KALETRA®
(lopinavir/ritonavir) tablets
(lopinavir/ritonavir) oral solution
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
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These highlights do not include all the information needed to use KALETRA safely and effectively. See full prescribing information for KALETRA. |
KALETRA (lopinavir and ritonavir) tablet, film coated for oral use
KALETRA (lopinavir and ritonavir) solution for oral use
Initial U.S. Approval: 2000
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RECENT MAJOR CHANGES
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Dosage and Administration, Pediatric Patients (2.2) 11/2007
Contraindications, Table 3 (4) 11/2007
Contraindications, Table 3 (4) 6/2008
Dosage and Administration, Pediatric Patients (2.2) 6/2008
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INDICATIONS AND USAGE
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KALETRA is an HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. (1)
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DOSAGE AND ADMINISTRATION
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Do not use once-daily administration of KALETRA in:
● Therapy-experienced patients (2.1)
● Combination with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir (2.1)
● Pediatric patients (2.2)
Tablets: May be taken with or without food, swallowed whole and not chewed, broken, or crushed. (2)
Oral Solution: Must be taken with food. (2)
ADULT PATIENTS Therapy-Naïve (2.1)
● 400/100 mg (two 200/50 mg tablets or 5 mL oral solution) twice-daily or
● 800/200 mg (four 200/50 mg tablets or 10 mL oral solution) once-daily.
ADULT PATIENTS Therapy-Experienced (2.1)
● 400/100 mg (two 200/50 mg tablets or 5 mL oral solution) twice-daily
PEDIATRIC PATIENTS (ages 14 days and older) (2.2)
● Twice-daily dose is based on body weight.
Concomitant Therapy in Adults and Pediatric Patients (2.1,2.2)
● Dose adjustments of KALETRA may be needed when co-administering with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir.
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DOSAGE FORMS AND STRENGTHS
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● Film-coated tablets: 200 mg lopinavir and 50 mg ritonavir (3)
● Film-coated tablets: 100 mg lopinavir and 25 mg ritonavir (3)
● Oral solution: 80 mg lopinavir and 20 mg ritonavir per milliliter (3)
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CONTRAINDICATIONS
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Hypersensitivity to KALETRA (e.g., Stevens-Johnson syndrome, erythema multiforme) or any of its ingredients, including ritonavir. (4)
Coadministration with:
● drugs highly dependent on CYP3A for clearance and for which elevated plasma levels may result in serious and/or life-threatening events. (4)
● potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross resistance. (4)
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WARNINGS AND PRECAUTIONS
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The following have been observed in patients receiving KALETRA:
● Drug Interactions: Consider drug-drug interaction potential to reduce risk of serious or life-threatening adverse reactions. (5.1)
● Pancreatitis: Fatalities have occurred; suspend therapy as clinically appropriate. (5.2)
● 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. (5.3, 8.6)
● Patients may develop new onset or exacerbations of diabetes mellitus, hyperglycemia (5.4), immune reconstitution syndrome (5.5), redistribution/accumulation of body fat. (5.6)
● Total cholesterol and triglycerides elevations. Monitor prior to therapy and periodically thereafter. (5.7)
● Hemophilia: Spontaneous bleeding may occur, and additional factor VIII may be required. (5.8)
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ADVERSE REACTIONS
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The most common adverse reactions (> 5%) were diarrhea, nausea, abdominal pain, asthenia, vomiting, headache, and dyspepsia. (6.1, 6.2)
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To report SUSPECTED ADVERSE REACTIONS, contact Abbott Laboratories at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
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DRUG INTERACTIONS
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Coadministration of KALETRA can alter the concentrations of other drugs and other drugs may alter the concentrations of lopinavir. The potential for drug-drug interactions must be considered prior to and during therapy. (4, 5.1, 7, 12.3)
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USE IN SPECIFIC POPULATIONS
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● Pregnancy: Physicians are encouraged to register patients in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. (8.1)
● Pediatric Use: The safety, efficacy, and pharmacokinetic profiles of KALETRA in pediatric patients below the age of 14 days have not been established. (8.4)
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 07/2008 |
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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*
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
KALETRA is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The following points should be considered when initiating therapy with KALETRA:
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The use of other active agents with KALETRA is associated with a greater likelihood of treatment response [see Clinical Pharmacology (12.4) and Clinical Studies (14)].
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Genotypic or phenotypic testing and/or treatment history should guide the use of KALETRA [see Clinical Pharmacology (12.4)]. The number of baseline primary protease inhibitor mutations affects the virologic response to KALETRA [see Clinical Pharmacology (12.4)].
