Usual Adult Dose for HIV Infection

Once-daily dosing regimen: Lopinavir 800 mg-ritonavir 200 mg orally once a day

Twice-daily dosing regimen: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Twice-daily dosing regimen in combination with efavirenz, nelfinavir, or nevirapine:

• Tablets: Lopinavir 500 mg-ritonavir 125 mg orally twice a day
• Oral solution: Lopinavir 520 mg-ritonavir 130 mg orally twice a day
• Capsules: Lopinavir 533 mg-ritonavir 133 mg orally twice a day

Comments:

• This drug can be given in once-daily or twice-daily dosing regimen at dosages recommended above.
• Once-daily dosing regimen is not recommended:
• In patients with at least 3 of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V.
• In combination with carbamazepine, efavirenz, nelfinavir, nevirapine, phenobarbital, or phenytoin.
• In pregnant patients.
• The dose of this drug must be increased when coadministered with efavirenz, nelfinavir, or nevirapine.
• Twice-daily dosing regimen (lopinavir 400 mg-ritonavir 100 mg orally twice a day) is recommended for pregnant patients with no documented lopinavir-associated resistance substitutions; insufficient data to recommend dosing in those with any documented lopinavir-associated resistance substitutions.
• Once-daily dosing is not recommended in pregnancy.
• Pregnant patients should avoid using the oral solution.
• No dose adjustment needed during postpartum period.

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

Usual Adult Dose for Occupational Exposure

US Public Health Service Working Group Recommendations:

• Preferred dosing: Lopinavir 400 mg-ritonavir 100 mg orally twice a day
• Alternative dosing: Lopinavir 800 mg-ritonavir 200 mg orally once a day

Duration of therapy: 28 days, if tolerated

Comments:

• This drug is recommended as a component in various alternative regimens for HIV postexposure prophylaxis.
• Prophylaxis should be started as soon as possible, preferably within hours of 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

ORAL SOLUTION:
14 Days to 6 Months: 16 mg/kg or 300 mg/m2 (lopinavir component) orally twice a day

Older Than 6 Months to Less Than 18 Years:

• Based on BSA: 230 mg/m2 (lopinavir component) orally twice a day
• Maximum dose: Lopinavir 400 mg-ritonavir 100 mg orally twice a day
• Based on weight:
• Weight less than 15 kg: 12 mg/kg (lopinavir component) orally twice a day
• Weight 15 to 40 kg: 10 mg/kg (lopinavir component) orally twice a day
• Weight greater than 40 kg: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Concomitant efavirenz, nelfinavir, or nevirapine:

• Based on BSA: 300 mg/m2 (lopinavir component) orally twice a day
• Maximum dose: Lopinavir 520 mg-ritonavir 130 mg orally twice a day
• Based on weight:
• Weight less than 15 kg: 13 mg/kg (lopinavir component) orally twice a day
• Weight 15 to 45 kg: 11 mg/kg (lopinavir component) orally twice a day
• Weight greater than 45 kg: Lopinavir 520 mg-ritonavir 130 mg orally twice a day

TABLETS:
Older Than 6 Months to Less Than 18 Years:

• Weight 15 to 25 kg or BSA 0.6 to less than 0.9 m2: Lopinavir 200 mg-ritonavir 50 mg orally twice a day
• Weight greater than 25 to 35 kg or BSA 0.9 to less than 1.4 m2: Lopinavir 300 mg-ritonavir 75 mg orally twice a day
• Weight greater than 35 kg or BSA at least 1.4 m2: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Concomitant efavirenz, nelfinavir, or nevirapine:

• Weight 15 to 20 kg or BSA 0.6 to less than 0.8 m2: Lopinavir 200 mg-ritonavir 50 mg orally twice a day
• Weight greater than 20 to 30 kg or BSA 0.8 to less than 1.2 m2: Lopinavir 300 mg-ritonavir 75 mg orally twice a day
• Weight greater than 30 to 45 kg or BSA 1.2 to less than 1.7 m2: Lopinavir 400 mg-ritonavir 100 mg orally twice a day
• Weight greater than 45 kg or BSA at least 1.7 m2: Lopinavir 500 mg-ritonavir 125 mg orally twice a day

CAPSULES:

• Children less than 12 years weighing greater than 40 kg or children greater than 12 years: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Concomitant efavirenz, nelfinavir, or nevirapine:

• Weight greater than 45 kg: Lopinavir 533 mg-ritonavir 133 mg orally twice a day

Comments:

• Once-daily dosing regimen is not recommended in patients younger than 18 years.
• The oral solution is not recommended in neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days has been reached.
• Total amounts of ethanol and propylene glycol from all products given to pediatric patients 14 days to 6 months of age should be considered to avoid toxicity from these excipients.
• The appropriate dose of this drug should be calculated for each individual pediatric patient based on body weight or BSA to avoid underdosing or exceeding the recommended adult dose.
• This drug should not be coadministered with efavirenz, nelfinavir, or nevirapine in patients younger than 6 months.
• The oral solution is available for patients with BSA less than 0.6 m2 or those who are unable to reliably swallow a tablet or capsule.
• Special attention should be given to accurate calculation of dose, transcription of medication order, dispensing information, and dosing instructions to reduce risk for medication errors and overdose; particularly important for infants and young children.

