ARMED FORCES OF THE PHILIPPINES HEALTH SERVICE COMMAND

VICTORIANO LUNA MEDICAL CENTER

DEPARTMENT OF INTERNAL MEDICINE
Camp Colonel Victoriano K Luna, V Luna Avenue., Quezon City

03 AUGUST 2023

DIM

SUBJECT: Procurement, Request for Everolimus

TO: Chief of Clinics, VLMC

Post
Attn: Chief, Pharmacy

1. References:
a. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell.
2006;124:471–84. [PubMed] [Google Scholar]

b. Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell
Biol. 2005;17:596–603. [PubMed] [Google Scholar]

2. Everolimus is indicated for the treatment of postmenopausal women with advanced hormone
receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with
exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of
adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with
unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients
with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.

3. In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours
after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is
dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax
is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg
dose range

4. Everolimus is a substrate of CYP3A4 and PgP (phosphoglycolate phosphatase). Three

monohydroxylated metabolites, two hydrolytic ring-opened products, and a phosphatidylcholine
conjugate of everolimus were the 6 primary metabolites detected in human blood. In vitro, everolimus
competitively inhibited the metabolism of CYP3A4 and was a mixed inhibitor of the CYP2D6 substrate
dextromethorphan.

5. For favorable consideration.

ROLAN OHMAR YUMUL
MAJ MC
Head, DIM