AFINITOR DISPERZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AFINITOR DISPERZ (AFINITOR DISPERZ).
Everolimus is an mTOR inhibitor that binds to FKBP-12, forming a complex that inhibits the mTOR serine-threonine kinase, thereby blocking cell cycle progression, angiogenesis, and cell growth.
| Metabolism | Everolimus is metabolized primarily by CYP3A4 and is a substrate of P-glycoprotein (P-gp). It is also a moderate inhibitor of CYP3A4 and P-gp. |
| Excretion | Primarily fecal (80%) with 22% as unchanged drug; renal excretion <5%. |
| Half-life | Terminal half-life is approximately 30 hours (range 28-35 hours) in patients with advanced solid tumors, supporting once-daily dosing. |
| Protein binding | Approximately 74% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Mean apparent volume of distribution is 47 L (approximately 0.6 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability of the tablet formulation is approximately 16% after a high-fat meal; dispersible tablet bioavailability is comparable when taken with food. |
| Onset of Action | Peak concentration reached 1-2 hours after oral administration; clinical antitumor effect typically observed within 2-4 weeks. |
| Duration of Action | Continuous mTOR inhibition over the dosing interval with once-daily dosing; clinical effect persists as long as treatment continues, with loss of effect upon discontinuation. |
10 mg orally once daily for advanced hormone receptor-positive, HER2-negative breast cancer; 10 mg orally once daily for advanced pancreatic neuroendocrine tumors; 10 mg orally once daily for advanced renal cell carcinoma; 7.5 mg orally once daily for subependymal giant cell astrocytoma (SEGA); 5 mg orally once daily for tuberous sclerosis complex (TSC)-associated renal angiomyolipoma.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | For CrCl 30-50 mL/min: no adjustment required. For CrCl <30 mL/min: contraindicated or not recommended due to lack of data. No specific GFR-based dose reduction recommended. |
| Liver impairment | Child-Pugh A: reduce dose to 7.5 mg daily. Child-Pugh B: reduce dose to 5 mg daily. Child-Pugh C: contraindicated. |
| Pediatric use | For SEGA in TSC: weight-based dosing targeting AUC similar to adult 10 mg/day. Initial dose 2.5 mg/m² once daily, titrate to trough concentration 5-15 ng/mL. For TSC-associated renal angiomyolipoma: not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor renal function and dose adjust per renal/hepatic status. Elderly patients may have increased risk of adverse effects such as stomatitis, infections, and metabolic disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AFINITOR DISPERZ (AFINITOR DISPERZ).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Due to potential serious adverse reactions in nursing infants (e.g., immunosuppression), breastfeeding is contraindicated during treatment and for 2 weeks after last dose. |
| Teratogenic Risk | Pregnancy Category D. Animal studies show embryotoxicity and fetotoxicity at subtherapeutic doses. First trimester: risk of major malformations. Second/third trimester: risk of fetal growth restriction, oligohydramnios, and spontaneous abortion. |
■ FDA Black Box Warning
There is no FDA black box warning for Afinitor Disperz. However, serious infections, including opportunistic infections, may occur.
| Serious Effects |
["Hypersensitivity to everolimus, sirolimus, or any component of the formulation","Severe hepatic impairment (Child-Pugh class C) (relative contraindication; use with caution in moderate impairment)"]
| Precautions | ["Non-infectious pneumonitis (including interstitial lung disease) has been reported; monitor for symptoms and consider interruption or discontinuation.","Increased risk of infections, including opportunistic infections (e.g., Pneumocystis jirovecii, TB); monitor and treat promptly.","Increased serum creatinine and proteinuria may occur; monitor renal function.","Angioedema, including life-threatening cases, can occur, especially in patients taking ACE inhibitors.","Stomatitis and mouth ulcers are common; manage with topical treatments and dose modification.","Impaired wound healing; use with caution perioperatively.","Increased risk of bleeding, especially in patients with renal angiomyolipoma and TSC.","Fetal harm can occur; advise effective contraception during treatment."] |
| Food/Dietary |
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| Fetal Monitoring |
| Monitor maternal complete blood count, serum glucose, lipid profile, renal function, and hepatic function. Fetal ultrasound for growth, amniotic fluid volume, and anatomy. Assess for signs of infections due to immunosuppression. |
| Fertility Effects | May impair fertility in females based on animal studies showing disruption of estrous cycles and ovarian follicular development. Reversibility unknown. Male fertility may be affected due to potential testicular toxicity. |
| Avoid grapefruit, grapefruit juice, and Seville oranges due to CYP3A4 inhibition. Avoid high-fat meals, as they reduce absorption; take on empty stomach or with light fat-free meal. St. John's wort reduces everolimus levels and should be avoided. |
| Clinical Pearls | AFINITOR DISPERZ (everolimus) is an mTOR inhibitor; tablets for oral suspension are not interchangeable with regular tablets due to different pharmacokinetics. Monitor for non-infectious pneumonitis, rash, stomatitis, metabolic effects (hyperglycemia, hyperlipidemia), and renal impairment. Dose adjustments required for hepatic impairment and concurrent strong CYP3A4/P-gp inhibitors or inducers. Avoid live vaccines during treatment. |
| Patient Advice | Take exactly as prescribed; do not crush or chew tablets for oral suspension. · Mix dose with water only, do not mix with juice or other liquids. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Report any new or worsening shortness of breath, cough, or chest pain immediately. · Use effective non-hormonal contraception during and for 8 weeks after last dose. · Avoid live vaccines and close contact with recently vaccinated individuals. · Monitor for mouth sores; use alcohol-free mouthwash and soft toothbrush. · Do not take St. John's wort or strong CYP3A4/P-gp inhibitors/inducers without consulting doctor. |