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Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.

Loperamide; Simethicone: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with loperamide. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Lopinavir; Ritonavir: (Major) Coadministration of ritonavir with vardenafil results in a 20% decrease in ritonavir AUC and a 49-fold increase in vardenafil AUC. Substantially increased vardenafil plasma concentrations may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.

If coadministered, use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions. Vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use of the orally disintegrating tablets with ritonavir is not recommended.

In addition, both ritonavir and vardenafil are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Major) Particular caution should be used when prescribing phosphodiesterase type 5 (PDE5) inhibitors to patients receiving lopinavir; ritonavir (Kaletra).

Coadministration of lopinavir; ritonavir (Kaletra) with these drugs is expected to substantially increase their plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. If coadministered, use vardenafil at reduced doses of 2.5 mg every 72 hours with increased monitoring for adverse reactions. In addition, QT prolongation in patients generic viagra soft tabs 100mg taking lopinavir; ritonavir has been reported. Coadministration of lopinavir; ritonavir with other drugs that prolong the QT interval, such as vardenafil, may result in additive QT prolongation.

Lorcaserin: (Major) Lorcaserin is a serotonin 2C receptor agonist, and priapism is a potential effect of 5-HT2C receptor agonism. Because there is little experience with the combination of lorcaserin and medications indicated for erectile dysfunction (e.g., phosphodiesterase inhibitors), combined use should be approached with caution. Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of vardenafil by decreasing its systemic exposure. Vardenafil is primarily metabolized by CYP3A4, and lumacaftor is a strong CYP3A inducer.

Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as vardenafil. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended.

Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Maprotiline: (Moderate) Use vardenafil with caution in combination with maprotiline due to increased risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval.

Mefloquine alone has not been reported to cause QT prolongation. Both therapeutic and supratherapeutic doses coupons for sildenafil 100mg of vardenafil produce an increase in QTc interval. Meperidine; Promethazine: (Moderate) Use vardenafil with caution in combination with promethazine due to increased risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Promethazine, a phenothiazine, is associated with a possible risk for QT coupons for sildenafil 100mg prolongation. Mesoridazine: (Major) Concomitant administration of mesoridazine with vardenafil may cause additive QT prolongation and should be used cautiously. Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits.

Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, methadone is a substrate for CYP3A4, CYP2D6, and P-glycoprotein (P-gp). Concurrent use of methadone with inhibitors of these enzymes may result in increased serum concentrations of methadone.

Drugs with a possible risk for QT prolongation and TdP that inhibit CYP2D6 include vardenafil. Metronidazole: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with metronidazole.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Potential QT prolongation has been reported in limited case reports with metronidazole.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Midostaurin: (Major) The concomitant use of midostaurin and vardenafil may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin.

Both therapeutic and supratherapeutic doses of vardenafil produced an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). Mifepristone: (Major) Due to an increased risk of QT prolongation and torsade de pointes (TdP), vardenfil and mifepristone should be used together carefully.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Mifepristone has been associated with dose-dependent prolongation of the QT interval.

To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mirtazapine: (Moderate) Use caution when using mirtazapine in combination with vardenafil as concurrent use may increase the risk of QT prolongation.

Mirtazapine has been associated with dose-dependent prolongation of the QT interval.

Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Mitotane: (Moderate) Use caution if mitotane and vardenafil are used concomitantly, and monitor for decreased efficacy of vardenafil and a possible change in dosage requirements.

Mitotane is a strong CYP3A4 inducer and vardenafil is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of vardenafil. Moxifloxacin: (Major) Concurrent use of vardenafil and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP).

Moxifloxacin has been associated with prolongation of the QT interval.

Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions.

The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.

Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil have also produced increases in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Nefazodone: (Moderate) Vardenafil is metabolized by hepatic cytochrome P450 3A4 and inhibitors of CYP3A4, such as nefazodone, can reduce vardenafil clearance.

Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects. Nelfinavir: (Major) Particular caution should be used when prescribing vardenafil to patients receiving nelfinavir. Coadministration is expected to substantially increase vardenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.

When used with nelfinavir, administer vardenafil at reduced doses of no more than 2.5 mg every 24 hours with increased monitoring for adverse reactions.

Nevirapine: (Minor) Vardenafil is metabolized by cytochrome P450 3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as nevirapine, will decrease plasma levels of vardenafil. Nicardipine: (Moderate) Vardenafil is metabolized by hepatic cytochrome P450 3A4 and to a lesser extent CYP2C9.

Inhibitors of CYP3A4, such as nicardipine, can reduce vardenafil clearance. Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects. Nifedipine: (Moderate) Nifedipine can have additive hypotensive effects when administered with phosphodiesterase inhibitors (PDE 5 inhibitors). The patient should be monitored carefully and the dosage should be adjusted based on clinical response.

For example, in patients whose hypertension was controlled with nifedipine, vardenafil produced mean additional supine systolic/diastolic blood pressure reductions of 3 to 4 mmHg (age group 65 to 69 years) and 5 to 6 mmHg (age group 70 to 80 years) compared to placebo.

Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval, such as vardenafil.

Additionally, nilotinib is a moderate CYP3A4 inhibitor and vardenafil is a CYP3A4 substrate; administering these drugs together may result in increased vardenafil levels. If the use of vardenafil is required, hold nilotinib therapy.

If the use of nilotinib and goodrx coupon sildenafil vardenafil cannot be avoided, a vardenafil dose reduction may be necessary; close monitoring of the QT interval is recommended. Nitrates: (Severe) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated.

Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction.

Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.

Nitroglycerin: (Severe) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.

Nitroprusside: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside.