Vardenafil is an oral, selective phosphodiesterase type 5 (PDE5) inhibitor. It is used for the treatment of erectile dysfunction (ED). In the treatment of men with ED, effectiveness extends to men with diabetes mellitus or those having undergone prostatectomy. Vardenafil is promoted to have a faster onset of action than sildenafil or tadalafil, as vardenafil achieves maximum plasma concentration sooner than these other PDE5 inhibitors. As with other PDE5 inhibitors, vardenafil should not be used by those who take nitrates because the combination can cause a sudden drop in blood pressure that can be dangerous. PDE5 inhibitors are first-line agents for ED according to guidelines. Although associated with high rates of success, approximately 35% of ED patients fail to respond to PDE5 inhibitor therapy. A course of an alternate PDE5 inhibitor may be considered if a patient does not respond to a PDE5 inhibitor trial; a treatment failure may be deemed after at least 4 unsuccessful trials. Those refractory to PDE5 inhibitors for ED should be counseled on appropriate use, potentially modifiable factors (e.g. hormonal abnormalities, food or drug interactions, lack of adequate sexual stimulation, heavy alcohol use, and the patient's relationship with their partner), and the risks and benefits of other therapies. Follow-up visits are necessary to determine whether therapy continues to be effective for ED or if cardiovascular health has significantly changed.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Vardenafil is administered orally approximately 1 hour before expected intercourse. May be administered with or without food.
-Orally disintegrating tablets: Place on tongue where tablet will disintegrate. Do not administer with any liquids. Administer immediately upon removal from blister packaging.
Flushing occurred in 11% of those receiving vardenafil film-coated tablets and in 7.6% of patients receiving orally disintegrating tablets. The incidence of flushing appears to increase as the dose increases. Anaphylactoid reactions (including laryngeal edema) occurred in less than 2% of patients. Other events occurring in < 2% of patients include allergic edema, facial edema (angioedema), pruritus, photosensitivity reaction, sweating (hyperhidrosis), erythema, and rash (unspecified). The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo.
Headache occurred in 15% of those receiving vardenafil film-coated tablets and in 14.4% of those receiving the orally-disintegrating tablets. The incidence of headache appears to increase as the dose increases. Neurologic effects that occurred in less than 2% of patients included asthenia, hypertonia, hypesthesia, dysesthesia, sleep disorders, amnesia, seizures, and paresthesias. The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo. Postmarketing reports indicate that seizures and seizure recurrence have occurred in temporal association with vardenafil use. The incidence of these adverse events is unknown. Transient global amnesia has been reported during post-marketing use of the drug.
Gastrointestinal (GI) adverse reactions occurring in at least 2% of patients taking vardenafil film-coated tablets and more frequently than placebo included dyspepsia (4% vs 1%) and nausea/vomiting (2% vs 1%). Dyspepsia also occurred in 2.8% of patients receiving the orally disintegrating tablets. GI effects that occurred in less than 2% of patients included abdominal pain, diarrhea, dysphagia, esophagitis, gastritis, gastroesophageal reflux, vomiting, and xerostomia. Dyspepsia and nausea appear to increase as the dose increases. The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo.
Arthralgia, myalgia, increased creatine phosphokinase (CPK), and increased muscle tone and cramping (muscle cramps) have been reported in less than 2% of patients receiving vardenafil during clinical trials. Neck pain has been reported with similar frequency. During controlled and uncontrolled clinical trials, back pain was reported in 2% of patients receiving vardenafil. The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo.
Dizziness occurred in 2% of those receiving vardenafil film-coated tablets and 2.3% of patients receiving orally disintegrating tablets. Dizziness has been associated with a sudden decrease in hearing. Centrally-mediated effects occurring in less than 2% of patients included insomnia, somnolence (drowsiness), and vertigo. The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo.
During clinical trials, cardiovascular adverse reactions that occurred in less than 2% of patients treated with vardenafil included angina pectoris, chest pain (unspecified), hypertension, hypotension, myocardial ischemia, myocardial infarction, orthostatic hypotension, palpitations, syncope, ventricular tachyarrhythmias (ventricular tachycardia), and sinus tachycardia. The effects of vardenafil on blood pressure were evaluated using single 20 mg doses of vardenafil in patients with erectile dysfunction. Vardenafil caused a mean maximum decrease in supine blood pressure of 7 mm Hg systolic and 8 mm Hg diastolic (compared to placebo), accompanied by a mean maximum increase in heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. After multiple dosing, the effects of vardenafil on blood pressure were similar on Day 31 as on Day 1. Vardenafil may add to the hypotensive effects of antihypertensive agents.
Respiratory conditions occurring in at least 2% of patients taking vardenafil film-coated tablets and more frequently than placebo included rhinitis (9% vs 3%), sinusitis (3% vs 1%), and flu-like syndrome (3% vs 2%). The incidence of rhinitis appears to increase as the dose increases. Nasal congestion occurred in 3.1% of patients receiving the orally disintegrating tablets. Respiratory-related effects which occurred in less than 2% of patients included dyspnea, sinus congestion, and pharyngitis. The discontinuation rate due to adverse reactions in placebo-controlled trials was 3.4% for vardenafil and 1.1% for placebo.
During clinical trials, ejaculation dysfunction occurred in less than 2% of patients treated with vardenafil. Prolonged erections greater than 4 hours and priapism have been reported rarely with PDE5 inhibitors, including vardenafil.
Epistaxis occurred in less than 2% of patients receiving vardenafil in clinical trials.
