Afinitor

Everolimus

Postmenopausal women w/ hormone receptor +ve advanced breast cancer in combination w/ an aromatase inhibitor after prior endocrine therapy. Patients w/ advanced neuroendocrine tumors of GI, lung or pancreatic origin; advanced renal cell carcinoma; tuberous sclerosis complex (TSC) who have renal angiomyolipoma or subependymal giant cell astrocytoma (SEGA) not requiring immediate surgery.

Hormone receptor +ve advanced breast cancer, advanced neuroendocrine tumor of GI, lung or pancreatic origin, advanced renal cell carcinoma & TSC w/ renal angiomyolipoma 10 mg once daily. Mild hepatic impairment (Child-Pugh A) 7.5 mg daily. Moderate hepatic impairment (Child-Pugh B) 5 mg daily. May be decreased to 2.5 mg if not well tolerated. Severe hepatic impairment (Child-Pugh C) Not recommended. If desired benefit outweighs the risk, must not exceed 2.5 mg daily. TSC w/ SEGA Initially 4.5 mg/m² daily. Mild hepatic impairment (Child-Pugh A) 75% of dose calculated based on BSA. Moderate hepatic impairment (Child-Pugh B) 50% of dose calculated based on BSA. Severe hepatic impairment (Child-Pugh C) Not recommended. If desired benefit outweighs the risk, must not exceed 25% of dose calculated based on BSA.

May be taken with or without food: Take at the same time every day, either consistently w/ or w/o food. Swallow whole, do not chew/crush. For patients w/ TSC w/ SEGA & swallowing difficulties, disperse tab in a glass of water & stir gently until it disintegrates (approx 7 min), then drink immediately. Rinse glass w/ the same vol of water & drink. Dispersible tab: To be taken as a suspension only & should not be swallowed whole/chewed/crushed. The susp can be prepared in an oral syringe (w/ 5 mL water) or in a small drinking glass (w/ 25 mL water) & should be administered immediately after preparation. Discard if not administered w/in 60 min. Prepare the suspension in water only.

Hypersensitivity to everolimus or other rapamycin derivatives.

Hypersensitivity reactions. Not recommended for use in patients w/ TSC & refractory seizures. Non-infectious pneumonitis including ILD. Localized & systemic infections including pneumonia, other bacterial, invasive fungal (eg, aspergillosis, candidiasis or Pneumocystis jirovecii pneumonia) & viral infections. Stomatitis including mouth ulceration & oral mucositis. Use in peri-surgical period. Monitor renal function (including measurement of BUN, urinary protein or serum creatinine), fasting serum glucose, blood cholesterol & triglycerides & CBC prior to start of therapy & periodically thereafter. Avoid alcohol-, hydrogen peroxide-, iodine- or thyme-containing products in treatment of stomatitis. Do not use antifungal agents unless fungal infection has been diagnosed. Avoid co-administration w/ strong CYP3A4/P-gp inhibitors & inducers. Avoid use of live vaccines & close contact w/ those who have received live vaccines during treatment. Concomitant use w/ ACE inhibitors; moderate CYP3A4/P-gp inhibitors; oral CYP3A4 substrates w/ narrow therapeutic index. Radiation therapy complications. Not recommended in patients ≥18 yr w/ severe hepatic impairment (Child-Pugh C) & patients <18 yr w/ TSC who have SEGA & concomitant hepatic impairment (Child-Pugh A, B or C). May compromise male & female fertility. Sexually-active females of reproductive potential should use effective contraception during & for up to 8 wk after treatment. Pregnancy. Not to be used during lactation & for 2 wk after last dose. Not recommended for use in ped cancer patients; ped patients w/ TSC who have renal angiomyolipoma; patient <18 yr w/ hepatic impairment & TSC w/ SEGA or TSC w/ seizures. Childn. Elderly.

Infections; anaemia; decreased appetite, hyperglycaemia, hypercholesterolaemia; dysgeusia, headache; pneumonitis, epistaxis, cough; stomatitis, diarrhoea, nausea; rash, pruritus; fatigue, asthenia, peripheral oedema; decreased wt. Thrombocytopenia, neutropenia, leukopenia, lymphopenia; hypertriglyceridaemia, hypophosphataemia, DM, hyperlipidaemia, hypokalaemia, dehydration; insomnia; haemorrhage, HTN, lymphoedema; dyspnoea; vomiting, dry mouth, abdominal & oral pain, dyspepsia, dysphagia; dry skin, nail disorder, acne, erythema, hand-foot syndrome; arthralgia; proteinuria, renal failure; irregular menstruation; pyrexia, mucosal inflammation; increased AST, ALT & blood creatinine.

Blood conc may be increased w/ strong CYP3A4/P-gp inhibitors (eg, ketoconazole, itraconazole, ritonavir, clarithromycin & telithromycin); moderate inhibitors of CYP3A4 (eg, erythromycin, verapamil, ciclosporin, fluconazole, diltiazem, amprenavir, fosamprenavir or aprepitant). Blood conc may be decreased w/ strong CYP3A4/P-gp inducers eg, rifampicin, rifabutin, St. John's wort, anticonvulsants (eg, carbamazepine, phenobarb, phenytoin) & anti-HIV agents (eg, efavirenz, nevirapine). Avoid concomitant use w/ grapefruit, grapefruit juice, star fruit, Seville oranges & other foods affecting cytochrome P450 & P-gp activity. May affect response to vaccination eg, live vaccines (eg, intranasal flu, MMR, oral polio, BCG, yellow fever, varicella & TY21a typhoid vaccines). May affect bioavailability of orally co-administered drugs which are CYP3A4 substrates.

Targeted Cancer Therapy

L04AH02 - everolimus ; Belongs to the class of mammalian target of rapamycin (mTOR) kinase inhibitors. Used as immunosuppressants.

Rx