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Temsirolimus: Drug information

Temsirolimus: Drug information
(For additional information see "Temsirolimus: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Torisel
Brand Names: Canada
  • Torisel
Pharmacologic Category
  • Antineoplastic Agent, mTOR Kinase Inhibitor
Dosing: Adult

Note: For infusion reaction prophylaxis, premedicate with an H1 antagonist (eg, diphenhydramine 25 to 50 mg IV) ~30 minutes prior to infusion.

Endometrial cancer (locally advanced, recurrent, and/or metastatic) (off-label use): IV: 25 mg once weekly; continue until disease progression or unacceptable toxicity (Oza 2011).

Renal cell cancer (RCC), advanced: IV: 25 mg once weekly; continue until disease progression or unacceptable toxicity

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild hepatic impairment (bilirubin >1 to 1.5 x ULN or AST >ULN with bilirubin ≤ULN): Reduce dose to 15 mg once weekly and use with caution.

Moderate-to-severe hepatic impairment (bilirubin >1.5 x ULN): Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity: ANC <1,000/mm3 or platelets <75,000/mm3: Withhold treatment until resolves and reinitiate treatment with the dose reduced by 5 mg weekly; minimum dose: 15 mg weekly if adjustment for toxicity is needed.

Nonhematologic toxicity: Any toxicity ≥grade 3: Withhold treatment until resolves to ≤grade 2; reinitiate treatment with the dose reduced by 5 mg weekly; minimum dose: 15 mg weekly if adjustment for toxicity is needed.

Infusion/hypersensitivity reaction: Interrupt infusion and observe for 30 to 60 minutes (depending on the severity); treatment may be resumed with discretion at a slower infusion rate (up to 60 minutes); administer an H1 antagonist (if not given as premedication) and/or an IV H2 antagonist ~30 minutes prior to resuming infusion.

Interstitial lung disease: Consider withholding treatment for clinically significant respiratory symptoms until after recovery of symptoms or radiographic improvement.

Nephrotic syndrome: Discontinue treatment.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Torisel: 25 mg/mL (1 mL) [contains alcohol, usp, polyethylene glycol, polysorbate 80, propylene glycol]

Generic: 25 mg/mL (1 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Torisel: 25 mg/mL (1.2 mL) [contains alcohol, usp, polyethylene glycol, polysorbate 80, propylene glycol]

Administration: Adult

IV: Infuse over 30 to 60 minutes via an infusion pump (preferred). Use polyethylene-lined non-DEHP, non-PVC administration tubing (if PVC-containing administration set must be used, it should not contain DEHP). Administer through an inline polyethersulfone filter ≤5 micron; if set does not contain an inline filter, a polyethersulfone end filter (0.2 to 5 micron) should be added (do not use both an inline and an end filter).

Premedicate with an H1 antagonist (eg, diphenhydramine 25 to 50 mg IV) ~30 minutes prior to infusion. Monitor during infusion; interrupt infusion for hypersensitivity/infusion reaction; monitor for 30 to 60 minutes; may reinitiate at a reduced infusion rate (over 60 minutes) with discretion, 30 minutes after administration of a histamine H1 antagonist and/or a histamine H2 antagonist (eg, famotidine). Administration should be completed within 6 hours of admixture.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Renal cell carcinoma, advanced: Treatment of advanced renal cell carcinoma (RCC)

Use: Off-Label: Adult

Endometrial cancer (locally advanced, recurrent, and/or metastatic)

Medication Safety Issues
Sound-alike/look-alike issues:

Temsirolimus may be confused with everolimus, sirolimus (conventional), sirolimus (protein bound), tacrolimus, temozolomide, tesamorelin

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

Temsirolimus requires a two-step dilution process prior to administration. The medication is supplied in a vial containing a total amount of 30 mg in a total volume of 1.2 mL (25 mg/mL). The vial must initially be diluted to 10 mg/mL (with provided 1.8 mL of diluent), then the intended dose should be withdrawn from the 10 mg/mL diluted vial (ie, 2.5 mL for a 25 mg dose) and further diluted for infusion in 250 mL sodium chloride 0.9%. Errors have occurred due to improper preparation.

