Usual Adult Dose for HIV Infection

Oral: 300 mg orally twice a day
IV: 1 mg/kg IV (infused over 1 hour) every 4 hours

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Panel on Antiretroviral Guidelines for Adults and Adolescents and Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission Recommendations: 300 mg orally twice a day or 200 mg orally 3 times a day

Comments:

• No change in dose suggested during pregnancy.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Reduction of Perinatal Transmission of HIV

Maternal Dosing:

• Greater than 14 weeks of pregnancy: 100 mg orally 5 times a day until start of labor
• During labor and delivery: 2 mg/kg IV (infused over 1 hour) followed by 1 mg/kg/hour (as a continuous IV infusion) until clamping of umbilical cord

Comments:

• Indication based on dosing regimen with 3 components, including antepartum and intrapartum treatment of HIV-1-infected mothers and postpartum treatment of HIV-1-exposed neonates
• The following should be considered before starting this drug in pregnant women for transmission prevention:
• In most cases, this drug should be used in combination with other antiretroviral agents.
• Transmission prevention has not been evaluated in patients who have used this drug for a prolonged duration before pregnancy.
• Since the risks of using this drug during the first 10 weeks of gestation (when the fetus is most susceptible to potential teratogenic effects of drugs) are not fully known, patients in the first trimester of pregnancy who do not need to start antiretroviral therapy immediately for their own health may consider delaying use; indication based on use after 14 weeks gestation.
• Neonates should also be treated for 6 weeks.
• Despite use of this regimen, transmission to infants may still occur in some cases.

Use: For the prevention of maternal-fetal HIV-1 transmission

Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission Recommendations:

• Active labor: 2 mg/kg IV loading dose followed by 1 mg/kg/hour continuous infusion from start of active labor until delivery

Comments:

• IV administration:
• Recommended for patients with HIV RNA greater than 1000 copies/mL (or unknown HIV RNA) near delivery
• May be considered for patients with HIV RNA between 50 and 999 copies/mL
• Not required for patients on antiretroviral therapy with HIV RNA up to 50 copies/mL during late pregnancy and near delivery and no concerns regarding treatment compliance
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Nonoccupational Exposure

US CDC Recommendations: 300 mg orally twice a day
Duration of therapy: 28 days

Comments:

• This drug and lamivudine plus (raltegravir or dolutegravir) is recommended as the preferred regimen for nonoccupational postexposure prophylaxis of HIV infection in adults with CrCl less than 60 mL/min; this drug and lamivudine plus darunavir/ritonavir is recommended as an alternative regimen for such patients. Dose should be adjusted to degree of renal function.
• If other alternatives are considered, this drug is recommended as a component in various regimens.
• Prophylaxis should be started as soon as possible, within 72 hours of exposure.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure

US Public Health Service Working Group Recommendations: 300 mg orally twice a day
Duration of therapy: 28 days, if tolerated

Comments:

• Recommended as a component in various alternative regimens for HIV postexposure prophylaxis
• Prophylaxis should be started as soon as possible, preferably within hours after exposure.
• The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection

4 weeks to less than 18 years:
Based on body weight:

• Weight 4 to less than 9 kg: 12 mg/kg orally twice a day or 8 mg/kg orally 3 times a day
• Weight 9 to less than 30 kg: 9 mg/kg orally twice a day or 6 mg/kg orally 3 times a day
• Weight at least 30 kg: 300 mg orally twice a day or 200 mg orally 3 times a day

Alternatively, based on BSA: 240 mg/m2 orally twice a day or 160 mg/m2 orally 3 times a day
Maximum dose: 600 mg/day

Comments:

• Dose should not exceed recommended adult dose.
• The dose calculated by body weight may not be the same as the dose calculated by BSA in some cases.

Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV Recommendations:
Neonates:
Gestational age less than 30 weeks at birth:

• Birth to age 4 weeks: 2 mg/kg orally twice a day
• Age 4 weeks to 8 to 10 weeks: 3 mg/kg orally twice a day
• Age greater than 8 to 10 weeks: 12 mg/kg orally twice a day

Gestational age 30 to less than 35 weeks at birth:

• Birth to age 2 weeks: 2 mg/kg orally twice a day
• Age 2 weeks to 6 to 8 weeks: 3 mg/kg orally twice a day
• Age greater than 6 to 8 weeks: 12 mg/kg orally twice a day

Gestational age at least 35 weeks at birth:

