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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 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 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 sildenafil teva 50 mg 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 sildenafil teva 50 mg 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 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.

Ofloxacin: (Moderate) Ofloxacin should be used cautiously 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. Quinolones have been associated with a risk of QT prolongation and TdP.

Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin.

These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.

Olanzapine: (Moderate) Caution is advised when administering olanzapine with vardenafil as concurrent use may increase the risk of QT prolongation. Limited sildenafil teva 50 mg 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. 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.

Ondansetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), ondansetron and vardenafil should be used together cautiously.

Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP.

If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended.

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

Oritavancin: (Minor) Vardenafil is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer.

Plasma concentrations and efficacy of vardenafil may be reduced if these drugs are administered concurrently. Osimertinib: (Major) Avoid coadministration of vardenafil with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Vardenafil is

associated

with QTc prolongation at both therapeutic and supratherapeutic doses.

Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of vardenafil with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Vardenafil is associated with QT prolongation at both therapeutic and supratherapeutic doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience. Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose.

According to the manufacturer, since paliperidone 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). If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.

Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended.

Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include vardenafil.

Pasireotide: (Moderate) Pasireotide should be used cautiously and with close monitoring with vardenafil as coadministration may have additive effects on the prolongation of the QT interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

QT prolongation has also occurred with pasireotide at therapeutic and supra-therapeutic doses.

Pazopanib: (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.

Inhibitors of CYP3A4 can reduce vardenafil clearance.

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

Therefore, it is advisable to closely monitor for adverse events when vardenafil is coadministered with drugs that inhibit CYP3A4 and prolong the QT interval, including pazopanib. Pentamidine: (Major) Pentamidine has been associated with QT prolongation.

Drugs with a possible risk for QT prolongation and torsades de pointes (

TdP

) that should be used cautiously with pentamidine include vardenafil.

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).

When vardenafil was given with prescriptive doses of another agent known to prolong the QT interval, an additive effect on the QT interval was observed. Perphenazine: (Minor) Use vardenafil with caution in combination with perphenazine due to increased risk of QT prolongation.

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

Perphenazine is associated with a possible risk for QT prolongation.

Perphenazine; Amitriptyline: (Minor) Use vardenafil with caution in combination with perphenazine due to increased risk of QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Perphenazine is associated with a possible risk for QT prolongation. Phenoxybenzamine: (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. Phentolamine: (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. 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. 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.

Phenytoin: (Minor) Vardenafil is metabolized by cytochrome P450 3A4.

It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as phenytoin, will decrease plasma levels of vardenafil, however, no interaction studies have been performed.

Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in

patients

receiving other medications known to prolong the QT interval. 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). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The sildenafil teva 50 mg effect of vardenafil on the QT interval should be considered when prescribing the drug. Coadministration may increase the risk for QT prolongation. Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of vardenafil with pimozide is contraindicated.

Pitolisant: (Major) Avoid coadministration of pitolisant 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. Posaconazole: (Severe) Concurrent use of posaconazole and vardenafil is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP).

Posaconazole is a potent 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, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as vardenafil. Prazosin: (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 costco pharmacy sildenafil concomitant use of vardenafil and an alpha-blocker. Primaquine: (Moderate) Due to the potential for QT interval prolongation with primaquine, caution is advised with vardenafil and other drugs that prolong the QT interval. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Procainamide: (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.

Prochlorperazine: (Minor) Use vardenafil with caution in combination with prochlorperazine due to increased risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Prochlorperazine is also associated with a possible risk for QT prolongation. 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.

Propafenone: (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 propafenone.

Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.

Quetiapine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.

According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with quetiapine 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).

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. Quinine: (Major) Concurrent use of quinine and vardenafil should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil also produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).

In addition, concentrations of vardenafil may be increased with concomitant use of quinine.

Vardenafil is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor. Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily).

However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such

drugs

may result in additive QT prolongation. In addition, in vitro studies indicate that ranolazine and its metabolite are inhibitors of CYP3A isoenzymes.

Drugs that are CYP3A4 substrates that also have a possible risk for QT prolongation and TdP that should be used cautiously with ranolazine 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). Ribociclib: (Major) Avoid coadministration of ribociclib with vardenafil due to an increased risk for QT prolongation and torsade de pointes (TdP).

Systemic exposure of vardenafil may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Vardenafil is a sensitive CYP3A4 substrate also associated with QT prolongation at both therapeutic and supratherapeutic doses.

Concomitant use may increase the risk for QT prolongation. Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with vardenafil due to an increased risk for QT prolongation and torsade de pointes (TdP).

Systemic exposure of vardenafil may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Vardenafil is a sensitive CYP3A4 substrate also associated with QT prolongation at both therapeutic and supratherapeutic doses. Concomitant use may increase the risk for QT prolongation.

Rifabutin: (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.

Rifampin: (Minor) Vardenafil is metabolized by cytochrome P450 3A4.



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20.07.2019 - BEZPRIDEL
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