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

Haloperidol: (Moderate) Consider

the

potential for additive QT effects if vardenafil is administered with haloperidol.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment.

Excessive doses cheap generic sildenafil (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Tacrolimus may prolong the QT interval and cause TdP. Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.

Hydralazine; Isosorbide Dinitrate, ISDN: (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.

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.

Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and vardenafil.

Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval.

Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine.

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

Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with vardenafil due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Ibutilide: (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 ibutilide. Ibutilide administration can cause QT prolongation and torsades teva sildenafil 100mg de pointes (TdP); proarrhythmic events should be anticipated.

The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.

Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vardenafil, a CYP3A substrate, as vardenafil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.

Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported.

According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as 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). Imatinib: (Major) Imatinib is a potent inhibitor of CYP3A4.

Vardenafil is metabolized by hepaticCYP3A4 and to a lesser extent CYP2C9.

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

In vivo studies report that several strong CYP3A4 inhibitors can significantly increase the AUC and Cmax of vardenafil when coadministered with vardenafil.

Vardenafil dose adjustments are required when vardenafil is administered with such agents. 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. Other potent CYP3A4 inhibitors such as, imatinib, STI-571, would be expected to have effects on vardenafil clearance when coadministered. Indinavir: (Major) Particular caution should be used when prescribing vardenafil in patients receiving indinavir. Coadministration is expected to substantially increase vardenafil plasma concentrations and may result in vardenafil-related adverse events including hypotension, visual changes, and priapism.

If used together, the vardenafil dose should not exceed 2.5 mg in a 24-hour period; advise patients to promptly report adverse events such as prolonged erection. Vardenafil

orally

disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use with potent CYP3A4 inhibitors such as indinavir is not recommended. Coadministration of indinavir (800 mg every 8 hours) with a single dose of vardenafil (10 mg) altered the pharmacokinetics of vardenafil with a 16-fold increase in AUC, a 7-fold increase in Cmax, and a 2-fold increase in half-life.

Conversely, vardenafil reduced the AUC and Cmax of indinavir by 30% and 40%, respectively. Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with vardenafil due to the potential for additive QT prolongation and risk of torsade de pointes (TdP).

If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment.

Inotuzumab has been associated with QT interval 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).

Isavuconazonium: (Moderate) Concomitant sildenafil 25 mg coupon use of isavuconazonium with vardenafil may result in increased serum concentrations of vardenafil. Vardenafil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, sildenafil 25 mg coupon the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.

Caution and close monitoring for adverse events, including hypotension, syncope, visual changes, and prolonged erection, are advised if these drugs are used together. Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Vardenafil is metabolized by cytochrome P450 3A4.

It can be expected that concomitant administration of CYP3A4 enzyme-inducers, like the rifamycins, will decrease plasma levels of vardenafil.

Isoniazid, INH; Rifampin: (Minor) Vardenafil is metabolized by cytochrome P450 3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, like the rifamycins, will decrease plasma levels of vardenafil.

Isosorbide Dinitrate, ISDN: (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.

Isosorbide Mononitrate: (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 cheapest sildenafil 20 mg 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. Itraconazole: (Major) Avoid use of vardenafil during and for 2 weeks after discontinuation of itraconazole.

If coadministration of itraconazole and vardenafil oral tablets cannot be avoided, the maximum single vardenafil dose is 5 mg every 24 hours in patients receiving itraconazole 200 mg daily; for patients receiving itraconazole 400 mg daily, the maximum single vardenafil dose is 2.5 mg every 24 hours.

The vardenafil orally disintegrating tablets (ODTs) provide increased exposure as compared to the regular tablets; therefore, use of the vardenafil ODTs with itraconazole is not recommended. Taking these drugs together increases exposure to vardenafil, and may cause additive effects on the QT interval.

Both itraconazole and vardenafil have been associated with QT prolongation; coadministration may increase this risk.

Ivosidenib: (Major) Avoid coadministration of ivosidenib with vardenafil due to an increased risk of QT prolongation; vardenafil exposure may also decrease.

If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib and/or vandetanib may be necessary if QT prolongation occurs.

Ivosidenib is a CYP3A4 inducer that has been associated with prolongation of the QTc interval and ventricular arrhythmias.

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

Ketoconazole: (Major) Caution is advised when administering ketoconazole with vardenafil due to the potential for additive effects on the QT interval and increased exposure to vardenafil.

Both ketoconazole and vardenafil have been associated with QT prolongation; coadministration may increase this risk. If these drugs must be administered together, a lower dose of vardenafil is required. The vardenafil orally disintegrating tablets (ODTs) provide increased exposure as compared to the regular tablets; therefore, use of the vardenafil ODTs with potent CYP3A4 inhibitors should be avoided. For patients receiving ketoconazole 200 mg daily, the maximum single vardenafil dose is 5 mg every 24 hours.

For patients receiving ketoconazole 400 mg daily, the maximum single vardenafil dose is 2.5 mg every 24 hours. In one study, health subjects receiving ketoconazole 200 mg PO daily with a single 5 mg vardenafil dose experienced a 10-fold increase in the AUC and a 4-fold increase in the Cmax of vardenafil. Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with vardenafil. Vardenafil is associated with QT prolongation at both therapeutic and supratherapeutic doses.

Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Lefamulin: (Major) Coadministration of lefamulin tablets is contraindicated with vardenafil due to increased vardenafil exposure which may result in QT prolongation and torsade de pointes (TdP).

If coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment.

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

Lefamulin is a CYP3A4 inhibitor that has a concentration dependent QTc prolongation effect.

The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.

Lenvatinib: (Major) Avoid coadministration of lenvatinib with vardenafil due to the risk of QT prolongation.

Prolongation of the QT interval has been reported with lenvatinib therapy.

Vardenafil is associated with QT prolongation at both therapeutic and supratherapeutic doses.

Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of vardenafil; monitor for potential reduction in efficacy. Vardenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.

Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of vardenafil; monitor for potential reduction in efficacy.

Vardenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.

Letermovir: (Major) Due to increased vardenafil exposure, do not use vardenafil orally disintegrating tablets with letermovir; decrease the dose of the vardenafil oral tablets if administered with letermovir. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.

Concurrent administration with strong inhibitors of CYP3A4 increased the maximum plasma concentration (Cmax) and exposure (AUC) of vardenafil by 4- to 7-fold and 10- to 16-fold, respectively. In addition, the half-life of vardenafil increased by 2-fold.

Moderate CYP3A4 inhibitors, increased the Cmax and AUC of vardenafil by 3-fold and 4-fold, respectively. Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.

Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.

Levofloxacin: (Moderate) Levofloxacin should be used cautiously with other agents, such as vardenafil, that may prolong the QT interval or increase the risk of torsade de pointes (TdP).

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin. Levomethadyl: (Severe) Concomitant administration of levomethadyl and vardenafil may cause additive QT prolongation and/or torsades de pointes.

Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval. Lithium: (Moderate) Lithium should be used cautiously and with close monitoring with vardenafil as concurrent use may increase the risk of QT prolongation. Vardenafil is also associated with QT prolongation.

Therapeutic (10 mg) and supratherapeutic (80 mg) sildenafil 25 mg coupon doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with vardenafil due to the potential for additive QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Lomefloxacin: (Moderate) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia.

Other medications which may prolong the QT interval, such as vardenafil, should be used cautiously when given concurrently with lomefloxacin. Long-acting beta-agonists: (Moderate) 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. Loperamide: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with loperamide.



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