TORISEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TORISEL (TORISEL).
Temsirolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), forms a complex with FKBP-12, which binds to and inhibits mTOR kinase activity, thereby blocking signaling pathways involved in cell growth, proliferation, and angiogenesis.
| Metabolism | Primarily hepatic via CYP3A4; sirolimus is a major active metabolite. |
| Excretion | Primarily fecal (78%), with renal elimination accounting for 4.6% of the administered dose. Less than 5% of the dose is excreted unchanged in urine or feces. |
| Half-life | Terminal elimination half-life of temsirolimus is approximately 17.3 hours (range: 11 to 26 hours). For its active metabolite sirolimus, half-life is about 15 hours (range: 10 to 30 hours). Steady-state is reached within 1 week. |
| Protein binding | Temsirolimus is approximately 88% bound to plasma proteins (mainly albumin and alpha-1-acid glycoprotein). The active metabolite sirolimus is about 97% bound. |
| Volume of Distribution | Central volume of distribution is approximately 172 L (non-weight-adjusted), with extensive tissue distribution. Volume of distribution at steady state for temsirolimus is large (mean 66 L), indicating extensive extravascular distribution. |
| Bioavailability | Not applicable for intravenous administration; intravenously administered, hence bioavailability is 100%. |
| Onset of Action | Clinical effects observed within 2 to 4 weeks after starting weekly intravenous infusion. |
| Duration of Action | Duration of action is approximately 1 week due to weekly dosing schedule. Effects persist with continued administration; response is typically evaluated after 2 months of therapy. |
25 mg intravenously over 30-60 minutes once weekly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment is required for renal impairment. However, caution is advised in patients with severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | For patients with mild hepatic impairment (Child-Pugh class A), reduce dose to 15 mg intravenously once weekly. For moderate hepatic impairment (Child-Pugh class B), reduce dose to 10 mg intravenously once weekly. Severe hepatic impairment (Child-Pugh class C) is not recommended. |
| Pediatric use | The safety and efficacy in pediatric patients have not been established. Use is not recommended. |
| Geriatric use | No specific dose adjustment is required based on age alone. However, elderly patients (≥65 years) may have higher incidence of adverse events (e.g., infections, dyspnea) and should be monitored closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TORISEL (TORISEL).
| Breastfeeding | No data on temsirolimus in human breast milk. M/P ratio is unknown. In lactating rats, temsirolimus and its metabolite are excreted in milk. Because of potential for serious adverse reactions in breastfed infants (e.g., immunosuppression, growth delay), breastfeeding is not recommended during treatment and for at least 3 weeks after last dose. |
| Teratogenic Risk | TORISEL (temsirolimus) is an mTOR inhibitor. Animal studies have shown embryo-fetal toxicity including increased resorption, reduced fetal weights, and skeletal abnormalities. There are no adequate human studies. Based on mechanism and animal data, there is a teratogenic risk throughout pregnancy. First trimester exposure carries risk of major malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and impaired renal function. Use is contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to temsirolimus or its metabolites","Concomitant use with strong CYP3A4 inducers or inhibitors requires caution"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Increased risk of infections","Interstitial lung disease","Renal failure","Bowel perforation","Wound healing complications","Metabolic complications (hyperglycemia, hyperlipidemia)","Immunosuppression-related risks","Pregnancy category D"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, urine protein), liver function tests, serum glucose, and lipid profile. Perform pregnancy test before initiation and periodically during treatment. Fetal monitoring includes serial ultrasound for growth restriction, amniotic fluid volume, and placental abnormalities. Monitor for signs of infection. |
| Fertility Effects | Temsirolimus may impair fertility in males and females based on animal studies. In rats, ovarian and testicular degeneration occurred. Human data are lacking; potential for reduced spermatogenesis and menstrual cycle disruption. |