LEVITRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVITRA (LEVITRA).
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 blood flow into the corpus cavernosum, thereby facilitating erection.
| Metabolism | Primarily hepatic via CYP3A4 (major) and CYP3A5 (minor). Metabolite M1 (desethylvardenafil) has similar PDE5 affinity but lower systemic exposure. |
| Excretion | Primarily hepatic metabolism via CYP3A4; metabolites excreted in feces (approximately 90-95% of dose) and urine (approximately 2-6% of dose as unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 4-5 hours in healthy subjects; prolonged in elderly (>65 years) and in hepatic impairment. |
| Protein binding | Approximately 94-96% bound to plasma proteins (mainly albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Approximately 1.1 L/kg (mean Vss after IV administration), indicating distribution into tissues. |
| Bioavailability | Oral bioavailability is approximately 15% (range 8-25%) due to extensive first-pass metabolism. |
| Onset of Action | Oral: Approximately 25-60 minutes (dose-dependent; faster with higher doses and on empty stomach). |
| Duration of Action | Up to 4-5 hours; clinical effect may persist for up to 12 hours in some patients, but maximal effect is within the first 4 hours. |
| Action Class | Synaptic vescicle 2 A protein ligand (AED) |
| Brand Substitutes | Acolev 500mg Tablet, Levepsy 500 Tablet, Levefree 500mg Tablet, Levigress 500 Tablet, Seiz-Free 500 Tablet, Verocet 250mg Tablet, Seiz-Free 250 Tablet, Levigress 250 Tablet, Levecad 250mg Tablet, Levipil 250 Tablet |
10 mg orally once daily as needed, 1 hour before sexual activity; range 5-20 mg based on efficacy and tolerability; maximum dosing frequency once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: no adjustment; CrCl <30 mL/min: not recommended due to lack of data; dialysis: not applicable (contraindicated). |
| Liver impairment | Child-Pugh A (mild): no adjustment; Child-Pugh B (moderate): start at 5 mg daily; Child-Pugh C (severe): contraindicated. |
| Pediatric use | Not indicated for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No initial dose adjustment required; consider starting at 5 mg daily due to increased sensitivity and potential for renal impairment (CrCl <30 mL/min: not recommended). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVITRA (LEVITRA).
| Breastfeeding | Excretion in human milk unknown; not recommended during breastfeeding due to potential for adverse effects in nursing infants. M/P ratio not determined. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; no adequate well-controlled studies in pregnant women. Potential for fetotoxicity (decreased fetal survival) at high doses in animals. Use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with nitrates (organic nitrates, nitrites)","Concomitant use with guanylate cyclase stimulators (e.g., riociguat)","Hypersensitivity to vardenafil or any component","Patients with severe hepatic impairment (Child-Pugh C)","Patients with end-stage renal disease requiring dialysis","Patients with hypotension (BP <90/50 mmHg)","Patients with recent stroke or myocardial infarction (within last 6 months)","Patients with hereditary degenerative retinal disorders (e.g., retinitis pigmentosa)","Concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) in patients with hepatic impairment"]
| Precautions | ["Risk of hypotension when used with nitrates or alpha-blockers","Cardiovascular risk: patients with severe cardiovascular disease, recent MI, stroke, or hypotension should not use","Prolonged erection (>4 hours) and priapism","Sudden hearing loss, tinnitus, or vision loss (non-arteritic anterior ischemic optic neuropathy, NAION)","Decreased blood pressure in patients with left ventricular outflow obstruction","Not recommended for patients with severe hepatic impairment (Child-Pugh C)","Use with caution in patients with retinitis pigmentosa or anatomical deformation of the penis"] |
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| Monitor maternal blood pressure and heart rate during administration. In case of priapism, immediate urologic consultation required. No specific fetal monitoring indicated beyond routine prenatal care. |
| Fertility Effects | No evidence of adverse effects on fertility in animal studies. In men, may improve erectile function and potentially facilitate conception. No effect on spermatogenesis or sperm parameters documented. |