TEMSIROLIMUS
Clinical safety rating: avoid
Contraindicated (not allowed)
Temsirolimus is a specific inhibitor of mTOR (mammalian target of rapamycin) kinase. It binds to FKBP-12, and the Temsirolimus-FKBP-12 complex binds to and inhibits mTOR, thereby blocking the translation of cell cycle regulatory proteins (e.g., cyclin D1, c-myc) and hypoxia-inducible factor (HIF) subunits, leading to cell cycle arrest in G1 phase and antiangiogenic effects.
| Metabolism | Primarily metabolized by CYP3A4 to its active metabolite sirolimus; both temsirolimus and sirolimus undergo further metabolism via CYP3A4 and are substrates of P-glycoprotein. |
| Excretion | Primarily via feces (78%) and urine (4.6%) after IV administration; unchanged drug is minimal, with metabolites abundant. |
| Half-life | 17.3 hours in patients with advanced solid tumors; range 9-27 hours. Renal impairment (CrCl <30 mL/min) may prolong half-life. No dose adjustment needed for mild-moderate hepatic impairment. |
| Protein binding | 99.5% bound to albumin and alpha-1-acid glycoprotein, with minimal binding to lipoproteins. |
| Volume of Distribution | 172 L (approximately 2.4 L/kg for a 70 kg patient); indicates extensive tissue distribution, with highest concentrations in liver, spleen, and kidney. |
| Bioavailability | Not applicable (IV only); oral bioavailability is <10% due to extensive first-pass metabolism. |
| Onset of Action | Peak sirolimus concentrations occur within 5-10 minutes after IV infusion; inhibition of mTOR signaling occurs within hours. |
| Duration of Action | Duration of mTOR inhibition lasts approximately 24-48 hours after single dose; weekly dosing maintains therapeutic effect. |
25 mg intravenously over 30-60 minutes once weekly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment; not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: 25 mg IV weekly; Child-Pugh B: reduce to 15 mg IV weekly; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; monitor for increased toxicity in patients >65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause hyperglycemia and interstitial lung disease.
| Breastfeeding | No human data on temsirolimus excretion in breast milk. M/P ratio unknown. Due to potential for serious adverse effects in the breastfed infant (immunosuppression, growth impairment), breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Temsirolimus is an mTOR inhibitor with teratogenic potential. Based on animal studies and its mechanism of action, there is a risk of fetal harm if used during pregnancy. First trimester exposure may increase the risk of congenital malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and potential renal or pulmonary effects due to disruption of normal fetal development. Adequate contraception is recommended during therapy. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Rash |
| Serious Effects |
["Severe hypersensitivity to temsirolimus, sirolimus, or any components of the formulation"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis) - premedicate with antihistamines","Increased risk of infections, including opportunistic infections","Interstitial lung disease (ILD) - monitor for new or worsening pulmonary symptoms","Renal failure - monitor renal function","Bowel perforation - discontinue if occurs","Hyperglycemia, hyperlipidemia, and hypertriglyceridemia - monitor blood glucose and lipids","Immunosuppression - avoid live vaccines","Hemorrhagic events - monitor for bleeding","Wound healing complications - temporarily discontinue perioperatively","Pregnancy - can cause fetal harm"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, renal function, liver function, and blood glucose levels due to risk of hypertension, proteinuria, hepatotoxicity, and hyperglycemia. Fetal surveillance includes serial ultrasound for growth and amniotic fluid volume assessment. Monitor for oligohydramnios if used in second or third trimester. |
| Fertility Effects | Temsirolimus may impair fertility in both males and females. In animal studies, it caused decreased spermatogenesis and ovarian atrophy. Reversible or irreversible infertility may occur. Patients should be counseled on potential impact on future fertility. |