CV: peripheral edema.
Derm: delayed wound healing, dry skin, pruritus, rash.
Endo: hyperglycemia.
GI: anorexia, constipation, diarrhea, mouth ulcers, mucositis, nausea, stomatitis, vomiting, HEPATIC ARTERY THROMBOSIS.
GU: ↓fertility, acute renal failure, amenorrhea, kidney arterial/venous thrombosis (Zortress), menstrual irregularities, proteinuria.
Hemat: anemia, leukopenia, thrombocytopenia, HEMOLYTIC UREMIC SYNDROME, THROMBOTIC MICROANGIOPATHY, THROMBOTIC THROMBOCYTOPENIC PURPURA.
Metab: hyperlipidemia, hypertriglyceridemia.
MS: extremity pain.
Neuro: fatigue, weakness, dysgeusia, headache.
Resp: cough, dyspnea, pulmonary embolism, INTERSTITIAL LUNG DISEASE, PULMONARY HYPERTENSION.
Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), INFECTION (INCLUDING ACTIVATION OF LATENT VIRAL INFECTIONS SUCH AS BK VIRUS-ASSOCIATED NEPHROPATHY), (ZORTRESS)LYMPHOMA/SKIN CANCER .
Advanced Renal Cell Carcinoma, Advanced Progressive Neuroendocrine Tumors, Advanced Neuroendocrine Tumors, Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer, and Renal Angiomyolipoma with Tuberous Sclerosis Complex (Afinitor)
- PO (Adults): 10 mg once daily until disease progression or unacceptable toxicity; Concurrent use of P-gp inhibitor and moderate CYP3A4 inhibitor: 2.5 mg once daily until disease progression or unacceptable toxicity; Concurrent use of P-gp inducer and strong CYP3A4 inducer:↑ dose in 5 mg increments up to 20 mg once daily; continue until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults): Mild hepatic impairment: 7.5 mg once daily until disease progression or unacceptable toxicity; may ↓ to 5 mg once daily if not well tolerated; Moderate hepatic impairment: 5 mg once daily until disease progression or unacceptable toxicity; may ↓ to 2.5 mg once daily if not well tolerated; Severe hepatic impairment: 2.5 mg once daily until disease progression or unacceptable toxicity.
Subependymal Giant Cell Astrocytoma with Tuberous Sclerosis Complex (Afinitor)
- PO (Adults and Children 1 yr): 4.5 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity; Concurrent use of P-gp inhibitor and moderate CYP3A4 inhibitor: 2.25 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity; Concurrent use of P-gp inducer and strong CYP3A4 inducer: 9 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults and Children 1 yr): Severe hepatic impairment: 2.5 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity.
Tuberous Sclerosis Complex-Associated Partial-Onset Seizures (Afinitor)
- PO (Adults and Children 2 yr): 5 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity; Concurrent use of P-gp inhibitor and moderate CYP3A4 inhibitor: 2.5 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity; Concurrent use of P-gp inducer and strong CYP3A4 inducer: 10 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity.
Hepatic Impairment
- PO (Adults and Children 2 yr): Severe hepatic impairment: 2.5 mg/m2 once daily. Titrate, as needed, at 2-wk intervals to achieve recommended whole blood trough concentration. Continue until disease progression or unacceptable toxicity.
Kidney Transplantation (Zortress)
- PO (Adults): 0.75 mg twice daily (with reduced-dose cyclosporine); titrate to achieve recommended whole blood trough concentration.
Hepatic Impairment
- PO (Adults): Mild hepatic impairment :↓ daily dose by 33%; Moderate or severe hepatic impairment:↓ daily dose by 50%.
Liver Transplantation (Zortress)
- PO (Adults): 1 mg twice daily (with reduced-dose tacrolimus) (start 30 days post-transplant); titrate to achieve recommended whole blood trough concentration.
Hepatic Impairment
- PO (Adults): Mild hepatic impairment :↓ daily dose by 33%; Moderate or severe hepatic impairment:↓ daily dose by 50%.
Afinitor, Afinitor Disperz, Zortress
Therapeutic Classification: antineoplastics, Immunosuppressant agents
Pharmacologic Classification: kinase inhibitors
Absorption: Well absorbed following oral administration.
Distribution: 20% confined to plasma.
Metabolism/Excretion: Mostly metabolized by liver via the CYP3A4 isoenzyme; metabolites are mostly excreted in feces (80%) and urine (5%).
Half-life: 30 hr.