FORTOVASE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FORTOVASE (FORTOVASE).
Saquinavir is a protease inhibitor that binds to the active site of HIV-1 protease, blocking the cleavage of viral polyprotein precursors into functional proteins, resulting in the production of immature, non-infectious viral particles.
| Metabolism | Primarily hepatic via CYP3A4; also a substrate of P-glycoprotein. |
| Excretion | Primarily hepatic metabolism via CYP3A4; 2% excreted unchanged in urine, 15% unchanged in feces; extensive biliary excretion of metabolites. |
| Half-life | Terminal elimination half-life is 1-2 hours in healthy subjects; prolonged to 2-5 hours in patients with hepatic impairment or when coadministered with ritonavir. |
| Protein binding | Approximately 97-99% bound to serum proteins, mainly alpha-1-acid glycoprotein. |
| Volume of Distribution | 6.8 L/kg; total Vd approximately 500 L, indicating extensive tissue distribution (e.g., lymph nodes, liver, spleen). |
| Bioavailability | Oral bioavailability is 10-15% without ritonavir; increases to 30-50% with ritonavir boosting due to CYP3A4 inhibition. |
| Onset of Action | Oral: Time to peak plasma concentration (Tmax) 2-4 hours; time to virologic suppression typically 2-4 weeks. |
| Duration of Action | Dosing interval every 8 hours; plasma concentrations fall below IC50 within 6-8 hours; requires boosting with ritonavir to extend duration. |
1200 mg orally three times daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for renal impairment; not significantly removed by hemodialysis. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C; use with caution in mild hepatic impairment (Child-Pugh A) with close monitoring. |
| Pediatric use | Not approved for use in patients below 16 years of age; safety and efficacy not established. |
| Geriatric use | No specific dosage adjustment recommended; use with caution due to potential for decreased hepatic, renal, or cardiac function and concomitant disease or therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FORTOVASE (FORTOVASE).
| Breastfeeding | Breastfeeding is not recommended for HIV-infected mothers due to the risk of HIV transmission. Saquinavir is excreted into human milk; the M/P ratio is unknown. In animal studies, saquinavir was found in milk. Because of the potential for HIV transmission and adverse effects in nursing infants, mothers should be advised not to breastfeed. |
| Teratogenic Risk | FORTOVASE (saquinavir) is Pregnancy Category B. Animal studies have shown no evidence of teratogenicity, but there are no adequate and well-controlled studies in pregnant women. HIV-infected pregnant women should not be treated with saquinavir alone; combination antiretroviral therapy is recommended. The drug crosses the placenta. First trimester: no increased risk of birth defects reported in human studies, but data are limited. Second and third trimesters: no significant fetal risks reported, but theoretical risk of mitochondrial toxicity and hyperlactatemia. Cases of preterm delivery, low birth weight, and stillbirth have been reported in association with protease inhibitors, but causal relationship not established. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to saquinavir or any component of the formulation.","Concomitant use with drugs that are highly dependent on CYP3A4 for clearance (e.g., rifampin, St. John's wort, certain benzodiazepines, etc.) due to risk of serious adverse reactions."]
| Precautions | ["Hepatotoxicity: Monitor liver function; risk of transaminase elevations and clinical hepatitis.","PR interval prolongation: Use caution in patients with pre-existing conduction abnormalities or receiving other drugs that prolong PR interval.","Lipodystrophy and metabolic abnormalities: May include hyperlipidemia, hyperglycemia, and body fat redistribution.","Immune reconstitution syndrome: Can occur with combination antiretroviral therapy.","Hemolytic anemia: Rare cases reported."] |
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| Fetal Monitoring | Monitor maternal liver function tests, serum glucose, lipid profile, and CBC periodically. Assess for signs of hyperglycemia and diabetic ketoacidosis. Monitor fetal growth and well-being with ultrasound and non-stress testing as clinically indicated. Consider monitoring for preterm labor. |
| Fertility Effects | Saquinavir has not been studied for effects on human fertility. In animal studies, no impairment of fertility was observed. HIV infection itself may impair fertility; antiretroviral therapy may improve fertility in some cases. No specific impact on spermatogenesis or oogenesis has been reported. |