rifapentine
Sources réglementaires consultées
Indications approuvées
- Tuberculose pulmonaire active sensible et traitement de l’infection tuberculeuse latente, toujours dans des schémas combinés précis.
Contre-indications
Absolues
- Hypersensibilité à la rifapentine ou aux autres rifamycines.
Mises en garde cliniques
- Elle peut provoquer une hépatotoxicité ; surveiller symptômes et bilan hépatique et arrêter en cas de lésion. — DailyMed, set_id f95d726e-5a09-48dd-b719-e4400fb91c8f
- Elle peut provoquer hypersensibilité, SCAR et diarrhée à C. difficile. Le schéma hebdomadaire de continuation avec isoniazide ne doit pas être utilisé chez les patients VIH et impose une prudence en cas de cavitation ou de culture positive à 2 mois. — DailyMed, set_id f95d726e-5a09-48dd-b719-e4400fb91c8f
Interactions médicamenteuses
- SévèreContraceptifs hormonaux, warfarine ou antirétroviraux
Mécanisme: L’induction enzymatique réduit les concentrations et l’effet.
Recommandation: Utiliser une contraception non hormonale ; surveiller l’INR et vérifier la compatibilité antirétrovirale.
DailyMed, set_id f95d726e-5a09-48dd-b719-e4400fb91c8f
Effets indésirables
Communs (≥1%)
Coloration orange des fluides, nausées, vomissements, élévation des transaminases et éruption
Rares mais graves
Hépatotoxicité, anaphylaxie et réactions cutanées sévères
Grossesse et allaitement
Les données humaines pendant la grossesse sont insuffisantes et les études animales indiquent un risque potentiel pour le fœtus ; évaluer soigneusement le bénéfice et le risque. Pendant l’allaitement, surveiller chez le nourrisson irritabilité, pleurs prolongés inexpliqués, ictère et coloration des urines ou des selles.
Bibliographie récente (PubMed)
The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.
Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabuti
Some individuals exposed to Mycobacterium tuberculosis develop a latent infection and remain at a lifelong risk of developing tuberculosis (TB) disease, a state called as TB infection (TBI). TB preventive treatment (TPT) aims to treat TBI and prevent progression to active TB in an exposed or infected person. Currently, it is not possible to confirm TBI microbiologically, but can be identified indirectly by means of immune-based tests [Tuberculin skin test (TST), interferon-gamma release assays (IGRAs)]. It is crucial to rule out active TB before initiating TPT. TPT regimens have evolved with time. The most widely used regimen is 6 mo of daily Isoniazid (INH) (6H). Another regime in pipeline for persons >2 y, but not yet widely available, is 3HP (3 mo of weekly Isoniazid and Rifapentine). TPT to contacts of drug resistant TB (DR-TB) patients needs to be tailored depending on the resistance pattern in the index case, and relies on a bacteriological confirmation of the same. Individuals receiving TPT should be closely monitored for emergence of any signs or symptoms suggestive of active TB disease while on TPT.