Peringatan Keamanan

Verapamil's reported oral TDLo is 14.4 mg/kg in women and 3.429 mg/kg in men.L10523 The oral LD50 is 150 mg/kg in rats and 163 mg/kg in mice.L10523

As there is no antidote for verapamil overdosage, treatment is largely supportive. Symptoms of overdose are generally consistent with verapamil's adverse effect profile (i.e. hypotension, bradycardia, arrhythmia) but instances of non-cardiogenic pulmonary edema have been observed following ingestion of large overdoses (up to 9 grams).L10478 In acute overdosage, consider the use of gastrointestinal decontamination with cathartics and/or bowel irrigation. Patients presenting with significant myocardial depression may require intravenous calcium, atropine, vasopressors, or other inotropes. Consider the formulation responsible for the overdose prior to treatment - sustained-release formulations may result in delayed pharmacodynamic effects, and these patients should be monitored closely for at least 48 hours following ingestion.L10478

Verapamil

DB00661

small molecule approved

Deskripsi

Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina,L8791 and was the first calcium channel antagonist to be introduced into therapy in the early 1960s.A188514 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.L8791 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.A188435

Struktur Molekul 2D

Berat 454.6016
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (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.[L8791] The elimination half-life is also prolonged in patients with hepatic insufficiency (14 to 16 hours) and in the elderly (approximately 20 hours).[L10478] Intravenously administered verapamil has rapid distribution phase half-life of approximately 4 minutes, followed by a terminal elimination phase half-life of 2 to 5 hours.[L10481]
Volume Distribusi Verapamil has a steady-state volume of distribution of approximately 300L for its R-enantiomer and 500L for its S-enantiomer.[A13983]
Klirens (Clearance) Systemic clearance following 3 weeks of continuous treatment was approximately 340 mL/min for R-verapamil and 664 mL/min for S-verapamil.[A188435] Of note, apparent oral clearance appears to vary significantly between single dose and multiple-dose conditions. The apparent oral clearance following single doses of verapamil was approximately 1007 mL/min for R-verapamil and 5481 mL/min for S-verapamil, whereas 3 weeks of continuous treatment resulted in apparent oral clearance values of approximately 651 mL/min for R-verapamil and 2855 mL/min for S-verapamil.[A188435]

Absorpsi

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.L8791 Absorption kinetic parameters are largely dependent on the specific formulation of verapamil involved. Immediate-release verapamil reaches peak plasma concentrations (i.e. Tmax) between 1-2 hours following administration,L8791 whereas sustained-release formulations tend to have a Tmax between 6 - 11 hours.L10478,L10637 AUC and Cmax values are similarly dependent upon formulation. Chronic administration of immediate-release verapamil every 6 hours resulted in plasma concentrations between 125 and 400 ng/mL.L8791 Steady-state AUC0-24h and Cmax values for a sustained-release formulation were 1037 ng?h/ml and 77.8 ng/mL for the R-isomer and 195 ng?h/ml and 16.8 ng/mL for the S-isomer, respectively.L10478 Interestingly, the absorption kinetics of verapamil are highly stereospecific - following oral administration of immediate-release verapamil every 8 hours, the relative systemic availability of the S-enantiomer compared to the R-enantiomer was 13% after a single dose and 18% at steady-state.L10478

Metabolisme

Verapamil is extensively metabolized by the liver, with up to 80% of an administered dose subject to elimination via pre-systemic metabolism - interestingly, this first-pass metabolism appears to clear the S-enantiomer of verapamil much faster than the R-enantiomer.L10478,A415 The remaining parent drug undergoes O-demethylation, N-dealkylation, and N-demethylation to a number of different metabolites via the cytochrome P450 enzyme system.A415 Norverapamil, one of the major circulating metabolites, is the result of verapamil's N-demethylation via CYP2C8, CYP3A4, and CYP3A5,A415 and carries approximately 20% of the cardiovascular activity of its parent drug.L10478 The other major pathway involved in verapamil metabolism is N-dealkylation via CYP2C8, CYP3A4, and CYP1A2 to the D-617 metabolite. Both norverapamil and D-617 are further metabolized by other CYP isoenzymes to various secondary metabolites. CYP2D6 and CYP2E1 have also been implicated in the metabolic pathway of verapamil, albeit to a minor extent.A415 Minor pathways of verapamil metabolism involve its O-demethylation to D-703 via CYP2C8, CYP2C9, and CYP2C18, and to D-702 via CYP2C9 and CYP2C18.A415 Several steps in verapamil's metabolic pathway show stereoselective preference for the S-enantiomer of the given substrate, including the generation of the D-620 metabolite by CYP3A4/5 and the D-617 metabolite by CYP2C8.A415

Rute Eliminasi

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.L8791

Farmakogenomik

1 Varian
ADRB1 (rs1801253)

Patients with this genotype require a lower dosage of verapamil to achieve a favourable rate-control response when treating atrial fibrillation.