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Once-daily administration of KALETRA is not recommended for therapy-experienced adult patients or any pediatric patients.
2 DOSAGE AND ADMINISTRATION
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.
2.1 Adult Patients
Therapy-Naïve Patients
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KALETRA tablets 400/100 mg (given as two 200/50 mg tablets) twice-daily taken with or without food.
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KALETRA oral solution 400/100 mg (5 mL) twice-daily taken with food.
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KALETRA tablets 800/200 mg (given as four 200/50 mg tablets) once-daily taken with or without food.
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KALETRA oral solution 800/200 mg (10 mL) once-daily taken with food.
When initiating treatment with KALETRA in therapy-naïve patients, it should be noted the incidence of diarrhea was greater with KALETRA capsules once-daily compared to KALETRA capsules twice-daily in Study 418 (57% vs. 35% - reactions of all grades; 16% vs. 5% - reactions of at least moderate severity) [See ADVERSE REACTIONS (6.1) and DOSAGE AND ADMINISTRATION (2.1)].
Therapy-Experienced Patients
Once-daily administration of KALETRA is not recommended in therapy-experienced patients.
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KALETRA tablets 400/100 mg (given as two 200/50 mg tablets) twice-daily taken with or without food.
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KALETRA oral solution 400/100 mg (5 mL) twice-daily taken with food.
Concomitant Therapy: Efavirenz, nevirapine, (fos)amprenavir or nelfinavir
[See CLINICAL PHARMACOLOGY (12.3) and DRUG INTERACTIONS (7.3)]
KALETRA tablets and oral solution should not be administered as a once-daily regimen in combination with efavirenz, nevirapine, (fos)amprenavir or nelfinavir.
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KALETRA 400/100 mg (given as two 200/50 mg tablets) can be used twice-daily in combination with these drugs with no dose adjustment in antiretroviral-naïve patients.
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A dose increase of KALETRA tablets to 600/150 mg (given as three 200/50 mg tablets) twice-daily may be considered when used in combination with efavirenz, nevirapine, (fos)amprenavir without ritonavir, or nelfinavir in treatment-experienced patients where decreased susceptibility to lopinavir is clinically suspected (by treatment history or laboratory evidence).
A dose increase is recommended for all patients who use KALETRA oral solution. The recommended dose of KALETRA oral solution is 533/133 mg (6.5 mL) twice-daily taken with food when used in combination with efavirenz, nevirapine, (fos)amprenavir or nelfinavir.
2.2 Pediatric Patients
KALETRA tablets and oral solution should not be administered once-daily in pediatric patients < 18 years of age.
Healthcare professionals should pay special attention to accurate calculation of the dose of KALETRA, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors, overdose, [see OVERDOSAGE ( 10)] and underdose.
Prescribers should calculate the appropriate dose of KALETRA for each individual child based on body weight (kg) or body surface area (BSA) and should not exceed 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)
The dose of the oral solution should be administered using a calibrated dosing syringe.
Before prescribing KALETRA 100/25 mg tablets, children should be assessed for the ability to swallow intact tablets. If a child is unable to reliably swallow a KALETRA tablet, the KALETRA oral solution formulation should be prescribed.
14 Days to 6 Months:
In pediatric patients 14 days to 6 months of age, the recommended dosage of lopinavir/ritonavir using KALETRA oral solution is 16/4 mg/kg or 300/75 mg/m2 twice daily. Prescribers should calculate the appropriate dose based on body weight or body surface area.
Because no data exists for dosage when administered with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir, it is recommended that KALETRA not be administered in combination with these drugs in patients < 6 months of age.
6 Months to 18 Years:
Without Concomitant Efavirenz, Nevirapine, (Fos)amprenavir or Nelfinavir
In children 6 months to 18 years of age, the recommended dosage of lopinavir/ritonavir using KALETRA oral solution without concomitant efavirenz, nevirapine, (fos)amprenavir, or nelfinavir is 230/57.5 mg/m2 given twice daily, not to exceed the recommended adult dose. If weight-based dosing is preferred, the recommended dosage of lopinavir/ritonavir for patients < 15 kg is 12/3 mg/kg given twice daily and the dosage for patients ≥ 15 kg to 40 kg is 10/2.5 mg/kg given twice daily.
Table 1 provides the dosing recommendations for pediatric patients 6 months to 18 years of age based on body weight or body surface area for KALETRA tablets.
