Dosing and uses of Lexiva (fosamprenavir)
Adult dosage forms and strengths
tablet
- 700mg
oral suspension
- 50mg/mL
HIV Infection
Therapy-naive patients
- 1400 mg PO q12hr (without ritonavir)
- 1400 mg PO qDay (with ritonavir 100-200 mg qDay)
- 700 mg PO q12hr (with ritonavir 100 mg q12hr)
Protease inhibitor-experienced patients
- 700 mg PO q12hr (with ritonavir 100 mg q12hr)
Coadministration with efavirenz
- 700 mg PO q12hr (with ritonavir 100 mg q12hr) plus 600 mg efavirenz qDay, or
- 1400 mg PO qDay (with ritonavir 300 mg qDay) plus 600 mg efavirenz qDay
Combination with maraviroc
- 700 mg PO q12hr (with ritonavir 100 mg q12hr) plus maraviroc 150 mg PO q12hr
Hepatic Impairment
Mild (Child-Pugh 5-6): 700 mg PO q12hr without ritonavir (therapy-naive); OR 700 mg q12hr with ritonavir 100 mg qDay (therapy-naive or protease inhibitor-experienced)
Moderate (Child-Pugh 7-9): 700 mg PO q12hr (therapy-naive) without ritonavir; OR 450 mg q12hr with ritonavir 100 mg qDay (therapy-naive or protease inhibitor-experienced)
Severe (Child-Pugh 10-15): 350 mg PO q12hr without ritonavir (therapy-naive); OR 300 mg q12hr with ritonavir 100 mg qD (therapy-naive or protease-inhibitor experienced)
Pediatric dosage forms and strengths
tablet
- 700mg
oral suspension
- 50mg/mL
HIV Infection (Protease Inhibitor Naive Patients)
<4 weeks: Safety and efficacy not established
Indicated for protease inhibitor-naive pediatric patients aged 4 weeks or older, and for protease inhibitor-experienced children aged 6 months or older
For infants, use only in those born at 38 weeks' gestation or greater and who have attained a postnatal age of 28 days
<11 kg: 45 mg/kg PO q12hr plus ritonavir 7 mg/kg q12hr
11 to <15 kg: 30 mg/kg PO q12hr plus ritonavir 3 mg/kg q12hr
15 kg to <20 kg: 23 mg/kg PO q12hr plus ritonavir 3 mg/kg q12hr
≥20 kg: 18 mg/kg PO q12hr plus ritonavir 3 mg/kg q12hr
NOTE: When dosing with ritonavir, do not exceed adult dose of 700 mg/ritonavir 100 mg q12hr
Alternatively, protease inhibitor-naive children aged 2 yr or older may be administered 30 mg/kg PO q12hr (without ritonavir)
Unboosted Regimen
- <2 years: Not recommended without ritonavir
- >2 years and <47 kg: 30 mg/kg/dose PO q12hr; not to exceed 1400 mg PO q12hr
- >2 years and ≥47 kg: 1400 mg PO q12hr
HIV Infection (Protease Inhibitor Experienced Patients)
<6 months
- Not recommended
>6 months
- <11 kg: 45 mg/kg/dose PO q12hr; not to exceed 700 mg fosamprenavir/100 mg ritonavir PO q12hr
- 11-15 kg: 30 mg/kg/dose PO q12hr plus 3 mg/kg/dose ritonavir PO q12hr; not to exceed 700 mg fosamprenavir/100 mg ritonavir PO q12hr
- 15 to <20 kg: 23 mg/kg/dose PO q12hr plus 3 mg/kg/dose ritonavir PO q12hr; not to exceed 700 mg fosamprenavir/100 mg ritonavir PO q12hr
- ≥20 kg: 18 mg/kg/dose PO q12hr plus 3 mg/kg/dose ritonavir PO q12hr; not to exceed 700 mg fosamprenavir/100 mg ritonavir PO q12hr
Lexiva (fosamprenavir) adverse (side) effects
>10%
Nausea (30-50%)
Rash (16-20%)
Fatigue (11-15%)
Diarrhea (5-13%)
Increased triglycerides (11%)
1-10%
Increased serum lipase, ALT, AST (5-10%) in pts. treatment with concomitant ritonavir
Vomiting (2-6%)
Headache (2-4%)
Pruritus (7-8%)
Nausea (3-7%)
Abdominal pain (≤ 2%)
Increased hepatic transaminases (4-8%)
<1%
Stevens-Johnson syndrome
Angioedema
Myocardial infarction
QT prolongation
Nephrolithiasis
Hypercholesterolemia
Frequency not defined
Spontaenous bleeding
Acute hemolytic anemia
Immune reconstitution syndrome
Diabetes Mellitus
Warnings
Contraindications
Hypersensitivity (eg, Stevens-Johnson syndrome) to fosamprenavir, amprenavir, or other component
Concomitant use of drugs that depend heavily on CYP3A4 for clearance; metabolite amprenavir is a strong CYP3A4 inhibitor; use w/ ritonavir another strong CYP3A4 inhibitor may have additive inhibitory effects; check Drug Interactions
Drugs that are contraindicated with fosamprenavir (with or without ritonavir) include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam
Cautions
New onset DM, exacerbation of pre-existing DM & hyperglycemia reported with unknown frequency/unknown causal relationship
Sulfonamide allergy
Monitor labs prior to and during treatment with Hepatitis B or C, or elevated transaminases
Few reports of spontaneous bleeding in patients. with Hemophilia A and B
During initial treatment, inflammatory response to indolent or residual opportunistic infections may occur and require treatment
Fat redistribution with "cushingoid appearance" and "buffalo hump" may occur
Increased risk for myocardial infarction (thought to be caused by protease inhibitors increasing risk of hyperlipidemia)
Monitor triglycerides and cholesterol levels before initiating, then periodically; initiate clinical management of lipid disorders as required
Combination treatment with ritonavir may lead to increased triglyceride leveL
Unknown effect on activity of subsequently administered protease inhibitors
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs; autoimmune disorders (eg Graves disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment
Vomiting more common in children
Cases of nephrolithiasis reported with fosamprenavir
Acute hemolytic anemia reported with amprenavir
Discontinue therapy if severe skin reactions including Stevens-Johnson syndrome occur
Pregnancy and lactation
Pregnancy category: C
Lactation: excreted in milk unknown; contraindicated
Pregnancy Registry: to monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral medications call 1-800-258-4263 or visit www.APRegistry.com
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Lexiva (fosamprenavir)
Mechanism of action
Prodrug converted to amprenavir (protease inhibitor) by cellular phosphatases in vivo; 700 mg fosamprenavir equivalent to 600 mg amprenavir
Binds to active site of HIV-1 protease and thereby prevents processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature noninfectious viral particle
Pharmacokinetics
Half-Life: 7.7 hr
Peak Plasma Time: 1.5-4 hr
Protein Bound: 90%
Absorption: 63%
Metabolism: hepatic CYP3A4
Enzymes inhibited: CYP3A4
Metabolite: Amprenavir
Excretion: Feces (75%); urine (15%)
Administration
Oral Administration
Tablet: Take with meals if boosted with ritonavir; take without regard to meals if not boosted with ritonavir
Oral suspension: Adults should take without food; children should take with food
If vomiting occurs within 30 min, repeat dose
Adult dosage tablet use in children
- ≥47 kg: May use adult dosage with tabs (without ritonavir)
- ≥39 kg: May use adult dosage with tabs (with ritonavir) q12hr
