Fosamprenavir Dosage and Use for HIV-1 Infection
Fosamprenavir is primarily used in combination regimens for HIV-1 treatment, with specific dosing based on treatment history and combination with ritonavir for pharmacokinetic boosting. The recommended dosages vary depending on whether the patient is treatment-naïve or treatment-experienced.
Recommended Dosing Regimens
For Treatment-Naïve Adults:
- Fosamprenavir 1,400 mg twice daily (unboosted regimen)
- Fosamprenavir 1,400 mg once daily plus ritonavir 200 mg once daily
- Fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily 1
For Treatment-Experienced Adults:
- Fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily is the only approved regimen 1
For Pediatric Patients:
- For children 2 to <6 years old: Fosamprenavir 23/3 mg/kg with ritonavir twice daily 2
- For children ≥6 years old: Fosamprenavir 18/3 mg/kg with ritonavir twice daily 2
- For adolescents: Fosamprenavir 700/100 mg with ritonavir twice daily 2
Clinical Efficacy
The efficacy of fosamprenavir-based regimens has been well-established:
- In treatment-naïve patients, fosamprenavir 1,400 mg/ritonavir 200 mg once daily demonstrated 72% of patients with viral load <400 copies/mL at 48 weeks when baseline viral load was ≤100,000 copies/mL 1
- For patients with baseline viral load >100,000 copies/mL, 66% achieved viral load <400 copies/mL at 48 weeks 1
- In protease inhibitor-experienced patients, fosamprenavir 700 mg/ritonavir 100 mg twice daily resulted in 58% of patients achieving viral load <400 copies/mL at 48 weeks 1
Important Administration Considerations
- Fosamprenavir tablets may be administered without regard to food intake 3
- For patients with hepatic impairment, dose adjustments may be required 4
- Fosamprenavir should be avoided in patients with known sulfonamide allergy 4
Drug Interactions
Fosamprenavir has significant drug interaction potential due to its metabolism by CYP3A4:
- Contraindicated medications: Midazolam, triazolam, astemizole, bepridil, dihydroergotamine, ergotamine, and cisapride 1, 4
- Use with caution: Other CYP3A4 substrates, inducers, or inhibitors 3
- When used with rifampin or rifabutin, dose adjustments may be necessary 4
Special Populations
Pregnancy:
- Limited data are available for fosamprenavir use during pregnancy
- Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily should only be considered in pregnant patients who are already on a stable regimen and virologically suppressed (HIV-1 RNA <50 copies/mL) 1
- Viral load should be monitored closely during pregnancy as amprenavir exposures may be lower during pregnancy compared to postpartum 1
Pediatric Use:
- Safety and efficacy have been established in children aged 2-18 years
- Appropriate weight-based dosing should be followed 2
- The median increase in CD4+ cell count was 340 cells/mm³ in children receiving unboosted fosamprenavir and 190 cells/mm³ in those receiving fosamprenavir/ritonavir 2
Long-term Safety
Long-term safety data (up to 8 years) show that fosamprenavir-containing regimens:
- Reveal no new safety concerns with extended treatment
- Maintain sustained antiviral responses with >70% of patients maintaining viral suppression <50 copies/mL 5
- Most common adverse events include vomiting, cough, and diarrhea 2
Role in Current Treatment Paradigms
While fosamprenavir is an effective protease inhibitor, it should be noted that in the setting of multiclass resistance (3-class resistance), newer regimens constructed using drugs from new classes are recommended, such as fostemsavir (evidence rating: AIb) or ibalizumab (evidence rating: BII) with at least one additional active drug in an optimized ART regimen 6.
When considering fosamprenavir as part of a treatment regimen, clinicians should evaluate the patient's treatment history, resistance profile, comorbidities, and potential drug interactions to select the most appropriate dosing regimen.