Afinitor Tablet 2.5 mg (Everolimus)

Adult dose

This medication should be taken once daily at the same time each day, either consistently with food or consistently on an empty stomach. Swallow the medication whole with a glass of water; do not chew or crush it. If it is difficult to swallow, place the medication in water (approximately 30 mL) and stir well until it is fully dispersed (approximately 7 minutes), then drink immediately. Rinse the cup with the same amount of water and drink all of the rinse to ensure the full dose is taken. Treatment with this medication should be initiated by a physician experienced in the use of anticancer therapy. Treatment should continue for as long as clinical benefit is observed or until unacceptable toxicity occurs. 1. Breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiomyolipoma associated with tuberous sclerosis complex (TSC) Recommended dosage Adult patients The recommended dosage is 10 mg orally once daily. 2. Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) The dose is individualized based on body surface area (BSA, m2) using the Dubois formula. (W; body weight (kg), H; height (cm)) BSA = (W0.425 x H0.725) x 0.007184 Starting dose and trough blood concentration The recommended starting dose of this medication for the treatment of patients with SEGA associated with TSC is 4.5 mg/m2. (Administer the nearest whole-tablet dose (n).) This medication may be combined with other strengths of this medication to achieve the total dose. The dose should be titrated to achieve a trough blood concentration of 5-15 ng/mL. The dose should be titrated in increments of 2.5 mg to achieve a trough blood concentration associated with optimal clinical response. When titrating the dose, consider efficacy, safety, concomitant medications, and the current trough blood concentration. Dose titration can be calculated using a simple proportion: New everolimus dose = current dose x (target concentration/current concentration) For example, for a patient whose steady-state concentration is 4 ng/mL based on current BSA and who is taking a dose of 2.5 mg, the new everolimus dose to achieve a trough concentration of at least 5 ng/mL (e.g., 8 ng/mL) is 5 mg (an increase of 2.5 mg from the current daily dose). The trough blood concentration should be assessed within 1-2 weeks after a dose change. If the adjusted dose is not a multiple of 2.5 mg, administer the nearest dose. Dose monitoring The whole blood concentration of everolimus should be assessed approximately 1-2 weeks after treatment initiation or a dose change. Assess SEGA volume approximately 3 months after starting treatment with this medication, and adjust the dose based on changes in SEGA volume, the corresponding trough blood concentration, and tolerability. Once a stable dose has been achieved, monitor the trough blood concentration every 3-6 months in patients whose BSA has changed and every 6-12 months in patients whose BSA is stable. 3. Dose adjustment (1) Adverse reactions: If severe or intolerable adverse drug reactions occur, temporary dose reduction or interruption may be necessary. If dose reduction is required, approximately 50% of the previous dose is recommended. If the dose is reduced to below the lowest dose of one tablet of this medication, consider administration every 2 days. The following table summarizes recommended dose reductions and treatment interruptions for this medication in the management of adverse drug reactions. Recommendations for general management are also provided. The management plan should be determined by the physician's clinical judgment based on an individual benefit/risk assessment. [Table] Dose adjustment and recommended management for adverse drug reactions Noninfectious pneumonitis Grade 1 Asymptomatic, with only clinical or diagnostic findings that do not require intervention No dose adjustment required Initiate appropriate monitoring Grade 2 Symptoms that do not affect activities of daily living (ADLc) Consider withholding treatment; rule out infection and consider corticosteroid treatment until symptoms improve to Grade 1 or lower Resume treatment at a lower dose Grade 3 Severe symptoms affecting activities of daily living (ADLc) and oxygen indicated Discontinue treatment if recovery does not occur within 4 weeks Withhold treatment until symptoms resolve to below Grade 1; rule out infection and consider corticosteroid treatment until symptoms resolve to below Grade 1 Resume treatment at a lower dose Consider discontinuing treatment if noninfectious pneumonitis recurs at Grade 3 Grade 4 Life-threatening respiratory symptoms requiring urgent intervention (e.g., tracheostomy or intubation) Discontinue treatment; rule out infection and consider corticosteroid treatment Stomatitis Grade 1 Asymptomatic, or mild symptoms not requiring intervention No dose adjustment required Rinse the mouth several times a day with non-alcoholic water or saline (0.9%). Grade 2 Moderate pain that does not interfere with oral intake and requires a modified diet Temporarily withhold treatment until recovery to Grade 1 or lower Resume treatment at the same dose If stomatitis recurs at Grade 2, withhold treatment until recovery to Grade 1 or lower. Resume treatment at a lower dose Treat with topical oral analgesics (e.g., benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, or