VARDENAFIL HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). It enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum. This results in increased cGMP levels, leading to smooth muscle relaxation and increased blood flow to the corpus cavernosum, thereby facilitating penile erection.
| Metabolism | Primarily metabolized by the cytochrome P450 (CYP) 3A4 isoenzyme, with minor contribution from CYP3A5 and CYP2C9. The major metabolite is the N-desethyl metabolite, which is less potent than the parent drug. Vardenafil is extensively metabolized and excreted primarily in the feces (approximately 91-95%) and urine (2-6%). |
| Excretion | Primarily hepatic metabolism (CYP3A4, minor CYP2C9) followed by fecal excretion (approximately 91-95% of dose as metabolites) and renal excretion (approximately 2-6% as unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 4-5 hours in healthy subjects. In elderly patients (≥65 years) or those with hepatic impairment (Child-Pugh A/B), half-life may be prolonged up to 6-8 hours. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5-0.8 L/kg, indicating moderate distribution into extravascular tissues. |
| Bioavailability | Oral bioavailability is approximately 15% due to extensive first-pass metabolism. When taken with a high-fat meal (50% fat), Cmax is reduced by 29-39% and Tmax is delayed by 1 hour. |
| Onset of Action | Oral: Rapid onset, with measurable plasma concentrations within 15-30 minutes; clinical effect (erection sufficient for intercourse) typically occurs within 25-60 minutes. Peak plasma concentrations achieved at 0.5-1 hour. |
| Duration of Action | Duration of erective response is up to 4-5 hours, with some effect persisting up to 8 hours. The window of responsiveness (ability to achieve erection with sexual stimulation) is approximately 4-6 hours post-dose. |
10 mg orally once daily as needed, approximately 60 minutes before sexual activity; maximum dose 20 mg; maximum frequency once daily.
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | For GFR 30-50 mL/min: no adjustment. For GFR <30 mL/min or on dialysis: not recommended due to increased exposure. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce starting dose to 5 mg; maximum dose 10 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not indicated for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No dose adjustment required based on age alone; consider hepatic and renal function; increased sensitivity possible, start at lowest dose (5 mg). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Nitrates can cause severe hypotension Can cause priapism and sudden hearing loss.
| Breastfeeding | Vardenafil is excreted in human milk in small amounts; no M/P ratio data are available. Caution should be exercised in nursing mothers due to potential adverse effects in the infant. Discontinue breastfeeding or the drug based on importance. |
| Teratogenic Risk | Vardenafil hydrochloride is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal harm, but no adequate and well-controlled studies exist in pregnant women. Use in the first trimester should consider potential risks unknown; in second and third trimesters, avoid use due to possible hypotension and decreased placental perfusion. Use only if clearly needed. |
■ FDA Black Box Warning
Not recommended for use in women and children. Do not use with organic nitrates (nitroglycerin, isosorbide dinitrate, etc.) as this combination can cause severe hypotension and potentially fatal cardiovascular events.
| Common Effects | Headache |
| Serious Effects |
["Concomitant use with organic nitrates (any form) or nitric oxide donors","Concomitant use with riociguat (a soluble guanylate cyclase stimulator)","Hypersensitivity to vardenafil or any component of the formulation","Patients with severe hepatic impairment (Child-Pugh class C)","Patients with end-stage renal disease requiring dialysis","Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) in patients with moderate hepatic impairment","Patients with preexisting cardiovascular conditions for whom sexual activity is inadvisable"]
| Precautions | ["Cardiovascular risk: Patients with underlying cardiovascular disease should not use vardenafil if sexual activity is inadvisable. Use with caution in patients with left ventricular outflow obstruction (e.g., aortic stenosis) or with hypotension (BP < 90/50 mmHg).","Priapism: Advise patients to seek immediate medical attention if an erection persists >4 hours. Use with caution in patients predisposed to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).","Concomitant use with alpha-blockers: May cause symptomatic hypotension; initiate vardenafil at lowest dose if used with alpha-blockers.","Hearing loss: Sudden decrease or loss of hearing has been reported rarely; consider discontinuation if sudden hearing loss occurs.","Vision loss: Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported rarely; advise discontinuation if sudden vision loss occurs."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate during therapy; assess for signs of hypotension or syncope. Fetal surveillance as per standard obstetrical care; no specific fetal monitoring required unless maternal hypotension occurs. |
| Fertility Effects | Vardenafil is used for erectile dysfunction and does not impair fertility; in males, no negative effects on spermatogenesis or semen parameters have been reported. No adverse effects on female fertility known. |