• Birth to age 4 weeks: 4 mg/kg orally twice a day
• Alternative simplified weight band dosing:
• Weight band 2 to less than 3 kg: 10 mg orally twice a day
• Weight band 3 to less than 4 kg: 15 mg orally twice a day
• Weight band 4 to less than 5 kg: 20 mg orally twice a day
• Age greater than 4 weeks: 12 mg/kg orally twice a day

Infants and Children (age at least 35 weeks post-conception and at least 4 weeks post-delivery [to less than 18 years] weighing at least 4 kg):
Based on body weight:

• Weight 4 to less than 9 kg: 12 mg/kg orally twice a day
• Weight 9 to less than 30 kg: 9 mg/kg orally twice a day
• Weight at least 30 kg: 300 mg orally twice a day

Alternatively, based on BSA: 180 to 240 mg/m2 orally every 12 hours

Comments:

• For neonates unable to tolerate oral drugs, the IV dose should be 75% of the oral dose, using the same dosing interval.
• The simplified weight band dosing provides about 4 mg/kg orally twice a day.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Reduction of Perinatal Transmission of HIV

Neonatal Dosing:

• Oral: 2 mg/kg orally every 6 hours
• IV: 1.5 mg/kg IV (infused over 30 minutes) every 6 hours

Comments:

• Dosing should begin within 12 hours after birth and continue through 6 weeks of age.
• This drug may be administered IV to neonates unable to receive oral dosing.

Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission Recommendations:
Neonates:
Gestational age less than 30 weeks at birth:

• Birth to age 4 weeks: 2 mg/kg orally twice a day
• Age 4 to 6 weeks: 3 mg/kg orally twice a day

Gestational age 30 to less than 35 weeks at birth:

• Birth to age 2 weeks: 2 mg/kg orally twice a day
• Age 2 weeks to 4 to 6 weeks: 3 mg/kg orally twice a day

Gestational age at least 35 weeks at birth:

• Birth to age 4 to 6 weeks: 4 mg/kg orally twice a day
• Alternative simplified weight band dosing:
• Weight band 2 to less than 3 kg: 10 mg orally twice a day
• Weight band 3 to less than 4 kg: 15 mg orally twice a day
• Weight band 4 to less than 5 kg: 20 mg orally twice a day

Comments:

• For neonates unable to tolerate oral drugs, the IV dose should be 75% of the oral dose, using the same dosing interval.
• For low risk of perinatal HIV transmission: 4 weeks of this drug
• For higher risk of perinatal HIV transmission and presumed neonate HIV exposure: Combination antiretroviral prophylaxis with 6 weeks of this drug plus 3 doses of nevirapine OR empiric HIV therapy using this drug plus nevirapine and lamivudine
• For neonates with confirmed HIV: 3-drug antiretroviral regimen at treatment dose
• Optimum duration of empiric HIV therapy in neonates at higher risk of perinatal HIV transmission is unknown; many experts use 6 weeks of combination therapy while others stop nevirapine and/or lamivudine after newborn testing returns negative; this drug should be continued for 6 weeks.
• Therapy should be started as close to time of birth as possible, preferably within 6 to 12 hours of delivery.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Nonoccupational Exposure

US CDC Recommendations:
INFANTS (birth to age 41 days):
Premature (age less than 30 weeks gestation at birth):
Day 14 to 28 of life:

• Syrup: 2 mg/kg orally twice a day
• IV: 1.5 mg/kg IV (infused over 30 minutes) every 12 hours

At 29 days of life:

• Syrup: Switch to 4 mg/kg orally twice a day

Premature (age 30 to 35 weeks gestation at birth):
Birth through day 14 of life:

• Syrup: 2 mg/kg orally twice a day
• IV: 1.5 mg/kg IV (infused over 30 minutes) every 12 hours

At 15 days of life:

• Syrup: Switch to 4 mg/kg orally twice a day

Full-term (age at least 35 weeks gestation at birth):

• Syrup: 4 mg/kg orally twice a day
• IV: 3 mg/kg IV (infused over 30 minutes) every 12 hours

INFANTS AND CHILDREN (age at least 35 weeks post-conception and at least 4 weeks post-delivery):
Syrup or Capsules:

• Weight 4 to less than 9 kg: 12 mg/kg orally twice a day
• Weight 9 to less than 30 kg: 9 mg/kg orally twice a day

Tablets:

• Weight at least 30 kg: 300 mg orally twice a day

ADOLESCENTS (13 years or older): 300 mg orally twice a day

Duration of therapy: 28 days

Comments:

