Important note: Information in this article was accurate in 2005. The state of the art may have changed since the publication date.
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Food and Drug Administration - October 28, 2005
Richard Klein, Kimberly Struble
Today (October 28, 2005) the Food and Drug Administration approved a new formulation of Kaletra. Kaletra (lopinavir/ritonavir) is now available as a film coated tablet (200mg/50mg) that provides advantages over the currently marketed capsule formulation for HIV-1 infected patients. Specifically, the tablet formulation:
The following additions and revisions were made to the package insert.
1. The CLINICAL PHARMACOLOGY section contains the following additions:
Pharmacokinetics
Plasma concentrations of lopinavir and ritonavir after administration of two 200/50 mg KALETRA tablets are similar to three 133.3/33.3 mg KALETRA capsules under fed conditions with less pharmacokinetic variability.
Effects of Food on Oral Absorption
KALETRA tablets
No clinically significant changes in Cmax and AUC were observed following administration of Kaletra tablets under fed conditions compared to fasted conditions. Relative to fasting, administration of KALETRA tablets with a moderate fat meal (500 – 682 Kcal, 23 to 25% calories from fat) increased lopinavir AUC and Cmax by 26.9% and 17.6%, respectively. Relative to fasting, administration of KALETRA tablets with a high fat meal (872 Kcal, 56% from fat) increased lopinavir AUC by 18.9%, but not Cmax. Therefore, Kaletra tablets may be taken with or without food.
Drug-drug Interactions
Tables 2 and 3 were updated to clarify which formulations of Kaletra (capsule, oral solution or tablets) were used in the drug-drug interaction studies. Results of the drug-drug interaction study between efavirenz and Kaletra tablets were included.
2. The following text was added and/or revised in the PRECAUTION: Information for patients section:
KALETRA tablets can be taken at the same time as didanosine without food. Patients taking didanosine should take didanosine one hour before or two hours after KALETRA oral solution.
KALETRA tablets may be taken with or without food. KALETRA oral solution should be taken with food to enhance absorption.
3. In the PRECAUTION section, Table 10: Established and Other Potentially Significant Drug Interactions, was revised to include the following:
4. The DOSAGE AND ADMINISTRATION section was revised to include the following information regarding the new tablet formulation:
The recommended oral dose of KALETRA is as follows: (Please refer also to INDICATIONS AND USAGE and ADVERSE REACTIONS)
Adults
Therapy-Naïve Patients
Therapy-Experienced Patients
Once-daily administration of KALETRA is not recommended in therapy-experienced patients.
Concomitant therapy: Efavirenz, nevirapine, fosamprenavir or nelfinavir
Increasing the dose of KALETRA tablets to 600/150 mg (3 tablets) twice-daily coadministered with efavirenz significantly increased the lopinavir plasma concentrations approximately 35% and ritonavir concentrations approximately 56% to 92% compared to KALETRA tablets 400/100 mg twice-daily without efavirenz (see CLINICAL PHARMACOLOGY– Drug-drug Interactions Table 2 and/or PRECAUTIONS – Table 10).
KALETRA tablets and oral solution should not be administered as a once-daily regimen in combination with efavirenz, nevirapine, amprenavir or nelfinavir.
5.The HOW SUPPLIED section was revised to include storage information for the Kaletra tablets as follows:
Recommended storage: Store KALETRA film-coated tablets at 20°- 25°C (68°-77°F); excursions permitted to 15°-30°C (59° to 86°F) [see USP controlled room temperature]. Dispense in original container. For patient use: exposure of this product to high humidity outside the original container for longer than 2 weeks is not recommended.
The capsule formulation will be phased out over time by the company.
Kaletra is a product of Abbott Laboratories. The original formulation was approved on September 15, 2000.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
SOURCE: Food and Drug Administration (FDA).
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