Avanafil 100 mg
During sexual stimulation, this drug can increase the blood flow to the penis and cause an erection. Avanafil helps to treat erectile dysfunction. It is present in the class of drug called phosphodiesterase (PDE) inhibitors.
Mechanism of action:
- The mechanism of penis erection involves the release of nitric oxide (NO) into the corpus cavernosum during sexual stimulation, which then activates the enzyme guanylate cyclase leading to increased cGMP levels, leading to spontaneous muscle relaxation in the corpus cavernosum and blood flow Is produced for a construction.
- Avanafil is more powerful than other known phosphodiesterases (over 100-fold for PDE6), over 1,000-fold for PDE4, PDE8 and PDE10, over 5,000-fold for PDE2 and PDE7, over 10,000-fold for PDE1, on PDE5. , PDE3, PDE9, and PDE11). Avanafil is 100 times more potent for PDE5 than PDE6, which is found in the retina and is responsible for phototransfection.
- Avanafil is rapidly absorbed after oral administration, a median of 30 to 45 minutes. Its pharmacokinetics are dose-proportional over the recommended dose range. It is mainly abolished by liver metabolism (mainly CYP3A4). Concomitant use of potent CYP3A4 inhibitors (such as ketoconazole and ritonavir) is associated with increased plasma risk of avanafil. Avanafil has a terminal half-life of approximately 6–17 hours.
- Absorption: Avanafil is rapidly absorbed. The maximum observed plasma concentrations are reached within 0.5 to 0.75 hours of oral dose in the fasting state. When avanafil is taken with a high-fat diet, the rate of absorption decreases with an average delay in Tmax of 1.25 hours and a mean decrease in Cmax of 39% (200 mg). There was no effect on the extent of exposure (AUC). Small changes in avanafil Cmax are considered to be of minimal clinical importance.
- Distribution: Avanafil is approximately 99% bound to plasma proteins. Protein binding is independent of total active substance concentrations, age, renal and liver function. Avanafil was not found to be deposited in plasma when 200 mg was applied twice daily over 7 days. Depending on the measurement of avanafil in the semen of healthy volunteers 45–90 minutes after the dose, less than 0.0002% of the administered dose may appear in the semen of the patients.
- Biotransforming: Avanafil is mainly cleared by CYP3A4 (major pathway) and CYP2C9 (minor pathway) liver microsomal isoenzymes. Plasma concentrations of the major circulating metabolites, M4 and M16, are approximately 23% and 29% of the parent compound. The M4 metabolite shows a phosphodiesterase selectivity similar to avanafil and has an in vitro inhibitory capacity for PDE5 18% of avanafil. Therefore, M4 accounts for about 4% of the total pharmacologic activity. The M16 metabolite was inactive against PDE5.
- Elimination: Avanafil is extensively metabolized in humans. After oral administration, avanafil is excreted primarily in the form of metabolites administered in feces (about 63% of the administered oral dose) and to some extent in the urine (about 21% of the administered oral dose).
- In vitro studies have shown that avanafil is highly selective for PDE5. Its effect is more potent on PDE5 than other known phosphodiesterase (> 100-fold for PDE6 ;> 1,000-fold for PDE4, PDE8 and PDE10 ;> 5,000-fold for PDE2 and PDE7 ;> 10,000-fold for PDE1, PDE3, and PDE9). , And PDE11). Avanafil> is 100 times more potent for PDE5 than PDE6, which is found in the retina and is responsible for phototransfection. Approximately 20,000-fold selectivity for PDE5 versus PDE3 and the enzyme found in the heart and blood vessels is important, as PDE3 is involved in the control of cardiac contraction.
- Compared to placebo, in the penile plethysmography (rigiscan) study in some men after an average of 20 minutes of these subjects for anaphyl, the production of avanafil 200 mg is considered sufficient for penetration (60% stiffness by rigiscan). , In a time interval of 20–40 minutes.
- Before using this medicine, tell your doctor or pharmacist your medical history, specifically: heart problems (such as heart attack or life-threatening irregular heartbeat in the past 6 months, chest pain / angina , Heart failure), stroke months in the past 6, kidney disease (dialysis), liver disease, high or low blood pressure, a serious loss of body water (dehydration), penis position (such as angulation, fibrosis / scarring, pyronie’s disease), History of painful / prolonged erections (priapism), conditions that may increase the risk of priapism (eg sickle cell anemia, leukemia, multiple myeloma), eye problems (eg retinitis pigmentosa, sudden vision loss, NAION) , Bleeding disorders, active stomach ulcers.
- This medicine may make you dizzy or cause vision changes. Alcohol or marijuana (cannabis) can make you dizzier. Do not drive a vehicle, use machinery, nor require alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
- Headache, flushing or dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist immediately. To reduce the risk of dizziness and lighthouse, rise slowly when getting up from a sitting or lying position.
- Remember that your doctor has prescribed this medicine because he or she has decided that the benefit to you outweighs the risk of side effects. Many people using this medicine do not have serious side effects.
- Sexual activity can put extra pressure on your heart, especially if you have heart problems. If you have a heart problem and experience any of these serious side effects while having sex, stop immediately and seek medical help: severe dizziness, fainting, chest / jaw / arm pain, nausea.
- Rarely, there may be a sudden loss of vision, including permanent blindness in one or both eyes (NAION). If this is a serious problem, stop taking avanafil and seek medical attention immediately. If you have heart disease, diabetes, high cholesterol, some other eye problems (“congested disc”), high blood pressure, if you are over 50, or if you smoke, you are slightly more likely to develop NAION.
- The recommended starting dose is 100 mg. Avanafil should be taken as necessary, approximately 15 minutes before sexual activity.
- A single dose of up to 800 mg of Avanafil is given for healthy subjects and patients are given multiple daily doses of 300 mg. Adverse reactions were similar to those seen at lower doses, but increased in rate and severity of occurrence. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance because avanafil is highly bound to plasma proteins and does not end up in the urine.
- If you have sudden vision loss, stop using Avanafil and get emergency medical help. During sexual activity, if you feel dizzy or nausea, or have pain, numbness or tingling in your chest, arms, neck, or jaw, stop and call your doctor immediately.
Duration of action:
- Avanafil has a plasma half-life (T1 / 2) of 3–5 hours and a maximum duration of action of 6 hours.
Drug- drug interactions:
- Avanafil when used with nitrates can cause a severe drop in your blood pressure, which can lead to dizziness, fainting, and rarely a heart attack or stroke. Do not use avanafil with any of the following: Some medications used for the treatment of chest pain / angina (nitrates such as nitroglycerin, isosorbide), recreational drugs called “poppers”, including amyl or butyl nitrite occur.
- If you are taking an alpha-blocker drug (such as doxazosin, tamulosin) to treat an enlarged prostate / BPH or high blood pressure, your blood pressure may be low enough to cause dizziness or fainting. Your doctor may begin treatment with a low dose of avanafil to reduce your risk of low blood pressure.
- Other medications may affect the removal of avanafil from your body, which may affect how avanafil works. Examples include azole antifungals (such as itraconazole, ketoconazole), cabonistat, macrolide antibiotics (such as clarithromycin, erythromycin), HIV protease inhibitors (such as indinavir, ranovir), hepatitis C virus protease inhibitors (such as boceprevir, telaprevir, nefazodone, ribosiclib, rifampin, among others.
- During sexual activity, if you feel dizzy or nausea, or have pain, numbness or tingling in your chest, arms, neck, or jaw, stop and call your doctor immediately. You can have serious side effects of Avanafil.
- Avanafil is not indicated for use in women. There are no data on the use of avanafil in pregnant women. Animal studies do not directly or indirectly indicate harmful effects in relation to pregnancy, fetal / fetal development, division or postpartum development.
- There was no effect on sperm motility or morphology after a single 200 mg oral dose of avanafil in healthy volunteers. In a clinical trial conducted in healthy volunteers and adult men with mild erectile dysfunction, daily administration of avanafil 100 mg oral dose over a period of 26 weeks was not associated with any unpleasant effects on sperm concentration, count, motility or morphology.
- Patients who have suffered from an infarction, stroke, or life-threatening arrhythmia within the past 6 months; Patients with resting hypotension (blood pressure <90/50 mmHg) or hypertension (blood pressure> 170/100 mmHg); Patients with unstable angina, angina with sexual intercourse, or congestive heart failure are classified as New York Heart Association Class 2 or higher. Patients with severe hepatic impairment (Bal-Pugh C). Patients with severe renal impairment (creatinine clearance <30 mL / min). Patients who have vision loss in one eye because of non-arterial anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in association with previous PDE5 inhibitor risk. Patients with known hereditary degenerative retinal disorders. Patients who are using potent CYP3A4 inhibitors (ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nalfinavir, saquinavir and telithromycin).
- This medicinal product does not require any special storage conditions. Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.
- There are no data on the use of avanafil during lactation.