Moderate Use caution if cyclophosphamide is used concomitantly with verapamil, and monitor for possible changes in the efficacy or toxicity profile of cyclophosphamide or a loss of blood pressure control. The clinical significance of this interaction is unknown.
The absorption of verapamil can be reduced by the cyclophosphamide, vincristine, procarbazine, prednisone COPP chemotherapeutic drug regimen. Also, cyclophosphamide is a prodrug that is hydroxylated and activated primarily by CYP2B6; the contribution of CYP3A4 to the activation of cyclophosphamide is variable.
N-dechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via CYP3A4. The active metabolites, 4-hydroxycyclophosphamide and aldophosphamide, are then inactivated by aldehyde dehydrogenase-mediated oxidation.
Verapamil is a moderate CYP3A4 inhibitor; conversion of cyclophosphamide to its active metabolites may be affected. In vitro, coadministration with troleandomycin, a CYP3A4 inhibitor, had little-to-no effect on cyclophosphamide metabolism. Moderate Coadministration of verapamil with cyclosporine can lead to increased cyclosporine concentrations and toxicity. Verapamil inhibits CYP3A4 metabolism and thereby can increase the serum concentrations of cyclosporine.
Verapamil should be used cautiously in patients stabilized on cyclosporine; cyclosporine dosage reduction may be required. Moderate Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein P-gp substrate, is coadministered with verapamil, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran while taking products containing verapamil including trandolapril; verapamil.
Concomitant administration of verapamil and dabigatran results in an increased Cmax and AUC of dabigatran; the extent depends on the formulation of verapamil and timing of administration. The greatest increase in exposure of dabigatran occurs when verapamil is present in the gut when dabigatran is taken. In a pharmacokinetic study, immediate-release verapamil given 1 hour prior to dabigatran administration produced the greatest increase in exposure.
If verapamil is administered 2 hours after dabigatran administration, the increase in AUC is negligible. Data from the RE-LY trial indicate no significant changes in dabigatran trough concentrations were seen in patients who received concomitant therapy with verapamil. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. In addition, the therapeutic effects of verapamil, a P-glycoprotein P-gp substrate, may be increased by daclatasvir, a P-gp inhibitor.
If these drugs are administered together, monitor patients for adverse effects, such as hypotension, headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. Moderate Dalfopristin; quinupristin is a major inhibitor of cytochrome P 3A4 and may decrease the elimination of drugs metabolized by this enzyme including verapamil. Moderate Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension.
Co-administration with verapamil may lead to an increase in serum levels of drugs that are CYP3A4 substrates, including darifenacin. Moderate As darunavir is a CYP3A substrate and inhibitor, interactions with calcium-channel blockers may occur. Complex interactions can be expected with coadministered with diltiazem or verapamil, as both are substrates and inhibitors of CYP3A4. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Moderate Concurrent administration of verapamil with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of all 5 drugs.
A verapamil dose reduction and close monitoring for adverse events i. If adverse events are observed, consider further verapamil dose reductions or an alternative to the calcium channel blocker.
Verapamil also inhibits the drug transporter P-glycoprotein P-gp ; dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Moderate Concurrent administration of verapamil with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of both drugs.
Moderate Concurrent administration of verapamil with ritonavir may result in elevated plasma concentrations of both drugs. Both verapamil and ritonavir are substrates and inhibitors of CYP3A4. Verapamil also inhibits the drug transporter P-glycoprotein P-gp ; ritonavir is a substrate of P-gp. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval including calcium channel blockers has not been evaluated.
If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Verapamil is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide single dose of 0. Although specific drug interaction studies of deferasirox and verapamil are not available, a similar interaction may occur. The dose of verapamil may need to be decreased if coadministered with deferasirox.
Major Decrease deflazacort dose to one third of the recommended dosage when coadministered with verapamil. Concurrent use may significantly increase concentrations of desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Moderate Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as verapamil, should be expected with concurrent use of delavirdine. Moderate Concomitant administration of dexmedetomidine and calcium-channel blockers could lead to additive hypotension and bradycardia; use together with caution.
Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that may lower the heart rate such as calcium-channel blockers. Moderate Dexmethylphenidate can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Periodic evaluation of blood pressure is advisable during concurrent use of dexmethylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of dexmethylphenidate. Major Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine.
Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed.
In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral alpha -blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension.
It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects. Moderate Verapamil inhibits CYP3A4 metabolism, and therefore may inhibit the metabolism of oxidized benzodiazepines, including diazepam. Moderate Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents.
This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Serum estrogen concentrations and estrogenic-related side effects e. Major Diethylpropion has vasopressor effects and may limit the benefit of calcium-channel blockers.
Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Measure serum digoxin concentrations before initiating verapamil. In addition to serum concentration information, the manufacturer of verapamil recommends adjusting the digoxin dosage according to clinical response, since digoxin serum concentrations may not accurately reflect response. Digoxin is a substrate for P-glycoprotein P-gp. Verapamil inhibits P-gp, an energy-dependent cellular drug efflux pump.
The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that verapamil inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations.
Both drugs slow conduction through the AV node, and for this reason, these drugs are sometimes used together for ventricular control in patients with atrial fibrillation or flutter. Additionally, the effect of verapamil on the pharmacokinetics of digoxin is magnified in patients with hepatic cirrhosis.
Moderate Be alert for symptoms of ergot toxicity if using dihydroergotamine and verapamil together is medically necessary. Concomitant use of verapamil, a CYP3A4 inhibitor, and dihydroergotamine, a CYP3A4 substrate with a narrow therapeutic range, may result in increased ergot alkaloid levels. Severe Disopyramide and verapamil should not be used concomitantly due to potential for additive negative inotropic effects which could result in left ventricular impairment. Avoid disopyramide administration within 48 hours before or 24 hours after verapamil administration.
In addition, verapamil can theoretically inhibit the CYP3A4 metabolism of disopyramide. Concurrent use of verapamil and dofetilide was also associated with a higher occurrence of torsade de pointes in dofetilide clinical trials.
Concurrent use may result in additive effects. Moderate Close clinical monitoring is advised when administering verapamil with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways.
Verapamil is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. The clinical effect of this interaction on the response to donepezil has not been determined. Moderate Additive pharmacodynamic effects are especially prominent when verapamil is co-administered with alpha-blockers.
The use of alpha-blockers with verapamil can lead to excessive hypotension. Moderate Cytochrome P enzyme inhibitors, such as verapamil, may inhibit the hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Major Avoid the concomitant use of doxorubicin and verapamil; use of these drugs together may increase doxorubicin concentrations and increase the risk of doxorubicin-induced toxicity.
Major Use caution if coadministration of dronabinol with verapamil is necessary, and monitor for an increase in dronabinol-related adverse reactions e.
Concomitant use may result in elevated plasma concentrations of dronabinol. Major If coadministered with dronedarone, initiate verapamil at a low dose and increase only after ECG verification of good tolerability. Both verapamil and dronedarone are substrates and moderate CYP3A4 inhibitors; increased exposure to both drugs may occur. Additionally, the conduction effects of dronedarone may be potentiated by concurrent use of calcium channel blockers with depressant effects on the sinus and AV nodes.
Minor Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients. Drospirenone; Ethinyl Estradiol; Levomefolate: Moderate Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
The clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor verapamil. Moderate The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects.
In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein P-gp substrate and verapamil is a P-gp inhibitor.
Increased concentrations of edoxaban may occur during concomitant use of verapamil; monitor for increased adverse effects of edoxaban. Moderate Use caution and careful monitoring when coadministering efavirenz with calcium-channel blockers; efavirenz induces CYP3A4, potentially altering serum concentrations of drugs metabolized by this enzyme such as some calcium-channel blockers. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates e.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Moderate Administering elbasvir; grazoprevir with verapamil may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects i. Verapamil is a substrate and moderate inhibitor of CYP3A.
If these drugs are used together, closely monitor for signs of hepatotoxicity. Moderate Monitor for increased eletriptan-related adverse effects if coadministered with verapamil. Coadministration of verapamil increased the eletriptan AUC by 3-fold in a drug interaction study. The coadministration of eliglustat with both verapamil and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Coadministration of eliglustat with CYP3A inhibitors, such as verapamil, may increase eliglustat exposure and the risk of serious adverse events e.
