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Inhibitors of CYP3A4, such as diltiazem, can reduce vardenafil clearance. Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects.

Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly. Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly.

Disopyramide: (Major) The manufacturer recommends that vardenafil be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine).

Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).

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.

Dofetilide: (Major) Coadministration of dofetilide and vardenafil is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).

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

Dolasetron: (Moderate) Administer dolasetron with caution in combination 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.

Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Dolutegravir; Rilpivirine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with vardenafil.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.

Donepezil: (Moderate) Use donepezil with caution in combination with vardenafil as concurrent use may increase the risk of QT prolongation.

Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.

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

Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with vardenafil as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.

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

Doxazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker 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 the alpha-blocker; 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 an alpha-blocker. Dronedarone: (Severe) Concomitant use of dronedarone and vardenafil is contraindicated.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.

Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily.

Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval.

Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP).

Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include vardenafil.

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).

Dutasteride; Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin 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 tamsulosin; 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 tamsulosin.

Duvelisib: (Moderate) Due to increased vardenafil exposure, do not use vardenafil orally disintegrating tablets with duvelisib; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets.

Moderate CYP3A4 inhibitors, increased the Cmax and AUC of vardenafil by 3-fold and 4-fold, respectively.

Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with vardenafil as concurrent use may increase

the

Vardenafil is also associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as vardenafil.

Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with vardenafil as concurrent use may increase the risk of QT prolongation.

QTc prolongation has been observed with the use of efavirenz.

Vardenafil is also associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as vardenafil.

Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with vardenafil as concurrent use may increase the risk of QT prolongation.

QTc prolongation has been observed with the use of efavirenz. Vardenafil is also associated with QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as vardenafil. Elbasvir; Grazoprevir: (Moderate) Administering vardenafil with elbasvir; grazoprevir may result in elevated vardenafil plasma concentrations. Vardenafil is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor.

If these drugs are used together, closely monitor for signs of adverse events. Eliglustat: (Moderate) Use vardenafil with caution in combination with eliglustat due to increased risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) When being administered with cobicistat, use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions.

Coadministration of vardenafil with cobicistat is expected to substantially increase the plasma concentrations of vardenafil and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) When being administered with cobicistat, use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions. Coadministration of vardenafil with cobicistat is expected to substantially increase the plasma concentrations of vardenafil and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.

Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with vardenafil. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.

Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with vardenafil.

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

Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.

Encorafenib: (Major) Avoid coadministration of encorafenib and vardenafil due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Concurrent use may also result in increased toxicity or decreased efficacy of vardenafil.

Encorafenib is associated with dose-dependent prolongation of the QT interval.

In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in

vivo

Vardenafil, a sensitive CYP3A4 substrate, is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Entrectinib: (Major) Avoid coadministration of entrectinib with vardenafil due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation.

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

Eribulin: (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).

When vardenafil (10 mg) was given with

gatifloxacin

The effect of vardenafil on the QT interval should be considered when prescribing the drug.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vardenafil include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.

Erythromycin: (Major) It may be prudent to avoid the use of vardenafil in patients being treated with erythromycin.

If these drugs must be used together, do so with extreme caution.

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 erythromycin. Erythromycin is generally considered by experts to have an established risk for QT prolongation and torsades de pointes (TdP). Vardenafil, at therapeutic (10 mg) and supratherapeutic (80 mg) doses, produces increases in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Coadministration could lead to the risk of additive QT prolongation.

Coadministration of erythromycin (500 mg tid) increased the AUC and Cmax of vardenafil 4-fold and 3-fold, respectively; increased vardenafil concentrations further increase the risk for serious side effects.

Erythromycin; Sulfisoxazole: (Major) It may be prudent to avoid the use of vardenafil in patients being treated with erythromycin.

If these drugs must be used together, do so with extreme caution. 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 erythromycin. Erythromycin is generally considered by experts to have an established risk for QT prolongation and torsades de pointes (TdP).

Vardenafil, at therapeutic (10 mg) and supratherapeutic (80 mg) doses, produces increases in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Coadministration could lead to the risk of additive QT prolongation.

Coadministration of erythromycin (500 mg tid) increased the AUC and Cmax of vardenafil 4-fold and 3-fold, respectively; increased vardenafil concentrations further increase the risk for serious side effects. Escitalopram: (Moderate) Use escitalopram with caution in combination with vardenafil as concurrent use may increase the risk of QT prolongation.

Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Etravirine: (Moderate) Etravirine is an inducer of CYP3A4; coadministration may result in decreased vardenafil concentrations. Dosage adjustments may be needed based on clinical efficacy. Ezogabine: (Moderate) Use vardenafil with caution in combination with ezogabine due to increased risk of QT prolongation as concurrent use may increase the risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Ezogabine has also been associated with QT prolongation.

Fedratinib: (Major) Due to increased vardenafil exposure, do not use vardenafil orally disintegrating tablets with fedratinib; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets.

Moderate CYP3A4 inhibitors, increased the Cmax and AUC of vardenafil by 3-fold and 4-fold, respectively. Fingolimod: (Moderate) Use vardenafil with caution in combination with fingolimod due to increased risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.

Flecainide: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval.

Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with flecainide include vardenafil. 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 suhagra price QT correction).

Fluconazole: (Severe) Concurrent use of fluconazole and vardenafil is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP).

Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of vardenafil.

These drugs used in combination may result in elevated vardenafil plasma concentrations, causing an increased risk for vardenafil-related adverse events, such as QT prolongation.

Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as vardenafil.

Fluoxetine: (Moderate) Use fluoxetine with caution in combination with vardenafil. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine.

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

Fluoxetine; Olanzapine: (Moderate) Caution is advised when administering olanzapine with vardenafil as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in the QTc interval. (Moderate) Use fluoxetine with caution in combination with vardenafil. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP).

QT prolongation and TdP have been reported in patients treated with fluoxetine.

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

Fluphenazine: (Minor) Use vardenafil with caution in combination with fluphenazine due to increased risk of QT prolongation.

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

Fluphenazine is also associated with a possible risk for QT prolongation. Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), or increased vardenafil concentrations during concurrent use of fluvoxamine and vardenafil. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). In addition, coadministration of vardenafil, a CYP3A4 substrate, with fluvoxamine, a moderate CYP3A4 inhibitor, may substantially increase vardenafil plasma concentrations and result in vardenafil-related adverse events including hypotension, visual changes, and priapism.

If used with fluvoxamine, vardenafil dosage adjustments may be necessary. Vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use with moderate or potent CYP3A4 inhibitors is not recommended.

Advise patients to promptly report adverse events such as prolonged erection.

Fosamprenavir: (Major) Coadministration of vardenafil with fosamprenavir, especially when 'boosted' with ritonavir, is expected to substantially increase vardenafil plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Use vardenafil at reduced doses of no more than 2.5 mg, every 24 hours when used with fosamprenavir or every 72 hours when used with ritonavir-'boosted' fosamprenavir, with increased monitoring for adverse reactions.

Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as vardenafil. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP).

Vardenafil is also associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.

Fosphenytoin: (Minor) Vardenafil is metabolized by cytochrome P450 3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as fosphenytoin, will decrease plasma levels of vardenafil.

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

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

Gemifloxacin may prolong the QT interval in some patients.

The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax AUC are slightly higher.

Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and vardenafil together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP).

If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and vardenafil is necessary.