The use of phosphodiesterase type 5 (PDE5) inhibitors may cause visual impairment of various types. Advise patients to stop use of all phosphodiesterase 5 (PDE5) inhibitors, including avanafil and seek medical attention in the event of a sudden visual disturbance in 1 or both eyes. Ophthalmic adverse reactions occurring in less than 2% of patients receiving vardenafil include blurred vision, chromatopsia, conjunctivitis (increased redness of the eye), dim vision, glaucoma, ocular pain, photophobia, visual impairment, ocular hyperemia, increased intraocular pressure, and watery eyes (lacrimation). Postmarketing reports with PDE5 inhibitors have included cases of visual disturbances including retinal vein occlusion, visual field defects, reduced visual acuity, and loss of vision (temporary or permanent). Non-arteritic anterior ischemic optic neuropathy (NAION) has also been reported rarely in patients using phosphodiesterase type 5 (PDE5) inhibitors. It is thought that the vasoconstrictive effect of phosphodiesterase inhibitors may decrease blood flow to the optic nerve, especially in patients with a low cup to disk ratio. Symptoms, such as blurred vision and loss of visual field in one or both eyes, are usually reported within 24 hours of use. Most, but not all, of these patients who reported this adverse effect had underlying anatomic or vascular risk factors for development of NAION. These risk factors include, but are not limited to: low cup to disc ratio ('crowded disc'), age over 50 years, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Additionally, two patients had retinal detachment and one patient had hypoplastic optic neuropathy. An observational, case-crossover study evaluated the risk of NAION when PDE5 inhibitor use occurred immediately before NAION onset compared to PDE5 inhibitor use in a prior time period. Results suggest a 2-fold increase in the risk of NAION (risk estimate of 2.15 [95% CI 1.06, 4.34]). A similar study reported consistent results (risk estimate of 2.27 [95% CI 0.99, 5.20]). Other risk factors for NAION may have contributed to the occurrence of NAION in these studies. A causal relationship between PDE5 inhibitor use and the occurrence of NAION cannot be substantiated based on the rare postmarketing reports or these observational studies. Patients receiving single oral doses of PDE5 inhibitors have also demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina.These effects diminished but were still present 6 hours after administration. In a single dose study of 25 healthy males, vardenafil 40 mg did not alter visual acuity, intraocular pressure, or funduscopic and slit lamp findings. In an 8-week, multiple-dose, placebo-controlled clinical trial, clinically significant changes in retinal function did not occur as assessed by ERG amplitudes or the Farnsworth-Munsell 100-hue test. The trial was designed to detect retinal function changes that might occur in more than 10% of patients. Of 52 enrollees, 32 subjects completed the study. Two patients in the vardenafil group reported transient cyanopsia (objects appear blue).
Adverse reactions affecting hearing or otic special senses and occurring in < 2% of patients in controlled clinical trials of vardenafil include hearing loss and tinnitus. In addition, 29 reports of sudden changes in hearing including hearing loss or decrease in hearing, usually in 1 ear only, have been reported to the FDA during post-marketing surveillance in patients taking sildenafil, tadalafil, or vardenafil; the reports are associated with a strong temporal relationship to the dosing of these agents. Many times, the hearing changes are accompanied by vestibular effects including dizziness, tinnitus, and vertigo. Follow-up has been limited in many of the reports; however, in approximately one-third of the patients, the hearing loss was temporary. Concomitant medical conditions or patient factors may play a role, although risk factors for the onset of sudden hearing loss have not been identified. Patients should be instructed to promptly contact their physician if they experience changes in hearing.
The effects of vardenafil on QT prolongation were evaluated in 59 healthy males using moxifloxacin (400 mg) as an active control. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produced similar increases in QTc interval (e.g., 4-6 msec calculated by individual QT correction) as moxifloxacin (7 msec). The potential effect of vardenafil on the QT interval should be considered when prescribing the drug; the manufacturer recommends against drug use in certain patient groups with risk factors for QT prolongation (see Precautions).
Changes in laboratory values have occurred infrequently. During controlled and uncontrolled clinical trials of vardenafil in over 4430 men (mean age 56, range 18-89 years), increased creatine kinase was reported in 2% of those receiving vardenafil versus 1% of those in the placebo group. Increased GGTP and elevated hepatic enzymes (e.g., abnormal liver function tests) were reported in less than 2% of patients.
Vardenafil is contraindicated in patients with a known hypersensitivity to any component of the tablet.
The safe and effective use of vardenafil in combination with other agents for treating erectile dysfunction has not been studied. Therefore, the use of such combinations is not recommended.
Vardenafil is contraindicated in individuals who are currently on nitrate/nitrite therapy or those taking guanylate cyclase (GC) stimulators. Review drug interactions. Consistent with its known effects on the nitric oxide/cGMP pathway, vardenafil may potentiate the hypotensive effects of organic nitrates, nitrites and GC stimulators. Patients receiving nitrates in any form are not to receive PDE5 inhibitors, including those taking intermittent nitrate therapies. It is unknown if it is safe for patients to receive nitrates once vardenafil has been administered. A suitable time interval following vardenafil dosing for safe administration of nitrates or nitric oxide donors has not been determined.
Vardenafil tablets are not recommended in patients with severe hepatic disease (Child-Pugh class C). Patients with moderate hepatic impairment require a reduction in the starting dose of the regular tablets and a lower maximum dosage. Patients with mild hepatic impairment do not require adjustments in the vardenafil tablet dosage. A dosage reduction is required during concomitant use of certain potent CYP3A4 inhibitors; review drug interactions. Vardenafil orally disintegrating tablets (ODT) provide increased exposure as compared to the regular tablets and the vardenafil ODT should not be used in patients with moderate or severe hepatic disease (Child-Pugh class B or C) as the ODT does not allow for dosage reduction needed for patients with moderate hepatic disease. Due to expected significant increases in vardenafil exposure, do not use vardenafil ODT in patients taking strong or moderate CYP3A4 inhibitors; review drug interactions.
Vardenafil tablets and orally disintegrating tablets (ODT) are not recommended in patients with end stage renal disease (renal failure) requiring renal dialysis as vardenafil has not been studied in this population.
There is a degree of cardiac risk associated with sexual activity; therefore, prescribers should evaluate the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction. Health care professionals should consider whether the individual would be adversely affected by vasodilatory events. In particular, caution should be used if vardenafil is prescribed in the following patient groups: patients who have suffered a myocardial infarction, stroke, or life-threatening cardiac arrhythmias in the last 6 months; patients with resting hypotension (BP less than 90/50) or resting hypertension (BP higher than 170/110); or patients with cardiac disease, severe heart failure or coronary artery disease (CAD) which causes unstable angina including those with left ventricular outflow obstruction (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis). Based on recommendations for sildenafil by the American College of Cardiology, it is recommended that vardenafil be used with caution in the following: patients with active coronary ischemia who are not taking nitrates (e.g., positive exercise test for ischemia); patients with congestive heart failure and borderline low blood pressure and borderline low volume status; patients on a complicated, multidrug, antihypertensive program; and patients taking drugs that can prolong the half-life of vardenafil. Vardenafil is contraindicated in patients currently on nitrate/nitrite therapy. In a double-blind, crossover, single-dose study of patients with stable CAD, vardenafil did not cause any impairment in exercise capabilities at levels equivalent to or greater than that achieved during sexual intercourse. The effects of vardenafil on the QT interval were evaluated in 59 healthy males using moxifloxacin (400 mg) as an active control. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produced similar increases in QTc interval (e.g., 4 to 6 milliseconds calculated by individual QT correction) as moxifloxacin. 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. The manufacturer recommends that vardenafil not be used in patients with congenital long QT syndrome and those taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic drugs. Use vardenafil with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.
Prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been associated with PDE5 inhibitor administration. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention. Vardenafil and other agents for the treatment of erectile dysfunction should be used with caution in patients with penile structural abnormality (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell disease, leukemia, multiple myeloma, polycythemia, or history of priapism). Of note, sickle cell disease may increase the risk of prolonging the QT interval when using vardenafil.
Patients should be reminded that vardenafil offers no protection against sexually transmitted disease. Counseling of patients about protective measures, including the prevention of transmission of human immunodeficiency virus (HIV) infection, should be considered. Of note, HIV infection may increase the risk of prolonging the QT interval when using vardenafil.
Advise patients to stop use of all phosphodiesterase 5 (PDE5) inhibitors, including vardanafil, and seek medical attention for evaluation in the event of a sudden visual disturbance in 1 or both eyes. Postmarketing reports with PDE5 inhibitors have included cases of visual disturbances including retinal vein occlusion, visual field defects, reduced visual acuity, and loss of vision (temporary or permanent). Vision loss is attributed to a condition known as non-arteritic anterior ischemic optic neuropathy (NAION), where blood flow is blocked to the optic nerve; this can cause permanent loss of vision; discontinue vardenafil if there is visual loss in 1 or both eyes. Patients with a history of NAION are at increased risk for recurrence. Only use a PDE5 inhibitor in these individuals if the anticipated benefit outweighs the risk. Patients with low cup to disc ratio ('crowded disc') are also at increased risk; however, this condition is uncommon, and there is insufficient evidence to support screening of prospective users of a PDE5 inhibitor. Vardenafil use is not recommended in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa. A minority of patients with the inherited condition retinitis pigmentosa have genetic disorders of retinal phosphodiesterases. Vardenafil use is not recommended in these patients until further information is available.
Vardenafil is not indicated for use in females. There are no adequate and well-controlled trials of vardenafil in humans during pregnancy. In animal reproduction studies, no adverse developmental outcomes were observed during organogenesis at exposures for unbound vardenafil and its major metabolite at 100 and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg.
Vardenafil is not indicated for use in females and is therefore not recommended during breast-feeding. There is no information on the presence of vardenafil and its major metabolite in human milk, the effects on the breast-fed infant, or the effects on milk production. Vardenafil is excreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma; following a single oral dose of 3 mg/kg, 3.3% of the administered dose was excreted into the milk within 24 hours.
Consider a lower starting dose of vardenafil regular tablets for geriatric adults (65 years and older) because they have higher exposures of vardenafil than younger adults (aged 18 to 45 years). However, no difference in safety or effectiveness compared to younger patients has been noted with clinical experience in geriatric adults with use of vardenafil tablets or orally disintegrating tablets (ODT). Geriatric adults who require lower doses of vardenafil should use the regular tablets and not the ODT, which cannot be dose reduced.
Vardenafil should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Like sildenafil, vardenafil can possibly decrease the tone of the lower esophageal sphincter and inhibit esophageal motility.
Vardenafil alone (doses up to 20 mg) does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. However, vardenafil has not been studied or administered to patients with bleeding disorders (coagulopathy) or significant active peptic ulcer disease; administer to these patients after careful benefit-risk assessment.
Patients with a sudden decrease or loss of hearing (hearing impairment) should stop taking vardenafil and seek prompt medical attention. Hearing loss, which may be accompanied by tinnitus and dizziness, has been reported in temporal association with the intake of PDE5 inhibitors, including vardenafil; however, it is unknown if the hearing loss is directly related to PDE5 inhibitors or to other factors.
The vardenafil orally disintegrating tablets contain aspartame, which is a source of phenylalanine. This may be harmful for people with phenylketonuria. Each tablet contains 1.01 mg of phenylalanine.
The vardenafil orally disintegrating tablets contain sorbitol. Patients with hereditary fructose intolerance should not take the orally disintegrating tablets.
For the treatment of erectile dysfunction (ED):
NOTE: Use the film-coated tablets for patients who require a lower dose of vardenafil. Vardenafil orally disintegrating tablets are not interchangeable with the film-coated tablets; vardenafil orally disintegrating tablets provide higher systemic exposure vs. vardenfil film-coated tablets.
Oral dosage (film-coated tablets):
Adults: 10 mg PO as needed approximately 60 minutes before anticipated sexual activity. May decrease dose to 5 mg or increase dose to 20 mg PO as needed approximately 60 minutes before anticipated sexual activity. Max: 1 dose/day and 20 mg/dose. Coadministration of certain drugs may need to be avoided or vardenafil dosage adjustments may be necessary; review drug interactions.
Older Adults: 5 mg PO as needed approximately 60 minutes before anticipated sexual activity. May increase dose up to 20 mg PO as needed approximately 60 minutes before anticipated sexual activity. Max: 1 dose/day and 20 mg/dose. Coadministration of certain drugs may need to be avoided or vardenafil dosage adjustments may be necessary; review drug interactions.
Oral dosage (orally disintegrating tablets):
Adults: 10 mg PO as needed approximately 60 minutes before anticipated sexual activity. Max: 1 dose/day and 10 mg/dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
For regular tablets (e.g., Levitra), 20 mg/day PO. For orally disintegrating tablets (e.g., Staxyn), 10 mg/day PO.
-Geriatric
For regular tablets (e.g., Levitra), 20 mg/day PO. For orally disintegrating tablets (e.g., Staxyn), 10 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Patients with mild hepatic impairment (Child-Pugh class A): No dose adjustment is required.
Patients with moderate hepatic impairment (Child-Pugh class B): Decrease starting dose to 5 mg/day PO using the regular tablets; the maximum dose should not exceed 10 mg/day PO. Do not use vardenafil orally disintegrating tablets in patients with moderate hepatic impairment.
Patients with severe hepatic impairment (Child-Pugh class C): Do not use.
Patients with Renal Impairment Dosing
CrCl 30 mL/minute or more: No dosage adjustments are needed.
Hemodialysis
Do not use vardenafil in patients requiring dialysis; vardenafil has not been studied in these patients.
*non-FDA-approved indication
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Acetaminophen; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Adagrasib: (Major) Avoid concomitant use of adagrasib and vardenafil due to the potential for increased vardenafil exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is necessary, use vardenafil oral tablets instead of orally disintegrating tablets and do not exceed a single dose of 2.5 mg per 24-hour period. Additionally, consider taking steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Vardenafil is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. Coadministration with other strong CYP3A inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Alfuzosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alfuzosin therapy before initiating therapy with the lowest starting dose of vardenafil. Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of alfuzosin; 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 alfuzosin. Concurrent use of these medications may also increase the risk for QT prolongation. Vardenafil is associated with 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) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Amiodarone: (Major) Concomitant use of amiodarone and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Concomitant use of vardenafil and amisulpride increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Do not use vardenafil orally disintegrating tablets with clarithromycin due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; clarithromycin is a strong CYP3A4 inhibitor. Use of vardenafil with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold. Use of these drugs together may increase the risk for QT prolongation or vardenafil-related side effects. Clarithromycin has an established risk of QT prolongation and torsade de pointes. Vardenafil may produce an increase in QTc interval at both therapeutic and supratherapeutic doses.
Anagrelide: (Major) Concomitant use of vardenafil and anagrelide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Apomorphine: (Moderate) Concomitant use of vardenafil and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aprepitant, Fosaprepitant: (Major) Do not use vardenafil orally disintegrating tablets with aprepitant, fosaprepitant due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; aprepitant is a moderate CYP3A4 inhibitor when administered as a 3-day oral regimen (125 mg/80 mg/80 mg). Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold. Fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. Monitor for an increase in vardenafil-related adverse effects for several days after administration of a multi-day aprepitant regimen.
Aripiprazole: (Moderate) Concomitant use of vardenafil and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Concomitant use of vardenafil and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) Concomitant use of vardenafil and lumefantrine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Asenapine: (Major) Concomitant use of vardenafil and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atazanavir: (Major) Do not use vardenafil orally disintegrating tablets with atazanavir due to increased vardenafil exposure. Use reduced doses of no more than 2.5 mg every 72 hours of vardenafil oral tablets with increased monitoring for adverse reactions. Vardenafil is primarily metabolized by CYP3A4/5; atazanavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold.
Atazanavir; Cobicistat: (Major) Do not use vardenafil orally disintegrating tablets with atazanavir due to increased vardenafil exposure. Use reduced doses of no more than 2.5 mg every 72 hours of vardenafil oral tablets with increased monitoring for adverse reactions. Vardenafil is primarily metabolized by CYP3A4/5; atazanavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold. (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Concomitant use of azithromycin and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) If possible, avoid the use of vardenafil with bedaquiline due to the risk of QT prolongation. Monitor ECGs if bedaquiline is used in patients receiving other drugs that prolong the QTc interval, such as vardenafil. Also monitor serum electrolytes. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or if a QTcF interval greater than 500 ms occurs. Both therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produce an increase in the QTc interval.
Berotralstat: (Major) Do not use vardenafil orally disintegrating tablets with berotralstat due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; berotralstat is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Brompheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Buprenorphine: (Major) Concomitant use of vardenafil and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of vardenafil and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of vardenafil and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Ceritinib: (Major) Do not use vardenafil orally disintegrating tablets with ceritinib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; ceritinib is a strong CYP3A inhibitor. Use of vardenafil with other strong CYP3A inhibitors increased the AUC of vardenafil by 10 to 16-fold. There may also be an increased potential for QT prolongation. Vardenafil can produce an increase in QTc interval at both therapeutic and supratherapeutic doses. Ceritinib has been reported to cause concentration-dependent QT prolongation. Periodically monitor ECGs and electrolytes during concurrent use of ceritinib and vardenafil oral tablets.
Chloramphenicol: (Major) Do not use vardenafil orally disintegrating tablets with chloramphenicol due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Chloroquine: (Major) Concomitant use of vardenafil and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Chlorpheniramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Chlorpromazine: (Major) Concomitant use of vardenafil and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ciprofloxacin: (Major) Do not use vardenafil orally disintegrating tablets with ciprofloxacin due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Vardenafil is primarily metabolized by CYP3A and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Cisapride: (Contraindicated) Avoid concomitant use of vardenafil and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of citalopram and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Do not use vardenafil orally disintegrating tablets with clarithromycin due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; clarithromycin is a strong CYP3A4 inhibitor. Use of vardenafil with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold. Use of these drugs together may increase the risk for QT prolongation or vardenafil-related side effects. Clarithromycin has an established risk of QT prolongation and torsade de pointes. Vardenafil may produce an increase in QTc interval at both therapeutic and supratherapeutic doses.
Class IA Antiarrhythmics: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Clofazimine: (Moderate) Concomitant use of clofazimine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Moderate) Concomitant use of vardenafil and clozapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cobicistat: (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Conivaptan: (Major) Do not use vardenafil orally disintegrating tablets with conivaptan due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; conivaptan is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Crizotinib: (Major) Do not use vardenafil orally disintegrating tablets with crizotinib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; crizotinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold. In addition, vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil may produce an increase in QTc interval. Crizotinib has also been associated with concentration-dependent QT prolongation. Monitor ECGs and electrolytes if crizotinib and vardenafil oral tablets are used together.
Cyclosporine: (Major) Do not use vardenafil orally disintegrating tablets with cyclosporine due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cyclosporine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Danazol: (Major) Do not use vardenafil orally disintegrating tablets with danazol due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Darunavir: (Major) Do not use vardenafil orally disintegrating tablets with darunavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; darunavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Darunavir; Cobicistat: (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold. (Major) Do not use vardenafil orally disintegrating tablets with darunavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; darunavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold. (Major) Do not use vardenafil orally disintegrating tablets with darunavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; darunavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Dasatinib: (Moderate) Concomitant use of vardenafil and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Delavirdine: (Major) Do not use vardenafil orally disintegrating tablets with delavirdine due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; delavirdine is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Desflurane: (Major) Concomitant use of vardenafil and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Moderate) Consider the potential for additive QT effects if vardenafil is administered with deutetrabenazine. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Dextromethorphan; Quinidine: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Diltiazem: (Major) Do not use vardenafil orally disintegrating tablets with diltiazem due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Additive effects on blood pressure are also possible. Vardenafil is primarily metabolized by CYP3A and diltiazem is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Diphenhydramine; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Disopyramide: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Dofetilide: (Major) Concomitant use of vardenafil and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Moderate) Concomitant use of vardenafil and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of vardenafil and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Moderate) Concomitant use of vardenafil and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Donepezil; Memantine: (Moderate) Concomitant use of vardenafil and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Doxazosin: (Moderate) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Dronedarone: (Contraindicated) Use of dronedarone with vardenafil is contraindicated due to an increased risk for QT prolongation and torsade de pointes. Increased vardenafil exposure may occur due to dronedarone inhibition of CYP3A4. An increase in vardenafil-related adverse effects, such as prolonged erection, hypotension, or QT prolongation, is possible. Dronedarone is associated with a dose-related increase in the QTc interval. Coadministration of other drugs that also prolong the QT interval may result in additive QT prolongation. Vardenafil is associated with QT prolongation. Therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Dronedarone is a moderate inhibitor of CYP3A4, the primary isoenzyme responsible for the metabolism of vardenafil. Increased systemic vardenafil exposure may occur.
Droperidol: (Major) Concomitant use of vardenafil and droperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dutasteride; Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin 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 tamsulosin; 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 tamsulosin.
Duvelisib: (Major) Do not use vardenafil orally disintegrating tablets with duvelisib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Efavirenz: (Moderate) Concomitant use of vardenafil and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of vardenafil and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of vardenafil and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Eliglustat: (Moderate) Concomitant use of vardenafil and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not use vardenafil orally disintegrating tablets with cobicistat due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; cobicistat is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to 16-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of vardenafil and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of vardenafil and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Concomitant use of vardenafil and encorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Entrectinib: (Major) Concomitant use of vardenafil and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Eribulin: (Major) Concomitant use of vardenafil and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin: (Major) Do not use vardenafil orally disintegrating tablets with erythromycin due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Vardenafil is primarily metabolized by CYP3A and erythromycin is a moderate CYP3A inhibitor. Coadministration with erythromycin increased the AUC of vardenafil by 4-fold.
Escitalopram: (Moderate) Concomitant use of vardenafil and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Etrasimod: (Moderate) Concomitant use of etrasimod and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fedratinib: (Major) Do not use vardenafil orally disintegrating tablets with fedratinib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; fedratinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Fexinidazole: (Major) Concomitant use of fexinidazole and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Finasteride; Tadalafil: (Major) Avoid coadministration of tadalafil and vardenafil. The safety and efficacy of combinations of tadalafil and other phosphodiesterase 5 (PDE5) inhibitors, such as vardenafil, has not been studied.
Fingolimod: (Moderate) Concomitant use of vardenafil and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of flecainide and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Contraindicated) Avoid concomitant use of vardenafil and fluconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase vardenafil exposure, further increasing the risk of adverse effects. If concomitant use of fluconazole and vardenafil oral tablets is required, the maximum single dose is 5 mg every 24 hours. Do not use vardenafil orally disintegrating tablets with fluconazole. Vardenafil is primarily metabolized by CYP3A and fluconazole is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Fluoxetine: (Moderate) Concomitant use of vardenafil and fluoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Use vardenafil with caution in combination with fluphenazine due to increased risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Fluphenazine is also associated with a possible risk for QT prolongation.
Fluvoxamine: (Major) Do not use vardenafil orally disintegrating tablets with fluvoxamine due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; fluvoxamine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold. There may also be an increased risk for QT prolongation and torsade de pointes (TdP) during coadministration. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in the QTc interval.
Fosamprenavir: (Major) Do not use vardenafil orally disintegrating tablets with fosamprenavir due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Foscarnet: (Major) Concomitant use of vardenafil and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fostemsavir: (Moderate) Concomitant use of vardenafil and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gemifloxacin: (Moderate) Concomitant use of vardenafil and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of vardenafil and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Moderate) Concomitant use of vardenafil and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Glasdegib: (Major) Concomitant use of vardenafil and glasdegib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Goserelin: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Granisetron: (Moderate) Concomitant use of vardenafil and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Grapefruit juice: (Major) Grapefruit and grapefruit juice should be avoided during treatment with vardenafil orally disintegrating tablets due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; grapefruit juice is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Guaifenesin; Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Halogenated Anesthetics: (Major) Concomitant use of vardenafil and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Moderate) Concomitant use of vardenafil and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Histrelin: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Hydralazine; Isosorbide Dinitrate, ISDN: (Contraindicated) 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.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of vardenafil and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) Concomitant use of vardenafil and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Idelalisib: (Major) Do not use vardenafil orally disintegrating tablets with idelalisib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; idelalisib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Iloperidone: (Major) Concomitant use of vardenafil and iloperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Imatinib: (Major) Do not use vardenafil orally disintegrating tablets with imatinib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Indinavir: (Major) Do not use vardenafil orally disintegrating tablets with indinavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; indinavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Inotuzumab Ozogamicin: (Major) Concomitant use of vardenafil and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isavuconazonium: (Major) Do not use vardenafil orally disintegrating tablets with isavuconazonium due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; isavuconazoniium is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Isoflurane: (Major) Concomitant use of vardenafil and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isosorbide Dinitrate, ISDN: (Contraindicated) 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: (Contraindicated) 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.
Itraconazole: (Major) Do not use vardenafil orally disintegrating tablets with itraconazole due to increased vardenafil exposure. Vardenafil is primarily metabolized by CYP3A4/5; itraconazole is a strong CYP3A4 inhibitor. If coadministration of itraconazole and vardenafil oral tablets is required, 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. In addition, both itraconazole and vardenafil have been associated with QT prolongation; coadministration may increase this risk.
Ivosidenib: (Major) Concomitant use of vardenafil and ivosidenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vardenafil due to an increased risk for QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of vardenafil, further increasing the risk for adverse effects, such as hypotension and syncope. If concomitant use of ketoconazole and vardenafil oral tablets is required, the maximum single vardenafil oral tablet dose is 5 mg every 24 hours for patients receiving ketoconazole 200 mg daily and 2.5 mg every 24 hours for patients receiving ketoconazole 400 mg daily. Do not use vardenafil orally disintegrating tablets (ODTs) with ketoconazole. Vardenafil is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the AUC of vardenafil by 10-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Do not use vardenafil orally disintegrating tablets with clarithromycin due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; clarithromycin is a strong CYP3A4 inhibitor. Use of vardenafil with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold. Use of these drugs together may increase the risk for QT prolongation or vardenafil-related side effects. Clarithromycin has an established risk of QT prolongation and torsade de pointes. Vardenafil may produce an increase in QTc interval at both therapeutic and supratherapeutic doses.
Lapatinib: (Moderate) Concomitant use of vardenafil and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
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). Avoid use of lefamulin injection with vardenafil; however, if coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment. Vardenafil is a primary CYP3A4 substrate that is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Lefamulin is a moderate CYP3A4 inhibitor that has a concentration-dependent QTc prolongation effect. Coadministration of vardenafil with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Lenacapavir: (Major) Do not use vardenafil orally disintegrating tablets with lenacapavir due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; lenacapavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Lenvatinib: (Major) Concomitant use of vardenafil and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letermovir: (Major) Do not use vardenafil orally disintegrating tablets with letermovir due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; letermovir is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Leuprolide: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vardenafil due to an increased risk for QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of vardenafil, further increasing the risk for adverse effects, such as hypotension and syncope. If concomitant use of ketoconazole and vardenafil oral tablets is required, the maximum single vardenafil oral tablet dose is 5 mg every 24 hours for patients receiving ketoconazole 200 mg daily and 2.5 mg every 24 hours for patients receiving ketoconazole 400 mg daily. Do not use vardenafil orally disintegrating tablets (ODTs) with ketoconazole. Vardenafil is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the AUC of vardenafil by 10-fold.
Lithium: (Moderate) Concomitant use of vardenafil and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Major) Concomitant use of vardenafil and lofexidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lonafarnib: (Major) Do not use vardenafil orally disintegrating tablets with lonafarnib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; lonafarnib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Loperamide: (Moderate) Concomitant use of vardenafil and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of vardenafil and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of vardenafil and lopinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Do not use vardenafil orally disintegrating tablets with ritonavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; ritonavir is a strong CYP3A4 inhibitor. Coadministration of ritonavir with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. Concomitant use may increase the risk of vardenafil-related adverse effects, such as prolonged erection or QT prolongation.
Lorcaserin: (Moderate) 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.
Macimorelin: (Major) Concomitant use of vardenafil and macimorelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Macitentan; Tadalafil: (Major) Avoid coadministration of tadalafil and vardenafil. The safety and efficacy of combinations of tadalafil and other phosphodiesterase 5 (PDE5) inhibitors, such as vardenafil, has not been studied.
Maprotiline: (Moderate) Concomitant use of vardenafil and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mefloquine: (Moderate) Concomitant use of vardenafil and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Methadone: (Major) Concomitant use of vardenafil and methadone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Metronidazole: (Moderate) Concomitant use of metronidazole and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Concomitant use of vardenafil and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Do not use vardenafil orally disintegrating tablets with mifepristone due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Vardenafil is primarily metabolized by CYP3A and mifepristone is a strong CYP3A inhibitor. Coadministration with other strong CYP3A inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Mirtazapine: (Moderate) Concomitant use of vardenafil and mirtazapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mobocertinib: (Major) Concomitant use of mobocertinib and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Concomitant use of vardenafil and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nefazodone: (Major) Do not use vardenafil orally disintegrating tablets with nefazodone due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; nefazodone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Nelfinavir: (Major) Do not use vardenafil orally disintegrating tablets with nelfinavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; nelfinavir is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Netupitant, Fosnetupitant; Palonosetron: (Major) Do not use vardenafil orally disintegrating tablets with netupitant due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; netupitant is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
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 known to prolong the QT interval, such as vardenafil. Sudden death and QT prolongation have occurred in patients receiving nilotinib therapy. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Also, nilotinib is a moderate CYP3A4 inhibitor and vardenafil is a primary CYP3A4 substrate; administering these drugs together may result in increased vardenafil concentrations. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold. Do not use vardenafil orally disintegrating tablets with nilotinib due to increased vardenafil exposure. If use of nilotinib and vardenafil oral tablets is required, do not exceed a single vardenafil oral tablet dose of 5 mg per 24-hour period.
Nirmatrelvir; Ritonavir: (Major) Consider withholding vardenafil during receipt of ritonavir-boosted nirmatrelvir. Coadministration may increase vardenafil exposure resulting in increased toxicity. Vardenafil is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Major) Do not use vardenafil orally disintegrating tablets with ritonavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; ritonavir is a strong CYP3A4 inhibitor. Coadministration of ritonavir with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. Concomitant use may increase the risk of vardenafil-related adverse effects, such as prolonged erection or QT prolongation.
Nirogacestat: (Major) Do not use vardenafil orally disintegrating tablets with nirogacestat due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; nirogacestat is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Nitrates: (Contraindicated) 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: (Contraindicated) 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: (Contraindicated) Concomitant use of nitroprusside and vardenafil is contraindicated due to the risk of additive hypotension. A suitable time interval after vardenafil dosing for the safe administration of nitrates has not been determined. In addition, vardenafil may potentiate the nitric oxide-mediated platelet anti-aggregatory effect of nitroprusside.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Concomitant use of vardenafil and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of vardenafil and fluoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of vardenafil and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Concomitant use of vardenafil and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ondansetron: (Major) Concomitant use of ondansetron and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osilodrostat: (Moderate) Concomitant use of vardenafil and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of vardenafil and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of vardenafil and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking vardenafil due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
Pacritinib: (Major) Concomitant use of pacritinib and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of vardenafil and paliperodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of vardenafil and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Concomitant use of vardenafil and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentamidine: (Major) Concomitant use of vardenafil and pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Phentolamine: (Moderate) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Phenylephrine: (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Pimavanserin: (Major) Concomitant use of vardenafil and pimavanserin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of vardenafil and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Pitolisant: (Major) Concomitant use of vardenafil and pitolisant increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking vardenafil due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
Posaconazole: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as vardenafil, is contraindicated. Posaconazole is associated with QT prolongation, and vardenafil may cause QT prolongation at both therapeutic and supratherapeutic doses. Also, posaconazole may inhibit the metabolism of vardenafil. Posaconazole is a potent CYP3A4 inhibitor. Elevated plasma concentrations of vardenafil may also increase the risk for other vardenafil-related adverse events, such as prolonged erection or potential for syncope.
Prazosin: (Moderate) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Primaquine: (Moderate) Concomitant use of vardenafil and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Procainamide: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. 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) Concomitant use of promethazine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Minor) The therapeutic effect of phenylephrine injection may be decreased in patients receiving phosphodiesterase inhibitors. A decreased pressor effect of phenylephrine might occur. Monitor for proper blood pressure when these drugs are used together.
Propafenone: (Major) Concomitant use of vardenafil and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of vardenafil and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Quinine: (Major) Concomitant use of vardenafil and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quizartinib: (Major) Concomitant use of quizartinib and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Concomitant use of vardenafil and ranolazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Relugolix: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ribociclib: (Major) Concurrent use of vardenafil orally disintegrating tablets with ribociclib should be avoided due to increased vardenafil exposure. If use of vardenafil oral tablets and ribociclib is required, do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Ribociclib is a strong CYP3A4 inhibitor and vardenafil is a primary CYP3A4 substrate. Also, coadministration of ribociclib with vardenafil should be avoided if possible due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Vardenafil is associated with QT prolongation. Vardenafil can produce QT prolongation at both therapeutic and supratherapeutic doses.
Ribociclib; Letrozole: (Major) Concurrent use of vardenafil orally disintegrating tablets with ribociclib should be avoided due to increased vardenafil exposure. If use of vardenafil oral tablets and ribociclib is required, do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Ribociclib is a strong CYP3A4 inhibitor and vardenafil is a primary CYP3A4 substrate. Also, coadministration of ribociclib with vardenafil should be avoided if possible due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Vardenafil is associated with QT prolongation. Vardenafil can produce QT prolongation at both therapeutic and supratherapeutic doses.
Rilpivirine: (Moderate) Concomitant use of vardenafil and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Riociguat: (Contraindicated) Use of riociguat and vardenafil is contraindicated due to the risk of hypotension. Discontinue riociguat at least 24 hours prior to vardenafil administration. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including vardenafil, may potentiate the hypotensive effects of riociguat.
Risperidone: (Moderate) Concomitant use of vardenafil and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ritlecitinib: (Major) Do not use vardenafil orally disintegrating tablets with ritlecitinib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; ritlecitinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Ritonavir: (Major) Do not use vardenafil orally disintegrating tablets with ritonavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; ritonavir is a strong CYP3A4 inhibitor. Coadministration of ritonavir with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. Concomitant use may increase the risk of vardenafil-related adverse effects, such as prolonged erection or QT prolongation.
Romidepsin: (Moderate) Concomitant use of vardenafil and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sapropterin: (Moderate) Sapropterin acts as a cofactor in the synthesis of nitric oxide and may cause vasorelaxation. Caution should be exercised when administering sapropterin in combination with drugs that affect nitric oxide-mediated vasorelaxation such as phosphodiesterase inhibitors. When given together these agents may produce an additive reduction in blood pressure. The combination of sapropterin and a phosphodiesterase (PDE5) inhibitor did not significantly reduce blood pressure when administered concomitantly in animal studies. The additive effect of these agents has not been studied in humans.
Saquinavir: (Contraindicated) Coadministration of saquinavir boosted with ritonavir is contraindicated with other drugs that may prolong the QT interval and which are primary CYP3A4 substrates, such as vardenafil. Saquinavir boosted with ritonavir is a strong CYP3A4 inhibitor that increases the QT interval in a dose-dependent fashion. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval.
Selpercatinib: (Major) Concomitant use of vardenafil and selpercatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Moderate) Concomitant use of vardenafil and sertraline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Concomitant use of vardenafil and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Silodosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin 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 silodosin; 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 silodosin.
Siponimod: (Major) Concomitant use of vardenafil and siponimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of vardenafil and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of vardenafil and sorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of vardenafil and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Stiripentol: (Moderate) Consider a dose adjustment of vardenafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of vardenafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Vardenafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Sunitinib: (Moderate) Concomitant use of vardenafil and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tacrolimus: (Moderate) Concomitant use of vardenafil and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tadalafil: (Major) Avoid coadministration of tadalafil and vardenafil. The safety and efficacy of combinations of tadalafil and other phosphodiesterase 5 (PDE5) inhibitors, such as vardenafil, has not been studied.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin 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 tamsulosin; 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 tamsulosin.
Telavancin: (Moderate) Concomitant use of vardenafil and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Terazosin: (Moderate) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Tetrabenazine: (Major) Concomitant use of vardenafil and tetrabenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Avoid concomitant use of vardenafil and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Tipranavir: (Major) Do not use vardenafil orally disintegrating tablets with tipranavir boosted with ritonavir due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 72-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; ritonavir is a strong CYP3A4 inhibitor. Coadministration of ritonavir with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax.
Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with vardenafil. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil also produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).
Toremifene: (Major) Concomitant use of vardenafil and toremifene increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trandolapril; Verapamil: (Major) Do not use vardenafil orally disintegrating tablets with verapamil due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Additive hypotensive effects are also possible. Vardenafil is primarily metabolized by CYP3A and verapamil is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Trazodone: (Major) Concomitant use of vardenafil and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Use vardenafil with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
Triptorelin: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tucatinib: (Major) Do not use vardenafil orally disintegrating tablets with tucatinib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; tucatinib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Vandetanib: (Major) Concomitant use of vardenafil and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Concomitant use of vemurafenib and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Venlafaxine: (Moderate) Concomitant use of vardenafil and venlafaxine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Verapamil: (Major) Do not use vardenafil orally disintegrating tablets with verapamil due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Additive hypotensive effects are also possible. Vardenafil is primarily metabolized by CYP3A and verapamil is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Vericiguat: (Contraindicated) Use of vericiguat and vardenafil is contraindicated due to the risk of hypotension. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including vardenafil, may potentiate the hypotensive effects of vericiguat.
Vigabatrin: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Voclosporin: (Moderate) Concomitant use of vardenafil and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Do not use vardenafil orally disintegrating tablets with clarithromycin due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; clarithromycin is a strong CYP3A4 inhibitor. Use of vardenafil with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10 to16-fold. Use of these drugs together may increase the risk for QT prolongation or vardenafil-related side effects. Clarithromycin has an established risk of QT prolongation and torsade de pointes. Vardenafil may produce an increase in QTc interval at both therapeutic and supratherapeutic doses.
Voriconazole: (Major) Do not use vardenafil orally disintegrating tablets with voriconazole due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; voriconazole is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold. In addition, voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval.
Vorinostat: (Moderate) Concomitant use of vardenafil and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Voxelotor: (Major) Do not use vardenafil orally disintegrating tablets with voxelotor due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; voxelotor is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the AUC of vardenafil by 4-fold.
Ziprasidone: (Major) Concomitant use of ziprasidone and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cGMP. Cyclic guanosine monophosphate causes smooth muscle relaxation in the corpus cavernosum thereby allowing inflow of blood; the exact mechanism by which cGMP stimulates relaxation of smooth muscles has not been determined. Phosphodiesterase type 5 is responsible for degradation of cGMP in the corpus cavernosum. Vardenafil enhances the effect of NO by inhibiting PDE5, thereby raising concentrations of cGMP in the corpus cavernosum. Vardenafil has no direct relaxant effect on isolated human corpus cavernosum and, at recommended doses, has no effect in the absence of sexual stimulation. Vardenafil has a greater selectivity for PDE5 versus PDE6, an enzyme found in the retina and involved in phototransduction. Sildenafil, another PDE inhibitor, has a lower selectivity for PDE5 versus PDE6 and is associated with abnormalities related to color vision with higher doses or plasma concentrations of the drug.
Vardenafil is administered orally. The mean steady-state volume of distribution is 208L, indicating extensive distribution throughout the body. Vardenafil and its major metabolite (M1) are highly bound to plasma proteins (approximately 95% for parent drug and M1). Vardenafil is metabolized predominantly in the liver by CYP3A4 (there is some contribution by CYP3A5 and CYP2C isoforms). The major metabolite M1 is the result of desethylation at the piperazine moiety of vardenafil and is further metabolized. M1 has phosphodiesterase selectivity similar to that of vardenafil and an in vitro inhibitory potency for phosphodiesterase 5 (PDE5) that is 28% of that of vardenafil. M1 accounts for about 7% of the total pharmacological activity. Vardenafil is excreted as metabolites predominantly in the feces (approximately 91% to 95% of an oral dose) and to a lesser extent in the urine (about 2% to 6% of an oral dose). The elimination half-life of vardenafil and M1 is about 4 to 5 hours with the use of the film-coated tablets. The elimination half-life of vardenafil is 4 to 6 hours and the elimination half-life of MI is 3 to 5 hours with the use of the orally disintegrating tablets.
Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Vardenafil is primarily a substrate of CYP3A4. Concomitant use of vardenafil with moderate or strong CYP3A4 inhibitors may require a reduction in vardenafil dosage to reduce the risk of adverse effects. In vitro data suggest that vardenafil may inhibit P-gp at therapeutic doses. While concomitant use of vardenafil did not significantly increase plasma concentrations of digoxin (a P-gp substrate), the effect of vardenafil on plasma concentrations of P-gp substrates more sensitive than digoxin (e.g., dabigatran) is unknown.
-Route-Specific Pharmacokinetics
Oral Route
Oral film-coated tablets:
Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. In healthy volunteers, peak plasma concentrations (Cmax) following administration of a single 20 mg oral tablet dose are usually reached between 30 minutes and 2 hours (median 60 minutes) in the fasted state. High-fat meals reduced Cmax by 18% to 50%. The onset of action is within 1 hour of administration.
Orally disintegrating tablets:
The orally disintegrating vardenafil tablets provide a higher systemic exposure than the film-coated tablets. In a study of patients with erectile dysfunction, the mean AUC was increased by 21% to 29% and the mean Cmax was decreased by 19% in geriatric patients and 8% in younger patients (18 to 45 years) as compared to the 10 mg film-coated tablets. In a study of healthy male volunteers (18 to 50 years), the mean Cmax was 15% higher and the mean AUC was 44% higher compared to the 10 mg film-coated tablets. The median time to reach Cmax in a fasted stated was 1.5 hours (range: 45 minutes to 2.5 hours). High fat meals had no effect on vardenafil AUC or Tmax in healthy volunteers, but reduced the Cmax by 35%. When the orally disintegrating vardenafil tablets were administered with water, the vardenafil AUC was reduced by 29% and the median Tmax was shortened by 60 minutes, while Cmax was not affected.
-Special Populations
Hepatic Impairment
Volunteers with mild hepatic impairment (Child-Pugh class A) showed an increase in vardenafil Cmax and AUC of 22% and 17%, respectively, following a 10 mg oral dose. In volunteers with moderate hepatic impairment (Child-Pugh class B), the Cmax and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Reduced doses are recommended for patients with moderate hepatic impairment. Vardenafil has not been studied in patients with severe (Child-Pugh class C) hepatic impairment and should be avoided in this population.
Renal Impairment
In volunteers with mild renal impairment (CrCl 50 to 80 mL/minute), vardenafil pharmacokinetics were similar to those observed in a control group with normal renal function. In those with moderate (CrCl 30 to 50 mL/minute) or severe (CrCl less than 30 mL/minute) renal impairment, the AUC of vardenafil was 20% to 30% higher compared to that observed in a control group with normal renal function. No dosage modifications are required in patients with mild, moderate, or severe renal impairment. Vardenafil pharmacokinetics have not been evaluated in patients needing renal dialysis; use should be avoided in this population.
Pediatrics
Pharmacokinetic trials have not been performed in pediatric patients.
Geriatric
In a healthy volunteer study of geriatric males (65 years or older) and younger males (18 to 45 years), mean Cmax and AUC were 34% and 52% higher for vardenafil film-coated tablets, respectively, in the geriatric males; lower starting doses of the film-coated tablets should be considered for patients 65 years of age and older. In trials with the orally disintegrating tablets, the AUC of vardenafil in geriatric patients was increased by 39% and the Cmax was increased by 21% as compared to patients 45 years or younger; however, no differences in safety and efficacy were observed between geriatric patients and those less than 65 years old in placebo-controlled trials.