Fosamprenavir
Mechanism :
Fosamprenavir is a prodrug that is rapidly hydrolysed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.
Indication :
Contraindications :
Coadministration is contraindicated with drugs that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. If amprenavir is coadministered with ritonavir, the antiarrhythmic agents flecainide and propafenone are also contraindicated. Because of the potential toxicity from the large amount of the excipient, propylene glycol, contained in the Oral Solution, that formulation is contraindicated in certain patient populations and should be used with caution in others. Contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product.
Dosing :
Oral
Protease Inhibitor (PI)-naive patients who are 2 years of age or older:
30 mg/kg (up to 1400 mg/dose) orally twice a day.
47 kg or more:
1400 mg orally twice a day.
PI-naive patients who are at least 4 weeks of age (including infants at a postnatal age of at least 28 days who were born at 38 weeks gestation or greater) and PI-experienced patients who are at least 6 months of age:
<11 kg:
Fosamprenavir 45 mg/kg plus
ritonavir 7 mg/kg orally twice a day.
11 to <15 kg:
Fosamprenavir 30 mg/kg plus
ritonavir 3 mg/kg orally twice a day.
15 to <20 kg:
Fosamprenavir 23 mg/kg plus
ritonavir 3 mg/kg orally twice a day.
≥20 kg:
Fosamprenavir 18 mg/kg (up to 700 mg/dose) plus
ritonavir 3 mg/kg (up to 100 mg/dose) orally twice a day.
39 kg or more:
Fosamprenavir 700 mg plus
ritonavir 100 mg orally twice a day.
Adverse Effect :
Nausea, vomiting, diarrhea, abdominal pain/discomfort, headache, fatigue, rash, increased serum lipase, ALT/AST in patients treated with concomitant ritonavir.
Interaction :
Rifabutin: An increase in the plasma concentrations of rifabutin and a decrease in the plasma concentrations of amprenavir.
Ketoconazole: An increase in the plasma concentrations of amprenavir, a dosage reduction should be considered.
Rifampin: Rifampin is a potent inducer of P450 (CYP3A4) which markedly diminishes plasma concentrations of amprenavir.
Other: Should not be administered concurrently with terfenadine, astemizole, cisapride, triazolam and midazolam because coadministration with inhibitors of P450 (CYP3A4) may result in inhibition of metabolism of these drugs and create the potential for serious and/or life-threatening events (i.e., cardiac arrhythmias or prolonged sedation).
Other drugs that induce CYP3A4 less potently than Rifampin, such as Phenobarbital, Phenytoin, Carbamazepine, and Dexamethasone: Should be used cautiously together since they could also diminish plasma concentrations of amprenavir.
Occupational Hazards: Dizziness and blurred vision have been reported. Patients should be advised to avoid driving or operating machinery if they experience these reactions.
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 | Unlikely to be dialysed. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
For adults:
Mild hepatic impairment: Use a reduced dose of 700 mg twice daily without ritonavir (in treatment-naive patients only) or 700 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced
patients).
Moderate hepatic impairment: Use a reduced dose of 700 mg twice daily without ritonavir (in treatment-naive patients only) or 450 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced patients).
Severe hepatic impairment: Use a reduced dose of 350 mg twice daily without ritonavir (in treatment-naive patients only) or 300 mg twice daily plus ritonavir 100 mg once daily (treatment-naive or experienced
patients).
For pediatric patients with hepatic impairment:
No data are available to define dosing recommendations.