Use of bedaquiline and delamanid in diabetes patients: clinical and pharmacological considerations

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Term Occurence Count Dictionary
metformin 10 endocrinologydiseasesdrugs
nateglinide 2 endocrinologydiseasesdrugs
pioglitazone 2 endocrinologydiseasesdrugs
repaglinide 2 endocrinologydiseasesdrugs
acarbose 2 endocrinologydiseasesdrugs
cycloserine 1 endocrinologydiseasesdrugs
diabetes mellitus 1 endocrinologydiseases
Colesevelam 1 endocrinologydiseasesdrugs
hypokalemia 5 endocrinologydiseases
niacin 1 endocrinologydiseasesdrugs
rosiglitazone 1 endocrinologydiseasesdrugs
sitagliptin 2 endocrinologydiseasesdrugs
bromocriptine 9 endocrinologydiseasesdrugs
Liraglutide 1 endocrinologydiseasesdrugs
hypoglycemia 2 endocrinologydiseases
Insulin 2 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Colesevelam 12955 inhibitory effect of gliquidone on CYP3A4 has also been shown, but the extent of inhibition is unknown.[33] Colesevelam , a non-absorbed, lipid-lowering agent approved for use as adjunctive therapy in patients with type 2
Insulin 30786 including hypokalemia resulting from insulin administration, and gastrointestinal or renal loss of K+. Insulin can induce hypokalemia because it promotes the entry of K+ into skeletal muscles and hepatic cells by
Insulin 43841 multidrug-resistant tuberculosis patients treated with bedaquiline/delamanidClinical impactMetformin Insulin analogsAdvantagesNo interaction at the ABCB1, CYP3A4, or protein-binding site levelsNo interaction at
Liraglutide 19006 bedaquiline and delamanid, at least 1 h before the injection of GLP-1 receptor agonists or pramlintide.[58] Liraglutide is the only drug from this group which may possibly interact with bedaquiline/delamanid at the protein-binding
acarbose 2514 adverse reactions may develop more frequently when these drugs are combined with thiazolidinediones and acarbose . Data from Phase III and postmarketing studies are needed to elucidate the effect of DM and hypoglycemic
acarbose 36816 Therefore, special attention should be given to the concurrent use of bedaquiline and thiazolidinediones and acarbose , also known for their hepatotoxic potential.[93],[94]Nausea and vomiting were reported as very common
bromocriptine 9763 bedaquiline/delamanid have not been performed, since other drugs that belong to this group, except bromocriptine , do not show significant potential to inhibit or induce the CYP3A4 enzyme. However, bedaquiline and
bromocriptine 12660 conclude that drugs whose clearance is mediated by CYP3A4, such as bedaquiline, should be combined with bromocriptine with special caution. Kim et al showed that glibenclamide also inhibits human CYP3A4 in human liver
bromocriptine 34499 CYP3A4, CYP3A4 inhibitors may further prolong the QTc interval, especially the potent CYP3A4 inhibitor bromocriptine .[22]Regarding other cardiovascular effects, hypotension was commonly seen in clinical studies with delamanid.[10]
bromocriptine 34772 also produces hypotension, and symptomatic orthostatic hypotension can occur in patients treated with bromocriptine mesylate for any indication.[31] In postpartum studies performed with bromocriptine mesylate, decreases
bromocriptine 34856 patients treated with bromocriptine mesylate for any indication.[31] In postpartum studies performed with bromocriptine mesylate, decreases in supine systolic and diastolic pressures have been observed in almost one-third
bromocriptine 37351 potentiated when bedaquiline/delamanid are combined with biguanides, alpha-glucosidase inhibitors, bromocriptine , glinides, and SGLT-2 inhibitors, which also produce gastrointestinal disturbances, similarly to insulin
bromocriptine 42299 share the same potential to block the cardiac voltage-gated potassium channels. The CYP3A4 inhibitor, bromocriptine , may prolong the QTc interval owing to potentially increased plasma bedaquiline concentrations. Among
