Afinitor

Subependymal giant cell astrocytoma (SEGA) associated w/ tuberous sclerosis complex (TSC) in adult & paed patients who require therapeutic intervention but are not amenable to surgery. Tab: In combination w/ exemestane for hormone receptor +ve, HER2/neu -ve advanced breast cancer 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 in patients whose disease has progressed on or after treatment w/ VEGF-targeted therapy. Renal angiomyolipoma associated w/ TSC in adults who are at risk of complications (based on factors eg, tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but who do not require immediate surgery. Dispersible tab: Adjunctive treatment of refractory partial-onset seizures (w/ or w/o secondary generalisation) associated w/ TSC in patients ≥2 yr.

SEGA associated w/ TSC Initially 4.5 mg/m². Patient 1 to <3 yr Initially 7 mg/m². Patient ≥18 yr w/ mild hepatic impairment 75% of recommended starting dose. Patient ≥18 yr w/ moderate hepatic impairment 50% of recommended starting dose. Patient ≥18 yr w/ severe hepatic impairment Only recommended if desired benefit outweighs risk. Max: 25% of calculated dose. Tab Breast cancer, neuroendocrine tumours & renal cell carcinoma 10 mg once daily. Reduce dose to ≥5 mg daily if required. Patient w/ mild hepatic impairment 7.5 mg daily. Patient w/ moderate hepatic impairment 5 mg daily. Patient w/ severe hepatic impairment Only recommended if desired benefit outweighs risk. Max: 2.5 mg daily. Renal angiomyolipoma associated w/ TSC 10 mg once daily. Patient w/ mild hepatic impairment 7.5 mg daily. Patient w/ moderate hepatic impairment 5 mg daily. Patient w/ severe hepatic impairment Only recommended if desired benefit outweighs risk. Max: 2.5 mg daily. Dispersible tab TSC w/ refractory seizures Patient ≥6 yr Initially 5 mg/m² (w/o CYP3A4/P-gp inducer) or 8 mg/m² (w/ CYP3A4/P-gp inducer), <6 yr Initially 6 mg/m² (w/o CYP3A4/P-gp inducer) or 9 mg/m² (w/ CYP3A4/P-gp inducer). Patient ≥18 yr w/ mild hepatic impairment 75% of recommended starting dose. Patient ≥18 yr w/ moderate hepatic impairment 50% of recommended starting dose. Patient ≥18 yr w/ severe hepatic impairment Only recommended if desired benefit outweighs risk. Max: 25% of calculated dose.

May be taken with or without food: Administer consistently either w/ or w/o food. Tab Swallow whole w/ water. Do not chew/crush. Patients w/ TSC who have SEGA & are unable to swallow tab: Disperse tab completely in approx 30 mL of water by gently stirring until fully disintegrated (approx 7 min), immediately prior to drinking. After swallowing the dispersion, re-disperse any residue in the same vol of water & swallow. Dispersible tab Do not swallow whole. Do not chew/crush. Take as susp only. Prepare susp in oral syringe or small glass, & use only water as vehicle. Administer susp immediately after prep. Discard if not administered w/in 30 min (oral syringe) or 60 min (small glass) of prep, & prepare new susp. Ensure entire dose is ingested.

Hypersensitivity to everolimus or other rapamycin derivatives.

