- Additional information
- Reviews (0)
The demonstration of Abamune’s benefit is mainly based on the results of studies conducted in adult patients who have never received antiretrovirals and treated with a 2-dose regimen.
Before starting any treatment containing abacavir, screening for the HLA-B * 5701 allele should be performed in any HIV-infected patient, irrespective of their ethnic origin. Screening is also recommended before reintroducing abacavir in patients whose HLA-B * 5701 status is unknown, and who have previously tolerated abacavir (see “Management after Abamune treatment interruption”). Abacavir should not be used in patients with the HLA-B * 5701 allele unless no other therapeutic alternative is available in these patients, taking into account treatment history and resistance testing.
Adults and adolescents (over 12 years of age): The recommended dosage of Abamune is 600 mg daily. This dose may be administered either as 300 mg (one tablet) twice daily or as 600 mg (2 tablets) once daily.
Children (less than 12 years old): Since obtaining a precise dosage with the tablet form is difficult to obtain, pharmacokinetic overdose may occur. As a result, these patients will need to be closely monitored for tolerance.
- at least 30 kg: 300 mg twice a day
- from 21 kg to 30 kg: half a tablet of Abamune in the morning and one tablet in the evening.
- from 14 to 21 kg: half a tablet of Abamune twice a day.
Form oral solution:
Abamune is also available as an oral solution for children over three months of age who weigh less than 14 kg or for patients for whom the tablet form is not appropriate.
Update of clinical data
Since its inclusion in the lists of reimbursable proprietary medicinal products, abacavir has been the subject of clinical studies mainly in the context of fixed associations.
In particular, the laboratory provided new comparative efficacy and safety data for non-pre-treated patients in the fixed-dose combination of KIVEXA including abacavir (lamivudine/abacavir) versus TRUVADA (fixed combination): emtricitabine/tenofovir).
- Efficacy in non-pretreated adult patients
HEAT3 study: In the HEAT study, the non-inferiority of KIVEXA to TRUVADA, in combination with lopinavir / ritonavir (KALETRA), was demonstrated at 48 weeks in terms of virological efficacy defined as the percentage of patients with viral load <50 copies / ml, whether in the global populationin groups of patients with a CV at 100,000 copies / ml.
Study A52024: The ACTG 5202 study showed in an intermediate subgroup analysis, in patients with an initial CV ≥ 100 000 copies / ml, a risk of virological failure 5 (primary endpoint) higher in the KIVEXA group only in the TRUVADA group (Hazard Ratio: 2.33, IC95% [1.46; 3.72]). In patients with an initial CV <100,000 copies / ml, there was no difference between TRUVADA and KIVEXA in terms of risk of virologic failure. In addition, there was no difference between the 2 groups in the virological response defined as CV ≤ 50 copies / ml at S48 (secondary endpoint) in patients with an initial CV ≥ 100 000 copies / ml (80 % in the TRUVADA group versus 75% in the KIVEXA group).
These new studies confirm the efficacy of the 2 fixed combinations KIVEXA and TRUVADA which are currently recommended treatments in naive patients. These data have been taken into account in the updating of the recommendations in force (annual report under the direction of Professor YENI of 2010) 6 who nonetheless recommend the preferential use of TRUVADA over KIVEXA in treatment-naive patients “if the viral load is ≥ 100,000 copies / ml, especially if combined with atazanavir / ritonavir (REYATAZ) or efavirenz (SUSTIVA).
- Efficacy in children:
Follow-up of the PENTA 57 study in non-pre-treated children compared 3 treatments:
lamivudine (EPIVIR) + zidovudine (RETROVIR): N = 36
- abacavir (Abamune) + zidovudine (RETROVIR): N = 44
- abacavir (Abamune) + lamivudine (EPIVIR): N = 46
associated with nelfinavir (VIRACEPT) or placebo.
At 5 years of age, the percentage of children with a viral load <50 copies / ml is greater in the abacavir + lamivudine group than:
- in the lamivudine + zidovudine group: 34/38 versus 10/31
- in the abacavir + zidovudine group: 34/38 versus 9/36
The overall analysis of the tolerance data through the various studies and the pharmacovigilance data 8 presented by the firm do not change the profile the safety of ZIAGEN, especially the risk of abacavir-related hypersensitivity reactions (see CT Notice) 9.
The cardiovascular safety of abacavir and, in particular, the finding in some studies or cohorts of an increased risk of myocardial infarction (MI) with this product has been re-evaluated by the CHMP.
The CHMP concluded that the data provided on the cardiovascular safety of abacavir were not robust and noted the following statement (Chapter 4.4 of the SPC):
“Observational studies have shown an association between myocardial infarction and taking abacavir.
The subjects studied were mainly patients previously treated with antiretrovirals. Data from clinical trials have shown a limited number of myocardial infarctions and can not exclude a slight increase in this risk.
Overall, available data from observational cohorts and randomized trials show a lack of consistency.
e in their results, and indeed do not allow to confirm or refute a causal link between the treatment with abacavir and the risk of myocardial infarction.
To date, no biological mechanism explaining a possible increase in this risk has been identified.
The prescription of ZIAGEN should be accompanied by measures to reduce all modifiable risk factors (eg, smoking, hypertension and hyperlipidemia) “.
These data do not give rise to a modification of the conclusions of the Transparency Committee’s previous opinion (TB opinion of 29 October 2008).