Recent
Announcements Regarding Treatment of HIV Infection in Children
The
U.S. Food and Drug Administration (FDA) last week granted approval for a new fixed-dose
combination pill to treat children outside the US. Also, Abbott Laboratories
sent a "Dear Health Care Provider" letter regarding lopinavir/ritonavir
(Kaletra) oral solution and accidental overdose in infants and children.
FDA
Announcement on New Generic Fixed-dose Combination
On
August 13, 2007, FDA granted tentative approval for a new fixed dose three-drug
combination pill containing generic lamivudine
[3TC], stavudine [d4T], and nevirapine
to treat HIV infection in children outside the United States. This is the first
combination of its kind available to meet the needs of children less than 12 years
of age, and represents a major advance in global AIDS treatment efforts. The generic
combination drug tablet is manufactured by Cipla Limited, of Mumbai, India.
The
new combination constitutes a complete HIV regimen that is taken twice daily,
once patients have tolerated 14 days of lead-in treatment with nevirapine taken
once daily in combination with separate doses of lamivudine and stavudine. The
combination tablet can be dissolved in water for children who cannot swallow tablets.
Each
ingredient of this generic tablet is currently approved to treat HIV-1 in combination
with other antiretroviral agents. The safety and effectiveness of the combination
of lamivudine/stavudine/nevirapine in lowering viral load and increasing CD4+
cells has been demonstrated in previously conducted controlled studies of the
individual ingredients used together.
The three drugs, combined in a single
twice-a-day tablet, are not only easier to administer to children, increasing
access and adherence to therapy, but also facilitate storage and distribution.
This new combination represents a significant advance in the treatment of children
infected with HIV in PEPFAR countries.
Tentative Approval means that FDA
has concluded that a drug product has met all required quality, safety, and efficacy
standards. But because of existing patents and/or exclusivity rights, it may not
be marketed in the U.S. The tentative approval does, however, make the product
eligible for consideration for purchase under the President's Emergency Plan for
AIDS Relief (PEPFAR) program.
The
tentative approvals of nevirapine and this triple fixed dose combination tablet
of lamivudine, stavudine and nevirapine represent the 50th and 51st approvals
or tentative approvals, respectively, by FDA under the expedited review provisions
developed for the President's Emergency Plan for AIDS Relief.
Abbott
Letter to Providers Regarding Lopinavir/ritonavir (Kaletra) Dosing in Infants
and Children
On
August 6, Abbott Laboratories sent out a Dear Healthcare Provider letter regarding
lopinavir/ritonavir oral solution and accidental overdose in children, highlighting
important information about dosing for pediatric patients.
The Direct Healthcare
Professional Communication indicated that Abbott was recently notified of an accidental
overdose when an infant received a significantly larger than recommended dose
of lopinavir/ritonavir oral solution.
The accidental overdose occurred
in a 44-day-old infant, born at 30 weeks gestation, who was given approximately
6.5 mL of lopinavir/ritonavir oral solution -- about 10 times the calculated volume.
The infant died 9 days later of cardiogenic shock.
Abbott reminded providers
that:
•
Lopinavir/ritonavir
oral solution is highly concentrated, containing 80 mg lopinavir and 20 mg ritonavir
per mL (not per bottle).
•
Children's dosages
are calculated based on body weight.
•
A child should receive
less than 5 mL oral solution per dose unless they are also receiving certain concomitant
antiretroviral medicines.
Special
attention must be paid to accurate calculation of the dose, transcription of the
medication order, dispensing information, and dosing instructions to minimize
the risk for medication errors.
The FDA web site has a pediatric HIV drug
page that provides additional information about pediatric dosing of antiretroviral
drugs, available at http://www.fda.gov/oashi/aids/pedlbl.html.
08/21/07
Sources
R
Klein (Office of Special Health Issues, Food and Drug Administration) and F Struble
(Division of Antiviral Drug Products, Food and Drug Administration). August 13,
2007.
Abbott Laboratories. Direct Healthcare Communication on Kaletra (lopinavir/ritonavir)
oral solution and accidental overdose in children. August 6, 2007.
