Clinical and pharmacological hallmarks of rifapentine’s use in diabetes patients with active and latent tuberculosis: do we know enough?

Abstract

Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug–drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored.

Hepatocytic transcriptional signatures predict comparative drug interaction potential of rifamycin antibiotics

“…Drug-susceptible TB is currently treated with 6 months of daily rifampin therapy, which is combined with other antibiotics such as isoniazid, pyrazinamide, and ethambutol 9 . Additionally, many of the current treatment options for latent tuberculosis infection (LTBI) and prophylactic regimens for TB involve the use of rifampin or rifapentine 9 – 11 . Rifamycin antbiotics are known to be a common cause of DDIs with co-administered medications via induction of drug metabolizing enzymes (DMEs).…”

“…Rifamycin antbiotics are known to be a common cause of DDIs with co-administered medications via induction of drug metabolizing enzymes (DMEs). Clinical DDI data guide the management of rifamycin DDIs during polypharmacy, but comprehensive clinical DDI data are not available across all rifamycin antibiotics to manage common medication therapies to treat co-morbidities such as HIV and OIs in TB patients 10,11 .…”

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

“…The results of CC analysis proved that intersection proteins participated in the cellular environment. Through MF analysis, we could demonstrate that some protein receptor activities were regulated by drugs, such as protein binding, which was closely related to proteinuria [ 50 ]. KEGG pathway enrichment analysis guides us to combine genomes with cellular and species to figure out the potential pathways of EH against NS.…”

Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study

“…Among WHO-recommended regimens, 3HP is recognized for its shorter course duration and simplicity, leading to a higher completion rate than the 9H regimen, regardless of its high rate of ADRs [ 34 ]. In patients with DM, 3HP poses more safety concerns because rifapentine is a potent inducer of cytochrome P450, interfering with the metabolism of oral antidiabetic drugs [ 19 ]. In the current study, only 3.5% of patients with pDM (2.9% in 3HP group and 4.8% in 9H group) experienced mild fluctuation in glucose level.…”

“…Compared with the 9H regimen, the 3-month weekly rifapentine plus isoniazid (3HP) regimen has a similar efficacy in TB prevention [ 12–16 ], a lower hepatotoxicity risk [ 12 , 13 , 17 ], a 10% higher completion rate [ 12–15 ] and to be more cost-effective [ 18 ]. However, the 3HP regimen flaws into a significantly higher risk of adverse events other than hepatotoxicity, particularly flu-like syndrome and systemic drug reactions (SDRs) [ 17 ], as well as potential drug interactions with antidiabetic drugs [ 19 ]. Studies have not yet evaluated the completion rate and safety profile of 3HP in patients with DM, preventing the widespread use of the 3HP regimen in this high-TB-risk population.…”