Repaglinide
Sources réglementaires consultées
Indications approuvées
- Traitement de l'adulte atteint de diabète de type 2 dont l'hyperglycémie n'est pas suffisamment contrôlée par le régime alimentaire, la perte de poids et l'exercice ; peut également être utilisé avec la metformine lorsque celle-ci seule n'assure pas un contrôle suffisant.
Contre-indications
Absolues
- Hypersensibilité au répaglinide ou à l'un des excipients.
- Diabète de type 1 avec peptide C négatif.
- Acidocétose diabétique, avec ou sans coma.
- Trouble sévère de la fonction hépatique.
- Utilisation concomitante de gemfibrozil.
Mises en garde cliniques
- Mise en garde majeure · Peut provoquer une hypoglycémie ; ajuster la dose en fonction des repas, de la fonction rénale, de l'état nutritionnel et des médicaments concomitants. — CIMA NOVONORM, registro 98076005
- Mise en garde majeure · Des événements cardiovasculaires graves, notamment une ischémie myocardique, ont été observés avec le répaglinide associé à l'insuline NPH. Le répaglinide n'est pas indiqué en association avec l'insuline NPH. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ae28683-28cc-408e-90f9-6a3dddfc668d
Interactions médicamenteuses
- SévèreGemfibrozil
Mécanisme: Le gemfibrozil inhibe le CYP2C8 et augmente fortement et durablement l'exposition au répaglinide et son effet hypoglycémiant.
Recommandation: L'administration concomitante est contre-indiquée.
https://cima.aemps.es/cima/dochtml/ft/98076005/FT_98076005.htmlCIMA registro 98076005
- ModéréeTraitement antiplaquettaire par clopidogrel
Mécanisme: Le clopidogrel augmente l'exposition au répaglinide et le risque d'hypoglycémie.
Recommandation: Commencer le répaglinide à 0,5 mg avant chaque repas et ne pas dépasser 4 mg par jour ; surveiller la glycémie.
https://cima.aemps.es/cima/dochtml/ft/98076005/FT_98076005.htmlhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ae28683-28cc-408e-90f9-6a3dddfc668d
- ModéréeTriméthoprime
Mécanisme: Le triméthoprime inhibe le CYP2C8 et augmente l'exposition au répaglinide.
Recommandation: Éviter si possible ; si nécessaire, surveiller étroitement la glycémie et l'état clinique.
https://cima.aemps.es/cima/dochtml/ft/98076005/FT_98076005.html
- ModéréeRifampicine et autres inducteurs puissants
Mécanisme: L'induction du CYP2C8/CYP3A4 peut réduire l'exposition au répaglinide et son efficacité.
Recommandation: Ajuster selon la glycémie lors de l'instauration, pendant le traitement et pendant environ 2 semaines après l'arrêt de l'inducteur.
https://cima.aemps.es/cima/dochtml/ft/98076005/FT_98076005.html
- SévèreCiclosporineL04AD01
Mécanisme: La ciclosporine a multiplié par 2,5 l'exposition à une faible dose de répaglinide.
Recommandation: Ne pas dépasser 6 mg de répaglinide par jour et augmenter la fréquence de surveillance de la glycémie.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ae28683-28cc-408e-90f9-6a3dddfc668d
Effets indésirables
Communs (≥1%)
Hypoglycémie · Douleur abdominale · Diarrhée
Rares mais graves
Coma ou perte de connaissance hypoglycémique · Réaction anaphylactique ou vascularite · Dysfonction hépatique sévère · Ischémie myocardique grave avec l'association à l'insuline NPH
Grossesse et allaitement
Éviter pendant la grossesse et l'allaitement.
