Drug Interactions Avanafil
Probability of Pharmacodynamic Interactions with
Administration of to patients who sadly are using any type of organic nitrate, is contraindicated. In a very clinical pharmacology trial, was that can potentiate the hypotensive effect of nitrates. Inside the patient having taken , where nitrate administration is deemed medically necessary within a life-threatening situation, at least 12 hours should elapse as soon as the last dose of before nitrate administration could possibly be generally known as. Such circumstances, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring [see Contraindications , Dosage and Administration , and Clinical Pharmacology ].
Caution is recommended when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including , and alpha-adrenergic blocking agents are vasodilators with blood pressure levels-lowering effects. When vasodilators utilized when combined, an additive relation to hypertension may be likely. Some patients, concomitant through the use of these drug classes can lower blood pressure levels levels significantly resulting in symptomatic hypotension (e.g., dizziness, lightheadedness, fainting) [see Warnings and Precautions , Dosage and Administration , and Clinical Pharmacology ].
PDE5 inhibitors, including , are mild systemic vasodilators. A clinical pharmacology trial was conducted to judge the consequence of within the potentiation within your bp-lowering connection between selected antihypertensive medications (amlodipine and enalapril). Additional reductions in hypertension of three to mmHg occurred following co-administration within your single 200 mg dose with one of these agents compared to placebo [see Warnings and Precautions and Clinical Pharmacology ].
Both alcohol and PDE5 inhibitors, including , work as vasodilators. When vasodilators are consumed combination, blood pressure-lowering link between each individual compound could be increased. Substantial usage of alcohol (e.g., over 3 units) in combination with can increase the probability of orthostatic signs, including increase in beats per minute, lowering in standing high blood pressure levels, dizziness, and headache. [see Drug Interactions and Clinical Pharmacology ].
Prospect of Other Drugs to Affect
is actually a substrate of and predominantly metabolized by CYP3A4. Decrease shown that drugs that inhibit CYP3A4 can increase avanafil exposure.
Strong CYP3A4 Inhibitors
Ketoconazole (400 mg daily), a selective and strong inhibitor of CYP3A4, increased 50 mg single-dose systemic exposure (AUC) and maximum concentration (Cmax) similar to 13-fold and 3-fold, respectively and prolonged the half-lifetime of avanafil to approximately 9 hours. Other potent inhibitors of CYP3A4 (e.g. , itraconazole, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir and telithromycin) is possibly anticipated having similar effects. Never use in patients taking strong CYP3A4 inhibitors [see Warnings and Precautions and Dosage and Administration ].
HIV PI Ritonavir (600 mg two times each day), a deep CYP3A4 inhibitor, that also inhibits CYP2C9, increased 50 mg single-dose Cmax and AUC equal to approximately 2-fold and 13-fold, and prolonged the half-life of avanafil to approximately 9 hours in healthy volunteers. Avoid in patients taking ritonavir.
Moderate CYP 3A4 Inhibitors
Erythromycin (500 mg two times per day) increased 200 mg single-dose Cmax and AUC corresponding to approximately 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours in healthy volunteers. Moderate CYP3A4 inhibitors (e.g., erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil) is envisioned having similar effects. Consequently, the maximum recommended dose of is 50 mg, not to ever exceed once every for 24 hours for patients taking concomitant moderate CYP3A4 inhibitors [see Warnings and Precautions and Drug Interactions ].
Although specific interactions haven't been studied, other CYP3A4 inhibitors, including grapefruit juice will most likely increase avanafil exposure.
Weak CYP3A4 Inhibitors
No in vivo drug-drug interaction studies with weak CYP3A4 inhibitors were conducted.
When administered with 200 mg, amlodipine (5 mg daily) increased the Cmax and AUC of avanafil by approximately 22% and 70%, respectively. The half-duration of was prolonged to approximately 10 hrs. The Cmax and AUC of amlodipine decreased by approximately 9% and 4%, respectively. [see Dosage and Administration ].
Cytochrome P450 Inducers
The choice effect of CYP inducers round the pharmacokinetics of avanafil will never be evaluated. The concomitant use of and CYP inducers isn't recommended.
7.3 Prospects for to Affect Other Drugs
Ex vivo studies
Avanafil had no effects on CYP1A1/2, 2A6, 2B6 and 2E1 (IC50 above 100 micromolar) and weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4). Major circulating metabolites of avanafil (M4 and M16) had no effects on CYPs 1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Avanafil as well as metabolites (M4 and M16) are unlikely to cause clinically significant inhibition of CYPs 1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4.
In vivo studies
Warfarin Just one single 200 mg dose of cannot customize the modifications in PT or INR induced by warfarin, and may not affect collagen-induced platelet aggregation or use the AUC or Cmax of R- or S-warfarin, a 2C9 substrate.
Desipramine 1 200 mg dose increased AUC and Cmax on the single 50 mg dose of desipramine, a CYP2D6 substrate, by 5.7% and 5.2%, respectively. Page 8 of 22
Omeprazole 1 200 mg dose increased AUC and Cmax of one specific 40 mg dose of omeprazole, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Rosiglitazone One 200 mg dose increased AUC by 2.0% and decreased Cmax by 14% of any single 8 mg dose of rosiglitazone, a CYP2C8 substrate.
Amlodipine A real 200 mg dose did not affect the pharmacokinetics of amlodipine (5 mg daily), a CYP3A4 substrate [see Dosage and Administration ].
Alcohol Just one single oral dose of 200 mg did not affect alcohol (0.5 g ethanol/kg) plasma concentrations [see Warnings and Precautions