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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 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 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

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 sildenafil 50 mg tablet coupon 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 amazon sildenafil 50 mg 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 lowest price for sildenafil citrate 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 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

Nitroglycerin: (Severe) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage

formulation

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. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside. Norfloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vardenafil with norfloxacin. Therapeutic (10 mg) and supratherapeutic (80 mg) best sildenafil coupon doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance.

These amazon sildenafil 50 mg reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.

Octreotide: (Moderate) Use octreotide with caution in combination with vardenafil.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration

could

Ofloxacin: (Moderate) Ofloxacin should be used cautiously with vardenafil as concurrent use may increase the risk of QT prolongation.

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

Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Olanzapine: (Moderate) Caution is advised when administering

olanzapine

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.

Ondansetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), ondansetron and vardenafil should be used together cautiously. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP. If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Oritavancin: (Minor) Vardenafil is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer.

Plasma concentrations and efficacy of vardenafil may be reduced if these drugs are administered concurrently.