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Concurrent use of these medications may also increase the risk for QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Alfuzosin may prolong the QT interval in a dose-dependent manner.

Alpha-blockers: (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.

Amiodarone: (Major) The concomitant use of amiodarone and vardenafil should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone.

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.

Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).

Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Amiodarone is an inhibitor of CYP3A4 and can reduce vardenafil clearance.

Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects.

Amoxicillin; Clarithromycin; Lansoprazole: (Major) The manufacturer of clarithromycin (a CYP3A4 inhibitor) recommends against concomitant use with vardenafil (a CYP3A4 substrate); as use of these drugs together will result in increased vardenafil exposure.

If these drugs must be administered concurrently, use the regular tablet formulation of vardenafil at a dose not to exceed 2.5 mg every 24 hours. The vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use of the orally disintegrating tablets with moderate or potent CYP3A4 inhibitors is not advised.

In addition, clarithromycin and vardenafil have been associated with prolongation of the QT interval; use of these drugs together may increase the risk for QT prolongation.

Amoxicillin; Clarithromycin; Omeprazole: (Major) The manufacturer of clarithromycin (a CYP3A4 inhibitor) recommends against concomitant use with vardenafil (a CYP3A4 substrate); as use of these drugs together will result in increased vardenafil exposure.

If these drugs must be administered concurrently, use the regular tablet formulation of vardenafil at a dose not to exceed 2.5 mg every 24 hours.

The vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use of the orally disintegrating tablets with moderate or potent CYP3A4 inhibitors is not advised. In addition, clarithromycin and vardenafil have been associated with prolongation of the QT interval; use of these drugs together may increase the risk for QT prolongation.

Amyl Nitrite: (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.

Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include vardenafil.

Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with vardenafil as concurrent use may increase the risk of QT prolongation.

Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines.

Vardenafil is also associated with QT prolongation at both therapeutic and supratherapeutic doses. Aprepitant, Fosaprepitant: (Moderate) Use caution if vardenafil and aprepitant, fosaprepitant are used concurrently and monitor for an increase in vardenafil-related adverse effects for several days after administration of a multi-day aprepitant regimen.

Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of vardenafil. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam sildenafil overnight shipping (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5.

After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively.

As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively.

After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.

Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4.

Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aripiprazole: (Moderate) Use caution when administering aripiprazole with vardenafil due to increased risk of QT prolongation.

Vardenafil is associated with an increase in QTc interval at both therapeutic and sildenafil citrate tablets 50mg price supratherapeutic doses.

QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to sildenafil citrate tablets 50mg price initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide 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). Artemether; Lumefantrine: (Major) Concurrent use of vardenafil and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if vardenafil must be used with or after artemether; lumefantrine treatment. Administration of artemether; lumefantrine is associated with prolongation of the QT interval. 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). Asenapine: (Major) Asenapine has been associated with QT prolongation.

According to the manufacturer of asenapine, the drug 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). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug. Atazanavir: (Major) Particular caution should be used when prescribing vardenafil to patients receiving atazanavir. Coadministration of atazanavir 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.

If coadministered, use vardenafil for erectile dysfunction at reduced doses of 2.5 mg, every 24 hours when used with atazanavir or every 72 hours when used with ritonavir-'boosted' atazanavir, with increased monitoring for adverse reactions.

The vardenafil orally disintegrating tablets provide increased exposure as compared to

the

Atazanavir; Cobicistat: (Major) Particular caution should be used when prescribing vardenafil to patients receiving atazanavir. Coadministration of atazanavir 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.

If coadministered, use vardenafil for erectile dysfunction at reduced doses of 2.5 mg, every 24 hours when used with atazanavir or every 72 hours when used with ritonavir-'boosted' atazanavir, 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 atazanavir. (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. Atomoxetine: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with atomoxetine as concurrent use may increase the risk of QT prolongation.

QT prolongation has occurred sildenafil citrate tablets 50mg price during therapeutic use of atomoxetine and following overdose.

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

Azithromycin: (Moderate) Due to an increased risk for QT prolongation and torsade de sildenafil citrate tablets 50mg price pointes (TdP), caution is advised when administering vardenafil with azithromycin.

Azithromycin has been associated with post-marketing reports of QT prolongation and TdP.

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

Barbiturates: (Minor) Vardenafil is metabolized by cytochrome P450 3A4. It can be expected that concomitant administration sildenafil citrate tablets 50mg price of CYP3A4 enzyme-inducers, such as barbiturates, will decrease plasma levels of vardenafil.

Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with vardenafil.