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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 sildenafil 200 mg online 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 buy teva sildenafil online 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) 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. 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 sildenafil for dogs online at reduced doses of 2.5 mg every 72 hours with increased monitoring for adverse reactions. In addition, QT prolongation in patients 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 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 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 sildenafil

for

dogs online 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 sildenafil online for sale 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 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. 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) 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 reports sildenafil for dogs online 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 theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.



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