Temsirolimus, for the treatment of advanced renal cell cancer, is a flat dose (25 mg if no dosage reductions) and is not based on body surface area (BSA).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Edema (35%), chest pain (16%)

Central nervous system: Pain (28%), headache (15%), insomnia (12%)

Dermatologic: Skin rash (47%), pruritus (19%), nail disease (14%), xeroderma (11%)

Endocrine & metabolic: Increased serum glucose (89%; grades 3/4: 16%), increased serum cholesterol (87%; grades 3/4: 2%), hypertriglyceridemia (83%; grades 3/4: 44%), hypophosphatemia (49%; grades 3/4: 18%), hyperglycemia (26%), hyperlipidemia (≥30%), hypokalemia (21%; grades 3/4: 5%), weight loss (19%)

Gastrointestinal: Mucositis (41%), nausea (37%), anorexia (32%), diarrhea (27%), abdominal pain (21%; grades 3/4: 4%), constipation (20%), dysgeusia (20%), stomatitis (20%), vomiting (19%)

Genitourinary: Urinary tract infection (15%)

Hematologic & oncologic: Decreased hemoglobin (94%; grades 3/4: 20%), lymphocytopenia (53%; grades 3/4: 16%), thrombocytopenia (40%; grades 3/4: 1%; dose-limiting toxicity), decreased white blood cell count (32%; grades 3/4: 1%), anemia (≥30%), decreased neutrophils (19%; grades 3/4: 5%)

Hepatic: Increased serum alkaline phosphatase (68%; grades 3/4: 3%), increased serum AST (38%; grades 3/4: 2%)

Infection: Infection (20%; grades 3/4: 3%; includes abscess, bronchitis, cellulitis, herpes simplex, herpes zoster)

Neuromuscular & skeletal: Weakness (51%), back pain (20%), arthralgia (18%)

Renal: Increased serum creatinine (57%; grades 3/4: 3%)

Respiratory: Dyspnea (28%), cough (26%), epistaxis (12%), pharyngitis (12%)

Miscellaneous: Fever (24%; grades 3/4: 1%)

1% to 10%:

Cardiovascular: Hypertension (7%), venous thromboembolism (2%; includes deep vein thrombosis and pulmonary embolism), pericardial effusion (1%), thrombophlebitis (1%)

Central nervous system: Chills (8%), depression (4%), convulsions (1%)

Dermatologic: Acne vulgaris (10%)

Endocrine & metabolic: Diabetes mellitus (5%)

Gastrointestinal: Gastrointestinal hemorrhage (1%)

Hematologic & oncologic: Rectal hemorrhage (1%)

Hepatic: Hyperbilirubinemia (8%)

Infection: Sepsis (1%), wound infection (1%)

Neuromuscular & skeletal: Myalgia (8%)

Ophthalmic: Conjunctivitis (8%; including lacrimation disorder)

Respiratory: Rhinitis (10%), pneumonia (8%), upper respiratory tract infection (7%), pleural effusion (4%)

Miscellaneous: Wound healing impairment (1%)

<1%, postmarketing, and/or case reports: Acute renal failure, angioedema, causalgia, cholecystitis, cholelithiasis, decreased glucose tolerance, extravasation reactions (with pain, swelling, warmth, erythema), hypersensitivity reaction, interstitial pulmonary disease, intestinal perforation, pancreatitis, pneumonitis, rhabdomyolysis, seizure, Stevens-Johnson syndrome

Contraindications

Bilirubin >1.5 times the upper limit of normal (ULN)

Canadian labeling: Additional contraindications (not in the US labeling): History of anaphylaxis after exposure to temsirolimus, sirolimus, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Angioedema has been reported in patients taking mTOR inhibitors in combination with ramipril and/or amlodipine; monitor for signs/symptoms of angioedema in patients receiving temsirolimus concurrently with ACE inhibitors or calcium channel blockers.

• Bone marrow suppression: Anemia, neutropenia, thrombocytopenia, and lymphocytopenia may commonly occur; grades 3 and 4 hematologic toxicity have been observed.

• Bowel perforation: Cases of bowel perforation (fatal) have occurred, usually presenting with abdominal pain, bloody stools, diarrhea, fever, or metabolic acidosis; promptly evaluate any new or worsening abdominal pain or bloody stools.

• Hyperglycemia: Increases in serum glucose commonly occur during treatment. Initiation or alteration of insulin and/or oral hypoglycemic therapy may be required. Monitor serum glucose before and during treatment. Use with caution in patients with diabetes.

• Hyperlipidemia: Use with caution in patients with hyperlipidemia; may increase serum lipids (cholesterol and triglycerides). Initiation or dosage adjustment of antihyperlipidemic agents may be required. Monitor cholesterol/triglyceride panel at baseline and periodically during treatment.

• Hypersensitivity/infusion reactions: Hypersensitivity/infusion reactions (eg, anaphylaxis, apnea, dyspnea, flushing, loss of consciousness, hypotension, and/or chest pain) have been reported. Infusion reaction may occur during the initial infusion (early in the infusion) or with subsequent infusions. Premedicate with an antihistamine (H1 antagonist) prior to infusion (use with caution in patients unable to receive antihistamine premedication); monitor throughout infusion (appropriate supportive care should be available); interrupt infusion for hypersensitivity reaction and observe patient for 30 to 60 minutes. With discretion, treatment may be resumed at a slower infusion rate; administer an H1 antagonist (if not given as premedication) and/or an IV H2 antagonist (eg, famotidine) ~30 minutes prior to resuming infusion. For severe infusion reactions, assess risk versus benefit of continued treatment. Use with caution in patients with hypersensitivity to temsirolimus, sirolimus (a metabolite), or polysorbate 80.

