Lexiva (Fosamprenavir) is a prodrug and converted to amprenavir. It belongs to the protease group of antiretroviral medicines and has similar efficacy as lopinavir. It is cheaper than lopinavir but causes hypercholesterolemia.

It is used in the treatment of HIV-1 infection in combination with other anti-retroviral Agents

Fosamprenavir (Lexiva) Dose in Adults

Dosage in the treatment of HIV-1 infection: 

• Antiretroviral therapy-naive patients:

  • Unboosted regimen:

    • 1,400 mg orally twice a day (without ritonavir).

  • ritonavir-boosted regimens:

    • Once-daily regimen:

      • Fosamprenavir 1,400 mg orally once a day with ritonavir 100 to 200 mg once daily

    • Twice-daily regimen:

      • Fosamprenavir 700 orally twice a day with ritonavir 100 mg twice daily

• Protease inhibitor (PI)-experienced patients:

  • Fosamprenavir 700 mg orally twice a day with ritonavir 100 mg twice daily.
  • Once-daily administration is not advised in protease inhibitor-experienced patients.

Fosamprenavir (Lexiva) Dose in Childrens

Lexiva in the treatment of HIV-1 infection:

• Use in combination along with other antiretroviral agents:

  • The maximum dose should not exceed more than adult dose.
  • Once-daily dosing of fosamprenavir is not advised in pediatric patients.

• Protease inhibitor-naive patients:

  • Fosamprenavir is used for initial therapy in pediatric patients

  • Ritonavir unboosted regimen:

    • Infants and Children  less than 2 years:

      • It is not approved for use.

    • Children older than 2 years and Adolescents:

      • AIDS info guidelines:

        • Do not use because of its low systemic exposure

      • Manufacturer's labeling:

        • 30 mg/kg/dose orally twice a day.
        • Maximum dose is 1,400 mg/dose

  • Ritonavir boosted regimen:

    • Infants, Children, and Adolescents:

      • AIDSinfo guidelines:

        • Do not use in infants younger than 6 months due to its low systemic exposure

      • Manufacturer's labeling:

        • Use only in infants born after 38 weeks GA and who are at least 28 days PNA:

          • <11 kg:

            • Fosamprenavir 45 mg/kg/dose orally is given plus ritonavir 7 mg/kg/dose twice a day

          • 11 to <15 kg:

            • Fosamprenavir 30 mg/kg/dose orally is given plus ritonavir 3 mg/kg/dose twice a day

          • 15 to <20 kg:

            • Fosamprenavir 23 mg/kg/dose orally is given plus ritonavir 3 mg/kg/dose twice a day

          • ≥20 kg:

            • Fosamprenavir 18 mg/kg/dose orally is given twice daily plus ritonavir 3 mg/kg/dose
            • maximum dose of fosamprenavir is 700 mg/dose
            • maximum dose of ritonavir 100 mg/dose
• When it is combined with ritonavir, fosamprenavir tablets could be administered to children who weigh ≥39 kg.

• Protease inhibitor-experienced:

  • Ritonavir boosted regimen:

    • Infants <6 months:

      • It is not approved for use.

    • Infants ≥6 months, Children, and Adolescents:

      • <11 kg:

        • Fosamprenavir 45 mg/kg/dose  is given plus ritonavir 7 mg/kg/dose twice a day

      • 11 to <15 kg:

        • Fosamprenavir 30 mg/kg/dose is given plus ritonavir 3 mg/kg/dose twice a day

      • 15 to <20 kg:

        • Fosamprenavir 23 mg/kg/dose is given plus ritonavir 3 mg/kg/dose twice a day

      • ≥20 kg:

        • Fosamprenavir 18 mg/kg/dose is given(maximum dose: 700 mg/dose) twice daily plus ritonavir 3 mg/kg/dose twice daily (maximum dose: 100 mg/dose) twice a day
• When combined with ritonavir, fosamprenavir tablets could be administered to children who weigh ≥39 kg

