Afinitor

Everolimus

Hormone receptor-positive & HER2/neu negative advanced breast cancer, in combination w/ exemestane, in postmenopausal women w/o symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. Unresectable or metastatic, well‑ or moderately‑differentiated neuroendocrine tumours of pancreatic origin in adults w/ progressive disease. Unresectable or metastatic, well-differentiated (Grade 1 or 2) non-functional neuroendocrine tumours of GI or lung origin in adults w/ progressive disease. Advanced renal cell carcinoma, that has progressed on or after treatment w/ VEGF‑targeted therapy. Renal angiomyolipoma associated w/ tuberous sclerosis complex (TSC) in adult patients who are at risk of complications but who do not require immediate surgery. Subependymal giant cell astrocytoma (SEGA) associated w/ TSC in patients who require therapeutic intervention but are not amenable to surgery.

Breast cancer, neuroendocrine tumours & renal cell carcinoma 10 mg once daily. Dose may be reduced to ≥5 mg daily if required. Mild hepatic impairment (Child‑Pugh A) 7.5 mg daily. Moderate hepatic impairment (Child‑Pugh B) 5 mg daily. Severe hepatic impairment (Child‑Pugh C) ≤2.5 mg daily. Only recommended if the desired benefit outweighs the risk. Renal angiomyolipoma associated w/ TSC 10 mg once daily. Mild hepatic impairment (Child‑Pugh A) 7.5 mg daily. Moderate hepatic impairment (Child‑Pugh B) 5 mg daily. Severe hepatic impairment (Child‑Pugh C) ≤2.5 mg daily. Only recommended if the desired benefit outweighs the risk. SEGA associated w/ TSC Initially 4.5 mg/m². Childn 1 to <3 yr Initially 7 mg/m². Patients ≥18 yr w/ mild hepatic impairment (Child-Pugh A) 75% of recommended starting dose. Moderate hepatic impairment (Child-Pugh B) 50% of recommended starting dose. Severe hepatic impairment (Child-Pugh C) 25% of calculated dose. Only recommended if the desired benefit outweighs the risk.

May be taken with or without food: Take consistently either always w/ or always w/o meals. Swallow whole, do not chew/crush. Avoid grapefruit juice.

Hypersensitivity to everolimus & other rapamycin derivatives.

Hypersensitivity reactions. Reports of non-infectious pneumonitis (eg, interstitial lung disease); corticosteroids may be used until moderate (Grade 2) or severe (Grade 3) symptoms resolve. Increased risk of infection; pre-existing infections should be treated & should have fully resolved prior to treatment initiation. Consider prophylaxis for Pneumocystis jirovecii (carinii) pneumonia (PJP/PCP) when concomitant use of corticosteroids or other immunosuppressive agents are required. Reports of stomatitis. Monitoring of renal function, blood glucose & lipids, & haematological parameters is recommended before therapy & periodically thereafter. Patients w/ functional carcinoid tumours; non-functional GI or lung neuroendocrine tumours. Impaired wound healing. Co-administration w/ ACE inhibitors (eg, ramipril); CYP3A4 &/or PgP inhibitors & inducers; live vaccines. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose‑galactose malabsorption. Minor or moderate influence on the ability to drive & use machines. Hepatic impairment. Renal failure. Women of childbearing potential must use a highly effective method of contraception during, & for up to 8 wk after ending treatment. Pregnancy & lactation. Paed population.

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

Increased blood conc w/ CYP3A4 or PgP inhibitors (potent: eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, atazanavir, saquinavir, darunavir, indinavir, nelfinavir; moderate: eg, erythromycin, imatinib, verapamil, oral ciclosporin, fluconazole, diltiazem, dronedarone, amprenavir, fosamprenavir, grapefruit juice or other foods affecting CYP3A4/PgP). Decreased blood conc w/ potent & moderate CYP3A4 or PgP inducers (eg, rifampicin, dexamethasone, carbamazepine, phenobarb, phenytoin, efavirenz, nevirapine, St. John's Wort). Increased risk of angioedema w/ ACE inhibitors (eg, ramipril). Reduced effectiveness of live vaccines (eg, intranasal flu, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, & TY21a typhoid vaccines).

Targeted Cancer Therapy

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

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