DRUG INTERACTIONS Avanafil
Possibility of Pharmacodynamic Interactions with STENDRA
Administration of STENDRA to patients who sadly are using any type of organic nitrate, is contraindicated. In a clinical pharmacology trial, STENDRA was proven to potentiate the hypotensive effect of nitrates. In the patient having taken STENDRA, where nitrate administration is deemed medically necessary within a life-threatening situation, a minimum of 12 hours should elapse after the last dose of STENDRA before nitrate administration may be known as. In 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 STENDRA, and alpha-adrenergic blocking agents are vasodilators with blood pressure level-lowering effects. When vasodilators are used when combined, an additive relation to blood pressure level may be anticipated. In some patients, concomitant by using these drug classes can lower blood pressure levels significantly resulting in symptomatic hypotension (e.g., dizziness, lightheadedness, fainting) [see Warnings and Precautions , Dosage and Administration , and Clinical Pharmacology ].
PDE5 inhibitors, including STENDRA, are mild systemic vasodilators. A clinical pharmacology trial was conducted to evaluate the consequence of STENDRA around the potentiation of your bp-lowering connection between selected antihypertensive medications (amlodipine and enalapril). Additional reductions in hypertension of three to mmHg occurred following co-administration of your single 200 mg dose STENDRA with one of these agents compared to placebo [see Warnings and Precautions and Clinical Pharmacology ].
Both alcohol and PDE5 inhibitors, including STENDRA, behave as vasodilators. When vasodilators are consumed combination, blood pressure-lowering link between each individual compound could be increased. Substantial usage of alcohol (e.g., more than 3 units) in combination with STENDRA can enhance the likelihood of orthostatic signs, including boost in heart rate, lowering in standing high blood pressure, dizziness, and headache. [see Drug Interactions and Clinical Pharmacology ].
Prospect of Other Drugs to Affect STENDRA
STENDRA is often 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 STENDRA 50 mg single-dose systemic exposure (AUC) and maximum concentration (Cmax) comparable to 13-fold and 3-fold, respectively and prolonged the half-life of avanafil to approximately 9 hours. Other potent inhibitors of CYP3A4 (e.g. , itraconazole, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir and telithromycin) could well be anticipated having similar effects. Never use STENDRA in patients taking strong CYP3A4 inhibitors [see Warnings and Precautions and Dosage and Administration ].
HIV PI — Ritonavir (600 mg two times a day), a deep CYP3A4 inhibitor, which also inhibits CYP2C9, increased STENDRA 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. Don't use STENDRA in patients taking ritonavir.
Moderate CYP 3A4 Inhibitors
Erythromycin (500 mg two times a day) increased STENDRA 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 STENDRA is 50 mg, not to ever exceed once every round the clock 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 probably increase avanafil exposure.
Weak CYP3A4 Inhibitors
No in vivo drug-drug interaction studies with weak CYP3A4 inhibitors were conducted.
When administered with STENDRA 200 mg, amlodipine (5 mg daily) increased the Cmax and AUC of avanafil by approximately 22% and 70%, respectively. The half-lifetime of STENDRA 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 possibility effect of CYP inducers around the pharmacokinetics of avanafil has not been evaluated. The concomitant usage of STENDRA and CYP inducers is not recommended.
7.3 Prospects for STENDRA to Affect Other Drugs
In vitro studies
Avanafil had no effects on CYP1A1/2, 2A6, 2B6 and 2E1 (IC50 greater than 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 and its 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 200 mg dose of STENDRA could not alter the changes in PT or INR induced by warfarin, and could not affect collagen-induced platelet aggregation or perhaps the AUC or Cmax of R- or S-warfarin, a 2C9 substrate.
Desipramine — 1 STENDRA 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 STENDRA 200 mg dose increased AUC and Cmax of one particular 40 mg dose of omeprazole, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.
Rosiglitazone — Just one STENDRA 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 — One particular STENDRA 200 mg dose failed to affect the pharmacokinetics of amlodipine (5 mg daily), a CYP3A4 substrate [see Dosage and Administration ].
Alcohol — Just one oral dose of STENDRA 200 mg did not affect alcohol (0.5 g ethanol/kg) plasma concentrations [see Warnings and Precautions ].