• Dosing adjustments done for concomitant therapy:

  • There are no pediatric-specific recommendations.
  • Bsed on experience in adult patients, can be considered dosing adjustment with concomitant efavirenz or maraviroc

Fosamprenavir (Lexiva) pregnancy Risk category: C

• Fosamprenavir is not able to transfer from the human placenta.
• Preterm births may be more likely if there is maternal antiretroviral treatment (ART).
• In some cases, there was an increased risk of stillbirth, low birthweight, and small gestational infants.
• Concerns about adverse neonatal outcomes should not stop maternal ART.
• All infants who have been exposed to antiretroviral medication should be followed up for a long time
• Potential mitochondrial dysfunction should be considered for children who have significant organ abnormalities, especially of the heart or CNS.
• Protease inhibitors have been shown to reduce hyperglycemia, diabetes mellitus recurrence, and diabetic ketoacidosis. It is unclear if pregnancy can increase this risk.
• Health and Human Services (HHS), Perinatal HIV Guidelines, do not recommend fosamprenavir use in pregnancy.
• Females who are pregnant with fosamprenavir must be switched to a recommended regimen.
• If it is continued in pregnant females who are virologically suppressed on a stable fosamprenavir-containing regimen, then fosamprenavir should only be given with standard ritonavir-boosted twice-daily dosage and close monitoring of viral load.
• It is not recommended to take unboosted fosamprenavir or a once-daily dose with ritonavir.
• To keep HIV-positive pregnant women under the age of 18 from contracting perinatal HIV, it is recommended that they receive ART.
• Monitoring during pregnancy is more common than monitoring in adults who are not pregnant.
• All HIV-positive women should receive ART post-partum. It can also be modified after delivery.

Fosamprenavir use during breastfeeding:

• It is unknown if fosamprenavir can be found in breast milk.
• The risk of HIV transmission after birth does not disappear with infant or maternal antiretroviral treatment.
• Additionally, multiclass-resistant viruses have been observed in infants who are breastfed despite receiving maternal therapy.
• To reduce the risk of HIV transmission, pregnant women with HIV should stop breastfeeding.

Fosamprenavir (Lexiva) Dose in Renal Disease:

• There are no dosage adjustments given in the manufacturer's labeling.

Fosamprenavir (Lexiva) Dose in Liver Disease:

• Mild impairment (Child-Pugh class A):

  • Decrease the dosage of fosamprenavir to 700 mg twice a day without concurrent ritonavir (therapy-naive) or fosamprenavir 700 mg twice a day plus ritonavir 100 mg once daily (therapy-naive or PI experienced).

• Moderate impairment (Child-Pugh class B):

  • Decrease the dosage of fosamprenavir to 700 mg twice a day without concurrent ritonavir (therapy-naive) or fosamprenavir 450 mg twice a day plus ritonavir 100 mg once daily (therapy-naive or PI experienced).

• Severe impairment (Child-Pugh class C):

  • Decrease the dosage of fosamprenavir to 350 mg twice a day without concurrent ritonavir (therapy-naive) or fosamprenavir 300 mg twice a day plus ritonavir 100 mg once daily (therapy-naive or PI experienced).

Common Side Effects of Fosamprenavir (Lexiva) Include:

• Dermatologic:

  • Skin rash

• Endocrine & metabolic:

  • Hypertriglyceridemia

• Gastrointestinal:

  • Diarrhea

Less Common Side Effects of Fosamprenavir (Lexiva) Include:

• Central nervous system:

  • Fatigue
  • Headache

• Dermatologic:

  • Pruritus

• Endocrine & metabolic:

  • Hyperglycemia

• Gastrointestinal:

  • Increased serum lipase
  • Nausea
  • Vomiting
  • Abdominal pain

• Hematologic & oncologic:

  • Neutropenia

• Hepatic:

  • Increased serum transaminases

Contraindications to Fosamprenavir (Lexiva) Include:

