Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

Table 3

Reported adverse effects of mTOR inhibitors.

General disorder classification	Specific adverse event	Reported percent incidence	Duration on Meds (days)	Agent	Clinical management options	Outcome
Cutaneous	Delayed wound healing			Multiple mTOR inhibitors		Manageable
	Skin rash			Ridaforolimus		Manageable
	Spongiotic dermatitis with eosinophils		14	Temsirolimus	Clobetasol	Resolution
Hematological	Thrombocytopenia	8–22.7		Everolimus and sirolimus	Interleukin 11	Manageable
	Anemia (microcytic)	9–20		Temsirolimus and everolimus and sirolimus	Erythropoietin	Manageable
	Leukopenia	18.2		Everolimus and sirolimus	Colony stimulating factor	Manageable
Hepatic	Transaminase Elevations	10		Everolimus	Periodic liver function tests
	Alkaline phosphatase elevations	8		Everolimus	Periodic liver function tests
Immunological	Severe infections	2.3
Metabolic	Hypercholesterolemia	50		Sirolimus and everolimus	Statin therapy	Manageable
	Hypertriglyceridemia	31.8		Sirolimus and everolimus	Fibrates	Manageable
	Hyperglycemia	11		temsirolimus	Glucose lowering agents	Manageable
	Fatigue	11		Temsirolimus
	Hypophosphatemia	5		Temsirolimus
	Hyperlipidemia	5		Everolimus	Lipid lovering drugs
Oral	Ulcerations	66	5	Deforolimus	Discontinuation	Reversible
	Mucositis	6			Discontinuation	Reversible
	Aphthous stomatitis	6			Discontinuation	Reversible
Pulmonary	Noninfectious pneumonitis	4.8–18	60–1500	Sirolimus and everolimus	Withdrawal, antibiotics and steroids	Reversible
	Dyspnea	9
	Grade 1 (asymptomatic)	3.3		Everolimus	Reduction	Reversible
	Grade 2 (Ok daily living)	6.6		Everolimus	Withdrawal	Reversible
	Grade 3 ( oxygen indicated)	3.6		Everolimus	Withdrawal, antibiotics and steroids	Reversible
	Grade 4 (life threatening)	0		Everolimus	None
Renal	Proteinuria	1.6–4.1	540–1500	Sirolimus and everolimus	Withdrawal	Reversible
	Proteinuria (grade 3 to 4)	25	273	Bevacizumab + everolimus	Discontinuation	Reversible
Reproductive	Infertility (oligospermia)	66.6	150–360	Sirolimus	Discontinuation	Full recovery
	amenorrhea	14.2	150–360	Sirolimus	Discontinuation	Reversible