Table 4.

Recommended clinical management strategy: infections [22, 27]

Grade	Description	Intervention	Everolimus dose adjustment
1	None	• Institute adequate treatment of infection with antibiotics, as appropriate	• If toxicity is tolerable, no dose adjustment required
		• Perform culture and be aware of atypical infections	• Initiate appropriate medical therapy and monitor
2	Localized infection, with local intervention indicated		• If toxicity is tolerable, no dose adjustment required
		• In patients who test positive for hepatitis B surface antigen, consider prophylaxis with entecavir or tenofovir	• Initiate appropriate medical therapy and monitor
			• If toxicity becomes intolerable, temporary dose interruption until recovery to grade ≤1. Reinitiate everolimus at the same dose
			• If toxicity recurs at grade 2, interrupt everolimus until recovery to grade ≤1. Reinitiate everolimus at a lower dose
3	IV antibiotic, antifungal, or antiviral intervention indicated; interventional radiology or surgery indicated	• Provide IV antibiotic, antifungala, or antiviral therapy; institute additional interventions as for grade 1	• Temporary dose interruption until recovery to grade ≤1
			• Initiate appropriate medical therapy and monitor
			• Consider reinitiating everolimus at a lower dose. If toxicity recurs at grade 3, consider discontinuation
4	Life-threatening consequences such as septic shock, hypotension, acidosis, or necrosis	• Provide appropriate standard therapy, as for grade 1	• Discontinue everolimus

IV intravenous

^aIf diagnosis of invasive systemic fungal infection is made, everolimus therapy should be promptly and permanently discontinued. Avoid coadministration of everolimus with strong cytochrome 3A4 inhibitors