Interaksi Makanan

3 Data
  • 1. Avoid alcohol. Verapamil significantly inhibits the elimination of alcohol, leading to elevated blood alcohol levels.
  • 2. Avoid grapefruit products. Co-administration with grapefruit may significantly increase serum concentrations.
  • 3. Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

Interaksi Obat

2065 Data
Duloxetine The risk or severity of orthostatic hypotension and syncope can be increased when Verapamil is combined with Duloxetine.
Levodopa The risk or severity of hypotension and orthostatic hypotension can be increased when Verapamil is combined with Levodopa.
Afatinib The serum concentration of Afatinib can be increased when it is combined with Verapamil.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Verapamil.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Verapamil.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Verapamil.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Verapamil.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Verapamil.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Verapamil.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Verapamil.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Verapamil.
Silodosin The excretion of Silodosin can be decreased when combined with Verapamil.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Verapamil.
Ceritinib Verapamil may increase the bradycardic activities of Ceritinib.
Ruxolitinib Ruxolitinib may increase the bradycardic activities of Verapamil.
Deferasirox The serum concentration of Verapamil can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Verapamil can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Verapamil can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Verapamil can be decreased when it is combined with Teriflunomide.
Dabrafenib The serum concentration of Verapamil can be decreased when it is combined with Dabrafenib.
Brexpiprazole The metabolism of Brexpiprazole can be decreased when combined with Verapamil.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Verapamil.
Flibanserin The metabolism of Flibanserin can be decreased when combined with Verapamil.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Verapamil.
Ivabradine The metabolism of Ivabradine can be decreased when combined with Verapamil.
Ivacaftor The metabolism of Ivacaftor can be decreased when combined with Verapamil.
Lurasidone The metabolism of Lurasidone can be decreased when combined with Verapamil.
Olaparib The metabolism of Olaparib can be decreased when combined with Verapamil.
Sonidegib The metabolism of Sonidegib can be decreased when combined with Verapamil.
Avanafil The metabolism of Avanafil can be decreased when combined with Verapamil.
Eplerenone The metabolism of Eplerenone can be decreased when combined with Verapamil.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Verapamil.
Dofetilide The serum concentration of Dofetilide can be increased when it is combined with Verapamil.
Cilostazol The metabolism of Cilostazol can be decreased when combined with Verapamil.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Verapamil.
Fentanyl The metabolism of Fentanyl can be decreased when combined with Verapamil.
Iloperidone The risk or severity of hypotension can be increased when Verapamil is combined with Iloperidone.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Verapamil.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Verapamil.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Verapamil.
Eszopiclone The metabolism of Eszopiclone can be decreased when combined with Verapamil.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Verapamil.
Lovastatin The risk or severity of myopathy and rhabdomyolysis can be increased when Verapamil is combined with Lovastatin.
Cimetidine The serum concentration of Verapamil can be increased when it is combined with Cimetidine.
Clopidogrel The therapeutic efficacy of Clopidogrel can be decreased when used in combination with Verapamil.
Efavirenz The serum concentration of Verapamil can be decreased when it is combined with Efavirenz.
Melatonin The therapeutic efficacy of Verapamil can be decreased when used in combination with Melatonin.
Nafcillin The therapeutic efficacy of Verapamil can be decreased when used in combination with Nafcillin.
Nitroprusside Verapamil may increase the hypotensive activities of Nitroprusside.
Disopyramide The risk or severity of sinus node depression can be increased when Verapamil is combined with Disopyramide.
Dantrolene The risk or severity of hyperkalemia can be increased when Dantrolene is combined with Verapamil.
Lithium citrate The risk or severity of adverse effects can be increased when Verapamil is combined with Lithium citrate.
Lithium carbonate The risk or severity of adverse effects can be increased when Verapamil is combined with Lithium carbonate.
Lithium hydroxide The risk or severity of adverse effects can be increased when Verapamil is combined with Lithium hydroxide.
Dapoxetine The metabolism of Dapoxetine can be decreased when combined with Verapamil.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Verapamil.
Mifepristone The metabolism of Mifepristone can be decreased when combined with Verapamil.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Verapamil.
Simvastatin The risk or severity of myopathy and rhabdomyolysis can be increased when Verapamil is combined with Simvastatin.
Atorvastatin The serum concentration of Verapamil can be increased when it is combined with Atorvastatin.
Dabigatran etexilate The serum concentration of Dabigatran etexilate can be increased when it is combined with Verapamil.
Fingolimod The risk or severity of bradycardia can be increased when Verapamil is combined with Fingolimod.
Flecainide The risk or severity of adverse effects can be increased when Verapamil is combined with Flecainide.
Risperidone The serum concentration of Risperidone can be increased when it is combined with Verapamil.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Verapamil.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Verapamil.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Verapamil.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Verapamil.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol 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.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Verapamil.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Verapamil.
Boceprevir The serum concentration of Verapamil can be increased when it is combined with Boceprevir.
Abiraterone The serum concentration of Verapamil can be increased when it is combined with Abiraterone.
Nicorandil Nicorandil may increase the hypotensive activities of Verapamil.
Vincristine The excretion of Vincristine can be decreased when combined with Verapamil.
Cyproterone acetate The metabolism of Verapamil can be increased when combined with Cyproterone acetate.
Lumacaftor The serum concentration of Verapamil can be decreased when it is combined with Lumacaftor.
Tiracizine Verapamil may increase the arrhythmogenic activities of Tiracizine.
Ethacizine Verapamil may increase the arrhythmogenic activities of Ethacizine.
Hydroquinine Verapamil may increase the arrhythmogenic activities of Hydroquinine.
Bioallethrin Verapamil may increase the arrhythmogenic activities of Bioallethrin.
Fosfructose Verapamil may increase the arrhythmogenic activities of Fosfructose.
Hydroquinidine Verapamil may increase the arrhythmogenic activities of Hydroquinidine.
Acetyldigitoxin Acetyldigitoxin may increase the arrhythmogenic activities of Verapamil.
Deslanoside Verapamil may increase the arrhythmogenic activities of Deslanoside.
Cymarin Verapamil may increase the arrhythmogenic activities of Cymarin.
Xylometazoline Verapamil may increase the arrhythmogenic activities of Xylometazoline.
Methsuximide Verapamil may increase the arrhythmogenic activities of Methsuximide.
Nylidrin Verapamil may increase the arrhythmogenic activities of Nylidrin.
Fasudil Verapamil may increase the arrhythmogenic activities of Fasudil.
SOR-C13 Verapamil may increase the arrhythmogenic activities of SOR-C13.
Nimodipine Nimodipine may increase the arrhythmogenic activities of Verapamil.
Cinnarizine Cinnarizine may increase the arrhythmogenic activities of Verapamil.
Adenosine Adenosine may increase the arrhythmogenic activities of Verapamil.
Levosimendan Verapamil may increase the arrhythmogenic activities of Levosimendan.
Prenylamine Verapamil may increase the arrhythmogenic activities of Prenylamine.
Fluspirilene Verapamil may increase the arrhythmogenic activities of Fluspirilene.
Azimilide Verapamil may increase the arrhythmogenic activities of Azimilide.
Tedisamil Verapamil may increase the arrhythmogenic activities of Tedisamil.