Table 1. Pediatric Dosing Recommendations for Patients 6 Months to 18 Years of Age Based on Body Weight or Body Surface Area for KALETRA Tablets Without Concomitant Efavirenz, Nevirapine, (Fos)amprenavir, or Nelfinavir
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Body Weight (kg) |
Body Surface Area (m2)* |
Recommended number of
100/25 mg Tablets Twice-Daily |
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* 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.
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15 to 25 |
≥0.6 to < 0.9 |
2 |
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>25 to 35 |
≥0.9 to < 1.4 |
3 |
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>35 |
≥1.4 |
4 (or two 200/50 mg tablets) |
Concomitant Therapy: Efavirenz, Nevirapine, (Fos)amprenavir, or Nelfinavir
A dose increase of KALETRA to 300/75 mg/m2 is needed when co-administered with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir in children (both treatment-naïve and treatment-experienced) 6 months to 18 years of age, not to exceed the recommended adult dose. If weight-based dosing is preferred, the recommended dosage for patients<15 kg is 13/3.25 mg/kg given twice daily and the dosage for patients>15 kg to 45 kg is 11/2.75 mg/kg given twice daily.
Table 2 provides the dosing recommendations for pediatric patients 6 months to 18 years of age based on body weight or body surface area for KALETRA tablets when given in combination with efavirenz, nevirapine, (fos)amprenavir, or nelfinavir.
Table 2. Pediatric Dosing Recommendations for Patients 6 Months to 18 Years of Age Based on Body Weight or Body Surface Area for KALETRA Tablets With Concomitant Efavirenz †, Nevirapine, (Fos)amprenavir † or Nelfinavir †
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Body Weight (kg) |
Body Surface Area (m2)* |
Recommended number of
100/25 mg Tablets Twice-Daily |
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* 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.
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15 to 20 |
≥0.6 to < 0.8 |
2 |
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>20 to 30 |
≥0.8 to < 1.2 |
3 |
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>30 to 45 |
≥1.2 to <1.7 |
4 (or two 200/50 mg tablets) |
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>45 |
≥1.7 |
4 or 6 (or two or three 200/50 mg tablets) See Dosage and Administration, Adult Patients (2.1) |
3 DOSAGE FORMS AND STRENGTHS
● KALETRA Tablets, 200 mg lopinavir/50 mg ritonavir
Yellow, film-coated, ovaloid tablets debossed with the corporate Abbott “A” logo and the Abbo-Code KA providing 200 mg lopinavir/50 mg ritonavir.
● KALETRA Tablets, 100 mg lopinavir/25 mg ritonavir
Pale yellow, film-coated, ovaloid tablets debossed with the corporate Abbott “A” logo and the Abbo-Code KC providing 100 mg lopinavir/25 mg ritonavir.
● KALETRA Oral Solution
Light yellow to orange colored liquid containing 400 mg lopinavir/100 mg ritonavir per 5 mL (80 mg lopinavir/20 mg ritonavir per mL).
4 CONTRAINDICATIONS
● KALETRA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme) to any of its ingredients, including ritonavir.
● Co-administration of 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.
● Co-administration of KALETRA is contraindicated with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance. These drugs are listed in Table 3.
Table 3. Drugs That Are Contraindicated With KALETRA
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Drug Class |
Drugs Within Class That Are Contraindicated With KALETRA |
Clinical comments: |
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aSee Drug Interactions, Table 9 for parenterally administered midazolam |
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Antimycobacterial |
Rifampin |
May lead to loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors or other co-administered antiretroviral agents. [see DRUG INTERACTIONS (7)] |
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Ergot Derivatives |
Dihydroergotamine, ergonovine, ergotamine, methylergonovine |
Potential for acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
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GI motility agent |
Cisapride |
Potential for cardiac arrhythmias. |
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Herbal Products |
St Johns wort (hypericum perforatum) |
May lead to loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors. |
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HMG-CoA Reductase Inhibitors |
Lovastatin, simvastatin |
Potential for myopathy including rhabdomyolysis. |
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Neuroleptic |
Pimozide |
Potential for cardiac arrhythmias. |
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Sedative/Hypnotics |
Triazolam;
orally administered midazolama |
Prolonged or increased sedation or respiratory depression. |
5 WARNINGS AND PRECAUTIONS
5.1 Drug Interactions
See Tables 3 and 9 for listing of drugs that are contraindicated for use with KALETRA due to potentially life-threatening adverse events, significant drug interactions, or loss of virologi
