Indications: This product is suitable for the treatment of penile erectile dysfunction.
[Usage and Dosage] The recommended initial dose is 100mg, taken orally as needed about 15 minutes before sexual activity. Depending on individual efficacy and tolerability, the dose may be increased to 200mg taken approximately 15 minutes before sexual activity or reduced to 50mg taken 30 minutes before sexual activity. The minimum therapeutic dose should be used. The maximum recommended dosing frequency is once per day. Sexual stimulation is required for therapeutic effect. May be taken with or without food.
1. Nitrates: This product is contraindicated in patients who are taking nitrates in any form, both regularly and/or intermittently. The effect of this product on nitric oxide/cyclic guanosine phosphate (cGMP) pathway can enhance the antihypertensive effect of nitrate drugs. Nitrates should not be used in patients with life-threatening conditions until at least 12 hours after their last use. In such cases, nitrates must be used under strict medical monitoring such as hemodynamic monitoring. (See [Usage and Dosage]) 2. Allergic reaction: It is forbidden for patients who are known to be allergic to any of the ingredients in this product. Allergic reactions have been reported, including itching and swelling of the eyelids. 3. Concomitant use with a guanylate cyclase (GC) agonist: Contraindicated in patients who are using A GC agonist, such as rioxiqua. PDE5 inhibitors, including avanafil, may enhance the antihypertensive effect of GC agonists. 4. Physicians should consider the potential cardiac risks of sexual activity in patients with existing cardiovascular disease before prescribing this product. This product is contraindicated in the following patients: ① Patients who have had myocardial infarction, stroke or life-threatening arrhythmia within the past 6 months; ② Patients with hypotension (170/100 mmHg); ③ Patients with unstable angina pectoris, angina pectoris during sexual intercourse, or congestive heart failure with New York Heart Function Grade 2 or above. 5. Patients with severe liver injury (Child-Pugh grade C) and severe kidney injury (creatinine clearance & LT; 30 ml/min) This product is prohibited. 6. This product is concomitant in patients with loss of vision in one eye due to non-arteritis anterior ischemic optic neuropathy (NAION), regardless of whether the event is related to prior exposure to a PDE5 inhibitor. 7. Contraindicated in patients with known hereditary degenerative retinal diseases. 8. This product is contraindicated in patients using potent CYP3A4 inhibitors including ketoconazole, ritonavir, azanavir, clarithromycin, indenavir, itraconazole, nefazolone, nefinavir, saquinavir, and telithromycin.
1. Cardiovascular risks Patients with pre-existing cardiovascular diseases may have potential cardiovascular risks during sexual activities. Therefore, erectile dysfunction medications, including avanafil, should generally not be used in patients with cardiovascular conditions that are not suitable for sexual activity. (see [Taboo]). Patients with left ventricular outflow tract obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and severely impaired autonomic blood pressure regulation are particularly sensitive to vasodilators, including avanafil. Like other PDE5 inhibitors, avanafil has systemic vasodilation and may increase the antihypertensive effect of other antihypertensive drugs. In healthy volunteers, 200mg of avanafil resulted in a temporary reduction in sitting blood pressure, with a decrease of 8.0mmHg in systolic blood pressure and 3.3mmHg in diastolic blood pressure, with the largest reduction at 1 hour after administration. This effect is minimal in most patients, but physicians should carefully consider the adverse effects of these effects in patients with underlying cardiovascular disease before prescribing this product, especially when considering the effects of sexual activity. 2. Combination with CYP3A4 inhibitors Avanafil is mainly metabolized by CYP450 subtype 3A4 (CYP3A4). CYP3A4 inhibitor may decrease the clearance rate of avanafil and increase its plasma concentration. This product should not be used in patients undergoing a combination of potent CYP3A4 inhibitors including ketoconazole, ritonavir, azanavir, clarithromycin, indenavir, itraconazole, nefazolone, nefinavir, saquinavir, and telithromycin (see Drug Interactions). For patients who are taking a combination of moderately potent CYP3A4 inhibitors, including erythromycin, apunavir, aprepitan, diltiazem, fluconazole, fosanavir, and verapamil, the recommended maximum dose is 50mg and should not be given more than once every 24 hours (see drug interactions). 3. Prolonged erectile duration Erectile duration of more than 4 hours and abnormal erectile duration (painful erectile duration of more than 6 hours) have been reported using other PDE5 inhibitors. If the erection lasts more than 4 hours, the patient should seek medical attention immediately. If erections are not addressed immediately, penile tissue may be damaged and permanent erectile dysfunction may result. Avanafil should be used with caution in patients with anatomical malformations of the penis (e.g., penile skewness, cavernous fibrosis, or Peyronie's disease) and disorders that predissect erection (e.g., sickle cell anemia, multiple myeloma, or leukemia). 4. Eye effects Doctors should inform patients to immediately stop taking all PDE5 inhibitors, including Avanafil, and consult their doctor in the event of sudden loss of vision in one or both eyes. This condition may be a manifestation of non-arteriatic anterior ischemic optic neuropathy (NAION), a rare condition that can cause vision loss including permanent loss. Rare time-dependent NAION has been reported in all post-marketing PDE5 inhibitors. According to the literature, the annual incidence of NAION in men aged ≥50 years ranges from 2.5 to 11.8 per 100,000. An observational study assessed the effect of a short period of use of a PDE5 inhibitor (within 5 half-lives) on the risk of developing NAION compared with a longer period of use of a PDE5 inhibitor before the onset of NAION. Results: The risk of NAION was approximately 2-fold, with a risk assessment value of 2.15 (95%CI: 1.06, 4.34). A similar study reported consistent results with a risk assessment value of 2.27 (95%CI: 0.99, 5.20). Other risk factors for NAION (e.g., optic disc "crowding") may be involved in the occurrence of NAION in these studies. Neither the rare post-marketing reports nor the association between the use of PDE5 inhibitors and NAION in observational studies have demonstrated a causal relationship between the use of PDE5 inhibitors and NAION (see [adverse reactions]). Physicians should consider whether the use of PDE5 inhibitors may adversely affect patients with potential NAION risk factors. Patients who have had NAION are at increased risk of having it again. Therefore, PDE5 inhibitors (including avanafil) should be used with caution in these patients and should be used when the expected benefits outweigh the risks. Patients with "congested" optic discs are also thought to have a higher risk of NAION compared to the general population, but there is insufficient evidence to screen potential users of PDE5 inhibitors, including Avanafil, for this abnormality. 5. Sudden hearing Loss The use of PDE5 inhibitors is associated with sudden hearing loss or loss, which may be accompanied by tinnitus or dizziness. However, it is not clear whether the occurrence of this symptom is directly related to the PDE5 inhibitor or other factors (see [adverse reactions]). Patients with these symptoms should be advised to stop using this product and seek medical attention immediately. 6. Alpha-blockers and other antihypertensives Physicians should inform patients of the potential for avanafil to enhance the antihypertensive effects of alpha-blockers and other antihypertensives. Caution should be exercised when PDE5 inhibitors are combined with alpha blockers (see drug interactions). PDE5 inhibitors (including avanafil) and alpha-blockers are vasodilators with antihypertensive effects. When vasodilators are combined, the expected effect on blood pressure may be cumulative. In some patients, the combination of the two medications can significantly lower blood pressure, leading to symptomatic hypotension (e.g., dizziness, lightheadedness, fainting). The following considerations should be taken into account: patients who buy a pill should reach a stable state on alpha blockers before being treated with a PDE5 inhibitor. Patients taking alpha-blockers alone for hemodynamic instability have an increased risk of symptomatic hypotension after concomitant use of PDE5 inhibitors. Patients who have reached a stable state of being treated with α -blockers at the cost of buying a PDE5 inhibitor should start at the lowest dose (50mg). For patients already taking an ideal dose of a PDE5 inhibitor, they spend time on α -blocker therapy starting at the lowest dose. Concomitant use of a PDE5 inhibitor may further lower blood pressure as the alpha blocker dose increases. The safety of PDE5 inhibitors in combination with alpha blockers may be affected by other factors, including hypovolemia and other antihypertensive agents (see usage and drug interactions). 7. Alcohol should inform patients that alcohol and PDE5 inhibitors (including Avanafil) are vasodilators. The antihypertensive effect of vasodilators is greater when used in combination than when used alone. Therefore, physicians should inform patients that the combination of avanafil with heavy alcohol consumption (e.g., more than 3 units of alcohol) may increase the incidence of postural signs and symptoms, including increased heart rate, decreased orthostatic blood pressure, dizziness, and headache. Concomitant use with other PDE5 inhibitors or other erectile dysfunction therapies The safety and efficacy of this product in combination with other treatments for erectile dysfunction have not been studied. Therefore, combination is not recommended. 9. Effect on bleeding The safety of this product in patients with hemorrhagic disease and active gastrointestinal ulcer is unknown. In vitro, the product enhanced the antiplatelet agglutination activity of sodium nitroprusside (a nitric oxide [NO] donor) on human platelets. 10. Patient advice on SEXUALLY transmitted diseases Avanafil has no protective effect on sexually transmitted diseases. Patients should be informed to take necessary measures to prevent sexually transmitted diseases (including human immunodeficiency virus, HIV)[Pharmacological Effects] During sexual stimulation, the penis is erect due to increased penile blood flow caused by the relaxation of penile artery and smooth muscle of penile cavernosa. This response is mediated by nitric oxide (NO) released by nerve endings and endothelial cells, which stimulates smooth muscle cells to synthesize cyclophosphamide (cGMP), which causes smooth muscle relaxation and increases blood flow to the penile cavernous body. Avanafil enhances erectile function by inhibiting phosphodiesterase 5 (PDE5) and increasing cGMP. Avanafil has NO direct relaxation effect on isolated human spongiform smooth muscle. Although inhibition of PDE5 can enhance the effect of NO, PDE5 inhibitor has NO effect in the absence of sexual stimulation because the release of local NO requires sexual stimulation. In vitro test results showed that avanafil was selective for PDE5. Its effect on PDE5 is much stronger than on other known phosphodiesterase types (100 times stronger than on PDE6, 1,000 times stronger than on PDE4, PDE8 and PDE10, 5,000 times stronger than on PDE2 and PDE7, and 10,000 times stronger than on PDE1, PDE3, PDE9 and PDE11). Avanafil's effects on PDE5 are 100 times stronger than those on PDE6, which is mainly present in the retina and is involved in light transmission. In addition to human spongy smooth muscle, PDE5 is found in other tissues, including platelets, blood vessels, visceral smooth muscle, skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testicles, and seminal vesicles. The inhibition of PDE5 in these tissues by avanafil may be the basis of NO's enhanced anti-platelet aggregation in vitro and peripheral vascular dilatation in vivo.