General Information

Kaletra is an HIV protease inhibitor. It consists of two components: lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV protease, which is a chemical necessary for HIV to multiply. Ritonavir inhibits the (CYP3A-mediated) metabolism of lopinavir, thereby increasing levels of lopinavir in the blood.

Kaletra is specifically indicated for the treatment of HIV-1 infection in adults and pediatric patients (14 days and older).

Kaletra is supplied as tablets and as an oral solution. Tablets may be taken with or without food, swallowed whole and not chewed, broken, or crushed. Oral solution must be taken with food. 

Kaletra can be given in once daily or twice daily dosing regimen at dosages noted in tables below.

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
• In pediatric patients younger than 18 years of age
• In pregnant women

Recommended Dosage in Adults - Kaletra Once Daily Regimen

Dosage Form	Recommended Dosage
200 mg/50 mg Tablets	800 mg/200 mg (4 tablets) once daily
80 mg/20 mg per mL Oral Solution	800 mg/200 mg (10 mL) once daily

Recommended Dosage in Adults - Kaletra Twice Daily Regimen

Dosage Form	Recommended Dosage
200 mg/50 mg Tablets	400 mg/100 mg (2 tablets) twice daily
80 mg/20 mg per mL Oral Solution	400 mg/100 mg (5 mL) twice daily

The dose of Kaletra must be increased when administered in combination with efavirenz, nevirapine or nelfinavir. The table below outlines the dosage recommendations for twice daily dosing when Kaletra is taken in combination with these agents.

Dosage Form	Recommended Dosage
200 mg/50 mg Tablets and 100 mg/25 mg Tablets	500 mg/125 mg (2 tablets of 200 mg/50 mg + 1 tablet of 100 mg/25 mg) twice daily
80 mg/20 mg per mL Oral Solution	520 mg/130 mg (6.5 mL) twice daily

 

Dosage Recommendations in Pediatric Patients

Kaletra tablets and oral solution are not recommended for once daily dosing in pediatric patients younger than 18 years of age. The dose of the oral solution should be administered using the calibrated cup (supplied) or oral dosing syringe. Kaletra 100/25 mg tablets should be considered only in children who have reliably demonstrated the ability to swallow the intact tablet.

Kaletra oral solution is not recommended in neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days has been attained.

Kaletra oral solution contains approximately 42% (v/v) ethanol and approximately 15% (w/v) propylene glycol. Total amounts of ethanol and propylene glycol from all medicines that are to be given to pediatric patients 14 days to 6 months of age should be taken into account in order to avoid toxicity from these excipients.

Pediatric Dosage Calculations

Calculate the appropriate dose of Kaletra for each individual pediatric patient based on body weight (kg) or body surface area (BSA) to avoid underdosing or exceeding the recommended adult dose. 

Kaletra Oral Solution Daily Dosage Recommendations in Pediatric Patients 14 days to Less Than 18 Years Without Concomitant Efavirenz, Nevirapine, or Nelfinavir

Patient Age	Based on Weight (mg/kg)	Based on BSA (mg/m2 )	Frequency
14 days to 6 months	16/4	300/75	Given twice daily
Older than 6 months to less than 18 years	Less than15 kg: 12/3 15 kg to 40 kg: 10/2.5	230/57.5	Given twice daily

Kaletra Tablet Daily Dosage Recommendations in Pediatric Patients > 6 Months to < 18 Years of Age Without Concomitant Efavirenz, Nevirapine, or Nelfinavir

Body Weight (kg)	Body Surface Area (m2 ) *	Recommended number of 100/25 mg Tablets Twice Daily
≥15 to 25	≥0.6 to < 0.9	2
>25 to 35	≥0.9 to < 1.4	3
>35	≥1.4	4

Kaletra oral solution is available for children with a BSA less than 0.6 m2 or those who are unable to reliably swallow a tablet