Do not use Afinitor tab & Afinitor dispersible tab interchangeably. Risk of non-infectious pneumonitis (including ILD); bacterial, fungal, viral or protozoal infections (including infections w/ opportunistic pathogens); hypersensitivity reactions; stomatitis (including mouth ulcerations & oral mucositis); haemorrhage; renal failure; impaired wound healing. Pre-existing infections should be treated appropriately & should have resolved fully before starting Afinitor treatment. Consider prophylaxis for Pneumocystis jirovecii (carinii) pneumonia when concomitant use of corticosteroids or other immunosuppressive agents are required. Reports of elevated serum creatinine & proteinuria; hyperglycaemia; dyslipidaemia (including hypercholesterolaemia & hypertriglyceridaemia); decreased Hb, lymphocytes, neutrophils & platelets. 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. Caution during concomitant use w/ active substances known to affect platelet function or that can increase risk of haemorrhage, & in patients w/ history of bleeding disorders. Caution w/ use in the peri-surgical period. Reports of serious & severe radiation reactions (eg, radiation oesophagitis, radiation pneumonitis & radiation skin injury) when everolimus was taken during or shortly after RT. Reports of radiation recall syndrome in patients taking everolimus who had received RT in the past. Caution w/ concomitant use of ACE inhibitors. Caution when taken in combination w/ orally administered CYP3A4 substrates w/ narrow therapeutic index (eg, pimozide, terfenadine, astemizole, cisapride, quinidine, ergot alkaloid derivatives, carbamazepine). Avoid co-administration w/ inhibitors & inducers of CYP3A4 &/or P-gp. Avoid use of live vaccines during treatment. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor or moderate influence on ability to drive & use machines. Not recommended during pregnancy & in women of childbearing potential not using contraception. Women of childbearing potential must use highly effective contraception during treatment & for up to 8 wk after ending treatment. Do not breast-feed during treatment & for 2 wk after the last dose. Male & female fertility may be compromised. Oncology indications: Safety & efficacy in patients w/ functional carcinoid tumours have not been established. Perform individual benefit-risk assessment prior to start of therapy in patients w/ non-functional GI or lung neuroendocrine tumours & good prognostic baseline factors eg, ileum as primary tumour origin & normal chromogranin A values or w/o bone involvement. Increased exposure to everolimus in patients w/ mild (Child-Pugh A), moderate (Child-Pugh B) & severe (Child-Pugh C) hepatic impairment. Safety & efficacy have not been established in childn ≤18 yr. TSC-related indications: Not recommended in patients <18 yr w/ SEGA or refractory seizures & hepatic impairment. Safety & efficacy have not been established in childn ≤18 yr w/ renal angiomyolipoma associated w/ TSC in the absence of SEGA. Safety, efficacy & pharmacokinetic profile have not been established in childn <1 yr w/ TSC who have SEGA. Safety, efficacy & pharmacokinetic profile have not been established in childn <2 yr w/ TSC & refractory seizures.

Oncology indications: 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, hypocalcaemia; insomnia; eyelid oedema; haemorrhage, HTN, lymphoedema; 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, skin lesion; arthralgia; proteinuria, increased blood creatinine, renal failure; irregular menstruation; pyrexia. TSC-related indications: Nasopharyngitis, URTI, pneumonia, UTI, sinusitis, pharyngitis; decreased appetite, hypercholesterolaemia; headache; HTN; cough; stomatitis, diarrhoea, vomiting; rash, acne; amenorrhoea, irregular menstruation; pyrexia, fatigue. Otitis media, cellulitis, streptococcal pharyngitis, viral gastroenteritis, gingivitis; anaemia, neutropenia, leucopenia, thrombocytopenia, lymphopenia; hypersensitivity; hypertriglyceridaemia, hyperlipidaemia, hypophosphataemia, hyperglycaemia; insomnia, aggression, irritability; lymphoedema; epistaxis, pneumonitis; constipation, nausea, abdominal pain, flatulence, oral pain, gastritis; dry skin, acneiform dermatitis, pruritus, alopecia; proteinuria; menorrhagia, ovarian cyst, vag haemorrhage; increased blood LDH & blood LH, & decreased wt.

Increased blood conc w/ potent CYP3A4/P-gp inhibitors (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, atazanavir, saquinavir, darunavir, indinavir, nelfinavir); moderate CYP3A4/P-gp inhibitors (eg, erythromycin, imatinib, verapamil, oral ciclosporin, fluconazole, diltiazem, dronedarone, amprenavir, fosamprenavir, grapefruit juice or other food affecting CYP3A4/P-gp); cannabidiol (P-gp inhibitor). Decreased blood conc w/ potent & moderate CYP3A4 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 influenza, MMR, oral polio, BCG, yellow fever, varicella, & TY21a typhoid vaccines). Potentiation of radiation treatment toxicity. Dispersible tab: Possibility of additive effect on adverse events when given in conjunction w/ ketogenic diet.

Targeted Cancer Therapy

L01EG02 - everolimus ; Belongs to the class of mammalian target of rapamycin (mTOR) kinase inhibitors. Used in the treatment of cancer.

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