is text of the FDA announcement describing the approval and detailing
changes to the Kaletra label information.
Kaletra (lopinavir/ritonavir) tablets and oral solution once daily
dosing regimen in certain adult patients
April 27, 2010, FDA approved a new dosing regimen for Kaletra
(lopinavir/ritonavir) tablets and oral solution. Kaletra can be
administered once daily (800/200 mg) in patients with less than
three lopinavir resistance associated substitutions. Once daily
administration of Kaletra is not recommended for 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. Of note, once daily administration
of Kaletra is not recommended in pediatric patients.
The major revisions to the package insert are summarized below.
complete revised label will be posted soon.
6.1 - Adults - Clinical Trials Experience:
In study 802, the incidence of diarrhea of any severity during
48 weeks of therapy was 50% in patients receiving Kaletra tablets
once daily compared to 39% in patients receiving Kaletra tablets
twice daily. Moderate or severe drug-related diarrhea occurred
in 14% of patients receiving Kaletra tablets once daily as compared
to 11% in patients receiving Kaletra tablets twice daily. At the
time of discontinuation, 19 (6.3%) patients receiving Kaletra
tablets once daily had ongoing diarrhea, as compared to 11 (3.7%)
patients receiving Kaletra tablets twice daily. Discontinuations
due to any adverse reaction occurred in 4.3% of patients receiving
Kaletra tablets once daily compared to 7.0% in patients receiving
Kaletra tablets twice daily.
A table for the treatment-emergent adverse reactions of moderate
or severe intensity and grade 3-4 laboratory abnormalities can
be found in the revised prescribing information.
12 - CLINICAL PHARMACOLOGY
12.3 - Pharmacokinetics
The pharmacokinetics of once daily Kaletra has also been evaluated
in treatment experienced HIV-1 infected subjects. Lopinavir exposure
(Cmax, AUC[0-24h], Ctrough) with once daily Kaletra administration
in treatment experienced subjects is comparable to the once daily
lopinavir exposure in treatment naive subjects.
14 - CLINICAL STUDIES
14.2 - Patients With Prior Antiretroviral
Study 802: Kaletra Tablets 800/200 mg Once Daily Versus 400/100
mg Twice Daily when Coadministered with Nucleoside/Nucleotide
Reverse Transcriptase Inhibitors in Antiretroviral Experienced,
HIV-1 Infected Subjects
M06-802 was a randomized open-label study comparing the safety,
tolerability, and antiviral activity of once daily and twice daily
dosing of Kaletra tablets in 599 subjects with detectable viral
loads while receiving their current antiviral therapy. Of the
enrolled subjects, 55% on both treatment arms had not been previously
treated with a protease inhibitor and 81-88% had received prior
NNRTIs as part of their anti HIV treatment regimen. Patients were
randomized in a 1:1 ratio to receive either Kaletra 800/200 mg
once daily (n = 300) or Kaletra 400/100 mg twice daily (n = 299).
Patients were administered at least two nucleoside/nucleotide
reverse transcriptase inhibitors selected by the investigator.
Mean age of patients enrolled was 41 years (range: 21 to 73);
51% were Caucasian, and 66% were male. Mean baseline CD4+ cell
count was 254 cells/mm3 (range: 4 to 952 cells/mm3) and mean baseline
plasma HIV-1 RNA was 4.3 log10 copies/mL (range: 1.7 to 6.6 log10
Treatment response and outcomes of randomized treatment through
Week 48 are presented in Table 18.
Outcomes of Randomized Treatment Through
Week 48 (Study 802)
Once Daily + NRTIs (n = 300)
Twice Daily +
NRTIs (n = 299)
Success (HIV-1 RNA < 50 copies/mL)
virologic data in Week 48 window
study due to adverse event or death (2)
study for other reasons (3),
Missing data during window but on study
Includes patients who discontinued prior to Week 48 for lack
or loss of efficacy and patients with HIV-1 RNA = 50 copies/mL
at Week 48.
2. Includes patients who
discontinued due to adverse events or death at any time from
Day 1 through Week 48 if this resulted in no virologic data
on treatment at Week 48.
3. Includes withdrawal
of consent, loss to follow-up, non-compliance, protocol violation
and other reasons.
48 weeks of treatment the mean change from baseline for CD4+ cell
count was 136 cells/mm3 for the QD group and 122 cells/mm3 for
the BID group.
This gives treatment-experienced patients who have HIV that responds
to Kaletra another dosing option as determined by their physician.
Klein and K Struble (U.S. Food and Drug Administration). New Kaletra
(lopinavir/ritonavir) Tablets and Oral Solution once daily dosing
regimen in certain adult patients. HIV/AIDS Update. April 27,
Abbott. Abbott Receives FDA Approval for Once-Daily Dosing of
Kaletra (lopinavir /ritonavir) for Treatment-Experienced Patients.
Press release. April 28, 2010.