Saquinavir
Mechanism :
It is a protease inhibitor (antiviral drug) used in the treatment of HIV infection.
Indication :
- For the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.
Contraindications :
Hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome)
QT and PR interval prolongation and torsades de pointes have been reported rarely; do not use saquinavir/ritonavir with congenital or documented acquired QT prolongation (>450 msec), refractory hypokalemia or magnesemia, and in combination with drugs that prolong QT interval.
Complete atrioventricular (AV) block without implanted pacemakers or high risk of complete AV block.
Severe hepatic impairment.
Coadministration of saquinavir/ritonavir with rifampin due to the risk of severe hepatotoxicity.
Drugs that are contraindicated with saquinavir (when coadministered ‘boosted’ with ritonavir) include CYP3A inhibitors that may result in increased saquinavir plasma levels and cause serious or life-threatening reactions (e.g., prolonged QT interval).
Drug contraindicated with saquinavir/ritonavir include alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), trazodone, rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, HMG-CoA reductase inhibitors (lovastatin, simvastatin), pimozide, sildenafil (when used for PAH), midazolam, and triazolam.
Dosing :
HIV Infection:
<16 years:
Safety and efficacy not established.
>16 years:
1000 mg (plus
ritonavir 100 mg) PO every 12 hours.
In treatment-experienced children:
<2 years:
Not recommended.
≥2 years:
5 to <15 kg:
50 mg/kg (plus
ritonavir 3 mg/kg) PO every 12 hours.
15-40 kg:
50 mg/kg (plus
ritonavir 2.5 mg/kg) PO every 12 hours.
≥40 kg:
50 mg/kg (plus
ritonavir 100 mg) PO every 12 hours.
Adverse Effect :
Rash, hyperglycemia, diarrhea, abdominal discomfort, nausea, abdominal pain, buccal mucosa ulceration, paresthesia, weakness.
Interaction :
Albuterol: Increase the toxicity by pharmacodynamic.
Alfuzosin: Increases the levels of alfuzosin by hepatic/intestinal metabolism.
Rifampin: Decreases the levels of saquinavir.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in normal renal function |
| HD | Unlikely to be dialysed. Dose as in normal renal function |
| HDF/High flux | Not dialysed. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
Mild to moderate hepatic impairment: No dosage adjustments are recommended but if a patient has an underlying liver disease like hepatitis B or C, cirrhosis there may be worsening. Therefore monitor liver function closely.
In severe hepatic impairment: Use is contraindicated.