LEVITRA

Indications

• Erectile dysfunction
• Pulmonary arterial hypertension

Dosage

Children: null

Adults: 5 mg once daily, may be adjusted to 2.5 mg once daily or increased to 40 mg once daily if tolerated, depending on indication and response.

Mechanism of action

Vardenafil inhibits cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), an enzyme responsible for the degradation of cGMP in the corpus cavernosum. During sexual stimulation, nitric oxide (NO) is released which stimulates guanylate cyclase, increasing cGMP levels leading to smooth muscle relaxation and enhanced blood flow into the penis. This process facilitates penile erection.

Pharmacodynamics

Vardenafil is a potent and selective inhibitor of PDE5. By preventing the degradation of cGMP, it promotes smooth muscle relaxation in the corpus cavernosum, increasing blood inflow and supporting erectile function. The drug's effects depend on sexual stimulation; without it, vardenafil does not induce an erection. Potential side effects include prolonged erections, sudden loss of vision, and hearing loss.

Pharmacokinetics

Vardenafil is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 1 hour post-dose. The drug has a half-life of about 4 to 5 hours. It is metabolized primarily in the liver by cytochrome P450 enzymes, and both the parent compound and its metabolites are eliminated through urine and feces. Its pharmacokinetics can be affected by food intake and co-administration with other medications.

Contra-indications

• Severe renal impairment
• Concurrent use of nitrates
• Cardiovascular conditions that make sexual activity inadvisable
• Hypotension (systolic blood pressure below 90 mmHg)
• History of priapism or predisposition to priapism (e.g., sickle-cell disease, multiple myeloma, leukemia)

Adverse effects

• Headache
• Flushing
• Dyspepsia
• Nasal congestion
• Visual disturbances
• Sudden loss of vision
• Sudden hearing loss
• Prolonged erection (priapism)

Interactions

• Crizotinib (increases exposure)
• Imatinib (increases exposure)
• Letermovir (increases exposure)
• Nilotinib (increases exposure)
• Antifungal azoles (unknown effect but may increase exposure)

Precautions

• Use with caution in patients with severe heart failure or significant cardiovascular risk
• Monitor for signs of prolonged erection or priapism
• Elderly patients may be at increased risk for adverse effects
• Assess renal and hepatic function before prescribing

Pregnancy

Not indicated for use in women.

Breast-feeding

Not indicated for use in women.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 5 mg, 10 mg

Mechanism of action

Vardenafil inhibits cyclic guanosine monophosphate (GMP) specific phosphodiesterase type 5 (PDE5), which is responsible for the degradation of cyclic GMP 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 cyclic GMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The tissue concentration of cyclic GMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs), and the most abundant PDE in the human corpus cavernosum is PDE5. Therefore, the inhibition of PDE5 by vardenafil enhances erectile function by increasing the amount of cyclic GMP. Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation. In vitro studies have shown that vardenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). The inhibitory effect of vardenafil is more selective on PDE5 than for other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10).

Pharmacodynamics

Vardenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), an enzyme responsible for the degradation of cGMP in the corpus cavernosum. The presence of cGMP in the corpus cavernosum leads to smooth muscle relaxation, an increased inflow of blood and an erection. Therefore, in patients with erectile dysfunction given vardenafil, normal sexual stimulation will increase cGMP levels in the corpus cavernosum. Without sexual stimulation and no cGMP production, vardenafil should not cause an erection. Vardenafil should not be used in men for whom sexual activity is not recommended due to their underlying cardiovascular status. There is also a risk of developing prolonged erections that last longer than 4 hours, as well as priapism. In the event of a sudden loss of vision in one or both eyes, patients should stop using vardenafil. Patients taking PDE5 inhibitors, such as vardenafil, may also develop sudden hearing loss and experience a prolonged QT interval.