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

Usual Pediatric Dose for Nonoccupational Exposure

US CDC Recommendations:
Children 14 days to 12 months:
Oral suspension: 16 mg/kg or 300 mg/m2 (lopinavir component) orally twice a day

Children older than 12 months to 18 years:
Oral suspension:

• Weight less than 15 kg: 12 mg/kg (lopinavir component) orally twice a day
• Weight 15 to 40 kg: 10 mg/kg (lopinavir component) orally twice a day
• Weight greater than 40 kg: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Tablets:

• Weight 15 to 25 kg: Lopinavir 200 mg-ritonavir 50 mg orally twice a day
• Weight greater than 25 to 35 kg: Lopinavir 300 mg-ritonavir 75 mg orally twice a day
• Weight greater than 35 kg: Lopinavir 400 mg-ritonavir 100 mg orally twice a day

Duration of Therapy: 28 days

Comments:

• Recommended for nonoccupational postexposure prophylaxis of HIV infection
• This drug is recommended as a component of a preferred (or alternative) 3-drug regimen in children at least 4 weeks of age (with a postmenstrual age of at least 42 weeks) to less than 2 years.
• This drug is recommended as a component of an alternative 3-drug regimen in children 2 to 12 years.
• Prophylaxis should be started as soon as possible, within 72 hours of exposure.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

Renal dysfunction: Data not available

Liver Dose Adjustments

Liver dysfunction: Caution recommended.

Precautions

CONTRAINDICATIONS:

• Previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to either active component or to any of the ingredients
• Coadministration with drugs highly dependent on CYP450 3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events, including alfuzosin, ranolazine, dronedarone, colchicine (in patients with renal and/or liver dysfunction), lurasidone, pimozide, dihydroergotamine, ergotamine, methylergonovine, cisapride, elbasvir-grazoprevir, lovastatin, simvastatin, lomitapide, oral midazolam, triazolam, sildenafil (for treatment of pulmonary arterial hypertension)
• Coadministration with potent CYP450 3A inducers where significantly reduced lopinavir plasma levels may result in loss of virologic response and possible resistance and cross-resistance, including apalutamide, rifampin, St. John's Wort

Safety and efficacy have not been established in patients younger than 14 days.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Comments:

• This drug is highly protein bound; significant removal via dialysis is unlikely.

Other Comments

Administration advice:

• Use in combination with other antiretroviral agents.
• Administer the oral solution with food to enhance absorption; administer the capsules with food to enhance bioavailability and lessen pharmacokinetic variability.
• May administer the tablets with or without food
• Swallow tablets whole; do not break, crush, or chew.
• If patient is unable to reliably swallow a tablet or capsule, use the oral solution; only consider using the lopinavir 100 mg-ritonavir 25 mg tablets in children who have reliably proven the ability to swallow the intact tablet.
• Use the calibrated cup (supplied) or oral dosing syringe to administer the oral solution.
• Do not use the oral solution in pregnant patients or in neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days has been reached.
• Do not use the oral solution (which contains ethanol and propylene glycol) with polyurethane feeding tubes due to potential incompatibility; feeding tubes compatible with ethanol and propylene glycol (e.g., silicone and polyvinyl chloride [PVC] feeding tubes) can be used to administer the oral solution; follow instructions for use of the feeding tube to administer this drug.

Storage requirements:

• Tablets: Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F); exposure to high humidity outside the recommended container for more than 2 weeks is not recommended.
• Oral solution and capsules (until dispensed): Store at 2C to 8C (36F to 46F); avoid exposure to excessive heat.
• Oral solution and capsules (patient use): Stable until labeled expiration date if refrigerated; should be used within 2 months if stored at room temperature up to 25C (77F)

General:

• Current HIV guidelines should be consulted for additional information.
• Limitations of Use: Genotypic or phenotypic testing and/or treatment history should guide use; virologic response affected by number of baseline lopinavir resistance-associated substitutions.
• The oral solution contains about 42% ethanol (v/v) and about 15% propylene glycol (w/v).

Monitoring:

• Cardiovascular: For PR interval prolongation
• General: For increases in serum osmolality and for toxicity related to the oral solution in preterm neonates in the immediate postnatal period
• Hepatic: Appropriate laboratory testing (before and during therapy); increased AST/ALT monitoring in patients with underlying chronic hepatitis or cirrhosis (especially during first several months of therapy)
• Metabolic: Triglycerides and total cholesterol (before starting and periodically during therapy); blood glucose levels
• Renal: For increases in serum creatinine in preterm neonates in the immediate postnatal period

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Pay special attention to accurate administration of your dose to reduce the risk of accidental overdose/underdose of this drug.
• For the oral solution: Administer using the calibrated dosing cup (supplied) or oral dosing syringe.
• Notify healthcare provider if your child's weight changes to ensure the child's dose is adjusted as needed.
• Do not alter the dose or discontinue therapy without consulting healthcare provider.
• Take this drug on a regular dosing schedule and avoid missing doses.
• Contact healthcare provider if symptoms of pancreatitis (e.g., nausea, vomiting, abdominal pain) or symptoms of PR and/or QT prolongation (e.g., dizziness, lightheadedness, abnormal heart rhythm, loss of consciousness) occur.
• Notify healthcare provider if a rash develops during therapy or if signs/symptoms of worsening liver disease (including loss of appetite, abdominal pain, jaundice, itchy skin) develop.
• Inform healthcare provider if signs/symptoms of diabetes mellitus (including frequent urination, excessive thirst, extreme hunger/unusual weight loss, and/or increased blood sugar) develop during therapy.