Fosamprenavir Dosage

Usual Adult Dose for HIV Infection

Therapy-naive patients:
Administered without ritonavir: 1400 mg orally twice a day
Administered in combination with ritonavir: Fosamprenavir 1400 mg plus ritonavir 200 mg orally once a day
or
Fosamprenavir 1400 mg plus ritonavir 100 mg orally once a day
or
Fosamprenavir 700 mg plus ritonavir 100 mg orally twice a day

Protease inhibitor (PI)-experienced patients: Fosamprenavir 700 mg plus ritonavir 100 mg orally twice a day

Usual Adult Dose for Nonoccupational Exposure

(Not approved by FDA)

Centers for Disease Control and Prevention recommendations: 1400 mg orally twice a day

Duration: 28 days

Prophylaxis should be initiated as soon as possible, within 72 hours of exposure. The alternative regimens recommended for nonoccupational postexposure HIV prophylaxis include fosamprenavir as part of PI-based regimens.

Usual Pediatric Dose for HIV Infection

Administered without ritonavir:
PI-naive patients who are 2 years of age or older:
Oral suspension: 30 mg/kg (up to 1400 mg/dose) orally twice a day

Tablets:
47 kg or more: 1400 mg orally twice a day

Administered in combination with ritonavir:
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):
Oral suspension:
Less than 11 kg: Fosamprenavir 45 mg/kg plus ritonavir 7 mg/kg orally twice a day
11 to less than 15 kg: Fosamprenavir 30 mg/kg plus ritonavir 3 mg/kg orally twice a day
15 to less than 20 kg: Fosamprenavir 23 mg/kg plus ritonavir 3 mg/kg orally twice a day
20 kg or more: Fosamprenavir 18 mg/kg (up to 700 mg/dose) plus ritonavir 3 mg/kg (up to 100 mg/dose) orally twice a day

Tablets:
39 kg or more: Fosamprenavir 700 mg plus ritonavir 100 mg orally twice a day

PI-experienced patients who are at least 6 months of age:
Oral suspension:
Less than 11 kg: Fosamprenavir 45 mg/kg plus ritonavir 7 mg/kg orally twice a day
11 to less than 15 kg: Fosamprenavir 30 mg/kg plus ritonavir 3 mg/kg orally twice a day
15 to less than 20 kg: Fosamprenavir 23 mg/kg plus ritonavir 3 mg/kg orally twice a day
20 kg or more: Fosamprenavir 18 mg/kg (up to 700 mg/dose) plus ritonavir 3 mg/kg (up to 100 mg/dose) orally twice a day

Tablets:
39 kg or more: Fosamprenavir 700 mg plus ritonavir 100 mg orally twice a day

Ritonavir capsules may be used for patients weighing at least 33 kg.

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Adult patients:
Mild dysfunction (Child-Pugh score ranging from 5 to 6):
Therapy-naive: 700 mg orally twice a day (without ritonavir) or fosamprenavir 700 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 700 mg orally twice a day plus ritonavir 100 mg once a day

Moderate dysfunction (Child-Pugh score ranging from 7 to 9):
Therapy-naive: 700 mg orally twice a day (without ritonavir) or fosamprenavir 450 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 450 mg orally twice a day plus ritonavir 100 mg once a day

Severe dysfunction (Child-Pugh score ranging from 10 to 15):
Therapy-naive: 350 mg orally twice a day (without ritonavir) or fosamprenavir 300 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 300 mg orally twice a day plus ritonavir 100 mg once a day

Pediatric patients: Data not available

Precautions

Fosamprenavir may potentially interact with many drugs. These interactions may be serious and/or life threatening. Concomitant administration of fosamprenavir is contraindicated with drugs that are highly dependent on CYP450 3A4 for clearance and for which elevated concentrations are associated with severe or life-threatening adverse effects. Drugs contraindicated with fosamprenavir (with or without ritonavir) include alfuzosin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort, pimozide, midazolam, triazolam, lovastatin, simvastatin, delavirdine, and sildenafil for treatment of pulmonary arterial hypertension. Fosamprenavir is contraindicated when coadministered with ritonavir in patients receiving flecainide and propafenone. Patients should be advised to report all concurrent medications they are taking.

