Erectile Dysfunction Hypersensitivity Soluble guanylate cyclase (sGC) stimulators (eg, riociguat); concomitant use can cause hypotension

Drugs for Erectile Dysfunction

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 flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by avanafil enhances erectile function by increasing the amount of cGMP.

Administration: May take with or without food Adult Dose: Erectile Dysfunction 100 mg PO initially as early as 15 min before sexual activity; not to exceed 1 dose/day Based on individual efficacy and tolerability, the dose may be increased to 200 mg taken as early as ~15 minutes before sexual activity, or decreased to 50 mg taken ~30 minutes before sexual activity Use lowest effective dose Hepatic impairment Mild to moderate impairment: Dose adjustment not necessary Severe impairment: Safety and efficacy not established; do not use Renal Dose: Renal Impairment Mild-to-moderate (CrCl ?30 mL/min): Dose adjustment not necessary Severe impairment (CrCl 15-29 mL/min): Safety and efficacy not established; do not use

Avanafil can potentiate the hypotensive effect of nitrates, alphablockers, antihypertensives, and alcohol. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) increase Avanafil exposure

Hypersensitivity Soluble guanylate cyclase (sGC) stimulators (eg, riociguat); concomitant use can cause hypotension

>2% Headache (5.6%) Flushing (3.5%) Nasal congestion (2.1%) Nasopharyngitis (3.4%) Back pain (2.5%) Upper respiratory infection (<2%) Bronchitis (<2%) Influenza (<2%) Sinusitis (<2%) Sinus congestion (<2%) Hypertension (<2%) Dyspepsia (<2%) Nausea (<2%) Constipation (<2%) Rash (<2%) <1% Peripheral edema Fatigue Angina Deep vein thrombosis Palpitations Gastritis Gastroesophageal reflux disease Hypoglycemia Hyperglycemia Oropharyngeal pain Stomach discomfort Vomiting Depression Insomnia Cough Dyspnea exertional Epistaxis Wheezing Pruritus Urinary tract infection Pollakiuria Nephrolithiasis Hematuria Increased erection Balanitis

Pregnancy Category C. Avanafil is not indicated for use in women. There are no adequate and well-controlled studies of Avanafil in pregnant women.

Precaution: Potential for cardiovascular risk during sexual activity in patients with underlying cardiovascular conditions Monitor patients with left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis) Dose should not exceed 50 mg/24hr when taking avanafil concomitantly with moderate CYP3A4 inhibitors Initiate therapy at 50 mg/24hr if coadministered with antihypertensive medications like alpha-blockers Priapism may occur especially in patients with predisposed conditions (eg, sickle cell anemia, multiple myeloma, or leukemia) Discontinue therapy if sudden loss of vision in one or both eyes occur (could be a sign of non-arteritic anterior ischemic optic neuropathy) Safety and efficacy not established in patients with hereditary retinal disorders, including retinitis pigmentosa (use not recommended) Sudden hearing loss may occur; discontinue therapy if tinnitus symptoms occur Alcohol may increase risk for orthostatic hypotension; may increase heart rate and cause dizziness and headache Lactation: Safety and efficacy not established

Single doses up to 800 mg have been given to healthy subjects, and multiple doses up to 300 mg have been given to patients. 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 is not significantly eliminated in the urine.

Store at 20-25°C

Drugs for Erectile Dysfunction

Sexual stimulation causes nitric oxide to be released in the corpus cavernosum; nitric oxide activates the enzyme guanylate cyclase, which in turn increases cGMP levels; increase in cGMP levels causes smooth muscle relaxation. Phosphodiesterase type 5 inhibitors enhance the effects of nitric oxide in smooth muscle relaxation of the corpus cavernosum by inhibiting the degradation of cGMP.

Pregnancy Category: C Lactation: Safety and efficacy not established