Bibliographie récente (PubMed)
Background: Diabetes is a risk factor for dementia, but we do not know whether specific diabetes medications ameliorate this risk. Objective: To systematically review and meta-analyze such medication's effect on the risk of developing dementia, mild cognitive impairment (MCI), or cognitive decline. Methods: We searched three databases until 21 November 2023. We included randomized controlled trials (RCT), cohort, and case-control studies assessing association between antidiabetic medication and future dementia, MCI, or cognitive decline. We meta-analyzed studies separately for individual drug classes and their comparators (no medication, placebo, or another drug). We appraised study quality using the Newcastle-Ottawa Scale and Physiotherapy Evidence Database Scale. Results: 42 studies fulfilled inclusion criteria. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus placebo reduced dementia risk by 53% in three RCTs (n = 15,820, RR = 0.47[0.25, 0.86]) and 27% in three case-control studies (n = 312,856, RR = 0.73[0.54, 0.99], I2 = 96%). Repaglinide was superior to glibenclamide by 0.8 points on the Mini-Mental State Examination scale in another RCT. Meta-analysis of seven longitudinal studies showed glitazones (n = 1,081,519, RR = 0.78[0.76, 0.81], I2 = 0%) were associated with reduced dementia risk. Metformin (n = 999,349, RR = 0.94[0.79, 1.13], I2 = 98.4%), sulfonylureas (RR = 0.98[0.78, 1.22], I2 = 83.3%), dipeptidyl peptidase-IV inhibitors (DPP-1V) (n = 192,802, RR = 0.86[0.65, 1.15], I2 = 92.9%) and insulin (n = 571,274, RR = 1.09[0.95, 1.25], I2 = 94.8%) were not. Most studies were observational and limited by confounding by indication. Conclusions: In people with diabetes, RCTs consistently showed GLP-RAs reduce future dementia risk. Glitazones consistently showed protective effects, without heterogeneity, suggesting potential generalizability of these results. Metformin, sulfonylureas, insulin, and DPP-1V studies had inconsistent findings. If informati
CYP2C8 is responsible for the metabolism of 5% of clinically prescribed drugs, including antimalarials, anti-cancer and anti-inflammatory drugs. Genetic variability is an important factor that influences CYP2C8 activity and modulates the pharmacokinetics, efficacy and safety of its substrates. We profiled the genetic landscape of CYP2C8 variability using data from 96 original studies and data repositories that included a total of 33,185 unrelated participants across 44 countries and 43 ethnic groups. The reduced function allele CYP2C8*2 was most common in West and Central Africa with frequencies of 16-36.9%, whereas it was rare in Europe and Asia (< 2%). In contrast, CYP2C8*3 and CYP2C8*4 were common throughout Europe and the Americas (6.9-19.8% for *3 and 2.3-7.5% for *4), but rare in African and East Asian populations. Importantly, we observe pronounced differences (> 2.3-fold) between neighboring countries and even between geographically overlapping populations. Overall, we found that 20-60% of individuals in Africa and Europe carry at least one CYP2C8 allele associated with reduced metabolism and increased adverse event risk of the anti-malarial amodiaquine. Furthermore, up to 60% of individuals of West African ancestry harbored variants that reduced the clearance of pioglitazone, repaglinide, paclitaxel and ibuprofen. In contrast, reduced function alleles are only found in < 2% of East Asian and 8.3-12.8% of South and West Asian individuals. Combined, the presented analyses mapped the genetic and inferred functional variability of CYP2C8 with high ethnogeographic resolution. These results can serve as a valuable resource for CYP2C8 allele frequencies and distribution estimates of CYP2C8 phenotypes that could help identify populations at risk upon treatment with CYP2C8 substrates. The high variability between ethnic groups incentivizes high-resolution pharmacogenetic profiling to guide precision medicine and maximize its socioeconomic benefits, particularly for
Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1/PD-L1 checkpoint. Here, we have reviewed several types of drugs known to alter the checkpoint, either directly via the blockade of PD-L1 or indirectly via an action on upstream effectors (such as STAT3) to suppress PD-L1 transcription or to induce its proteasomal degradation. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, and a few other modulators of the PD-1/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.
Isavuconazole is an azole antifungal drug, which is used for invasive aspergillosis and mucormycosis. The objective of this study was to comprehensive review the impact of drug-drug interactions (DDIs) on isavuconazole pharmacokinetics by categorizing concomitant medications as enzyme inducers (eg, rifampicin), inhibitors (eg, ritonavir), or neutral agents. Additionally, we aimed to evaluate whether the duration of combination therapy modulates the magnitude of DDIs and provide references for clinical medication. The literature concerning the interactions of isavuconazole was systematically retrieved from three retrieval platforms, PUBMED, EMBASE, and the Cochrane Library, using the search terms: "isavuconazole" or "isavuconazonium" or "Cresemba" and "interact*", or "cotreatment", or "coadministration", or "combination", or "concomitant". A total of 1051 articles were retrieved and then conduct screening according to the inclusion and exclusion criteria. Eleven studies involving 23 drugs were included in this study. Rifampicin, flucloxacillin, and phenobarbital decreased the exposure of isavuconazole. Ketoconazole and ritonavir significantly increased the exposure of isavuconazole. Esomeprazole, had no significant effects on the exposure of isavuconazole. Although midazolam, estradiol/norethisterone, atorvastatin, digoxin, metformin, methotrexate, bupropion, repaglinide, dextromethorphan, caffeine, methadone, warfarin, cyclosporine, tacrolimus, sirolimus, prednisone, and mycophenolate mofetil had also no significant effect on isavuconazole pharmacokinetics, a single-dose administration cannot induce or inhibit metabolic enzymes stably, and we consider the results to be unreliable. Therefore, these drugs still need to be used with caution. This review demonstrates that drug interactions of isavuconazole are predominantly mediated by the CYP3A4/P-glycoprotein pathway: strong inducers (eg, rifampicin) reduce its exposure, while strong inhibitors (eg, ketoconazole) incr