Posology : מינונים

2 DOSAGE AND ADMINISTRATION
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 (11.4)].
•   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 11.3)].

•   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 (11.3)].


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 and            500 mg/125 mg (2 tablets of 200 mg/50 mg
100 mg/25 mg Tablets                + 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 Oral Solution is intended for pediatric patients > 6 months of age.
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 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 contains approximately 42 % (v/v) ethanol and approximately 15 % (w/v) propylene glycol.


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 6 Months to Less Than 18 Years: Table 4 summarizes the recommended daily dosing regimen for pediatric patients > 6 months 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 > 6 months to Less Than 18 Years Without Concomitant Efavirenz, Nevirapine, or Nelfinavir Patient Age                             Based on Weight        Based on BSA      Frequency (mg/kg)              (mg/m2)
Older than 6 months to less than 18 Less than 15 kg 12/3                         Given twice 230/57.5
years                               15 kg to 40 kg   10/2.5                         daily 

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 (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.


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

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 (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 [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.


2.5 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 [see Use in Specific Populations (8.1) and Clinical Pharmacology (11.3)].
•    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 [see Use in Specific Populations (8.1)].