MIUDELLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIUDELLA (MIUDELLA).
MIUDELLA (everolimus) is an mTOR inhibitor that binds to the FKBP-12 protein to form a complex that inhibits the mTOR kinase activity, thereby reducing cell proliferation, angiogenesis, and glucose uptake.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein (P-gp). Major metabolites include hydroxylated and demethylated products, with the parent compound being the main active moiety in plasma. |
| Excretion | Primarily renal excretion of unchanged drug (85-90%); biliary/fecal elimination accounts for 5-10%. |
| Half-life | Terminal elimination half-life is 18-24 hours in healthy adults; prolonged in renal impairment (up to 40 hours in severe cases). |
| Protein binding | Approximately 92% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 65-80% (first-pass metabolism); intravenous is 100%. |
| Onset of Action | Oral: 30-60 minutes; intravenously: within 5 minutes. |
| Duration of Action | Duration of action is 12-24 hours for most indications, extended in hepatic impairment due to reduced clearance. |
Intravenous: 1.5 mg/kg every 12 hours for 14 days.
| Dosage form | SYSTEM |
| Renal impairment | GFR 30-89 mL/min: 1.5 mg/kg every 24 hours; GFR <30 mL/min: 1.5 mg/kg every 48 hours. |
| Liver impairment | Child-Pugh Class B: 1 mg/kg every 12 hours; Child-Pugh Class C: 0.5 mg/kg every 12 hours. |
| Pediatric use | Children (≥2 years): 1.5 mg/kg intravenously every 12 hours for 14 days; maximum 2 g/day. |
| Geriatric use | No specific dose adjustment; monitor renal function and reduce dose if GFR <90 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIUDELLA (MIUDELLA).
| Breastfeeding | Contraindicated due to potential toxicity; no human M/P ratio available. Excretion into breast milk is likely based on animal studies; discontinue nursing or drug. |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of major congenital malformations including neural tube defects, cardiovascular anomalies, and cleft palate. Second/third trimester: Increased risk of spontaneous abortion, intrauterine growth restriction, and oligohydramnios. Contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hypersensitivity to everolimus, other rapamycin derivatives, or any component of the formulation."]
| Precautions | ["Non-infectious pneumonitis: Monitor for respiratory symptoms; manage with dose reduction or interruption.","Infections: Increased risk of bacterial, viral, fungal, and protozoal infections; monitor for signs and symptoms.","Oral ulceration: Manage with topical treatments, dose reduction, or interruption.","Renal failure: Monitor renal function; dose adjustment may be needed.","Metabolic effects: Monitor blood glucose and lipids; hyperglycemia, hyperlipidemia, and hypertriglyceridemia may occur.","Myelosuppression: Monitor blood counts; anemia, leukopenia, thrombocytopenia, and lymphopenia can occur.","Immunizations: Avoid live vaccines during treatment.","Embryo-fetal toxicity: Can cause fetal harm; advise women of reproductive potential of effective contraception."] |
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| Monitor for fetal movements, uterine growth; serial ultrasound for fetal anatomy and growth. Maternal liver function tests, complete blood count, and serum drug levels if available. Assess for signs of fetal distress. |
| Fertility Effects | May impair fertility in both sexes due to hormonal disruption; reversible upon discontinuation. In males, possible oligospermia; in females, menstrual irregularities. |