Table 4.

Treatment Challenges during TB Treatment in Pediatric Transplant Patients.^9,85,87,93

Adverse effects	Medications	Management considerations
Drug-drug Interactions with Rifampin9,93,a	Antiretroviral agents:	Rifabutin is preferred with protease inhibitors, as it is a less strong inducer of cytochrome p450 activity. Dose adjustments may be necessary when using rifampin with NNRTIs and INSTIs.93
	HIV-1 protease inhibitors, NNRTIs, INSTIs
	Anti-microbials:
	1) Macrolide antibiotics (azithromycin, clarithromycin, erythromycin)	1) Azithromycin has no interaction with. Clarithromycin and erythromycin have interactions with rifampin; recommend use of alternative agents.
	2) Azole antifungal agents (fluconazole, voriconazole, itraconazole)	2) Dosing of azoles may be sub-therapeutic with rifampin. Recommend laboratory monitoring and considering increase in azole dose with co-administration of rifampin.
	3) Doxycycline	3) Rifampin may decrease serum concentration of doxycycline; consider alternative agent.
	4) Atovaquone	4) Use alternate drug for PJP prophylaxis.
	Immunosuppressive agents:
	1) Calcineurin inhibitors (cyclosporine, tacrolimus)	1) Monitoring of calcineurin inhibitor serum concentrations may assist with dosing. Consider replacing rifampin with rifabutin to help maintain immunosuppressant levels.
	2) mTOR inhibitors (sirolimus)	2) Monitoring of mTOR inhibitor serum concentrations may assist with dosing.
	3) Corticosteroids	3) Recommend clinical monitoring, as may require 2-3 fold increase in corticosteroid dose.
	Hormone therapy: Ethinylestradiol, norethindrone	Women on oral contraceptives should use a barrier method of contraception while on rifampin.
	Cardiovascular agents:90 Propanolol, metroprolol	Clinical monitoring recommended; may require alternate cardiovascular drug.
	Anticoagulants: Warfarin	Monitor prothrombin time; may require 2-3 fold warfarin dose increase.
	Anticonvulsants: Phenytoin, lamotrigine	TDM recommended; may require dose increase in anticonvulsant dose.
Hepatoxicity84,86	Rifampin, Pyrazinamide, Ethionamide/Prothionamide, Bedaquiline, Clofazimine, Delamanid, PAS	Stop all drugs if ALT/AST >5 times upper limit of normal. Allow liver enzymes to normalize. Re-introduce drugs one-by-one, starting with least hepatotoxic drugs. If symptoms recur or ALT increases, the last drug added should be stopped.

Table adapted from ATS/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.⁹³

Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor; TDM, therapeutic drug monitoring; PJP, Pneumocystis jiroveci pneumonia.

^aNot all available drug-drug interactions with rifampin are listed here.