bromocriptine 43565 (gliquidone)3A43A4DPP-IV inhibitorsJanuvia® (sitagliptin)3A4/2C83A4Onglyza® (saxagliptin)3A43A4OtherCycloset® ( bromocriptine mesylate)3A43A4Abbreviations: NC, no crossing; DPP-IV, dipeptidyl peptidase IV.Table 2Advantages and
bromocriptine 45043 inhibitors)UnclearHepatic metabolism levelDecreased exposure to bedaquiline/delamanid with strong CYP3A4 inducers ( bromocriptine )Lack of antituberculosis efficacyIncreased exposure to oral hypoglycemic agents mainly metabolized by
cycloserine 8399 isoniazid/pyrazinamide, nevirapine, lopinavir/ritonavir, ethambutol, kanamycin, pyrazinamide, ofloxacin, and cycloserine .[9] Significant alterations in bedaquiline plasma concentrations were observed with rifampin and ketoconazole,
metformin 14199 apparently does not use P-glycoprotein for its transport. There are various preclinical studies showing that metformin may interact pharmacokinetically with many drugs.[38],[39] However, in humans, metformin is cleared
metformin 14288 showing that metformin may interact pharmacokinetically with many drugs.[38],[39] However, in humans, metformin is cleared from the body by tubular secretion and excreted unchanged in the urine. As metformin is not
metformin 14384 humans, metformin is cleared from the body by tubular secretion and excreted unchanged in the urine. As metformin is not metabolized, the possibilities of pharmacokinetic drug–drug interactions are minimal; therefore,
metformin 14623 could be a key compound for combination with bedaquiline and delamanid.Studies have suggested that metformin suppresses the inflammatory response by nuclear factor κB inhibition via adenosine monophosphate (AMP)-activated
metformin 14817 monophosphate (AMP)-activated protein kinase-dependent and -independent pathways,[40],[41] and that metformin anti-inflammatory properties are exerted irrespective of DM status.[42]Besides its favorable pharmacokinetic
metformin 14952 properties are exerted irrespective of DM status.[42]Besides its favorable pharmacokinetic profiles, these metformin characteristics make it very suitable for use in severe infections, such as MDR-TB.Bedaquiline and delamanid
metformin 18426 and delamanid should be considered.Positive and negative aspects of the use of insulin analogs and metformin in diabetes patients with MDR-TB are sum-marized in Table 2.Bedaquiline and delamanid with GLP-1 receptor
metformin 42440 interval owing to potentially increased plasma bedaquiline concentrations. Among oral hypoglycemic drugs, metformin possibly has the most favorable pharmacokinetic and safety profile when combined with bedaquiline and
metformin 43728 DPP-IV, dipeptidyl peptidase IV.Table 2Advantages and disadvantages of the use of insulin analogs and metformin in multidrug-resistant tuberculosis patients treated with bedaquiline/delamanidClinical impactMetforminInsulin
metformin 44259 prolongationNo risk of QT prolongationMore predictable hypoglycemic effect in severe infection compared to metformin Allowed in renal and hepatic impairmentDisadvantagesEnhanced gastrointestinal toxicityUnpredictable hypoglycemic
nateglinide 43233 hypoglycemic agentNovel antituberculosis drug Sirturo®(bedaquiline)Deltyba®(delamanid)MeglitinidesStarlix® ( nateglinide )3A43A4Prandin® (repaglinide)3A4/2C83A4ThiazolidinedionesActos® (pioglitazone)3A4/2C83A4Avandia® (rosiglitazone)2C8NCSulfonylureasGlyburide®
nateglinide 45167 antituberculosis efficacyIncreased exposure to oral hypoglycemic agents mainly metabolized by CYP3A4 ( nateglinide , sitagliptin, saxagliptin) due to inhibitory effect of M2Hypoglycemic episodesIncreased exposure to
niacin 17184 pentoxifylline, salicylates, somatostatin analogs, sulfonamide antibiotics) and reduce it (corticosteroids, niacin , danazol, diuretics, sympathomimetic agents, glucagon, isoniazid, phenothiazine derivatives, somatropin,
