Abacavir (Page 6 of 8)

14.2 Pediatric Trials

Therapy-Experienced Pediatric Subjects

CNA3006 was a randomized, double-blind trial comparing abacavir 8 mg per kg twice daily plus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m2 twice daily versus lamivudine 4 mg per kg twice daily plus zidovudine 180 mg per m2 twice daily. Two hundred and five therapy-experienced pediatric subjects were enrolled: female (56%), white (17%), black (50%), Hispanic (30%), median age of 5.4 years, baseline CD4+ cell percent greater than 15% (median = 27%), and median baseline plasma HIV-1 RNA of 4.6 log10 copies per mL. Eighty percent and 55% of subjects had prior therapy with zidovudine and lamivudine, respectively, most often in combination. The median duration of prior nucleoside analogue therapy was 2 years. At 16 weeks, the proportion of subjects responding based on plasma HIV-1 RNA less than or equal to 400 copies per mL was significantly higher in subjects receiving abacavir plus lamivudine plus zidovudine compared with subjects receiving lamivudine plus zidovudine, 13% versus 2%, respectively. Median plasma HIV-1 RNA changes from baseline were -0.53 log10 copies per mL in the group receiving abacavir plus lamivudine plus zidovudine compared with -0.21 log10 copies per mL in the group receiving lamivudine plus zidovudine. Median CD4+ cell count increases from baseline were 69 cells per mm3 in the group receiving abacavir plus lamivudine plus zidovudine and 9 cells per mm3 in the group receiving lamivudine plus zidovudine.

Once-Daily Dosing

ARROW (COL105677) was a 5-year randomized, multicenter trial which evaluated multiple aspects of clinical management of HIV-1 infection in pediatric subjects. HIV-1–infected, treatment-naive subjects aged 3 months to 17 years were enrolled and treated with a first-line regimen containing abacavir and lamivudine, dosed twice daily according to World Health Organization recommendations. After a minimum of 36 weeks of treatment, subjects were given the option to participate in Randomization 3 of the ARROW trial, comparing the safety and efficacy of once-daily dosing with twice-daily dosing of abacavir and lamivudine, in combination with a third antiretroviral drug, for an additional 96 weeks. Of the 1,206 original ARROW subjects, 669 participated in Randomization 3. Virologic suppression was not a requirement for participation at baseline for Randomization 3 (following a minimum of 36 weeks of twice-daily treatment), 75% of subjects in the twice-daily cohort were virologically suppressed compared with 71% of subjects in the once-daily cohort.

The proportions of subjects with HIV-1 RNA less than 80 copies per mL through 96 weeks are shown in Table 11. The differences between virologic responses in the two treatment arms were comparable across baseline characteristics for gender and age.

Table 11. Virologic Outcome of Randomized Treatment at Week 96a (ARROW Randomization 3)
a Analyses were based on the last observed viral load data within the Week 96 window. b Predicted difference (95% CI) of response rate is -4.5% (-11% to 2%) at Week 96. c Includes subjects who discontinued due to lack or loss of efficacy or for reasons other than an adverse event or death, and had a viral load value of greater than or equal to 80 copies per mL, or subjects who had a switch in background regimen that was not permitted by the protocol.d Other includes reasons such as withdrew consent, loss to follow-up, etc. and the last available HIV-1 RNA less than 80 copies per mL (or missing).
Outcome Abacavir plus Lamivudine Twice-Daily Dosing (n=333) Abacavir plus Lamivudine Once-Daily Dosing (n=336)
HIV-1 RNA <80 copies/mLb HIV-1 RNA ≥80 copies/mLc No virologic data Discontinued due to adverse event or death Discontinued study for other reasonsd Missing data during window but on study 70%28%1%0%1% 67%31%<1%<1%1%

16 HOW SUPPLIED/STORAGE AND HANDLING

Abacavir Oral Solution USP: It is a clear to opalescent, yellowish, strawberry-banana-flavored liquid. Each mL of the solution contains abacavir sulfate USP equivalent to 20 mg of abacavir. It is packaged in opaque bottles with child-resistant closure. This product does not require reconstitution.
Bottles of 240 mL NDC 64980-405-24

Store at 20° to 25 °C (68° to 77 °F). [see USP Controlled Room Temperature ]. DO NOT FREEZE. May be refrigerated.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Hypersensitivity Reactions

Inform patients:

  • that a Medication Guide and Warning Card summarizing the symptoms of the abacavir hypersensitivity reaction and other product information will be dispensed by the pharmacist with each new prescription and refill of abacavir, and instruct the patient to read the Medication Guide and Warning Card every time to obtain any new information that may be present about abacavir. The complete text of the Medication Guide is reprinted at the end of this document.
  • to carry the Warning Card with them.
  • how to identify a hypersensitivity reaction [see Warnings and Precautions (5.1), Medication Guide].
  • that if they develop symptoms consistent with a hypersensitivity reaction they should call their healthcare provider right away to determine if they should stop taking abacavir.
  • that a hypersensitivity reaction can worsen and lead to hospitalization or death if abacavir is not immediately discontinued.
  • to not restart abacavir or any other abacavir-containing product following a hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
  • that if they have a hypersensitivity reaction, they should dispose of any unused abacavir to avoid restarting abacavir.
  • that a hypersensitivity reaction is usually reversible if it is detected promptly and abacavir is stopped right away.
  • that if they have interrupted abacavir for reasons other than symptoms of hypersensitivity (for example, those who have an interruption in drug supply), a serious or fatal hypersensitivity reaction may occur with reintroduction of abacavir.
  • to not restart abacavir or any other abacavir-containing product without medical consultation and only if medical care can be readily accessed by the patient or others.

Lactic Acidosis/Hepatomegaly with Steatosis

Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogues and other antiretrovirals. Advise patients to stop taking abacavir if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.2)].

Immune Reconstitution Syndrome

Advise patients to inform their healthcare provider immediately of any signs and symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when abacavir is started [see Warnings and Precautions (5.3)].

Pregnancy Registry


Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir during pregnancy [see Use in Specific Populations (8.1)].

Lactation

Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)].

Missed Dose

Instruct patients that if they miss a dose of abacavir, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose [see Dosage and Administration (2)].

Availability of Medication Guide

Instruct patients to read the Medication Guide before starting abacavir and to re-read it each time the prescription is renewed. Instruct patients to inform their physician or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.

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