Avanafil

Avanafil

The main ingredient of this product is avanafil. Excipients: mannitol, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, fumaric acid, calcium carbonate, magnesium stearate.

1. Potential pharmacodynamic interactions with avanafil Nitrate drugs Patients who are taking any form of nitrate drugs are prohibited from taking this product. In clinical pharmacology trials, avanafil can enhance the antihypertensive effect of nitrate drugs. Patients using this product should not use nitrate drugs until at least 12 hours have passed since the last use of this product if nitrate drugs must be used in life-threatening situations. In this case, nitrate drugs must be used under close medical monitoring such as hemodynamic monitoring. (See [Dosage and Administration] and [Contraindications]) Alpha-blockers PDE5 inhibitors should be used with caution when used in combination with alpha-blockers. PDE5 inhibitors (including avanafil) and alpha-blockers are vasodilators with antihypertensive effects. When vasodilators are used in combination, it is expected that the effects on blood pressure may be additive. In some patients, the combination of these two types of drugs can significantly lower blood pressure and lead to symptomatic hypotension (e.g., dizziness, lightheadedness, and fainting). (See [Dosage and Administration] and [Precautions]) Antihypertensive drugs PDE5 inhibitors (including avanafil) are mild systemic vasodilators. A clinical pharmacology trial evaluated the enhancement of the antihypertensive effect of avanafil on several antihypertensive drugs (amlodipine and enalapril). Compared with placebo, a single dose of 200 mg of avanafil combined with the above antihypertensive drugs can further reduce blood pressure by 3-5 mmHg. (See [Precautions] and [Pharmacology and Toxicology]) Alcohol Alcohol and PDE5 inhibitors (including avanafil) are both vasodilators. When vasodilators are used together, the antihypertensive effect is enhanced compared to when used alone. Therefore, the co-administration of avanafil with heavy drinking (e.g., more than 3 units of alcohol) may increase the occurrence of postural symptoms and signs, including increased heart rate, decreased orthostatic blood pressure, dizziness, and headache. (See [Precautions]) 2. Effects of other drugs on avanafil Avanafil is a substrate of CYP3A4 and is mainly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 increase the exposure level of avanafil. (See [Precautions]) Strong CYP3A4 inhibitors Ketoconazole (400 mg/day), a selective strong inhibitor of CYP3A4, can increase the systemic exposure (AUC) and maximum blood concentration (Cmax) of avanafil 50 mg single dose by 13 times and 3 times, respectively, and the half-life of avanafil is extended to about 9 hours. Other strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) have similar effects. Patients who are taking strong CYP3A4 inhibitors should not use this product. (See [Dosage and Administration] and [Precautions]) HIV protease inhibitor - ritonavir (600 mg, twice daily) is a strong CYP3A4 inhibitor that can also inhibit CYP2C9, which can increase the Cmax and AUC of a single dose of 50 mg of avanafil to about 2 times and 13 times, respectively, and extend the half-life of avanafil to about 9 hours in healthy subjects. Patients who are taking ritonavir should not use this product. Moderate CYP3A4 inhibitors In healthy subjects, erythromycin (500 mg, twice daily) increases the Cmax and AUC of a single dose of 200 mg of avanafil by about 2 times and 3 times, respectively, and extends the half-life of avanafil to about 8 hours. Moderate CYP3A4 inhibitors (e.g., erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil) are expected to have similar effects. Therefore, for patients who are taking a moderate CYP3A4 inhibitor, the maximum recommended dose of avanafil is 50 mg, and the frequency of administration should not exceed once every 24 hours. (See [Precautions]) Although specific interactions have not been studied, other CYP3A4 inhibitors (including grapefruit juice) may also increase the exposure of avanafil. Weak CYP3A4 inhibitors have not conducted in vivo drug interaction studies with weak CYP3A4 inhibitors. When the CYP3A4 substrate amlodipine (5 mg, once a day) was co-administered with avanafil 200 mg, the Cmax and AUC of avanafil increased by approximately 22% and 70%, respectively. And the half-life of avanafil was extended to approximately 10 hours. The Cmax and AUC of amlodipine decreased by approximately 9% and 4%, respectively. Cytochrome P450 inducers The potential effects of CYP inducers on the pharmacokinetics of avanafil have not been evaluated. It is not recommended to use avanafil with CYP inducers. 3. Potential effects of avanafil on other drugs In vitro tests, avanafil had no effect on CYP1A1/2, 2A6, 2B6 and 2E1 (IC50 greater than 100μmoL), and only had weak inhibitory effects on other subtypes (CYP2C8, 2C9, 2C19, 2D6, 3A4). The main circulating metabolites of avanafil (M4 and M16) had no effect on CYPs1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Avanafil and its metabolites (M4 and M16) had no significant clinical inhibitory effects on CYPs1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4. In vivo studies Warfarin - A single oral dose of 200 mg avanafil did not alter the PT or INR after warfarin administration, did not affect collagen-induced platelet aggregation, and did not affect the AUC or Cmax of R- or S-warfarin (substrates of 2C9). Desipramine - A single oral dose of 200 mg avanafil increased the AUC and Cmax of a single oral dose of 50 mg desipramine (substrate of CYP2D6) by 5.7% and 5.2%, respectively. Omeprazole - A single oral dose of 200 mg avanafil increased the AUC and Cmax of 40 mg omeprazole (substrate of CYP2C19) taken once daily for 8 days by 5.9% and 8.6%, respectively. Rosiglitazone - A single oral dose of 200 mg avanafil increased the AUC and Cmax of a single oral dose of 8 mg rosiglitazone (substrate of CYP2C8) by 2.0% and decreased the Cmax by 14%. Amlodipine - A single oral dose of 200 mg of avanafil does not affect the pharmacokinetics of amlodipine (CYP3A4 substrate, 5 mg taken orally once daily). Alcohol - A single oral dose of 200 mg of avanafil does not affect the plasma concentration of alcohol (0.5 g ethanol/kg) (see [Precautions]).