This dosage information may not include all the information needed to use Lopinavir/Ritonavir safely and effectively. See additional information for Lopinavir/Ritonavir.
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Usual Adult Dose for:
Usual Pediatric Dose for:
Additional dosage information:
Usual Adult Dose for HIV Infection
Lopinavir 400 mg-ritonavir 100 mg orally twice a day; alternatively, patients with less than 3 lopinavir resistance-associated substitutions may use lopinavir 800 mg-ritonavir 200 mg orally once a day
Concomitant amprenavir, efavirenz, nelfinavir, or nevirapine therapy:
Tablets: Lopinavir 500 mg-ritonavir 125 mg orally twice a day
Oral solution: Lopinavir 533 mg-ritonavir 133 mg orally twice a day
Usual Adult Dose for Nonoccupational Exposure
Lopinavir 400 mg-ritonavir 100 mg orally every 12 hours in combination with zidovudine plus (lamivudine or emtricitabine)
Prophylaxis should be initiated as soon as possible, within 72 hours of exposure.
Duration: 28 days
Usual Pediatric Dose for HIV Infection
Pediatric dosage should not exceed the usual adult dosage.
14 days to 6 months: 16 mg/kg or 300 mg/m2 (lopinavir component) orally twice a day; the oral solution should not be given to neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days has been reached
Lopinavir-ritonavir should not be administered in combination with amprenavir, efavirenz, nelfinavir, or nevirapine in patients less than 6 months of age.
6 months to 18 years:
Based on body surface area (BSA): 230 mg/m2 (lopinavir component) orally twice a day
Based on weight:
Less than 15 kg: 12 mg/kg (lopinavir component) orally twice a day
15 to 40 kg: 10 mg/kg (lopinavir component) orally twice a day
Greater than 40 kg: Lopinavir 400 mg-ritonavir 100 mg orally twice a day
Concomitant amprenavir, efavirenz, nelfinavir, or nevirapine:
Based on BSA: 300 mg/m2 (lopinavir component) orally twice a day
Based on weight:
Less than 15 kg: 13 mg/kg (lopinavir component) orally twice a day
Greater than 15 to 45 kg: 11 mg/kg (lopinavir component) orally twice a day
Greater than 45 kg: Lopinavir 533 mg-ritonavir 133 mg orally twice a day
6 months to 18 years:
15 to 25 kg or BSA 0.6 to less than 0.9 m2: Lopinavir 200 mg-ritonavir 50 mg orally twice a day
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
Greater than 35 kg or BSA greater than or equal to 1.4 m2: Lopinavir 400 mg-ritonavir 100 mg orally twice a day
Concomitant amprenavir, efavirenz, nelfinavir, or nevirapine:
15 to 20 kg or BSA 0.6 to less than 0.8 m2: Lopinavir 200 mg-ritonavir 50 mg orally twice a day
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
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
Greater than 45 kg or BSA greater than or equal to 1.7 m2: Lopinavir 500 mg-ritonavir 125 mg orally twice a day
Renal Dose Adjustments
No adjustment recommended.
Liver Dose Adjustments
The manufacturer recommends caution when administering this drug to patients with liver dysfunction.
Once-daily dosing is not recommended for adult patients with 3 or more lopinavir resistance-associated substitutions including L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V. Lopinavir-ritonavir should not be administered once daily in pediatric patients less than 18 years of age. The once-daily regimen should not be given in combination with amprenavir, carbamazepine, efavirenz, nelfinavir, nevirapine, phenobarbital, or phenytoin.
Coadministration of lopinavir-ritonavir is contraindicated with drugs highly dependent on CYP450 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Coadministration of lopinavir-ritonavir is contraindicated with potent CYP450 3A inducers where significantly reduced lopinavir plasma levels may result in loss of virologic response and possible resistance and cross-resistance. Contraindicated drugs include alfuzosin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort, pimozide, oral midazolam, triazolam, lovastatin, simvastatin, and sildenafil for treatment of pulmonary arterial hypertension.
Starting lopinavir-ritonavir in patients receiving medications metabolized by CYP450 3A or starting medications metabolized by CYP450 3A in patients maintained on lopinavir-ritonavir may result in elevated plasma levels of concomitant medications. Higher plasma levels of concomitant medications can result in increased or prolonged therapeutic or adverse effects and may lead to severe, life-threatening, or fatal events. Prior to and during lopinavir-ritonavir therapy, the potential for drug interactions must be considered. Concurrent medications should be reviewed and patients should be monitored for side effects during lopinavir-ritonavir therapy.
Patients coinfected with hepatitis B or C or with marked elevations in transaminase prior to therapy may be at greater risk for developing or worsening of transaminase elevations or hepatic decompensation with lopinavir-ritonavir use. Appropriate laboratory testing should be conducted before starting lopinavir-ritonavir treatment and patients should be monitored closely during therapy. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis or cirrhosis, especially during the first several months of lopinavir-ritonavir therapy.
Pancreatitis, including fatal cases, has been observed in patients receiving lopinavir-ritonavir therapy, including those who developed hypertriglyceridemia. Although a causal relationship has not been established, marked triglyceride elevations are a risk factor for the development of pancreatitis. Patients who experience signs or symptoms of pancreatitis should be evaluated and lopinavir-ritonavir should be stopped if a diagnosis of pancreatitis is made.
