STENDRA- avanafil tablet
VIVUS, Inc.
1 INDICATIONS AND USAGE
STENDRA is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.
2 DOSAGE AND ADMINISTRATION
2.1 Erectile Dysfunction
The recommended starting dose is 100 mg. STENDRA should be taken orally as needed as early as approximately 15 minutes before sexual activity.
Based on individual efficacy and tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity, or decreased to 50 mg taken approximately 30 minutes before sexual activity. The lowest dose that provides benefit should be used. Based on individual efficacy and tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity, or decreased to 50 mg taken approximately 30 minutes before sexual activity. The lowest dose that provides benefit should be used.
The maximum recommended dosing frequency is once per day. Sexual stimulation is required for a response to treatment.The maximum recommended dosing frequency is once per day. Sexual stimulation is required for a response to treatment.
2.2 Use with Food
STENDRA may be taken with or without food.
2.3 Concomitant Medications
Nitrates
Concomitant use of nitrates in any form is contraindicated [see Contraindications (4.1)].
Alpha-Blockers
If STENDRA is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating treatment with STENDRA, and STENDRA should be initiated at the 50 mg dose [see Warnings and Precautions (5.6), Drug Interactions (7.1), and Clinical Pharmacology (12.2)].
CYP3A4 Inhibitors
For patients taking concomitant strong CYP3A4 inhibitors (including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin), do not use STENDRA [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].
For patients taking concomitant moderate CYP3A4 inhibitors (including erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil), the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].
3 DOSAGE FORMS AND STRENGTHS
STENDRA (avanafil) is supplied as oval, pale yellow tablets containing 50 mg, 100 mg, or 200 mg avanafil debossed with dosage strength.
4 CONTRAINDICATIONS
4.1 Nitrates
Administration of STENDRA with any form of organic nitrates, either regularly and/or intermittently, is contraindicated. Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, STENDRA has been shown to potentiate the hypotensive effects of nitrates.
In a patient who has taken STENDRA, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 12 hours should elapse after the last dose of STENDRA before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring [see Contraindications (4.1), Dosage and Administration (2.3), and Clinical Pharmacology (12.2)] .
DESCRIPTION
STENDRA (avanafil) is a selective inhibitor of cGMP-specific PDE5.
Avanafil is designated chemically as (S)-4-[(3-Chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]- N -(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide
Avanafil occurs as white crystalline powder, molecular formula C 23 H 26 ClN 7 O 3 and molecular weight of 483.95 and is slightly soluble in ethanol, practically insoluble in water, and soluble in 0.1 mol/L hydrochloric acid. STENDRA, for oral administration, is supplied as oval, pale yellow tablets containing 50 mg, 100 mg, or 200 mg avanafil debossed with dosage strengths. In addition to the active ingredient, avanafil, each tablet contains the following inactive ingredients: mannitol, fumaric acid, hydroxypropylcellulose, low substituted hydroxypropylcellulose, calcium carbonate, magnesium stearate, and ferric oxide yellow.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Avanafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum. Because sexual stimulation is required to initiate the local release of NO, the inhibition of PDE5 has no effect in the absence of sexual stimulation.
