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Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Verapamil has been shown to be an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Methadone: Verapamil may increase methadone serum concentrations via inhibition of CYP3A4 metabolism of methadone. Inhibition of methadone metabolism can lead to toxicity including CNS adverse effects and potential for QT prolongation and torsades de pointes when high doses of methadone are used. Methamphetamine: Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium channel blockers.
Methohexital: Barbiturates have been shown to enhance the hepatic clearance of verapamil. Methoxsalen: Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylergonovine: Because of its potential to cause coronary vasospasm, methylergonovine could theoretically antagonize the therapeutic effects of calcium-channel blockers.
Imatinib, STI-571: Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including verapamil. Imipramine serum concentrations are suggested to monitor imipramine therapy when adding verapamil therapy or changing verapamil dosage. Indacaterol: Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and verapamil are used concurrently. By inhibiting CYP3A4 and P-gp, verapamil alters indacaterol metabolism.
In drug interaction studies, coadministration of indacaterol 300 mcg single dose with verapamil 80 mcg 3 times daily for 4 days resulted in a 2-fold increase in indacaterol AUC 0-24and 1.
Indinavir: Coadministration of ritonavir with verapamil may increase the serum concentrations of verapamil, potentially resulting in verapamil toxicity. Indomethacin: If nonsteroidal anti-inflammatory drugs NSAIDs and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Isavuconazonium: Concomitant use of isavuconazonium with verapamil may result in increased serum concentrations of both drugs.
Isocarboxazid: Additive hypotensive effects may be seen when monoamine oxidase inhibitors MAOIs are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Dosages of verapamil may need to be adjusted while the patient is receiving rifampin. Isoproterenol: The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
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Phenelzine: Additive hypotensive effects may be seen when monoamine oxidase inhibitors MAOIs are combined with antihypertensives. Phenobarbital: Barbiturates have been shown to enhance the hepatic clearance of verapamil. Phenoxybenzamine: Additive pharmacodynamic effects are especially prominent when verapamil is co-administered with alpha-blockers or beta-blockers. Phentolamine: Additive pharmacodynamic effects are especially prominent when verapamil is co-administered with alpha-blockers.
Phenylephrine: Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Photosensitizing agents: Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Pimozide: Concurrent use of pimozide and verapamil should be avoided. Pimozide is metabolized primarily through CYP3A4, and verapamil is a CYP3A4 inhibitor.
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Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. There are many drug interactions that can potentiate the effects of antihypertensives. Congestive heart failure or severe hypotension also can occur. The combination of beta-blockers and verapamil should be avoided in patients with poor ventricular function due to increased negative inotropic effects. The exact mechanism and clinical significance of this interaction is unknown.
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Co-administration with verapamil may lead to an increase in serum levels of drugs that are CYP3A4 substrates including ethosuximide. Etodolac: If nonsteroidal anti-inflammatory drugs NSAIDs and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Etomidate: The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers.
Etonogestrel: Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as verapamil may increase the serum concentration of etonogestrel.
Etoposide, VP-16: Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with verapamil. Coadministration may cause accumulation of etoposide and decreased metabolism, resulting in increased etoposide concentrations. Concurrent administration of verapamil, a moderate CYP3A4 inhibitor and Pgp inhibitor, and everolimus increased everolimus Cmax and AUC 2.
In addition, verapamil is a substrate of CYP3A4 and Pgp.
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If indicated, dosage of the antihypertensive agents should be reduced.
Verapamil should be used cautiously in patients with GI obstruction or ileus, fecal impaction, or pre-existing constipation.
Metoprolol: Verapamil can inhibit the metabolism of some beta-blockers e.
Atazanavir: Coadministration of ritonavir with verapamil may increase the serum concentrations of verapamil, potentially resulting in verapamil toxicity.
Research studies with animals found harmful effects on unborn babies. Talk with your doctor. Skip to side effects section.
Our bottom lineVerapamil works well to lower blood pressure and prevent chest pain, but you have to be okay with avoiding alcohol.
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The addition of verapamil to high-dose beta-blockers induced modest negative inotropic and chronotropic effects that were not severe enough to limit short-term 48 hours combination therapy in this study.
Ibuprofen lysine: NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways.