Stendra

Phosphodiesterase Inhibitors for ED

Oral Administration

For erectile dysfunction, may be taken 15 to 30 minutes before sexual activity depending on the dose being prescribed; the maximum dosing frequency is once daily.
May be administered without regard to meals.

Severe

thrombosis / Delayed / 0-1.0
hearing loss / Delayed / 0-1.0
stroke / Early / Incidence not known
cardiac arrest / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
visual impairment / Early / Incidence not known
non-arteritic anterior ischemic optic neuropathy / Delayed / Incidence not known

Moderate

hypertension / Early / 1.0-2.0
constipation / Delayed / 1.0-2.0
nephrolithiasis / Delayed / 0-1.0
hematuria / Delayed / 0-1.0
depression / Delayed / 0-1.0
orthostatic hypotension / Delayed / 0-1.0
palpitations / Early / 0-1.0
hypotension / Rapid / 0-1.0
angina / Early / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
wheezing / Rapid / 0-1.0
dyspnea / Early / 0-1.0
peripheral edema / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
hyperglycemia / Delayed / 0-1.0
priapism / Early / Incidence not known
amnesia / Delayed / Incidence not known
blurred vision / Early / Incidence not known

Mild

headache / Early / 5.1-12.1
flushing / Rapid / 3.2-10.1
pharyngitis / Delayed / 0.9-5.1
nasal congestion / Early / 0.7-4.1
back pain / Delayed / 1.1-3.2
dizziness / Early / 1.0-2.0
rash / Early / 1.0-2.0
diarrhea / Early / 1.0-2.0
nausea / Early / 1.0-2.0
dyspepsia / Early / 1.0-2.0
influenza / Delayed / 1.0-2.0
sinusitis / Delayed / 1.0-2.0
arthralgia / Delayed / 1.0-2.0
increased urinary frequency / Early / 0-1.0
infection / Delayed / 0-1.0
urinary urgency / Early / 0-1.0
insomnia / Early / 0-1.0
vertigo / Early / 0-1.0
drowsiness / Early / 0-1.0
syncope / Early / 0-1.0
pruritus / Rapid / 0-1.0
tinnitus / Delayed / 0-1.0
abdominal pain / Early / 0-1.0
gastroesophageal reflux / Delayed / 0-1.0
vomiting / Early / 0-1.0
cough / Delayed / 0-1.0
epistaxis / Delayed / 0-1.0
muscle cramps / Delayed / 0-1.0
myalgia / Early / 0-1.0
musculoskeletal pain / Early / 0-1.0
fatigue / Early / 0-1.0

Stendra

Rx

An oral phosphodiesterase type 5 (PDE5) inhibitor
Used for erectile dysfunction (ED) and taken prior to anticipated sexual activity
As with other PDE5 inhibitors, contraindicated for use with nitrates because the combination can cause a sudden drop in blood pressure

For the treatment of erectile dysfunction (ED). Oral dosage Adults

100 mg PO as needed as early as 15 minutes before anticipated sexual activity. May decrease the dose to 50 mg or increase the dose to 200 mg PO as needed as early as 15 minutes before sexual activity. Max: 1 dose/day and 200 mg/dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Hepatic Impairment

Mild to moderate hepatic impairment (Child Pugh Class A or B): No dosage adjustments necessary.
Severe hepatic impairment (Child Pugh Class C): No data available; avoid use.

Renal Impairment

CrCl 30 to 89 mL/minute: No dosage adjustment is necessary.
CrCl less than 30 mL/minute: No data available; avoid use in patients with severe renal impairment or renal failure.
 
Intermittent hemodialysis
No data available; avoid use.

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) Do not use avanafil in patients receiving adagrasib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A substrate; adagrasib is a strong CYP3A inhibitor. Coadministration of other strong CYP3A inhibitors increased the avanafil AUC by 13-fold.
Alfuzosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alfuzosin therapy before initiating therapy with avanafil at the lowest dose. Conversely, patients already receiving an optimized dose of avanafil 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 avanafil and alfuzosin.
Alpha-blockers: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
Amiodarone: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving amiodarone. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Amlodipine: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Atorvastatin: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Benazepril: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Celecoxib: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Olmesartan: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Valsartan: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Amobarbital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of avanafil and clarithromycin is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; clarithromycin is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; clarithromycin would be expected to have similar effects. (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Apalutamide: (Major) Coadministration of avanafil with apalutamide is not recommended by the manufacturer of avanafil due to the potential for decreased efficacy. Avanafil is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Aprepitant, Fosaprepitant: (Moderate) Use caution if avanafil and a multi-day regimen of oral aprepitant are used concurrently and monitor for an increase in avanafil-related adverse effects for several days after administration. During coadministration of a multi-day aprepitant regimen, the maximum recommended adult dose of avanafil is 50 mg, not to exceed once every 24 hours. Avanafil is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of avanafil. Moderate CYP3A4 inhibitors may increase plasma concentrations of avanafil. For example, erythromycin increased avanafil Cmax and AUC by 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours. The AUC of another CYP3A4 substrate, midazolam (single dose), increased by 2.3-fold on day 1 and by 3.3-fold on day 5 when coadministered with a 5-day oral aprepitant regimen. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. The effect of weak CYP3A4 inhibitors on avanafil plasma concentrations has not been studied.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Aspirin, ASA; Omeprazole: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Atazanavir: (Major) Concomitant use of avanafil and atazanavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; atazanavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; atazanavir would be expected to have similar effects.
Atazanavir; Cobicistat: (Major) Concomitant use of avanafil and atazanavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; atazanavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; atazanavir would be expected to have similar effects. (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Barbiturates: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Belzutifan: (Major) Coadministration of avanafil with belzutifan is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and belzutifan is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Berotralstat: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving berotralstat. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Bosentan: (Minor) Avanafil is primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers, such as bosentan, will decrease plasma levels of avanafil, however, no interaction studies have been performed. Concomitant use is not recommended.
Brigatinib: (Major) Coadministration of avanafil with brigatinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
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.
Butabarbital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Butalbital; Acetaminophen: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Butalbital; Acetaminophen; Caffeine: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Carbamazepine: (Major) Coadministration of avanafil with carbamazepine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Cenobamate: (Major) Coadministration of avanafil with cenobamate is not recommended due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Ceritinib: (Major) Do not use avanafil in patients receiving ceritinib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Chloramphenicol: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including chloramphenicol, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
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; Dihydrocodeine; 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.
Ciprofloxacin: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving ciprofloxacin. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Clarithromycin: (Major) Concomitant use of avanafil and clarithromycin is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; clarithromycin is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; clarithromycin would be expected to have similar effects.
Cobicistat: (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Codeine; Phenylephrine; Promethazine: (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.
Conivaptan: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving conivaptan. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Crizotinib: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving crizotinib. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; crizotinib is a moderate CYP3A inhibitor. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Dabrafenib: (Major) Avoid the concomitant use of dabrafenib and avanafil; decreased avanafil concentrations and loss of efficacy may occur. Use of an alternative agent is recommended. Dabrafenib is a moderate CYP3A4 inducer and avanafil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Darunavir: (Major) Coadministration of avanifil with darunavir is not recommended. Concurrent use may increase avanafil concentrations. Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors, including darunavir, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Darunavir; Cobicistat: (Major) Coadministration of avanifil with darunavir is not recommended. Concurrent use may increase avanafil concentrations. Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors, including darunavir, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day. (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of avanifil with darunavir is not recommended. Concurrent use may increase avanafil concentrations. Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors, including darunavir, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day. (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Delavirdine: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors including delavirdine, should not take avanafil.
Desipramine: (Minor) Avanafil is a weak inhibitor of CYP2D6 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single desipramine (50 mg) dose, a CYP2D6 substrate, by 5.7% and 5.2%, respectively.
Dexamethasone: (Major) Coadministration of avanafil with dexamethasone is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and dexamethasone is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
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.
Diltiazem: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving diltiazem. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
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.
Doxazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
Dronedarone: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including dronedarone, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
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 avanafil. Conversely, patients already receiving an optimized dose of avanafil 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 avanafil and tamsulosin.
Duvelisib: (Major) Do not exceed an avanfil dose of 50 mg once every 24 hours during coadministration with duvelisib as avanafil serum conentrations may be increased. Avanafil is a substrate of and primarily metabolized by CYP3A4; duvelisib is a moderate inhibitor of CYP3A4. In drug interaction studies, another moderate CYP3A inhibitor increased avanafil Cmax and AUC equal to approximately 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours.
Efavirenz: (Moderate) Avanafil is a substrate of and primarily metabolized by CYP3A4. Efavirenz is an inducer of CYP3A4; coadministration may result in decreased avanafil concentrations. The concomitant use of avanafil and CYP inducers is not recommended.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avanafil is a substrate of and primarily metabolized by CYP3A4. Efavirenz is an inducer of CYP3A4; coadministration may result in decreased avanafil concentrations. The concomitant use of avanafil and CYP inducers is not recommended.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avanafil is a substrate of and primarily metabolized by CYP3A4. Efavirenz is an inducer of CYP3A4; coadministration may result in decreased avanafil concentrations. The concomitant use of avanafil and CYP inducers is not recommended.
Elagolix: (Major) Coadministration of avanafil with elagolix is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Elagolix; Estradiol; Norethindrone acetate: (Major) Coadministration of avanafil with elagolix is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Elbasvir; Grazoprevir: (Major) Administering avanafil with grazoprevir may result in elevated avanafil plasma concentrations. Avanafil is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not use avanafil in patients receiving cobicistat due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Encorafenib: (Moderate) Coadministration of encorafenib with avanafil may result in increased avanafil toxicity or reduced efficacy. Avanafil is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Enzalutamide: (Major) Coadministration of avanafil with enzalutamide is not recommended by the manufacturer of avanafil due to the potential for decreased efficacy. Avanafil is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations of avanafil may decrease.
Erythromycin: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving erythromycin. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with erythromycin increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Ethanol: (Major) Inform patients that substantial consumption of alcohol (e.g., greater than 3 units) in combination with avanafil may increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Both alcohol and PDE5 inhibitors including avanafil act as vasodilators. Concomitant use may attenuate the blood-pressure-lowering effects of each individual compound.
Etravirine: (Moderate) The concomitant use of avanafil and etravirine is not recommended. Coadministration may result in decreased avanafil concentrations. Avanafil is a substrate of and primarily metabolized by CYP3A4. Etravirine is an inducer of CYP3A4.
Fedratinib: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving fedratinib. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Fluconazole: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving fluconazole. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Fluvoxamine: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including fluvoxamine, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Fosamprenavir: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving fosamprenavir. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Fosphenytoin: (Major) Coadministration of avanafil with fosphenytoin is not recommended due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Glycerol Phenylbutyrate: (Major) Coadministration of avanafil with glycerol phenylbutyrate is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and glycerol phenylbutyrate is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Grapefruit juice: (Moderate) Avanafil serum concentrations may increase with concurrent consumption of grapefruit juice and grapefruit-containing foods; it is possible that avanafil-induced side effects could also be increased in some individuals, although this specific interaction have not been studied. Avanafil is a primary substurate of CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Grapefruit juice has been reported to decrease the metabolism of drugs metabolized via this enzyme. Grapefruit juice contains a furano-coumarin compound, 6,7dihydroxybergamottin that inhibits CYP3A4 in enterocytes in the GI tract.
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.
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.
Idelalisib: (Major) Avoid the concomitant use of idelalisib and avanafil; significantly increased avanafil exposure may occur resulting in avanafil-related adverse events. Idelalisib is a strong CYP3A4 inhibitor and avanafil is a sensitive CYP3A substrate. Coadministration with other strong CYP3A4 inhibitors increased exposure to avanafil by 13-fold.
Imatinib: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including imatinib, STI-571, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Indinavir: (Major) Concomitant use of avanafil and indinavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; indinavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; indinavir would be expected to have similar effects.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with avanafil may result in increased serum concentrations of avanafil. Avanafil is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifampin, may decrease avanafil plasma levels. Concomitant use is not recommended.
Isoniazid, INH; Rifampin: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifampin, may decrease avanafil plasma levels. Concomitant use is not recommended.
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: (Contraindicated) Avanafil is contraindicated for use during and for 2 weeks after itraconazole therapy. Use of these drugs together increases avanafil serum concentrations and may result in serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; itraconazole is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; itraconazole would be expected to have similar effects.
Ivosidenib: (Major) Coadministration of avanafil with ivosidenib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and ivosidenib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Ketoconazole: (Major) Do not use avanafil in patients receiving ketoconazole due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the avanafil AUC by 13-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of avanafil and clarithromycin is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; clarithromycin is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; clarithromycin would be expected to have similar effects.
Lefamulin: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving oral lefamulin. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Lenacapavir: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving lenacapavir. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of avanafil; monitor for potential reduction in efficacy. Avanafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of avanafil; monitor for potential reduction in efficacy. Avanafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Major) Do not exceed an avanafil dose of 50 mg every 24 hours when administered concurrently with letermovir due to increased avanafil exposure. Concurrent use should be avoided if the patient is also receiving cyclosporine, because the magnitude of the interaction may be increased. Avanafil is a sensitive substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. The AUC of avanafil was increased by approximately 3-fold in the presence of a moderate CYP3A4 inhibitor and by 13-fold with a strong inhibitor.
Levamlodipine: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Levoketoconazole: (Major) Do not use avanafil in patients receiving ketoconazole due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the avanafil AUC by 13-fold.
Lonafarnib: (Major) Do not use avanafil in patients receiving lonafarnib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Lopinavir; Ritonavir: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors such as ritonavir, should not take avanafil. For example, ketoconazole increased avanafil AUC and Cmax equal to 13-fold and 3-fold, respectively and prolonged the half-life of avanafil to approximately 9 hours. Likewise, coadministration of ritonavir with avanafil resulted in an approximate 13-fold increase in AUC and 2.4-fold increase in Cmax of avanafil. Therefore, concomitant use with strong CYP3A4 inhibitors is not recommended.
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.
Lorlatinib: (Major) Coadministration of avanafil with lorlatinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and lorlatinib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of avanafil by decreasing its systemic exposure; concomitant use is not recommended. Avanafil is a primary substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer.
Mavacamten: (Major) Coadministration of avanafil with mavacamten is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and mavacamten is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Metformin; Rosiglitazone: (Minor) Avanafil is a weak inhibitor of CYP2C8 isoenzymes. A single avanafil (200 mg) dose increased AUC by 2% and decreased Cmax by 14% of a single rosiglitazone (8 mg) dose, a CYP2C8 substrate.
Methohexital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Mifepristone: (Major) Do not use avanafil in patients receiving mifepristone due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Mitapivat: (Major) Coadministration of avanafil with mitapivat is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and mitapivat is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Mitotane: (Major) The concomitant use of mitotane with avanafil is not recommended; if coadministration cannot be avoided, monitor for decreased efficacy of avanafil. Mitotane is a strong CYP3A4 inducer and avanafil is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of avanafil. The potential effect of CYP inducers on avanafil has not been evaluated.
Mobocertinib: (Major) Coadministration of avanafil with mobocertinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and mobocertinib is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Nefazodone: (Major) Concomitant use of avanafil and nefazodone is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; nefazodone is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; nefazodone would be expected to have similar effects.
Nelfinavir: (Major) Concomitant use of avanafil and nelfinavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; nelfinavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; nelfinavir would be expected to have similar effects.
Nevirapine: (Major) Coadministration of avanafil with nevirapine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and nevirapine is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
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.
Nirmatrelvir; Ritonavir: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors such as ritonavir, should not take avanafil. For example, ketoconazole increased avanafil AUC and Cmax equal to 13-fold and 3-fold, respectively and prolonged the half-life of avanafil to approximately 9 hours. Likewise, coadministration of ritonavir with avanafil resulted in an approximate 13-fold increase in AUC and 2.4-fold increase in Cmax of avanafil. Therefore, concomitant use with strong CYP3A4 inhibitors is not recommended. (Major) Consider temporary discontinuation of avanafil during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase avanafil exposure resulting in increased toxicity. Avanafil is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
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 avanafil is contraindicated due to the risk of additive hypotension. If the patient has taken avanafil, at least 12 hours must elapse before nitroprusside administration is considered; monitor hemodynamics closely. In addition, avanafil may potentiate the nitric oxide-mediated platelet anti-aggregatory effect of nitroprusside.
Odevixibat: (Major) Coadministration of avanafil with odevixibat is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and odevixibat is a weak CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Olutasidenib: (Major) Coadministration of avanafil with olutasidenib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and olutasidenib is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Omaveloxolone: (Major) Coadministration of avanafil with omaveloxolone is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and omaveloxolone is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Omeprazole: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively. (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifabutin, may decrease avanafil plasma levels. Concomitant use is not recommended.
Omeprazole; Sodium Bicarbonate: (Minor) Avanafil is a weak inhibitor of CYP2C19 isoenzymes. A single avanafil (200 mg) dose increased the AUC and Cmax of a single omeprazole (40 mg) dose, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Pentobarbital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Perindopril; Amlodipine: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Pexidartinib: (Major) Coadministration of avanafil with pexidartinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Phenobarbital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Phenoxybenzamine: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
Phentolamine: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
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.
Phenytoin: (Major) Coadministration of avanafil with phenytoin is not recommended due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and phenytoin is a strong CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Posaconazole: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including posaconazole, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Prazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
Primidone: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Promethazine; 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.
Quinine: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including quinine, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Ribociclib: (Major) Do not use avanafil in patients receiving ribociclib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inh

ibitors increased the avanafil AUC by 13-fold.
Ribociclib; Letrozole: (Major) Do not use avanafil in patients receiving ribociclib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Rifabutin: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifabutin, may decrease avanafil plasma levels. Concomitant use is not recommended.
Rifampin: (Minor) Avanafil is primarily metabolized by CYP3A4, and although no studies have been performed, concomitant administration of CYP3A4 inducers, such as rifampin, may decrease avanafil plasma levels. Concomitant use is not recommended.
Rifapentine: (Major) Coadministration of avanafil with rifapentine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Riociguat: (Contraindicated) Use of riociguat and avanafil is contraindicated due to the risk of hypotension. Discontinue riociguat at least 24 hours prior to avanafil administration. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including avanafil, may potentiate the hypotensive effects of riociguat.
Ritlecitinib: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving ritlecitinib. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Ritonavir: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors such as ritonavir, should not take avanafil. For example, ketoconazole increased avanafil AUC and Cmax equal to 13-fold and 3-fold, respectively and prolonged the half-life of avanafil to approximately 9 hours. Likewise, coadministration of ritonavir with avanafil resulted in an approximate 13-fold increase in AUC and 2.4-fold increase in Cmax of avanafil. Therefore, concomitant use with strong CYP3A4 inhibitors is not recommended.
Rosiglitazone: (Minor) Avanafil is a weak inhibitor of CYP2C8 isoenzymes. A single avanafil (200 mg) dose increased AUC by 2% and decreased Cmax by 14% of a single rosiglitazone (8 mg) dose, a CYP2C8 substrate.
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: (Major) Concomitant use of avanafil and saquinavir is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; saquinavir is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; saquinavir would be expected to have similar effects.
Secobarbital: (Minor) Avanafil is a substrate of and primarily metabolized by CYP3A4. It can be expected that concomitant administration of CYP3A4 enzyme-inducers will decrease plasma levels of avanafil, however, no interaction studies have been performed. CYP3A4 inducers include barbiturates.
Silodosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil 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 avanafil and silodosin.
Sodium Phenylbutyrate; Taurursodiol: (Major) Coadministration of avanafil with taurursodiol is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and taurursodiol is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Sotorasib: (Major) Coadministration of avanafil with sotorasib is not recommended due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
St. John's Wort, Hypericum perforatum: (Major) Coadministration of avanafil with St. John's Wort is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and St. John's Wort is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Stiripentol: (Moderate) Consider a dose adjustment of avanafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of avanafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Avanafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tamsulosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on tamsulosin therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil 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 avanafil and tamsulosin.
Telmisartan; Amlodipine: (Moderate) Monitor blood pressure closely during concomitant use of avanafil and amlodipine as coadministration may increase the risk of additive hypotension. Avanafil is a substrate of CYP3A and amlodipine is a CYP3A inhibitor. Coadministration with amlodipine increased the AUC of avanafil by approximately 70% and the half-life was prolonged to approximately 10 hours. A mean maximum decrease in supine systolic blood pressure of 1.2 mmHg (compared to placebo), accompanied by a mean maximum increase in pulse rate of 1 beat per minute was observed.
Telotristat Ethyl: (Major) Coadministration of avanafil with telotristat is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Terazosin: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
Ticagrelor: (Contraindicated) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including ticagrelor, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Tipranavir: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors including tipranavir, should not take avanafil.
Trandolapril; Verapamil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving verapamil. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Tucatinib: (Major) Do not use avanafil in patients receiving tucatinib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Verapamil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving verapamil. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Administration of another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Vericiguat: (Contraindicated) Use of vericiguat and avanafil is contraindicated due to the risk of hypotension. Monitor for signs and symptoms of hypotension during transition of therapy. PDE5 inhibitors, including avanafil, 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.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of avanafil and clarithromycin is not recommended due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a substrate of and primarily metabolized by CYP3A4; clarithromycin is a strong inhibitor of CYP3A4. Coadministration of avanafil with other strong inhibitors of CYP3A4 has resulted in significantly increased exposure to avanafil; clarithromycin would be expected to have similar effects.
Voriconazole: (Major) Do not use avanafil in patients receiving voriconazole due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Voxelotor: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving voxelotor. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A substrate; voxelotor is a moderate CYP3A inhibitor. Administration of another moderate CYP3A inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Zafirlukast: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including zafirlukast, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Zanubrutinib: (Major) Coadministration of avanafil with zanubrutinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and zanubrutinib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.

Avanafil/Stendra Oral Tab: 50mg, 100mg, 200mg

Adults

200 mg/day PO.

Geriatric

200 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. 

Avanafil 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 (PDE5) is responsible for degradation of cGMP in the corpus cavernosum. Avanafil enhances the effect of NO by inhibiting PDE5 thereby raising concentrations of cGMP in the corpus cavernosum. Avanafil has no direct relaxant effect on isolated human corpus cavernosum and, at recommended doses, has no effect in the absence of sexual stimulation. In vitro studies show that avanafil is selective for PDE5, with a greater effect on PDE5 versus PDE6, an enzyme found in the retina and involved in phototransduction. PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle.

Avanafil is administered orally. The drug is approximately 99% bound to plasma proteins. It is predominately metabolized by hepatic cytochrome P450 (CYP) enzymes. CYP3A4 is the major metabolizing enzyme and CYP2C is a minor one. In vitro, an active metabolite (M4), has been found to have 18% of the inhibitory potency for PDE5 of that of the parent drug and accounts for approximately 4% of the pharmacologic activity of avanafil. Avanafil is excreted as metabolites; approximately 62% and 21% of the dose appears in the feces and urine, respectively. The half-life is approximately 5 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP2D6
For patients taking concomitant strong CYP3A4 inhibitors, avanafil use is contraindicated. When used with concomitant moderate CYP3A4 inhibitors, an avanafil dose reduction is necessary. Avanafil has weak inhibitory effects toward CYP2C8, 2C9, 2C19, 2D6, and 3A4 isoforms.

Oral Route

Following oral administration, avanafil exhibits a median Tmax of 30 to 45 minutes in the fasted state. A high fat meal reduces avanafil drug exposure, delaying Tmax to 1.12 to 1.25 hours, reducing Cmax by 24% to 39% (depending on dose), and decreasing AUC by approximately 3.8%. These changes are not considered clinically significant. Avanafil may be administered without regard to food or meals.

Pregnancy

Avanafil is not indicated for use in females. There are no adequate and well-controlled trials of avanafil in humans during pregnancy. Based on animal data, avanafil is predicted to have a low risk for major developmental abnormalities in humans.

Avanafil is not indicated for use in females and is therefore not recommended during breast-feeding. It is not known if avanafil is excreted in human breast milk.