Table 5.

Summary of previous reports on mTOR inhibitor dosing in neonates

mTOR inhibitor	AAO of mTOR inhibitor	Dosing regimen	Dose [mg/m2/d]	Trough levels [ng/ml]	Duration	AE	Prophylaxis	Reference
EVE	NA	0.25 mg twice per day 2 days per week	NA	5–15	2.5 months	Increase of TG Self-limiting diarrhea Decreased CD/CD8 ratio lymphopenia	TMP/SMX	(Demir et al. 2012)
Sirolimus	10 days	0.4 mg daily	NA	NA	24 days	Increase of TG	TMP/SMX	(Breathnach et al. 2014)
EVE	20 days	0.1 mg daily	0.64	11	34 days	Transient hypokalemia	NA	(Mohamed et al. 2014)
EVE	2 days	0.25 mg twice per day 2 days per week	NA	3.6–7.8	3 months	NA	NA	(Dogan et al. 2015)
EVE	4 days	0.1 mg daily	0.64	11.5	42 days	NA	NA	(Goyer et al. 2015)
EVE	9 days	0.1 mg daily	0.64	10.2	NA	NA	NA
EVE	21 days	NA	3	4–5	NA	Hyponatremia	antibiotic prophylaxis	(Mlczoch et al. 2015)
EVE	NA	0.25 mg twice per day 2 days per week	NA	NA	4 weeks	NA	NA	(Oztunc et al. 2015)
EVE	2 days	0.15–0.2 mg daily	1	10–15	19 days	Toxic levels of 108 ng/ml under initial dose of 0.4–0.45 mg (=1.5-2 mg/m2)	NA	(Wagner et al. 2015)
EVE	7 days	0.25 mg daily	1	NA	10 weeks	Mild mucositis Increase of TG	NA	(Colaneri et al. 2016)
EVE	NA	0.25 mg twice per day 2 days per week	NA	5–10	NA	NA	NA	(Emir et al. 2017)
EVE	NA	0.5 mg daily	NA	NA	NA	NA	NA	(Hoshal et al. 2016)
EVE	20 days	0.1 mg daily	NA	13.7	34 days	Suspected infection	NA	(Aw et al. 2017)
EVE	4 days	NA	NA	11	42 days	None	NA
EVE	9 days	0.1 mg daily	NA	10.2	NA	Oral ulcers	NA
EVE	1 day	0.1 mg daily	NA	10.2	36 days	None	NA
EVE	NA	0.03125 mg daily	0.12	3–7	2 weeks	Adenovirus pneumonia High trough levels of 20 ng/ml under 0.125 mg (0.0558 mg/m2)	NA	(Chang et al. 2017)
EVE	NA	NA	0.35	1.81	NA	NA	NA
EVE	NA	0.125 mg daily	0.51	NA	Na	NA	NA

AAO age at onset, AE adverse events, EVE everolimus, NA not available, TG triglycerides, TMP/SMX trimethoprim/sulfamethoxazole