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Risperidone: (Moderate) Use risperidone and vardenafil together with caution due sildenafil sandoz price to the potential for additive QT prolongation and risk of torsade de pointes (TdP).

Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.

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

Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with vardenafil as concurrent use may increase the risk of QT prolongation.

Romidepsin has been reported to prolong the QT interval.

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

Sapropterin: (Moderate) Sapropterin acts as a cofactor in the synthesis of nitric oxide and may cause vasorelaxation.

Caution should be exercised when

administering

When given together these agents may produce an additive reduction in blood pressure.

The combination of sapropterin and a phosphodiesterase (PDE5) inhibitor did not significantly reduce blood pressure when administered concomitantly in animal studies. The additive effect of these agents has not been studied in humans. Saquinavir: (Major) Particular caution should be used when prescribing phosphodiesterase type 5 (PDE5) inhibitors to patients receiving saquinavir as there is an increased risk for serious adverse effects.

Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as vardenafil, if possible. Coadministration of saquinavir, especially when 'boosted' with ritonavir, with vardenafil is expected to substantially increase vardenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. In addition, saquinavir boosted with topical sildenafil cream ritonavir increases the QT and PR intervals in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP).

Although it is best to avoid this drug combination if possible, if no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy (see Contraindications), and use vardenafil at reduced doses of no more than 2.5 mg, every 24 hours when used with saquinavir or every 72 hours when used with ritonavir-'boosted' saquinavir, with increased monitoring for adverse reactions.

The vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, do not use the orally disintegrating tablets with moderate or potent CYP3A4 inhibitors, such as saquinavir.

Sertraline: (Moderate) Use caution and monitor patients for QT prolongation when administering vardenafil with sertraline.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). Short-acting beta-agonists: (Minor) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). The effect of vardenafil on the QT interval should be considered when prescribing the drug.

Drugs with a possible risk for QT prolongation that should be used cautiously with vardenafil include the beta agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.

Silodosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of vardenafil. Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of vardenafil and silodosin.

Simeprevir: (Moderate) Coadministration of vardenafil with simeprevir, an intestinal CYP3A4 inhibitor, may result in mild increases in vardenafil plasma concentrations. No dose adjustments are required when treating erectile dysfunction.

Siponimod: (Major) Avoid coadministration of siponimod and vardenafil due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required.

Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Solifenacin: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with vardenafil. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with vardenafil is necessary; correct any electrolyte abnormalities.

An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Sorafenib has also been associated with QT prolongation. Sotalol: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). The effect of vardenafil on the QT interval should be considered when prescribing the drug. The manufacturer recommends that vardenafil be avoided in patients taking sotalol.

Sotalol administration is associated with QT prolongation and torsades de pointes (TdP).

Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.

Sparfloxacin: (Moderate) Sparfloxacin is associated with an established risk for QT prolongation and torsades de pointes.

This risk my be increased if combined with other drugs that may prolong the QT interval, such as vardenafil.

Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with vardenafil.

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

Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with vardenafil. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP).