Sildenafil
Mechanism :
Sildenafil 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 cavernosum 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 sildenafil enhances erectile function by increasing the amount of cGMP.
Indication :
- Pulmonary arterial hypertension
Contraindications :
Hypersensitivity to drug/class/component in pediatric patients, Pulmonary veno-occlusive disease.
Caution in elderly patients, hepatic impairment, cardiovascular disease, uncontrolled C HTN, hypotension, hypovolemia, aortic stenosis, IHSS, autonomic dysfunction, retinitis pigmentosa, degenerative retinal disorders, penile deformities, conditions predisposing to priapism, sickle cell disease, coagulation disorder, active PUD.
Dosing :
0.5-1 mg/kg PO thrice daily.
Adverse Effect :
Serious Reactions: Hypotension, retinal hemorrhage, non-arteritic anterior ischemic optic neuropathy, vision loss, hearing loss, hypersensitivity reaction, seizures.
Common Reactions: Headache, dyspepsia, flushing, epistaxis, diarrhea, insomnia, dyspnea, myalgia, erythema, fever, gastritis, paresthesia, visual disturbance.
Interaction :
Contraindicated:
Atazanavir, Boceprevir, Cobicistat, Darunavir, Fosamprenavir, Indinavir, Isosorbide Dinitrate, Isosorbide Mononitrate, Lopinavir/Ritonavir, Mifepristone, Nelfinavir, Nitroglycerin, Riociguat, Ritonavir, Saquinavir, Telaprevir, Tipranavir.
Avoid/Use Alternative:
Alprostadil, Avanafil, Clarithromycin, Conivaptan, Crizotinib, Dabrafenib, Delavirdine, Erythromycin, Fluconazole, Fluvoxamine, Imatinib, Itraconazole, Ketoconazole, Nefazodone, Nitrite, Pazopanib, Posaconazole, Rufinamide, Sildenafil, Tadalafil, Telithromycin, Vardenafil, Voriconazole, Yohimbe, Yohimbine.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 30-50 | Dose as in normal renal function |
| 10-30 | Dose as in normal renal function ED: Initial dose 25 mg and increase if required |
| <10 | Dose as in normal renal function ED: Initial dose 25 mg and increase if required |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Not dialysed. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unlikely to be dialysed. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Consider starting dosage at half of normal dosing.