AUKELSO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUKELSO (AUKELSO).
Selective inhibitor of the mammalian target of rapamycin (mTOR) kinase, specifically the mTORC1 complex, leading to inhibition of cell proliferation, angiogenesis, and glucose uptake.
| Metabolism | Primarily metabolized by CYP3A4 |
| Excretion | Primarily hepatic metabolism with biliary excretion; ~20% renal elimination of unchanged drug. Fecal excretion of metabolites accounts for ~65% of total clearance. |
| Half-life | Terminal elimination half-life approximately 24 hours (range 20–28 h), supports once-daily dosing; prolonged in severe hepatic impairment. |
| Protein binding | High protein binding, approximately 99.8%, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution ~0.15 L/kg (range 0.12–0.18 L/kg), indicating limited extravascular distribution, predominantly confined to plasma and extracellular fluid. |
| Bioavailability | Oral bioavailability ~85%; unaffected by food. |
| Onset of Action | Oral: 2–4 hours to measurable therapeutic effect; peak plasma concentration at 6–8 hours. |
| Duration of Action | Duration of action ~24 hours with once-daily dosing due to sustained receptor occupancy; clinical effect persists for duration of therapy. |
400 mg orally twice daily with food.
| Dosage form | INJECTABLE |
| Renal impairment | GFR ≥60 mL/min: no adjustment; GFR 30-59 mL/min: 200 mg twice daily; GFR <30 mL/min: 200 mg once daily; hemodialysis: 200 mg three times weekly after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg twice daily; Child-Pugh C: 200 mg once daily. |
| Pediatric use | Body weight 10-20 kg: 200 mg twice daily; 20-40 kg: 300 mg twice daily; ≥40 kg: 400 mg twice daily. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUKELSO (AUKELSO).
| Breastfeeding | No human data on milk excretion or infant effects. M/P ratio unknown. Due to potential for serious adverse reactions (e.g., immunosuppression), advise against breastfeeding during treatment and for 2 weeks after last dose. |
| Teratogenic Risk | First trimester: Avoid use due to potential for fetal harm based on animal studies showing developmental toxicity (including cardiovascular and skeletal malformations). Second and third trimesters: Use only if maternal benefit outweighs fetal risk; may cause fetal growth restriction or oligohydramnios in off-label experience. No adequate human data. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to everolimus or any component of the formulation"]
| Precautions | ["Non-infectious pneumonitis","Infections (including opportunistic infections)","Hypersensitivity reactions","Renal impairment","Metabolic effects (hyperglycemia, hyperlipidemia)","Interstitial lung disease","Hemorrhagic events","Wound healing complications","Immunosuppression","Increased risk of thrombosis"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice; may increase drug levels. Take with or without food, but high-fat meals may increase absorption. Avoid alcohol due to hepatotoxicity risk. |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, urine protein), and liver enzymes monthly. Serial fetal ultrasound for growth and amniotic fluid volume every 4 weeks starting at 20 weeks. If oligohydramnios develops, consider dose reduction or discontinuation. |
| Fertility Effects | Based on animal studies, may impair female fertility (disrupted estrous cycle, reduced ovulation) and male fertility (decreased sperm count and motility). Human effects unknown; advise fertility counseling if planning pregnancy. |
| Clinical Pearls |
| Monitor for QT prolongation, electrolyte abnormalities, and hepatotoxicity. Adjust dose in renal impairment (CrCl <30 mL/min). Avoid use with strong CYP3A4 inhibitors or inducers. Note potential for phototoxicity; advise sun avoidance. |
| Patient Advice | Take exactly as prescribed; do not change dose or stop without consulting doctor. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during therapy and for 1 month after last dose. · Report symptoms like irregular heartbeat, fainting, severe nausea/vomiting, or yellowing of skin/eyes immediately. · Use sunscreen and protective clothing; avoid sun exposure, even through glass. |