LEXIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEXIVA (LEXIVA).
Fosamprenavir is a prodrug of amprenavir, a protease inhibitor (PI) that competitively inhibits HIV-1 protease, preventing cleavage of viral Gag-Pol polyprotein, resulting in immature, non-infectious viral particles.
| Metabolism | Fosamprenavir is rapidly hydrolyzed to amprenavir by cellular phosphatases; amprenavir is primarily metabolized by CYP3A4. It is also a substrate of CYP2D6 and glucuronidation. |
| Excretion | Renal (approximately 82% in urine, with 14% as parent drug and 68% as metabolites); fecal (approximately 16%, with 7% as parent drug). |
| Half-life | Terminal elimination half-life is 2.8 to 5.7 hours; with ritonavir boosting, half-life increases to 7-10 hours, allowing once-daily dosing. |
| Protein binding | Approximately 99% bound to human plasma proteins, primarily alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 0.3-0.6 L/kg (approximately 24 L), indicating distribution into total body water and tissues. |
| Bioavailability | Oral bioavailability is not well defined but is moderate; food does not significantly affect absorption. |
| Onset of Action | Oral: Peak plasma concentrations occur 1-2 hours after administration; antiviral effect begins within hours of achieving therapeutic levels. |
| Duration of Action | Duration of antiviral activity is 8-12 hours when dosed twice daily without ritonavir; with ritonavir boosting, once-daily dosing provides 24-hour coverage. |
1400 mg orally twice daily (with ritonavir 100 mg) or 1400 mg orally once daily (with ritonavir 100 mg and cobicistat 150 mg). For treatment-naïve patients, 1400 mg orally once daily with ritonavir 100 mg or cobicistat 150 mg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. For patients on hemodialysis, no specific recommendation available. |
| Liver impairment | For Child-Pugh class A: no dose adjustment. Child-Pugh class B: reduce to 1400 mg orally once daily (with ritonavir 100 mg). Child-Pugh class C: contraindicated. |
| Pediatric use | For children ≥2 years and weighing ≥15 kg: 14 mg/kg/dose (max 1400 mg) orally twice daily with ritonavir 7 mg/kg/dose (max 100 mg) twice daily. For children weighing ≥30 kg: adult dosing may be used. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider increased risk of comorbidities. Use with caution due to potential age-related reductions in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEXIVA (LEXIVA).
| Breastfeeding | Fosamprenavir is excreted in human milk; M/P ratio not established; potential for HIV transmission and adverse effects in infant; breastfeeding not recommended. |
| Teratogenic Risk | No increased risk of major birth defects based on human data; placental transfer occurs; consider risk-benefit in first trimester. |
| Fetal Monitoring | Monitor liver function tests, serum glucose, and lipid profile; fetal ultrasound for growth assessment. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to fosamprenavir, amprenavir, or any component of the formulation.","Concomitant use with drugs highly dependent on CYP3A4 for clearance (e.g., alfuzosin, dihydroergotamine, ergotamine, methylergonovine, cisapride, pimozide, lurasidone, triazolam, oral midazolam, lovastatin, simvastatin, rifampin, sildenafil [for pulmonary hypertension], St. John's wort)."]
| Precautions | ["Hepatotoxicity: cases of hepatic dysfunction including fatalities, especially in patients with underlying liver disease (e.g., hepatitis B/C).","Nephrolithiasis: reports of kidney stones (including in pediatric patients); consider temporary interruption.","Severe skin reactions: Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).","Hyperglycemia/diabetes mellitus: new-onset or exacerbation.","Hemophilia: increased bleeding in patients with hemophilia A/B.","Fat redistribution/accumulation: lipodystrophy.","Immune reconstitution syndrome: autoimmune disorders may occur during initial treatment.","Drug interactions: coadministration with certain drugs (e.g., rifampin, St. John's wort) contraindicated."] |
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| Fertility Effects | No evidence of impaired fertility in animal studies; limited human data. |