In addition, coadministration of eliglustat with P-gp substrates e. Moderate Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control. Emtricitabine; Rilpivirine; Tenofovir alafenamide: Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: Emtricitabine; Tenofovir disoproxil fumarate: Major Avoid coadministration of encorafenib and verapamil due to increased encorafenib exposure.
If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of verapamil. If verapamil is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of verapamil. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib 0.
Major 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. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Moderate Monitor blood pressure and heart rate if coadministration of verapamil with enzalutamide is necessary. Major The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. Major Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant treatment with epirubicin and calcium-channel blockers.
Individuals receiving these medications concurrently are at increased risk of developing heart failure. Major Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response.
In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Verapamil is a CYP3A4 inhibitor. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. Moderate Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents.
This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response. Co-administration with verapamil may lead to an increase in serum levels of drugs that are CYP3A4 substrates, such as ergoloid mesylates. Major Because of its potential to cause coronary vasospasm, ergonovine could theoretically antagonize the therapeutic effects of anti-anginal agents including calcium-channel blockers.
In addition, calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, and verapamil, may also reduce the hepatic metabolism of ergonovine and increase the risk of ergot toxicity. Major Avoid coadministration of erlotinib with verapamil if possible due to the increased risk of erlotinib-related adverse reactions.
If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Major Avoid administration of erythromycin and a calcium-channel blocker, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving calcium-channel blocker therapy. Erythromycin may also decrease the clearance of calcium-channel blockers e.
Concurrent use of erythromycin with diltiazem and verapamil has been associated with sudden cardiac death. This interaction is likely due to the combined inhibition of CYP3A by erythromycin and the calcium channel blockers leading to increases in the serum concentrations of erythromycin and the calcium channel blockers.
Moderate Oral calcium-channel blockers and beta-blockers like esmolol are used together for their therapeutic benefits to reduce angina and improve exercise tolerance. Moderate Verapamil is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Major Verapamil has been found to significantly inhibit ethanol elimination resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol. The patient may experience an increase in sedation, dizziness, hypotension, and CNS depression. Advise the patient to limit alcohol ingestion during verapamil therapy.
Ethinyl Estradiol; Ethynodiol Diacetate: Minor Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as verapamil may increase the serum concentration of etonogestrel.
Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: Ethinyl Estradiol; Norethindrone Acetate: Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Co-administration with verapamil may lead to an increase in serum levels of drugs that are CYP3A4 substrates including ethosuximide. Major 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. Caution is warranted if these drugs are coadministered. Major A dose adjustment of everolimus is necessary when prescribed with verapamil due to increased plasma concentrations of everolimus.
For patients with breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiolipoma with tubular sclerosis complex TSC , reduce the dose of Afinitor to 2. If verapamil is discontinued, increase everolimus to its original dose after 3 days. Change to every other day dosing if the reduced dose is lower than the lowest available strength.
Zortress dosing for prophylaxis of organ rejection should be guided by TDM. Coadministration with verapamil increased everolimus exposure by 3. Carefully weigh the benefits of combined use of verapamil and simvastatin against the potential risks. Verapamil increases the simvastatin exposure by approximately 2-fold.
The interaction is presumed due to increased simvastatin bioavailability via inhibition of CYP3A4 metabolism and reduction of first-pass metabolism by verapamil. Moderate Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of verapamil is necessary. If verapamil is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a sensitive CYP3A4 substrate, and coadministration with a CYP3A4 inhibitor like verapamil can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl.
If verapamil is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl. Moderate Fesoterodine is rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4.
In theory, the CYP3A4 inhibitory effects of verapamil may result in an increase in plasma concentrations of 5-hydroxymethyltolterodine. Major If possible, do not start fingolimod in a patient who is taking a drug that slows the heart rate or atrioventricular conduction such as verapamil.
Use of these drugs during fingolimod initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating fingolimod.
After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients who cannot stop taking drugs that slow the heart rate or atrioventricular conduction. Experience with fingolimod in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction is limited. Major Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction.
A study in healthy volunteers has shown that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Severe The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as verapamil, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope.
