.J.; Herscheid, Jacobus D.M.; Lammertsma, Adriaan A.; Franssen, Eric J.F. (2002). "Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomography". Journal of Labelled Compounds and Radiopharmaceuticals. 45 (14): 1199–207. doi:10.1002/jlcr.632.

External linksEdit