• A pediatric HIV-specialist should be consulted for neonates (age 0 to 27 days).
• This drug is recommended as a component of a preferred (or alternative) 3-drug regimen for nonoccupational postexposure prophylaxis of HIV infection in children age 4 weeks to 2 years and as a component of an alternative 3-drug regimen in children age 2 to 12 years.
• This drug and lamivudine plus (raltegravir or dolutegravir) is recommended as the preferred regimen for nonoccupational postexposure prophylaxis of HIV infection in adolescents (13 years or older) with CrCl less than 60 mL/min; this drug and lamivudine plus darunavir/ritonavir is recommended as an alternative regimen for such patients. Dose should be adjusted to degree of renal function.
• If other alternatives are considered, this drug is recommended as a component in various regimens.
• Prophylaxis should be started as soon as possible, within 72 hours of exposure.
• Premature infants exposed to HIV after day 1 of life should be switched to full-term infant dose at 29 days of life.
• IV dosing may be used in infants unable to receive oral dosing.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

CrCl less than 15 mL/min:

• Oral: 100 mg orally every 6 to 8 hours
• IV: 1 mg/kg IV (infused over 1 hour) every 6 to 8 hours

Liver Dose Adjustments

Liver dysfunction or liver cirrhosis: Data not available

Comments:

• Frequent monitoring of hematologic toxicities recommended.

Dose Adjustments

Significant anemia (hemoglobin less than 7.5 g/dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells/mm3 or reduction greater than 50% from baseline): May require dose interruption until proof of marrow recovery observed

Comments:

• In patients who develop significant anemia, dose interruption may not eliminate the need for transfusion.
• If marrow recovery occurs after dose interruption, may be appropriate to resume dose using adjunctive therapy such as epoetin alfa at recommended doses; depends on hematologic indices (e.g., serum erythropoietin level) and patient tolerance.

Precautions

US BOXED WARNINGS:

• RISK OF HEMATOLOGIC TOXICITY: This drug has been associated with hematologic toxicity (including neutropenia and severe anemia), especially in patients with advanced HIV-1 disease.
• MYOPATHY: Symptomatic myopathy associated with prolonged use of this drug.
• LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS: Lactic acidosis and severe hepatomegaly with steatosis (including fatalities) reported with use of nucleoside analogs alone or in combination, including this drug and other antiretrovirals. This drug should be discontinued if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity.

CONTRAINDICATIONS:
Potentially life-threatening hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to the active component or any of the ingredients

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis or peritoneal dialysis:

• Oral: 100 mg orally every 6 to 8 hours
• IV: 1 mg/kg IV (infused over 1 hour) every 6 to 8 hours

Other Comments

Administration advice:

• Injection: Administer via IV infusion at a constant rate over 1 hour in adults and over 30 minutes in neonates; avoid rapid infusion or bolus injection. Do not administer IM.
• Injection: As an extra precaution, administer the diluted solution within 8 hours if stored at 25C (77F) or 24 hours if refrigerated.
• Use the IV injection only until oral therapy can be administered.
• May administer without regard to food
• If patient is unable to reliably swallow a tablet or capsule, use the oral syrup.
• Use an appropriate-sized oral syringe with 0.1-mL graduation to ensure accurate dosing of the oral syrup in neonates.

Storage requirements:

• Store at 15C to 25C (59F to 77F).
• Capsules: Protect from moisture.
• Injection: Protect from light; after dilution, solution is physically and chemically stable for 24 hours at room temperature and 48 hours if refrigerated at 2C to 8C (36F to 46F).

Reconstitution/preparation techniques:

• Injection: The manufacturer product information should be consulted.

IV compatibility:

• Compatible diluent: 5% Dextrose injection solution

General:

• Pediatric doses are calculated based on body weight or BSA; special vigilance recommended during calculation of dose, transcription of medication order, dispensing information, and dosing instructions to reduce risk of medication errors.
• The vial stoppers for the injection contain dry natural rubber.

Monitoring:

• Dermatologic: For signs of lipoatrophy (regularly)
• Hematologic: Blood counts (during therapy; the manufacturer product information should be consulted regarding frequency); for hematologic toxicities in patients with liver dysfunction (often during therapy)

Patient advice:

• Contact healthcare provider immediately if rash develops as it may be a sign of a more serious reaction.
• Extremely important to have blood counts monitored closely during therapy, especially with advanced symptomatic HIV-1 disease.
• Stop taking this drug if clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity develop.
• Consult healthcare provider immediately regarding any signs/symptoms of infection.
• Consult physician if muscle weakness, shortness of breath, symptoms of hepatitis/pancreatitis, or any other unexpected side effect occurs during therapy.