If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. Moderate Fluconazole may decrease the clearance of calcium-channel blockers, including verapamil, via inhibition of CYP3A4 metabolism.
Moderate Fluoxetine may decrease the clearance of calcium-channel blockers, including verapamil, via inhibition of CYP3A4 metabolism. Moderate Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Moderate CYP3A4 inhibitors, such as verapamil, may reduce the metabolism of flurazepam and increase the potential for benzodiazepine toxicity. Moderate Umeclidinium is a P-gp substrate. When verapamil, a moderate P-gp transporter inhibitor, was given to healthy adult subjects at a dose of mg once daily in combination with umeclidinium, no effect on umeclidinium Cmax was observed.
However, an approximately 1. Moderate The incidence of marijuana associated adverse effects may change following coadministration with verapamil. Verapamil is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, deltatetrahydrocannabinol DeltaTHC. Major Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and verapamil are used concomitantly; this also applies to trandolapril; verapamil. Gefitinib is metabolized significantly by CYP3A4 and verapamil is a moderate CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations.
Minor In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available. Moderate Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result.
Moderate Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme.
More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result. Moderate Caution is advised with the coadministration of glecaprevir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and verapamil are both substrates and inhibitors of P-glycoprotein P-gp. Moderate Caution is advised with the coadministration of pibrentasvir and verapamil as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects.
Pibrentasvir and verapamil are both substrates and inhibitors of P-glycoprotein P-gp. Major Grapefruit juice contains an unknown compound that can inhibit the cytochrome P CYP3A4 isozyme in the gut wall.
Grapefruit juice can increase the serum concentrations and oral bioavailability of verapamil. Co-administration of oral verapamil with grapefruit juice significantly increases the AUC and peak plasma concentrations of verapamil.
It is generally recommended to avoid grapefruit juice during verapamil therapy. During concomitant therapy with verapamil, it may be prudent to advise patients to limit or minimize the intake of caffeinated products such as green tea.
Major Verapamil may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release ER guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release IR guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia.
Upon verapamil discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Minor Caffeine is an active component of guarana.
Verapamil reduces the clearance of caffeine and increases serum caffeine concentrations, presumably via inhibition of hepatic metabolism. During concomitant therapy with verapamil, it may be prudent to advise patients to limit or minimize the intake of caffeinated products such as guarana and beverages including coffee, teas, or colas in an effort to minimize caffeine-related side effects.
Moderate Drugs which significantly inhibit cytochrome CYP3A4, such as verapamil, may lead to an inhibition of halofantrine metabolism, placing the patient at risk for halofantrine cardiac toxicity.
If concurrent use of halofantrine and a CYP3A4 inhibitor is warranted, it would be prudent to use caution and monitor the ECG periodically. Moderate In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. Verapamil is a substrate and inhibitor of CYP3A4. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6.
Moderate Hawthorn, Crataegus laevigata also known as C. Following hawthorn administration, the cardiac action potential duration is increased and the refractory period is prolonged. Hawthorn may also lower peripheral vascular resistance. Patients with hypertension or heart failure should be advised to only use hawthorn with their prescribed medications after discussion with their prescriber. Patients who choose to take hawthorn should receive periodic blood pressure and heart rate monitoring.
Moderate Hydantoin anticonvulsants i. Patients receiving verapamil should be monitored for loss of therapeutic effect if any hepatic enzyme inducing drugs are added to their treatment regimen.
Moderate Verapamil can inhibit the metabolism of some beta-blockers e. Oral calcium-channel blockers and beta-blockers are used together for their therapeutic benefits to reduce angina and improve exercise tolerance. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: The metabolism of progesterone is inhibited by ketoconazole, a known inhibitor of cytochrome P 3A4 hepatic enzymes.
Theoretically, the metabolism of hydroxyprogesterone may also be inhibited by ketoconazole. It has not been determined whether other drugs which inhibit CYP3A4 hepatic enzymes, like verapamil, would have a similar effect. Resume ibrutinib at the previous dose if verapamil is discontinued. Monitor patients for ibrutinib toxicity e. Moderate Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents.
If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position.