Kaletra Oral Solution Daily Dosage Recommendations for Pediatric Patients > 6 Months to < 18 Years of Age With Concomitant Efavirenz, Nevirapine, or Nelfinavir

Patient Age	Based on Weight (mg/kg)	Based on BSA (mg/m2	Frequency
> 6 months to < 18 years	<15 kg: 13/3.25 ≥15 kg to 45 kg: 11/2.75	300/75	given twice daily

Kaletra Tablet Daily Dosage Recommendations for Pediatric Patients > 6 Months to < 18 Years of Age With Concomitant Efavirenz† , Nevirapine, or Nelfinavir

Body Weight (kg)	Body Surface Area (m2 )	Recommended number of 100/25 mg Tablets Twice Daily
≥15 to 20	≥0.6 to < 0.8	2
>20 to 30	≥0.8 to < 1.2	3
>30 to 45	≥1.2 to <1.7	4
>45	≥1.7	5

Kaletra oral solution is available for children with a BSA less than 0.6 m2 or those who are unable to reliably swallow a tablet.

† Please refer to the individual product labels for appropriate dosing in children.

Dosage Recommendations in Pregnancy

• Administer 400/100 mg of Kaletra twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions.
• Once daily Kaletra dosing is not recommended in pregnancy
• There are insufficient data to recommend dosing in pregnant women with any documented lopinavir-associated resistance substitutions.
• No dosage adjustment of Kaletra is required for patients during the postpartum period.
• Avoid use of Kaletra oral solution in pregnant women

Mechanism of Action

Lopinavir, an inhibitor of the HIV protease, prevents cleavage of the Gag-Pol polyprotein, resulting in the production of immature, non-infectious viral particles. Ritonavir inhibits the (CYP3A-mediated) metabolism of lopinavir, thereby increasing levels of lopinavir in the blood.

Side Effects

Possible side effects of Kaletra include (but are not limited to) the following:

• Abnormal bowel movements
• Diarrhea
• Feeling weak/ tired
• Headache
• Nausea
• Abdominal pain

Additionally, some patients taking Kaletra can develop serious problems with their pancreas. Patients should immediately inform their doctor if nausea, vomiting, or abdominal pain occurs, as these may be signs of pancreatitis.

Clinical Trial Results

Patients Who Have Not Received Prior Antiretroviral Therapy

Study 863 is an ongoing, randomized, double-blind, multicenter trial comparing treatment with Kaletra versus nelfinavir. Both products were administered with stavudine and lamivudine - two nucleoside reverse transcriptase inhibitors (NRTI) - to 653 patients new to HIV therapy. Through 24 weeks of therapy, the proportion of patients with HIV RNA <50 copies/ mL was 65% in the group receiving Kaletra, and 60% in the nelfinavir group. Additionally, the mean increase from baseline in CD4 cell count was 154 cells/ mm3 for the Kaletra group and 150 cells/ mm3 for the nelfinavir group.

Study 720 is an ongoing, randomized, blinded, multicenter trial evaluating treatment with Kaletra at three dose levels (plus lamivudine and stavudine) in 100 patients. Through 72 weeks of treatment, the proportion of patients with undetectable levels of the virus (HIV RNA <400 copies/ mL) was 80% and the mean increase from baseline in CD4 cell count was 256 cells/ mm3 for the 51 patients originally receiving a 400/ 100 mg dose of Kaletra.

Patients Who Have Received Prior Antiretroviral Therapy

Study 765 is an ongoing, randomized, blinded, multicenter trial evaluating treatment with Kaletra at two dose levels plus nevirapine and two NRTIs. The treatment group consisted of 70 patients who had not previously taken a non-nucleoside reverse transcriptase inhibitor (NNRTI) but were single protease inhibitor experienced. Through 72 weeks of treatment, the proportion of patients with HIV RNA <400 copies/ mL was 75% and the mean increase from baseline in CD4 cell count was 174 cells/ mm3 for the 36 patients receiving the 400/ 100 mg dose of Kaletra.