pioglitazone 38861 MDR-TB treatment. However, combining bedaquiline with other drugs that may cause muscle damage, such as pioglitazone or insulin glargine, may be dangerous. Pioglitazone was reported to cause severe acute rhabdomyolysis,
pioglitazone 43311 drug Sirturo®(bedaquiline)Deltyba®(delamanid)MeglitinidesStarlix® (nateglinide)3A43A4Prandin® (repaglinide)3A4/2C83A4ThiazolidinedionesActos® ( pioglitazone )3A4/2C83A4Avandia® (rosiglitazone)2C8NCSulfonylureasGlyburide® (glibenclamide)3A43A4Diamicron® (gliclazide)2C8NCGlurenorm®
repaglinide 13995 is CYP3A4*18, which plays a major role in the interindividual variability in the pharmacokinetics of repaglinide .[37]Metformin is an oral hypoglycemic agent that is not metabolized via CYP450 and apparently does not
repaglinide 43262 drug Sirturo®(bedaquiline)Deltyba®(delamanid)MeglitinidesStarlix® (nateglinide)3A43A4Prandin® ( repaglinide )3A4/2C83A4ThiazolidinedionesActos® (pioglitazone)3A4/2C83A4Avandia® (rosiglitazone)2C8NCSulfonylureasGlyburide®
rosiglitazone 43345 (nateglinide)3A43A4Prandin® (repaglinide)3A4/2C83A4ThiazolidinedionesActos® (pioglitazone)3A4/2C83A4Avandia® ( rosiglitazone )2C8NCSulfonylureasGlyburide® (glibenclamide)3A43A4Diamicron® (gliclazide)2C8NCGlurenorm® (gliquidone)3A43A4DPP-IV
sitagliptin 43497 (glibenclamide)3A43A4Diamicron® (gliclazide)2C8NCGlurenorm® (gliquidone)3A43A4DPP-IV inhibitorsJanuvia® ( sitagliptin )3A4/2C83A4Onglyza® (saxagliptin)3A43A4OtherCycloset® (bromocriptine mesylate)3A43A4Abbreviations:
sitagliptin 45180 antituberculosis efficacyIncreased exposure to oral hypoglycemic agents mainly metabolized by CYP3A4 (nateglinide, sitagliptin , saxagliptin) due to inhibitory effect of M2Hypoglycemic episodesIncreased exposure to bedaquiline in
Select Disease Character Offset Disease Term Instance
diabetes mellitus 1648 clinical particularities related to the use of bedaquiline and delamanid in patients with type 1 and 2 diabetes mellitus (DM), as well as pharmacological aspects of the concurrent use of these agents with oral and injectable
hypoglycemia 15287 Endocrinologists recommends the use of insulin analogs, as their action is more predictable, resulting in reduced hypoglycemia . Once the disease starts settling, oral hypoglycemic agents may be used.[43] In severe infections, the
hypoglycemia 31013 activity of the Na+/K+-ATPase pump.[84] The increased epinephrine secretion caused by insulin-induced hypoglycemia could play a contributory role.[85] Special precautions should be taken when delamanid is administered
hypokalemia 30693 patient group.[9],[10]HypokalemiaDiabetes patients often present electrolyte disturbances, including hypokalemia resulting from insulin administration, and gastrointestinal or renal loss of K+. Insulin can induce
hypokalemia 30805 resulting from insulin administration, and gastrointestinal or renal loss of K+. Insulin can induce hypokalemia because it promotes the entry of K+ into skeletal muscles and hepatic cells by increasing the activity
hypokalemia 31146 contributory role.[85] Special precautions should be taken when delamanid is administered to patients with hypokalemia , as it frequently induces this electrolyte disturbance itself (≥1/10).[10]Low potassium levels may
hypokalemia 41666 patients aged >65 years and those with severe renal and hepatic impairment, as well as patients with hypokalemia . Based on the available data, insulin analogs appear to be safe to combine with bedaquiline and delamanid,
hypokalemia 41820 analogs appear to be safe to combine with bedaquiline and delamanid, although potential insulin-induced hypokalemia should be cautiously monitored, as it could potentially prolong the QTc. Moreover, the anti-inflammatory,

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