• Clinically significant hypersensitivity (eg Stevens-Johnson syndrome), to fosamprenavir or amprenavir or any component of the formulation
• Drug coadministration is dependent on CYP3A4 clearance. Elevated plasma concentrations can lead to life-threatening events, such as alfuzosin and rifampin.
• Flecainide, Lurasidone, and Propafenone can be used in combination with Ritonavir therapy.
• Coadministration with antihistamines, GI motility agents, amiodarone, diazepam, flurazepam, lidocaine (systemic) is also prohibited

Warnings and precautions

• Increased body fat
  • Increased body fat can be a problem.
• Hemolytic anemia
  • Amprenavir has been associated with acute hemolytic anemia.
• Hepatic effects
  • Transaminase elevations and hepatitis can occur.
  • Patients with underlying liver disease such as cirrhosis or hepatitis B, C, or cirrhosis should be cautious.
• Hypersensitivity reactions
  • There have been cases of protease inhibitors being used in hypersensitivity reactions (some severe), such as rash, bronchospasm (rare), anaphylaxis, anaphylaxis, anaphylaxis, anaphylaxis, anaphylaxis, angioedema and/or Stevens Johnson syndrome (rare).
  • If severe rash occurs or moderate symptoms are present, it is a good idea to discontinue treatment.
• Immune reconstitution syndrome:
  • The immune reconstitution syndrome can occur in patients who have started HIV treatment.
• Elevations of the lipids
  • There have been increases in total cholesterol and triglycerides
  • Screening should always be performed before and during treatment.
• Nephrolithiasis
  • Postmarketing surveillance has been used to report cases.
  • If symptoms persist, it is worth considering temporary or permanent discontinuation therapy.
• Allergy to sulfonamide
  • Patients with a sulfonamide allergy should be cautious.
• Diabetes:
  • Patients who have received protease inhibitors have experienced changes in glucose tolerance, hyperglycemia and exacerbation or diabetes.
• Hemophilia A and B:
  • Patients with hemophilia A and B should be cautious.
  • Reports indicate that there was an increase in bleeding after receiving protease inhibitor therapy.
• Hepatic impairment
  • Avoid liver damage
  • Adjustment of dosage is necessary.

Monitoring Parameters:

• Before initiation and periodically during therapy
• monitoring of viral load, CD4 count, triglycerides and cholesterol; glucose, liver function tests (in patients with underlying hepatitis B or C).

How to take Fosamprenavir (Lexiva)?

Oral suspension:

• Give without food.
• Readminister dose of suspension if vomiting occurs within 30 minutes after dosing.
• Suspension should be shaken vigorously prior to use.
• Administer with food if taken with ritonavir.
• May be given without regard to food if not taken with ritonavir.

Mechanism of action of Fosamprenavir (Lexiva):

• Cellular phosphatases in vivo convert fosamprenavir quickly to amprenavir.
• Amprenavir attaches at the HIV-1 protease activity site and inhibits the conversion of viral Gag-Pol precursors into functional proteins necessary for HIV infection.
• This results in the formation of non-infectious, immature viral particles.

Absorption is 63%

• Protein-binding: almost 90% (to alpha -acid glycoprotein
• It is decreased in hepatic impairment

Metabolism:

• Fosamprenavir is quickly and almost completely converted to amprenavir by cellular phosphatases in the gut epithelium
• Amprenavir is metabolized via hepatic route by CYP isoenzymes (primarily CYP3A4); glucuronide conjugation of oxidized metabolites also occurs

Bioavailability: Food does not have a remarkable effect on the absorption of tablets.

Half-life elimination: almost 7.7 hours (amprenavir)

Time to peak, plasma: 1.5 - 4 hours (median: 2.5 hours)

Excretion:

• Minimal excretion of unchanged drug by urine (1%) and feces;
• 75% of dose excreted as metabolites through biliary tract into feces and 14% excreted as metabolites in urine

International Brands of Fosamprenavir:

• Lexiva
• Telzer

Fosamprenavir (Lexiva) Brands in Pakistan:

No brands available in Pakistan