Lopinavir and Ritonavir

KALETRA is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 14 days and older. Limitations of Use: Genotypic or phenotypic testing and/or treatment history should guide the use of KALETRA. The number of baseline lopinavir resistance-associated substitutions affects the virologic response to KALETRA. KALETRA is an HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients (14 days and older).

KALETRA is a fixed-dose combination of HIV-1 antiviral drugs lopinavir and ritonavir. As co-formulated in KALETRA, ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir.

Tablets: May be taken with or without food, swallowed whole and not chewed, broken, or crushed. Oral solution: must be taken with food. KALETRA oral solution is not recommended for use with polyurethane feeding tubes due to potential incompatibility. Feeding tubes composed of silicone or polyvinyl chloride (PVC) can be used. Adults: Total recommended daily dosage is 800/200 mg given once or twice daily. KALETRA can be given as once daily or twice daily regimen. See Full Prescribing Information for details. KALETRA once daily dosing regimen is not recommended in: • Adult patients with three or more 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, phenobarbital, or phenytoin. • In combination with efavirenz, nevirapine, or nelfinavir.

KALETRA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir. KALETRA is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions.

The following have been observed in patients receiving KALETRA: The concomitant use of KALETRA and certain other drugs may result in known or potentially significant drug interactions. Consult the full prescribing information prior to and during treatment for potential drug interactions. Toxicity in preterm neonates: KALETRA oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities. A safe and effective dose of KALETRA oral solution in this patient population has not been established. Pancreatitis: Fatalities have occurred, suspend therapy as clinically appropriate. Hepatotoxicity: Fatalities have occurred. Monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations.

The following adverse reactions are discussed in greater detail in other sections of the labeling. QT Interval Prolongation, PR Interval Prolongation Drug Interactions Pancreatitis Hepatotoxicity Commonly reported adverse reactions to KALETRA included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia.

Co-administration of KALETRA can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of lopinavir. The potential for drug-drug interactions must be considered prior to and during therapy.

Tablets Store KALETRA tablets at 20°- 25°C (68°- 77°F), excursions permitted to 15°- 30°C (59°- 86°F). Oral Solution Store KALETRA oral solution at 2°- 8°C (36°- 46°F) until dispensed. For patient use: refrigerated KALETRA oral solution remains stable until the expiration date printed on the label. If stored at room temperature up to 25°C (77°F), oral solution should be used within 2 months.