phenol), with or without a topical corticosteroid (triamcinolone oral paste)d Grade 3 Severe pain that interferes with oral intake Temporarily withhold treatment until recovery to Grade 1 or lower Resume treatment at a lower dose Treat with topical oral analgesics (e.g., benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, or phenol), with or without a topical corticosteroid (triamcinolone oral paste)d Grade 4 Life-threatening consequences requiring urgent intervention Discontinue treatment and manage with appropriate medical treatment Other nonhematologic toxicity (excluding metabolic reactions) Grade 1 No dose adjustment is required if the toxicity is tolerable Initiate appropriate medical treatment and monitor Grade 2 No dose adjustment is required if the toxicity is tolerable Initiate appropriate medical treatment and monitor If the toxicity is not tolerable, withhold treatment until recovery to Grade 1 or lower; resume treatment at the same dose If the toxicity recurs at Grade 2, withhold treatment until recovery to Grade 1 or lower. Resume treatment at a lower dose Grade 3 Temporarily withhold treatment until recovery to Grade 1 or lower; initiate appropriate medical treatment and monitor Consider resuming treatment at a lower dose Discontinue treatment if other nonhematologic toxicity recurs at Grade 3. Grade 4 Discontinue treatment and manage with appropriate medical treatment Metabolic reactions (e.g., hyperglycemia, dyslipidemia) Grade 1 No dose adjustment required Initiate appropriate medical treatment and monitor Grade 2 No dose adjustment required Manage with appropriate medical treatment and monitor Grade 3 Temporarily withhold treatment Resume treatment at a lower dose Manage with appropriate medical treatment and monitor Grade 4 Discontinue treatment and manage with appropriate medical treatment Thrombocytopenia (Decreased platelet count) Grade 1 (< lower limit of normal e - 75,000/mm3; < lower limit of normal e - 75.0 x 109/L) No dose adjustment required Grade 2 (< 75,000-50,000/mm3; < 75.0 – 50.0 x 109/L) Temporarily withhold treatment until recovery to Grade 1 Resume treatment at the same dose Grade 3 (< 50,000-25,000/mm3; < 50.0 – 25.0 x 109/L) Temporarily withhold treatment until recovery to Grade 1 Resume treatment at a lower dose or Grade 4 (< 25,000/mm3; < 25.0 x 109/L) Neutropenia (Decreased neutrophil count) Grade 1 (< lower limit of normal e - 1,500/mm3; < lower limit of normal e - 1.5 x 109/L) No dose adjustment required or Grade 2 (< 1,500-1,000/mm3; < 1.5 – 1.0 x 109/L) Temporarily withhold treatment until recovery to Grade 2 Resume treatment at the same dose Grade 3 (< 1,000-500/mm3; < 1.0 – 0.5 x 109/L) Temporarily withhold treatment until recovery to Grade 2 Resume treatment at a lower dose Grade 4 (< 500/mm3; < 0.5 X 109/L) Febrile neutropenia Grade 3 Absolute neutrophil countf < 1,000/mm3 with a single temperature > 38.3 ℃ or sustained temperature ≥ 38 ℃ for more than 1 hour Temporarily withhold treatment until recovery to Grade 2 and fever has resolved Resume treatment at a lower dose Grade 4 Life-threatening consequences requiring urgent intervention Discontinue treatment a Severity grade definitions: 1=mild symptoms; 2=moderate symptoms; 3= severe symptoms; 4=life-threatening symptoms Grades according to NCI-CTCAE b If dose reduction is required, the recommended dose is approximately 50% of the previous dose. c Activities of daily living (ADL) d When treating stomatitis, avoid preparations containing alcohol, hydrogen peroxide, iodine, or thyme derivatives because they may worsen oral ulcers. e Lower limit of normal (LLN) f Absolute Neutrophil Count (ANC) Elderly patients (65 years and older) No dose adjustment is required in elderly patients. Patients with renal impairment No dose adjustment is required in patients with renal impairment. Patients with hepatic impairment - Breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiomyolipoma associated with tuberous sclerosis complex (TSC): • Mild hepatic impairment (Child-Pugh A): The recommended dose is 7.5mg once daily. If not tolerated, the dose may be reduced to 5mg. • Moderate hepatic impairment (Child-Pugh B): The recommended dose is 5mg once daily. If not tolerated, the dose may be reduced to 2.5mg. • Severe hepatic impairment (Child-Pugh C): Administration is not recommended. Administer only if the therapeutic benefit outweighs the risk, and do not exceed 2.5mg once daily. The dose should be adjusted if the patient's hepatic status (Child-Pugh) changes during treatment. - Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) (1) Patients 18 years and older • Mild hepatic impairment (Child-Pugh A): The recommended dose is 75% of the dose calculated based on BSA. (Administer the nearest whole-tablet dose (1 tablet).) • Moderate hepatic impairment (Child-Pugh B): The recommended dose is 50% of the dose calculated based on BSA. (Administer the nearest whole-tablet dose (1 tablet).) • Severe hepatic impairment (Child-Pugh C): Administration is not recommended. The whole blood trough concentration of everolimus should be measured 1 - 2 weeks after starting treatment or after a change in hepatic status (Child-Pugh). The dose should be titrated to achieve a trough concentration of 5-15ng/mL. The dose should be adjusted if the patient's hepatic status (Child-Pugh) changes during treatment.

