27.11.2018
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Chlorpheniramine; 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. Chlorpheniramine; 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. Chlorpromazine: (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 (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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vardenafil include chlorpromazine. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Cimetidine: (Major) Phosphodiesterase inhibitors are metabolized principally by cytochrome P450 (CYP) 3A4 (major route) and 2C9 (minor route) isoenzymes. Cimetidine is a known inhibitor of hepatic CYP enzymes. Cimetidine (800 mg) caused a 56% increase in plasma sildenafil concentrations when coadministered with sildenafil 50 mg to healthy volunteers. Population data from patients in clinical trials also indicate a reduction in sildenafil clearance when it was coadministered with cimetidine. If possible, cimetidine use should be avoided in patients who take phosphodiesterase inhibitors Ciprofloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering ciprofloxacin with vardenafil. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Both therapeutic and supratherapeutic doses of vardenafil produce and increase in QTc interval. Cisapride: (Severe) 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. Because of the potential for torsade de pointes (TdP), use of cisapride with vardenafil is contraindicated. Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram 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). Clarithromycin: (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 over the counter generic sildenafil 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. Class IA Antiarrhythmics: (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. Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with vardenafil. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Clozapine: (Moderate) Use vardenafil with caution in combination with clozapine due to increased risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Treatment with clozapine has also been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Cobicistat: (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. Codeine; Phenylephrine; Promethazine: (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. (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. Codeine; Promethazine: (Moderate) Use vardenafil with caution in combination with promethazine due to increased risk of QT prolongation. Both therapeutic sildenafil in farmacia and supratherapeutic doses of vardenafil produce an increase in QTc interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as vardenafil, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with vardenafil. Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects. Treatment with vardenafil may be initiated no sooner than 1 week after completion of conivaptan therapy. Crizotinib: (Major) Due to increased vardenafil exposure, avoid coadministration of vardenafil orally disintegrating tablets with crizotinib; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Additionally, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Vardenafil is a sensitive CYP3A4 substrate that is associated with QT prolongation at both therapeutic and supratherapeutic doses. Crizotinib is a moderate CYP3A inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another moderate CYP3A4 inhibitor increased the AUC and Cmax of vardenafil by 4-fold and 3-fold, respectively. Dabrafenib: (Major) The concomitant use of dabrafenib and vardenafil may lead to decreased vardenafil concentrations and loss of efficacy. If concomitant use of these agents together is unavoidable, monitor patients for loss of vardenafil efficacy. Dabrafenib is a moderate CYP3A4 inducer and vardenafil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%. Darunavir: (Major) Coadministration of darunavir with vardenafil is expected to substantially increase vardenafil plasma concentrations and may result in increased adverse events including hypotension, syncope, visual changes, and prolonged erection. Use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions. Darunavir; Cobicistat: (Major) Coadministration of darunavir with vardenafil is expected to substantially increase vardenafil plasma concentrations and may result in increased adverse events including hypotension, syncope, visual changes, and prolonged erection. Use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions. (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. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of darunavir with vardenafil is expected to substantially increase vardenafil plasma concentrations and may result in increased adverse events including hypotension, syncope, visual changes, and prolonged erection. Use vardenafil at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse reactions. (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. Dasabuvir; Ombitasvir; Paritaprevir; 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. Dasatinib: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and vardenafil. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Delavirdine: (Major) If used together, the vardenafil tablet dose should not exceed 2.5 mg in a 24-hour period; advise patients to promptly report adverse events such as dizziness, faintness on standing, or prolonged erection. Vardenafil orally disintegrating tablets (ODT) provide increased exposure as compared to the regular tablets; therefore, use with potent CYP3A4 inhibitors such as delavirdine is not recommended. Delavirdine is expected to substantially increase vardenafil plasma concentrations and may result in vardenafil-related adverse events including hypotension, visual changes, and priapism. Deutetrabenazine: (Moderate) Use vardenafil with caution in combination with deutetrabenazine as concurrent use may increase the risk of QT prolongation. For patients taking a deutetrabenazine dosage more than 24 mg/day with vardenafil, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Dexamethasone: (Minor) Vardenafil is metabolized by cytochrome P450 3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as dexamethasone, will decrease plasma levels of vardenafil. Dextromethorphan; 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. Dextromethorphan; Guaifenesin; 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. Dextromethorphan; 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. Dextromethorphan; Quinidine: (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. Diltiazem: (Moderate) Vardenafil is metabolized by hepatic cytochrome P450 3A4.
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