Target Protein

Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C
Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B
Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A
ATP-sensitive inward rectifier potassium channel 11 KCNJ11
Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G
Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H
Voltage-gated inwardly rectifying potassium channel KCNH2 KCNH2
Sodium-dependent serotonin transporter SLC6A4
Alpha-1A adrenergic receptor ADRA1A
Alpha-1B adrenergic receptor ADRA1B
Alpha-1D adrenergic receptor ADRA1D
Voltage-dependent calcium channel CACNG1
ATP-dependent translocase ABCB1 ABCB1

Referensi & Sumber

Synthesis reference: Philippe Baudier, Arthur De Boeck, Jacques Fossion, "Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms." U.S. Patent US4859469, issued April, 1987.
Artikel (PubMed)
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    Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83.
  • PMID: 1956867
    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.
  • PMID: 16892180
    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.
  • PMID: 19125880
    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.
  • PMID: 11372000
    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.
  • PMID: 12883317
    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.
  • PMID: 21149638
    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.
  • PMID: 18974361
    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.
Menampilkan 8 dari 16 artikel.

Contoh Produk & Brand

Produk: 437 • International brands: 11
Produk
  • Alti-verapamil - 120mg
    Tablet • 120 mg • Oral • Canada • Generic • Approved
  • Alti-verapamil - 80mg
    Tablet • 80 mg • Oral • Canada • Generic • Approved
  • Apo-verap SR
    Tablet, extended release • 120 mg • Oral • Canada • Generic • Approved
  • Apo-verap SR
    Tablet, extended release • 180 mg • Oral • Canada • Generic • Approved
  • Apo-verap SR
    Tablet, extended release • 240 mg • Oral • Canada • Generic • Approved
  • Apo-verap Tab 80mg
    Tablet • 80 mg • Oral • Canada • Generic • Approved
  • Apo-verap Tablet 120mg
    Tablet • 120 mg • Oral • Canada • Generic • Approved
  • Calan
    Tablet, film coated • 120 mg/1 • Oral • US • Approved
Menampilkan 8 dari 437 produk.
International Brands
  • Bosoptin — Bosnalijek
  • Isoptin — Abbott
  • Verisop — Gerard
  • Vermin — Ratiopharm
  • Vermine — Pharmasant
  • Verogalid — Ivax
  • Verogalid ER — Ivax
  • Verpamil — Mylan
  • Vertab — Trinity-Chiesi
  • Vetrimil — CCPC

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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