Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers

Fleishaker, Joseph C.; Sisson, Theresa A.; Carel, Barbara J.; Azie, Nkechi

doi:10.1067/mcp.2000.106292

Cited by 39 publications

(23 citation statements)

References 9 publications

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“…Clinical studies have shown that verapamil inhibits the metabolism of CYP3A substrates, such as midazolam, cyclosporin A, simvastatin, buspirone, and almotriptan (Robson et al, 1988;Backman et al, 1994;Kantola et al, 1998;Lamberg et al, 1998;Fleishaker et al, 2000). However, the mechanism of verapamil-mediated drug interactions has been unclear.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Cytochrome P450 3a Inhibition by Verapamil Enantiomers and Their Metabolites

Wang¹,

Jones²,

Hall³

2004

Drug Metab Dispos

190

195

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Section: Discussionmentioning

confidence: 99%

Prediction of Cytochrome P450 3a Inhibition by Verapamil Enantiomers and Their Metabolites

Wang¹,

Jones²,

Hall³

2004

Drug Metab Dispos

190

195

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“…The N-demethylation and N-oxidation of the dimethylaminoethyl group are minor metabolic reactions both in vitro and in vivo. Different clinical trials conducted to study the effect of CYP3A4, CYP2D6, and MAO-A on the pharmacokinetics of almotriptan showed that verapamil and fluoxetine modestly inhibited almotriptan clearance, a result consistent with the assignement of CYP3A4 and CYP2D6 as the enzymes responsible for the oxidation of the pyrrolidine moiety (Fleishaker et al, 2000(Fleishaker et al, , 2001a. Moreover, moclobemide increased plasma concentrations of almotriptan by 37%, thus confirming that oxidative deamination of almotriptan by MAO-A was the major route of metabolism and that the degree of interaction was much less than that seen previously for sumatriptan, rizatriptan, or zolmitriptan given with moclobemide (Fleishaker et al, 2001b).…”

mentioning

confidence: 79%

Identification of the Human Liver Enzymes Involved in the Metabolism of the Antimigraine Agent Almotriptan

Salvà

Jansat²,

Martinez-Tobed³

et al. 2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Almotriptan is a novel highly selective 5-hydroxytryptamine 1B/1D agonist developed for the acute oral treatment of migraine. The in vitro metabolism of almotriptan has been investigated using human liver subcellular fractions and cDNA-expressed human enzymes, to study the metabolic pathways and identify the enzymes responsible for the formation of the major metabolites.

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“…Therefore, CYP 3A4 inducers and inhibitors are likely to result in decreased and increased plasma levels of verapamil, respectively [30–32]. Co-medication with other drugs indicated in CH such as triptans, prednisolone or ergotamine, which are also metabolized by CYP 3A4, could induce a drug–drug interaction with verapamil [33, 34]. Verapamil is also a probe inhibitor of transporter P-glycoprotein (P-gp).…”

Section: Discussionmentioning

confidence: 99%

High-Dose Verapamil in Episodic and Chronic Cluster Headaches and Cardiac Adverse Events: Is It as Safe as We Think?

Alexandre

Humbert

Sassier

et al. 2015

Drug Saf - Case Rep

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Cluster headache (CH) is a primary headache disorder with relatively effective treatments. Although few sufficiently controlled trials are available, verapamil is recommended as the first-line prophylactic drug for CH by the French Headache Society (with a low level of evidence, level B) and by the EFNS (European Federation of Neurological Societies, level A). Daily doses of more than 480 mg (and up to 1200 mg daily) are frequently used off-label, while 360 mg daily is the only dosage to have demonstrated its effectiveness in a double-blind trial against placebo, and the usual label posology used by cardiologists is 240 mg daily in hypertension. We report the case of a 19-year-old man who was self-reported to our cardiology consultation for dyspnea and asthenia for 18 months. His medical history consisted of CH crisis for 4 years treated by verapamil 720 mg/day for 18 months with relatively good efficiency. His electrocardiogram (ECG) showed a sinus bradycardia at 40 bpm with a first-degree atrio-ventricular block. Evolution was favorable after progressive verapamil discontinuation. Analysis performed on the French Pharmacovigilance Database between July 1, 2000 and December 1, 2014 found four other cases of cardiac adverse events related to high-dose verapamil used in CH prevention (two cases of syncope with complete atrio-ventricular block with verapamil 1200 and 240 mg daily, respectively, one syncope related to sick sinus syndrome with verapamil 360 mg daily, and one case of sinus bradycardia with verapamil 720 mg daily). Although available studies seem to demonstrate an apparent good tolerance, this off-label practice should not be considered as standard of care and requires strict cardiac monitoring, as suggested by the Agence Nationale de Sécurité du Médicament (ANSM) in a recent re-evaluation of the benefit/risk ratio of high-dose verapamil used in CH prevention.

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Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers

Cited by 39 publications

References 9 publications

Prediction of Cytochrome P450 3a Inhibition by Verapamil Enantiomers and Their Metabolites

Prediction of Cytochrome P450 3a Inhibition by Verapamil Enantiomers and Their Metabolites

Identification of the Human Liver Enzymes Involved in the Metabolism of the Antimigraine Agent Almotriptan

High-Dose Verapamil in Episodic and Chronic Cluster Headaches and Cardiac Adverse Events: Is It as Safe as We Think?

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