raltegravir
Sources réglementaires consultées
Indications approuvées
- Traitement combiné du VIH-1 chez les patients pédiatriques pesant au moins 11 kg, avec la présentation à croquer et le schéma adaptés au poids.
Contre-indications
Absolues
- Hypersensibilité au raltégravir.
Mises en garde cliniques
- Il peut provoquer réactions cutanées sévères ou DRESS avec atteinte hépatique ; arrêter en cas d’hypersensibilité sévère. — CIMA/AEMPS, ficha técnica 107436004
- Mise en garde majeure · Myopathie et rhabdomyolyse ont été rapportées ; évaluer douleur ou faiblesse musculaire et créatine kinase selon la clinique. — CIMA/AEMPS, ficha técnica 107436004
Interactions médicamenteuses
- SévèreAntiacides contenant aluminium ou magnésium
Mécanisme: Les cations réduisent l’absorption du raltégravir.
Recommandation: L’administration concomitante n’est pas recommandée.
CIMA/AEMPS, ficha técnica 107436004
- SévèreRifampicine
Mécanisme: Elle induit UGT1A1 et réduit le raltégravir.
Recommandation: N’ajuster qu’avec la présentation et le schéma autorisés ; ne pas doubler la dose des comprimés à croquer.
CIMA/AEMPS, ficha técnica 107436004
Effets indésirables
Communs (≥1%)
Nausées, céphalées, diarrhée, fatigue, insomnie et augmentation des transaminases
Rares mais graves
DRESS, syndrome de Stevens-Johnson, rhabdomyolyse et hépatite
Grossesse et allaitement
Les données pendant la grossesse sont insuffisantes ; n’utiliser le raltégravir que si le bénéfice attendu justifie le risque possible. Ne pas allaiter pendant le traitement du VIH.
Bibliographie récente (PubMed)
Integrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the emergence of viral resistance and have a high rate of cross-resistance. To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC). However, HIV is also able to develop resistance mechanisms against the second-generation of INSTIs. This review describes the mode of action of INSTIs and then summarizes and evaluates some typical resistance mutations, such as substitution and insertion mutations. The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future.
Advances in antiretroviral drug development have led to safer drugs with improved tolerability, enhanced activity against drug-resistant HIV, higher genetic barrier to resistance, and fewer drug-drug interactions. Genetic polymorphisms in drug-metabolizing enzymes, transporters, and immune pathways contribute to interindividual variability in antiretroviral pharmacokinetics and toxicity. HLA-B *57:01 screening prior to abacavir initiation is an example of clinically implemented pharmacogenetics in high-income settings. Conversely, despite robust evidence linking UGT1A1 variants to atazanavir-associated hyperbilirubinaemia, routine UGT1A1 testing has not been widely adopted. We conducted a narrative review of genetic polymorphisms associated with the toxicity and pharmacokinetics of current antiretroviral therapy. We searched Pharmacogenomics Knowledgebase (PharmGKB®) for abacavir, tenofovir disoproxil fumarate, tenofovir alafenamide, lamivudine, emtricitabine, dolutegravir, elvitegravir, raltegravir, bictegravir, cabotegravir, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, lenacapavir, rilpivirine and doravirine. We supplemented our review with targeted searches in PubMed®. We found that most pharmacogenetic associations for current antiretroviral drugs come from single studies and lack replication. Although UGT1A1 loss-of-function alleles increase dolutegravir and cabotegravir exposure, no association with toxicity has been shown. No relevant studies were identified for doravirine, lenacapavir or bictegravir. Actionable pharmacogenetic associations with antiretroviral drugs remain limited to abacavir. Future research should prioritize replicating pharmacogenetic associations across diverse populations and establishing clinical relevance.