Avanafil Indications Contraindications, Warning Avanafil Indications Contraindications/Avanafil is an orally available phosphodiesterase type 5 (PDE5) inhibitor with vasodilatory activity. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, thereby prolonging penile erection. Avanafil is a new phosphodiesterase-5 inhibitor that is faster acting and more selective than other drugs belonging to the same class. Chemically, it is a derivative of pyrimidine and is only available as the S-enantiomer. Avanafil acts by inhibiting a specific phosphodiesterase type 5 enzyme which is found in various body tissues, but primarily in the corpus cavernosum penis, as well as the retina. The advantage of avanafil is that it has a very fast onset of action compared with other PDE5 inhibitors. It is absorbed quickly, reaching a maximum concentration in about 30–45 minutes. About two-thirds of the participants were able to engage in sexual activity within 15 minutes. Mechanism of Action of Avanafil Avanafil is a selective phosphodiesterase 5 (PDE5) enzyme inhibitor used for the treatment of erectile dysfunction caused by diabetes, age-induced oxidative stress or other complications. Avanafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flows into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by avanafil enhances erectile function by increasing the amount of cGMP. Indications of Avanafil Erectile Dysfunction Premature ejaculation Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the patient wishes; and Marked personal distress or interpersonal difficulty as a consequence of PE; and Poor control over ejaculation; A history of premature ejaculation in the majority of intercourse attempts over the prior 6 months. Very short sexual intercourse Sexual erectile dysfunction Inability to sustain a satisfactory erection to complete intercourse Treatment of erectile dysfunction in males. You Might Also Read Naproxen; Uses, Dosage, Side Effects, Interactions, PregnancyContra-Indications of Avanafil Multiple myelomas Leukemia Sickle cell anemia increased risk of bleeding due to a clotting disorder Pigmentary retinopathy Hearing loss Severe uncontrolled high blood pressure Heart Attack Unpredictable severe constricting chest Pain Narrowing of the aortic heart valve hypertrophic cardiomyopathy prolonged QT interval on EKG Life-threatening irregular heart rhythm Chronic heart failure Heart attack (within the last 6 months) or Hypertension (high blood pressure), uncontrolled or Retinal disorders (eye problem) or Retinitis pigmentosa (an inherited eye disorder) or Stroke (within the last 6 months) Bleeding disorders or Stomach ulcers Leukemia (blood-related cancer) or Multiple myeloma (bblood-related cancer) or Sickle-cell anemia (blood disorder) Dosages of Avanafil Strengths: 50 mg; 100 mg; 200 mg Erectile Dysfunction Initial dose: 100 mg orally as needed approximately 30 minutes before sexual activity. Maintenance dose: 50 to 200 mg orally as needed 30 minutes before sexual activity. Maximum dose: 200 mg orally once a day Initiate treatment at lowest dose, 50 mg PO once daily, approximately 30 minutes before sexual activity. Monitor for dose tolerance, due to potential additive effect on blood pressure. Patients should be stable on alpha-blocker therapy prior to initiating ED treatment. All Currently Available PDE5 Inhibitors in the United States Avanafil Sildenafil Vardenafil Tadalafil Onset of action 15-30 minutes 30-60 minutes 30-60 minutes 60-120 minutes Plasma half-life 3 hours 4 hours 4 hours 17.5 hours Duration of action Up to 6 hours Up to 12 hours Up to 10 hours Up to 36 hours Effect of food intake Not affected High-fat meals decrease efficacy High-fat meals decrease efficacy Not affected Unique side effects Vision abnormalities (PDE6) Vision abnormalities (PDE6) Back pain, myalgias Side Effects of Avanafil The most common nausea, vomiting, loss of appetite; anxiety, sleep problems (insomnia); dry mouth, unusual taste; little or no urinating; constipation; vision changes; breast swelling (in men or women); or decreased sex drive, impotence, or difficulty having an orgasm. blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights; restless muscle movements in your eyes, tongue, jaw, or neck; a light-headed feeling, like you might pass out; seizure (convulsions); new or worsening chest pain, pounding heartbeats or fluttering in your chest; sudden numbness or weakness, problems with vision, speech, or balance; fever, sore throat, easy bruising, unusual bleeding; painful or difficult urination; You Might Also Read Repaglinide;Uses, Dosage, Side Effects, Drug InteractionsCommon Abdominal or stomach pain agitation blurred vision burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings change in consciousness changes in patterns and rhythms of speech chest pain or discomfort cold sweats confusion Rare Abdominal or stomach pain agitation or irritability blurred vision change in urination chest pain or discomfort confusion about identity, place, and time convulsions cool, pale skin dizziness, faintness, or lightheadedness when getting up suddenly from a lying or Anxiety change in vision seizures weight loss chest pain or tightness confusion cough Agitation arm, back, or jaw pain blurred vision chest pain or discomfort convulsions hallucinations headache irritability muscle pain or cramps pale or yellowed skin, dark colored urine, fever, confusion or weakness; sore throat, and headache with a severe blistering peeling, and red skin rash; swelling, rapid weight gain, feeling short of breath (even with mild exertion); or increased thirst, loss of appetite, urinating less than usual or not at all. Drug Interactions of Avanafil Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take. Amyl Nitrite Erythrityl Tetranitrate Isosorbide Dinitrate Isosorbide Mononitrate Itraconazole Nitroglycerin Pentaerythritol Tetranitrate Propatyl Nitrate Riociguat Atazanavir Boceprevir Clarithromycin Darunavir Efavirenz Etravirine Indinavir Ketoconazole Lopinavir Nefazodone Nelfinavir Netupitant Nevirapine Posaconazole Ritonavir Saquinavir Telaprevir Telithromycin Voriconazole Doxazosin Erythromycin Tamsulosin Other medical abnormality Other medical abnormality, if that is present, use the avanafil with consulting with a doctor Abnormal penis, including curved penis and birth defects of the penis—Chance of problems occurring may be increased and this medicine should be used with caution in these patients. Age greater than 50 years or Coronary artery disease or Crowded disc or low cup to disc ratio in the eye (an eye disorder) or Diabetes or Heart disease or Hyperlipidemia (high fats in the blood) or Hypertension (high blood pressure) or Non-arteritic anterior ischemic optic neuropathy or NAION (a serious eye condition), history of or Smoking—May increase the chance for a serious side effect in the eye called NAION. Angina (severe chest pain), unstable or Arrhythmia (irregular heartbeat, within the last 6 months) or Blood vessel problems (eg, aortic stenosis, idiopathic subaortic stenosis) or Congestive heart failure or Heart attack (within the last 6 months) or Hypertension (high blood pressure), uncontrolled or Hypotension (low blood pressure) or Retinal disorders (eye problem) or Retinitis pigmentosa (an inherited eye disorder) or Stroke (within the last 6 months)—Should not be used in patients with these conditions. Bleeding disorders or Stomach ulcers—Chance of problems occurring may be increased; it is not known if the medicine is safe for use in these patients. Leukemia (blood-related cancer) or Multiple myelomas (blood-related cancer) or Sickle-cell anemia (blood disorder)—Avanafil should be used with caution in these patients as problems with prolonged erection of the penis may occur. You Might Also Read Flupentixol; Uses, Dosage, Side Effects, InteractionsPregnancy & Lactation FDA Pregnancy category- C Pregnancy Avanafil is not indicated for use in females. There are no adequate and well-controlled trials of avanafil in humans during pregnancy. Based on animal data, avanafil is predicted to have a low risk for major developmental abnormalities in humans. Lactations Avanafil is not indicated for use in females and is therefore not recommended in breastfeeding-feeding. It is not known if avanafil is excreted in human breast milk. There is no known indication for the use of avanafil in neonates, infants, or children. Avanafil should not be prescribed to these populations. References DrugBank http://www.drugbank.ca/drugs/DB06237 http://www.drugbank.ca/drugs/DB06237#targets http://www.drugbank.ca/drugs/DB06237#enzymes EPA DSStox https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID50186727 ClinicalTrials.gov https://clinicaltrials.gov/ DailyMed https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=AVANAFIL FDA Pharm Classes https://www.accessdata.fda.gov/spl/data/140fc316-00a1-4f59-b43c-7469f1d7dde4/140fc316-00a1-4f59-b43c-7469f1d7dde4.xml https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm LiverTox https://livertox.nlm.nih.gov/Avanafil.htm NCIt https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C74354 FDA/SPL Indexing Data https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/ EU Community Register of Medicinal Products https://ec.europa.eu/health/documents/community-register/html/h841.htm WHO ATC https://www.whocc.no/atc/ https://www.whocc.no/atc_ddd_index/ FDA Orange Book https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm PubMed Health http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009158/ Springer Nature Read more … Wikipedia https://en.wikipedia.org/wiki/Avanafil https://pubchem.ncbi.nlm.nih.gov MeSH https://www.ncbi.nlm.nih.gov/mesh/67553414 http://www.nlm.nih.gov/mesh/meshhome.html ChEBI http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology Show More