Table 3.

Possible PK interactions between rifapentine/rifampicin and hypoglycemic agents and their expected clinical effects

Interaction level	Possible PK interaction	Expected clinical effect
Transporter level (ABCB1)	Rifapentine: competition with SU and SGLT-2 inhibitors. Decreased levels of SU and SGLT-2 inhibitors	Lack of hypoglycemic efficacy, possibly greater with rifampicin
	Rifampicin: competition with SU and SGLT-2 inhibitors and induction of ABCB1.
	Decreased levels of SU and SGLT-2 inhibitors
Protein-binding level	Rifapentine: competition for protein-binding sites with SU, glinides, SGLT-2 inhibitors, detemir, degludec, and liraglutide. Increased levels of oral antidiabetic drugs and/or rifapentine	Possible potentiation of hypoglycemic and/or antituberculosis effects, and increased risk of dose-dependent adverse effects.
	Rifampicin: competition for protein-binding sites with SU, glinides, SGLT-2 inhibitors, detemir, degludec, and liraglutide. Increased levels of oral antidiabetic drugs and/or rifampicin	The interaction may be stronger with rifapentine than with rifampicin
Hepatic metabolism level	Rifapentine: induction of CYP3A4 and CYP2C8/9 and decreased levels of nateglinide, repaglinide, pioglitazone, rosiglitazone, glibenclamide, gliquidone, gliclazide, sitagliptin, and saxagliptin	Rifapentine: hyperglycemia
	Rifampicin: induction of CYP3A4, CYP2C8/9/19, CYP1A2, and auto-induction. Decreased levels of nateglinide, repaglinide, pioglitazone, rosiglitazone, glibenclamide, gliquidone, gliclazide, sitagliptin, saxagliptin, and rifampicin itself	Rifampicin: hyperglycemia and diminished antituberculosis efficacy over time
	Rifapentine/rifampicin: induction by antidiabetics with CYP3A4-inducing potential, like bromocriptine. Decreased levels of both rifapentine and rifampicin Rifapentine/rifampicin/antidiabetics: inhibition of CYP450 in severe infection. Increased levels of oral antidiabetic drugs and/or rifapentine/rifampicin	Lack of antituberculosis efficacy, possibly greater with rifampicin owing to auto-induction Possible potentiation of hypoglycemic and/or antituberculosis effects, and increased risk of dose-dependent adverse effects

Abbreviations: PK, pharmacokinetic; SU, sulfonylureas; CYP, cytochrome P.