Moderate Imatinib is a potent inhibitor of cytochrome P 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. Minor Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and verapamil are used concurrently. In drug interaction studies, coadministration of indacaterol mcg single dose with verapamil 80 mcg 3 times daily for 4 days resulted in a 2-fold increase in indacaterol AUC , and 1.
Moderate Concomitant use of isavuconazonium with verapamil may result in increased serum concentrations of both drugs. Verapamil is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein P-gp ; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp.
Moderate 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. Major Rifampin is a potent inducer of the cytochrome P hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of verapamil.
Dosages of verapamil may need to be adjusted while the patient is receiving rifampin. You should not breast-feed while using this medicine. How should I take verapamil? Take verapamil exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose.
Do not use this medicine in larger or smaller amounts or for longer than recommended. Do not crush, chew, or break an extended-release tablet or capsule. If you have trouble swallowing an extended-release capsule whole, ask your doctor or pharmacist if it is safe for you to open the capsule and sprinkle the medicine into a spoonful of applesauce to make swallowing easier.
Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule. Your blood pressure will need to be checked often. Your kidney or liver function may also need to be checked. If you need surgery, tell the surgeon ahead of time that you are using this medicine.
You should not stop using verapamil suddenly. Stopping suddenly may make your condition worse. If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life. Digitalis Clinical use of verapamil in digitalized patients has shown the combination to be well tolerated if digoxin doses are properly adjusted.
In patients with hepatic cirrhosis, the influence of verapamil on digoxin kinetics is magnified. Maintenance and digitalization doses should be reduced when verapamil is administered, and the patient should be reassessed to avoid over- or under-digitalization.
Whenever over-digitalization is suspected, the daily dose of digitalis should be reduced or temporarily discontinued. On discontinuation of Calan use, the patient should be reassessed to avoid under-digitalization. Antihypertensive agents Verapamil administered concomitantly with oral antihypertensive agents e.
Patients receiving these combinations should be appropriately monitored. Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in a reduction in blood pressure that is excessive in some patients.
Such an effect was observed in one study following the concomitant administration of verapamil and prazosin. Antiarrhythmic agents Disopyramide Until data on possible interactions between verapamil and disopyramide are obtained, disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.
Flecainide A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of atrioventricular conduction.
Quinidine In a small number of patients with hypertrophic cardiomyopathy IHSS , concomitant use of verapamil and quinidine resulted in significant hypotension. Until further data are obtained, combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided. The electrophysiologic effects of quinidine and verapamil on AV conduction were studied in 8 patients.
Verapamil significantly counteracted the effects of quinidine on AV conduction. There has been a report of increased quinidine levels during verapamil therapy.
Other agents Nitrates Verapamil has been given concomitantly with short- and long-acting nitrates without any undesirable drug interactions. The pharmacologic profile of both drugs and the clinical experience suggest beneficial interactions. Cimetidine The interaction between cimetidine and chronically administered verapamil has not been studied. Variable results on clearance have been obtained in acute studies of healthy volunteers; clearance of verapamil was either reduced or unchanged.
Lithium Increased sensitivity to the effects of lithium neurotoxicity has been reported during concomitant verapamil-lithium therapy; lithium levels have been observed sometimes to increase, sometimes to decrease, and sometimes to be unchanged.
Patients receiving both drugs must be monitored carefully. Carbamazepine Verapamil therapy may increase carbamazepine concentrations during combined therapy. This may produce carbamazepine side effects such as diplopia, headache, ataxia, or dizziness. Rifampin Therapy with rifampin may markedly reduce oral verapamil bioavailability. Phenobarbital Phenobarbital therapy may increase verapamil clearance.
Cyclosporine Verapamil therapy may increase serum levels of cyclosporine. Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. Inhalation anesthetics Animal experiments have shown that inhalation anesthetics depress cardiovascular activity by decreasing the inward movement of calcium ions. When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, should each be titrated carefully to avoid excessive cardiovascular depression.
Neuromuscular blocking agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents curare-like and depolarizing. Telithromycin Hypotension and bradyarrhythmias have been observed in patients receiving concurrent telithromycin, an antibiotic in the ketolide class.
Clonidine Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil.
Monitor heart rate in patients receiving concomitant verapamil and clonidine.
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