Kaletra

KALETRA- lopinavir and ritonavir tablet, film coated
KALETRA- lopinavir and ritonavir solution
AbbVie Inc.

1 INDICATIONS AND USAGE

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 [see Microbiology ( 12.4)].

2 DOSAGE AND ADMINISTRATION

BSA

2.1 General Administration Recommendations

KALETRA tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed. KALETRA oral solution must be taken with food.

2.2 Administering Oral Solution by Feeding Tube

Because KALETRA oral solution contains ethanol and propylene glycol, it is not recommended for use with polyurethane feeding tubes due to potential incompatibility. Feeding tubes that are compatible with ethanol and propylene glycol, such as silicone and polyvinyl chloride (PVC) feeding tubes, can be used for administration of KALETRA oral solution. Follow instructions for use of the feeding tube to administer the medicine.

2.3 Dosage Recommendations in Adults

KALETRA can be given in once daily or twice daily dosing regimen at dosages noted in Tables 1 and 2. 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 [see Microbiology ( 12.4)].
  
• In combination with carbamazepine, phenobarbital, or phenytoin [see Drug Interactions ( 7.3)].
  
• In combination with efavirenz, nevirapine, or nelfinavir [see Drug Interactions ( 7.3) and Clinical Pharmacology ( 12.3)].
  
• In pediatric patients younger than 18 years of age [see Dosage and Administration ( 2.4)].
• In pregnant women [see Dosage and Administration ( 2.5), Use in Specific Populations ( 8.1) and Clinical Pharmacology ( 12.3)].

Table 1. Recommended Dosage in Adults — KALETRA Once Daily Regimen

KALETRA 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

Table 2. Recommended Dosage in Adults — KALETRA Twice Daily Regimen

KALETRA 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. Table 3 outlines the dosage recommendations for twice daily dosing when KALETRA is taken in combination with these agents.

Table 3. Recommended Dosage in Adults — KALETRA Twice Daily Regimen in Combination with Efavirenz, Nevirapine, or Nelfinavir

KALETRA Dosage Form	Recommended Dosage
200 mg/50 mg Tablets and100 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

2.4 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 [see Warnings and Precautions ( 5.2)].

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 [see Warnings and Precautions ( 5.2) and Overdosage ( 10)].

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.

Body surface area (BSA) can be calculated as follows:

The KALETRA dose can be calculated based on weight or BSA:

Based on Weight:

Patient Weight (kg) × Prescribed lopinavir dose (mg/kg) = Administered lopinavir dose (mg)

Based on BSA:

Patient BSA (m²) × Prescribed lopinavir dose (mg/m²) = Administered lopinavir dose (mg)

If KALETRA oral solution is used, the volume (mL) of KALETRA solution can be determined as follows:

Volume of KALETRA solution (mL) = Administered lopinavir dose (mg) ÷ 80 (mg/mL)

Oral Solution Dosage Recommendation in Pediatric Patients 14 Days to Less Than 18 Years:

Table 4 summarizes the recommended daily dosing regimen for pediatric patients 14 days to less than 18 years of age using the oral solution.

KALETRA administered in combination with efavirenz, nevirapine, or nelfinavir in patients younger than 6 months of age is not recommended. Total dose of KALETRA oral solution in pediatric patients should not exceed the recommended adult daily dose of 400/100 mg (5mL) twice daily.

Table 4. 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/m 2 )	Frequency
14 days to 6 months	16/4		300/75	Given twicedaily
Older than 6 months to less than 18 years	Less than15 kg	12/3	230/57.5	Given twicedaily
	15 kg to 40 kg	10/2.5

Tablet Dosage Recommendation in Pediatric Patients Older than 6 Months to Less than 18 Years:

Table 5 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for KALETRA tablets.

Table 5. 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 (m 2 ) *	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.

Concomitant Therapy: Efavirenz, Nevirapine, or Nelfinavir

Dosing recommendations using oral solution

Table 6 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for KALETRA Oral Solution when given in combination with efavirenz, nevirapine, or nelfinavir:

Table 6. 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/m 2 )	Frequency
> 6 months to< 18 years	<15 kg	13/3.25	300/75	Given twicedaily
	≥15 kg to 45 kg	11/2.75

Dosing recommendations using tablets

Table 7 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for KALETRA tablets when given in combination with efavirenz, nevirapine, or nelfinavir.

Table 7. 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 (m 2 ) *	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 [see Dosage and Administration ( 2.4)]
* 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.† Please refer to the individual product labels for appropriate dosing in children.