Severe and life-threatening skin reactions, including at least 1 case of Stevens-Johnson syndrome, have occurred in patients treated with fosamprenavir in clinical trials. Patients should notify their physician if a rash develops. Fosamprenavir should be discontinued if the rash is severe, life-threatening, or associated with systemic symptoms.

Hyperglycemia, new onset diabetes mellitus, and exacerbation of preexisting diabetes mellitus have been reported during postmarketing experience with protease inhibitors. In some cases, diabetic ketoacidosis has occurred. No causal relationship has been established. Careful monitoring of blood glucose levels should be done and either initiation or dose adjustments of insulin or oral hypoglycemic agents may be needed.

Spontaneous bleeding episodes have been reported in hemophiliac patients while receiving protease inhibitors. No causal relationship has been established, however, hemophiliacs should be monitored closely for bleeding during protease inhibitor therapy.

Fosamprenavir/ritonavir therapy has been associated with increased triglyceride and cholesterol levels. Triglyceride and cholesterol testing are recommended before starting and periodically during fosamprenavir therapy. Lipid disorders should be managed as clinically appropriate.

A link between fosamprenavir/amprenavir exposure and increased risk of myocardial infarction has been reported during a case control study. In addition to appropriate clinical management of lipid disorders, other modifiable risk factors for cardiovascular disease (such as diabetes mellitus, hypertension, and smoking) should be monitored in HIV-infected patients and managed as clinically appropriate.

Redistribution and accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance," have been observed in patients receiving antiretroviral therapy. Evaluation for physical signs of fat redistribution is recommended during clinical examination.

Immune reconstitution syndrome has occurred during combination antiretroviral therapy. Patients responding to therapy may develop an inflammatory response to indolent or residual opportunistic infections and require evaluation and treatment.

Caution is recommended in patients with hepatic impairment because increased amprenavir concentrations may result. Patients with underlying hepatitis B or C may have an increased risk of developing or worsening transaminase elevations. Close monitoring of liver function tests is recommended. Administration of higher than recommended doses of fosamprenavir/ritonavir or concomitant use of oral contraceptives and fosamprenavir/ritonavir is not recommended because transaminase elevations may result.

Fosamprenavir discontinuation or temporary interruption may be considered if signs or symptoms of nephrolithiasis occur.

Fosamprenavir should always be used in combination with other antiretroviral agents.

The potential for HIV cross-resistance among protease inhibitors exists but has not been fully explored. It is unknown what effect fosamprenavir therapy will have on the activity of subsequently administered protease inhibitors. Selection of antiretroviral agents for a patient's medication regimen should be done carefully and in consultation with an infectious disease specialist.

Once-daily administration of fosamprenavir plus ritonavir is not recommended for adult PI-experienced patients. Once-daily dosing of fosamprenavir alone or in combination with ritonavir is not recommended for any pediatric patients. Twice-daily dosing of fosamprenavir without ritonavir is not recommended in pediatric patients less than 2 years of age. Fosamprenavir alone or in combination with ritonavir is not recommended for PI-experienced pediatric patients less than 6 months of age.

Safety and efficacy have not been established in pediatric patients less than 4 weeks of age. Fosamprenavir should only be administered to infants born at 38 weeks gestation or greater and who have attained a postnatal age of 28 days.

Dialysis

Data not available

Other Comments

Fosamprenavir tablets may be taken without regard to food. Fosamprenavir oral suspension should be taken without food in adult patients and with food in pediatric patients.

Fosamprenavir oral suspension should be re-dosed in patients vomiting within 30 minutes following administration.