Lopinavir-ritonavir therapy has resulted in large increases in the concentration of total cholesterol and triglycerides. Triglyceride and cholesterol baseline levels should be obtained prior to initiation of therapy and at periodic intervals during therapy. Lipid disorders should be managed as clinically appropriate.
Episodes of hyperglycemia, new onset diabetes mellitus, and exacerbation of preexisting diabetes mellitus have been reported during postmarketing studies in HIV-infected patients receiving protease inhibitors. In some cases, diabetic ketoacidosis has occurred. No causal relationship has been established. Careful monitoring of blood glucose levels should be done and either initiation or dose adjustments of insulin or oral hypoglycemic agents may be needed.
The PR interval has been prolonged in some patients receiving lopinavir-ritonavir. Cases of second or third degree atrioventricular block have been reported. Patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies should use lopinavir-ritonavir with caution as the risk of developing cardiac conduction abnormalities may be increased in these patients. Caution and clinical monitoring are recommended during concomitant use of lopinavir-ritonavir with other drugs that prolong the PR interval, especially with drugs metabolized by CYP450 3A.
QT interval prolongation and torsades de pointes have been reported during postmarketing experience; however, causality of lopinavir-ritonavir could not be established. Lopinavir-ritonavir should be avoided in patients with congenital long QT syndrome, those with hypokalemia, and with other drugs that prolong the QT interval.
Spontaneous bleeding episodes have been reported in hemophilia type A and B patients while receiving protease inhibitors. No causal relationship has been established, however, the FDA and the manufacturers of protease inhibitors recommend that hemophiliacs be monitored closely for bleeding during therapy.
Immune reconstitution syndrome has occurred in patients on combination antiretroviral therapy, including lopinavir-ritonavir. Inflammatory responses to indolent or residual opportunistic infections (e.g., Mycobacterium avium infections, cytomegalovirus infection, Pneumocystis pneumonia, tuberculosis) may occur during the initial phase of combination therapy. Further medical evaluation and treatment may be necessary.
Lopinavir-ritonavir should always be used in combination with other antiretroviral agents. Lopinavir-ritonavir should generally not be added as a single agent when antiretroviral regimens are changed due to the development of drug resistance and loss of virological response.
The potential for HIV cross-resistance among protease inhibitors exists but has not been fully explored. It is unknown what effect lopinavir-ritonavir therapy will have on the activity of subsequently administered protease inhibitors. Selection of antiretroviral agents for a patient's medication regimen should be done carefully, and HIV genotyping/phenotyping should be considered if available.
The appropriate dose of lopinavir-ritonavir should be calculated for each individual child based on body weight or body surface area to avoid underdosing or exceeding the recommended adult dose.
Lopinavir-ritonavir oral solution is very concentrated. It contains 80 mg lopinavir and 20 mg ritonavir per mL (not per bottle). An accidental overdose has been reported in which a 44-day-old infant was administered approximately 10 times the calculated volume and consequently died of cardiogenic shock.
Lopinavir-ritonavir oral solution contains 42.4% (v/v) alcohol and 15.3% (v/v) propylene glycol. Significant toxicity (potentially lethal) could result from ingestion of more than the recommended dose by an infant or young child. When administered together, ethanol competitively inhibits propylene glycol metabolism, which may lead to higher concentrations. Preterm neonates may be at greater risk of propylene glycol-associated side effects due to diminished ability to metabolize propylene glycol. Life-threatening cases of cardiac toxicity (including complete atrioventricular block, bradycardia, and cardiomyopathy), lactic acidosis, acute renal failure, central nervous system (CNS) depression, and respiratory complications leading to death have been reported during postmarketing experience, mainly in preterm neonates receiving lopinavir-ritonavir oral solution.
Lopinavir-ritonavir oral solution should be avoided in preterm neonates until 14 days after their due date, or in full-term neonates less than 14 days of age unless the benefit of using lopinavir-ritonavir oral solution to treat HIV infection immediately after birth outweighs the potential risks. In such cases, infants should be monitored closely for increases in serum osmolality and serum creatinine, and for toxicity related to the oral solution including hyperosmolality, with or without lactic acidosis, renal toxicity, CNS depression (including stupor, coma, and apnea), seizures, hypotonia, cardiac arrhythmias and electrocardiogram changes, and hemolysis. Total amounts of alcohol and propylene glycol from all medications that are to be given to infants should be considered so as to avoid toxicity from these excipients.
Due to the high concentration, alcohol content, and propylene glycol content of lopinavir-ritonavir oral solution, special attention should be given to accurate calculation of the dose, transcription of the medication order, dispensing information, and dosing instructions to reduce the risk for medication errors and overdose. This is particularly important for infants and young children.
Safety and efficacy have not been established in pediatric patients less than 14 days of age.
Lopinavir-ritonavir is not significantly removed by hemodialysis.
To improve the bioavailability and lessen the pharmacokinetic variability lopinavir-ritonavir oral solution should be taken with food. The tablets may be taken with or without food.
Lopinavir-ritonavir should always be used in combination with other antiretroviral agents.
The tablets should be swallowed whole and not broken, crushed, or chewed. If a patient is unable to reliably swallow a lopinavir-ritonavir tablet, then the oral solution should be used. The oral solution should be administered using a calibrated dosing syringe.
The lopinavir 100 mg-ritonavir 25 mg tablets are not recommended for patients weighing less than 15 kg; the oral solution is recommended instead.