Child dose

Breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiomyolipoma associated with tuberous sclerosis complex (TSC): The safety and efficacy of this drug have not been established in pediatric patients under 18 years of age. Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): The recommended dose of this drug for pediatric patients aged 1 year and older is the same as that for adult patients. Patients under 1 year of age with SEGA associated with TSC: This drug has not been studied in patients under 1 year of age with SEGA associated with TSC or in patients under 18 years of age with SEGA associated with TSC who have hepatic impairment; therefore, its use is not recommended. (2) Patients under 18 years of age This drug is not recommended for patients under 18 years of age with SEGA associated with TSC who have hepatic impairment.

This drug can cause non-infectious pneumonia, so if symptoms such as difficulty breathing or cough appear, you should immediately inform your doctor. This drug suppresses the immune system, making it easier to contract various infections such as bacterial, fungal, and viral; thus, if you have any signs of infection, you should receive treatment immediately. Allergic reactions may occur while taking this drug, so if symptoms like difficulty breathing or skin rashes arise, you should consult medical personnel right away. Inflammation or ulcers in the mouth may frequently occur, so it's advisable to maintain oral hygiene and avoid irritating foods or alcoholic products. As it may affect kidney function, regular blood tests should be conducted to monitor kidney status. While taking this drug, various laboratory tests, including blood glucose, cholesterol, and blood cell counts, should be performed regularly to monitor health status. There are many drug interactions, so especially when taken with certain antifungals, antibiotics, heart medications, etc., you should consult your doctor. Patients with severely impaired liver function are recommended not to take this drug, and the decision to use it should be made in accordance with liver status. Live vaccinations should be avoided during this drug treatment and vaccination plans should be discussed in advance before starting treatment. Pregnant or breastfeeding women should not take this drug, and women of childbearing age should ensure effective contraception while taking and after stopping this medication. There is no specific antidote for overdose, so general treatment will be provided according to the symptoms. This drug should be stored in its original container, in a safe place out of reach of children.

Non-infectious pneumonia, hypoxia, pleural effusion, cough, dyspnea, pneumonia, bacterial infection, aspergillosis, candidiasis, Pneumocystis pneumonia, viral infection, septic shock, sepsis, respiratory failure, liver failure, anaphylaxis, flushing, chest pain, vascular edema, stomatitis, oral ulcer, oral mucositis, acute renal failure, elevated serum creatinine, proteinuria, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, reduced hemoglobin, lymphopenia, neutropenia, thrombocytopenia, anemia, taste disorder, rash, fatigue, diarrhea, nausea, decreased appetite, pneumonia, peripheral edema, asthenia, pruritus, weight loss, epistaxis, headache, aphthous stomatitis, oral and tongue ulcers, glossitis, glossodynia, dry skin, nail disorder, rash, angioedema, arthralgia, renal failure, menstrual irregularities, amenorrhea, fever, mucosal inflammation, non-cardiac chest pain, impaired wound healing, increased blood creatinine, pneumonia, interstitial lung disease, lung infiltration, alveolitis, pulmonary hemorrhage, pulmonary toxicity, diarrhea, vomiting, dry mouth, abdominal pain, oral pain, dyspepsia, dysphagia, pruritus, acne, erythema, hand-foot syndrome, angioedema, rhabdomyolysis, proteinuria, menorrhagia, ovarian cysts, vaginal bleeding, delayed menstruation, fever, insomnia, aggressiveness, hypersensitivity, headache, taste abnormalities, congestive heart failure, bleeding, hypertension, deep vein thrombosis, hemoptysis, pulmonary embolism, acute respiratory distress syndrome, epistaxis, cough, nasopharyngitis, upper respiratory infection, urinary tract infection, sinusitis, pharyngitis, otitis media, cellulitis, streptococcal pharyngitis, viral gastroenteritis, gingivitis, herpes zoster, viral bronchitis, thrombocytopenia, pancytopenia, pure red cell aplasia, hypersensitivity, hypophosphatemia, diabetes, hyperlipidemia, hypokalemia, dehydration, dry skin, acneiform dermatitis, hair loss, rhabdomyolysis, menstrual irregularities, amenorrhea, increased serum lactate dehydrogenase, increased serum luteinizing hormone, increased serum follicle-stimulating hormone, lymphedema, sputum disease, leg pain, hypercalcemia, hyponatremia, leukocytosis, hypothyroidism, black stools, ocular hemorrhage, radiation recall syndrome, duodenal ulcer hemorrhage, skin ulcer, hematuria, no efficacy, sore throat, cheilitis, azotemia, skin lesions, sensory abnormalities, sensory loss, urticaria, dizziness, hyperpigmentation of the skin, skin toxicity, confusional state, increased blood urea, hypothyroidism, deterioration of health, convulsions, hyperuricemia, myalgia, eyelid edema, paralysis, peripheral neuropathy, epigastric discomfort, decreased glomerular filtration rate, blurred vision, heart failure, facial edema, external otitis, communication disorders, generalized edema, nasal inflammation, chapped lips, pulmonary edema, decreased serum sodium, decreased serum albumin, increased serum creatine

This drug should be stored in a sealed container to prevent air and moisture from entering, and the temperature should be maintained between 1 degree and 30 degrees Celsius. Additionally, it is best to store it in a dark place away from direct sunlight.

Appearance

White to pale yellow, elongated tablets

Package unit

30 tablets (10 tablets/PTP packaging x 3)