Usual Adult Dose for HIV Infection

Delayed-release Capsules:

• Less than 60 kg: 250 mg orally once a day
• At least 60 kg: 400 mg orally once a day

Oral Solution:
Preferred dosing:

• Less than 60 kg: 125 mg orally twice a day
• At least 60 kg: 200 mg orally twice a day

For patients requiring once-daily dosing:

• Less than 60 kg: 250 mg orally once a day
• At least 60 kg: 400 mg orally once a day

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

Usual Pediatric Dose for HIV Infection

Delayed-release capsules:
20 to less than 25 kg: 200 mg orally once a day
25 to less than 60 kg: 250 mg orally once a day
At least 60 kg: 400 mg orally once a day

Oral solution:
2 weeks to 8 months: 100 mg/m2 orally twice a day
Older than 8 months: 120 mg/m2 orally twice a day

• Maximum dose:
• Less than 60 kg: 125 mg/dose
• At least 60 kg: 200 mg/dose

Comments:

• Oral solution: The adult dose should not be exceeded.

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

Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV Recommendations:
Delayed-release capsules:
6 years or older:
20 to less than 25 kg: 200 mg orally once a day
25 to less than 60 kg: 250 mg orally once a day
At least 60 kg: 400 mg orally once a day

Oral solution:
2 weeks to less than 3 months: 50 mg/m2 orally every 12 hours
3 to 8 months: 100 mg/m2 orally every 12 hours
Older than 8 months: 120 mg/m2 (dose range: 90 to 150 mg/m2) orally every 12 hours

• Maximum dose:
• Less than 60 kg: 250 mg/day
• At least 60 kg: 400 mg/day

Comments:

• This drug is not recommended due to significant toxicity and availability of safer agents.
• Viral suppression has been effective in therapy-naive patients (3 years or older) administered 240 mg/m2 orally once a day (either formulation).
• BSA-based dosing should not exceed maximum adult dose.
• Combination therapy with tenofovir disoproxil fumarate (DF) is not recommended.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

Adult Patients:
Delayed-release capsules:
CrCl 30 to 59 mL/min:

• Less than 60 kg: 125 mg orally once a day
• At least 60 kg: 200 mg orally once a day

CrCl 10 to 29 mL/min:

• Less than 60 kg: 125 mg orally once a day
• At least 60 kg: 125 mg orally once a day

CrCl less than 10 mL/min:

• Less than 60 kg: Not recommended; an alternate formulation should be used.
• At least 60 kg: 125 mg orally once a day

Oral solution:
CrCl 30 to 59 mL/min:

• Less than 60 kg: 150 mg orally once a day OR 75 mg orally twice a day
• At least 60 kg: 200 mg orally once a day OR 100 mg orally twice a day

CrCl 10 to 29 mL/min:

• Less than 60 kg: 100 mg orally once a day
• At least 60 kg: 150 mg orally once a day

CrCl less than 10 mL/min:

• Less than 60 kg: 75 mg orally once a day
• At least 60 kg: 100 mg orally once a day

Pediatric Patients: Insufficient data to recommend specific dose adjustment; dose reduction should be considered (see above dosing in adult patients with renal dysfunction).

Comments:

• Coadministration with tenofovir DF: The appropriate dose of this drug has not been established in adults with CrCl less than 60 mL/min.

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

Coadministration of either formulation with tenofovir DF:
Adult patients (CrCl at least 60 mL/min):

• Less than 60 kg: 200 mg orally once a day
• At least 60 kg: 250 mg orally once a day

Pediatric patients: Data not available

Comments:

• Delayed-release capsules: Should be taken together with tenofovir DF and a light meal (up to 400 kcal, up to 20% fat) or in the fasted state
• Oral solution: May be taken together with tenofovir DF in the fasted state; alternatively, if tenofovir DF is taken with food, this formulation should be taken on an empty stomach.
• Patients should be monitored closely for didanosine-related side effects.
• According to some experts, this combination is not generally recommended.

Precautions

US BOXED WARNINGS:

• PANCREATITIS: Fatal and nonfatal pancreatitis have occurred during therapy with this drug used alone or in combination regimens in both therapy-naive and therapy-experienced patients (regardless of degree of immunosuppression). This drug should be suspended if pancreatitis is suspected and discontinued if confirmed.
• 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. Fatal lactic acidosis reported in pregnant women who received this drug plus stavudine with other antiretroviral agents. Coadministration of this drug with stavudine is contraindicated due to increased risk of serious and/or life-threatening events. Therapy should be suspended if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity.

Safety and efficacy have not been established in patients younger than 2 weeks.

• Safety and efficacy of the delayed-release capsules have not been established in patients weighing less than 20 kg.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis or CAPD:
Adult Patients:
Delayed-release capsules:

• Less than 60 kg: Not recommended; an alternate formulation should be used.
• At least 60 kg: 125 mg orally once a day

Oral solution:

• Less than 60 kg: 75 mg orally once a day
• At least 60 kg: 100 mg orally once a day

Pediatric Patients: Insufficient data to recommend specific dose adjustment; dose reduction should be considered (see above dosing in adult patients requiring hemodialysis or CAPD).

Comments:

• No supplemental dose required after hemodialysis.

Other Comments

Administration advice:

• Administer each formulation on an empty stomach; administer the oral solution at least 30 minutes before or 2 hours after a meal.
• Delayed-release capsules: Swallow whole; do not break, chew, crush, dissolve, or open.
• For patients unable to reliably swallow a capsule, use the pediatric powder for oral solution.
• Oral solution: Shake well before each use; discard any unused portion after 30 days.

Storage requirements:

• Capsules: Store in tightly-closed bottle at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
• Pediatric powder for oral solution: Store the bottles of powder at 15C to 30C (59F to 86F); may store the reconstituted solution (final admixture) in the refrigerator at 2C to 8C (36F to 46F) for up to 30 days

Reconstitution/preparation techniques:

• Pediatric powder for oral solution: The manufacturer product information should be consulted.

Monitoring:

• General: Ultrasonography
• Hematologic: For early signs of portal hypertension, such as thrombocytopenia and splenomegaly (during routine medical visits); albumin, complete blood count, INR
• Hepatic: Liver enzymes, serum bilirubin; liver function in patients with preexisting liver dysfunction (according to standard practice)
• Ocular: Retinal examinations (periodically during therapy)
• Renal: Renal function in elderly patients (during therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Do not use this drug with stavudine and/or hydroxyurea.
• Get regular eye examinations while using this drug.