• Infection: Treatment may result in immunosuppression, may increase risk of opportunistic infections and/or sepsis. Pneumocystis jirovecii pneumonia (PCP) has been reported; some cases were fatal. Development of PCP may be associated with the use of concomitant corticosteroids or other immunosuppressive agents; consider PCP prophylaxis in patients receiving concomitant immunosuppressive or corticosteroid therapy.

• Proteinuria: Proteinuria, including nephrotic syndrome, is associated with temsirolimus. Monitor for proteinuria at baseline and periodically throughout therapy; discontinue use if nephrotic syndrome occurs.

• Pulmonary toxicity: Interstitial lung disease (ILD), sometimes fatal, has been reported; symptoms include dyspnea, cough, hypoxia and/or fever, although asymptomatic or mild cases may present; promptly evaluate worsening respiratory symptoms. If symptoms develop, consider withholding temsirolimus until symptom recovery and radiographic improvement occur. Consider empiric treatment with corticosteroids and/or antibiotic therapy. Baseline chest radiographic assessment (CT scan or x-ray) is recommended; follow periodically, even in the absence of clinical pulmonary symptoms.

• Renal failure: Acute renal failure with rapid progression (unrelated to disease progression) has been reported, including cases unresponsive to dialysis. An increased incidence of rash, infection and dose interruptions have been reported in patients with renal insufficiency (CrCl ≤60 mL/minute) who received mTOR inhibitors for the treatment of renal cell cancer (Gupta, 2011).

• Wound healing: May be associated with impaired wound healing; use caution in the perioperative period.

Disease-related concerns:

• CNS metastases/tumors: May be at increased risk for developing intracerebral bleeding (may be fatal).

• Hepatic impairment: Use with caution and reduce the dose in patients with mild hepatic impairment (bilirubin >1 to 1.5 x ULN or AST >ULN with bilirubin ≤ULN). Use is contraindicated in patients with moderate-to-severe hepatic impairment (bilirubin >1.5 x ULN). Temsirolimus is predominantly cleared by the liver. Toxicities were increased in patients with baseline bilirubin >1.5 x ULN.

Concurrent drug therapy issues:

• Anticoagulants: Patients who are receiving anticoagulant therapy may be at increased risk for developing intracerebral bleeding (may be fatal).

• Drug-drug interactions: Avoid concomitant use with strong CYP3A4 inhibitors and strong CYP3A4 inducers; consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.

• Sunitinib: Combination therapy with temsirolimus and sunitinib has resulted in dose-limiting toxicities, including grade 3 or 4 rash, gout, and/or cellulitis.

Special populations:

• Older adult: Older adult patients may be more likely to experience adverse reactions, including diarrhea, edema, and pneumonia.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer's labeling.

Other warnings/precautions:

• Immunizations: Patients should not be immunized with live viral vaccines during or shortly after treatment and should avoid close contact with recently vaccinated (live vaccine) individuals.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Angiotensin-Converting Enzyme Inhibitors: Temsirolimus may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA vaccine at least 28 days after the primary vaccine dose. Patients should also receive 2 booster doses of mRNA vaccine - one 2 months after the 2nd (additional) dose and another 4 months after the first booster dose. Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series, and a booster dose 3 months after the 3rd dose in the primary series, to patients taking immunosuppressive medications. Patients 12 years of age and older should also receive a 2nd booster 4 months after the first booster. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CycloSPORINE (Systemic): Temsirolimus may enhance the adverse/toxic effect of CycloSPORINE (Systemic). An increased risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy (HUS/TTP/TMA) has been described with concomitant sirolimus use. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

DexAMETHasone (Systemic): May decrease serum concentrations of the active metabolite(s) of Temsirolimus. Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Rifabutin: May decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Rifabutin may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

SUNItinib: Temsirolimus may enhance the adverse/toxic effect of SUNItinib. Risk X: Avoid combination

Tacrolimus (Systemic): Temsirolimus may enhance the adverse/toxic effect of Tacrolimus (Systemic). Tacrolimus (Systemic) may enhance the adverse/toxic effect of Temsirolimus. Temsirolimus may decrease the serum concentration of Tacrolimus (Systemic). Temsirolimus may increase the serum concentration of Tacrolimus (Systemic). Risk X: Avoid combination

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Grapefruit and grapefruit juice may increase the levels/effects of sirolimus. Management: Avoid grapefruit and grapefruit juice.

Reproductive Considerations

Females of reproductive potential should be advised to avoid pregnancy and use effective contraception during treatment and for 3 months after the last temsirolimus dose. Male patients with female partners of reproductive potential should also use effective birth control during treatment and for 3 months after the last temsirolimus dose.

Pregnancy Considerations

Based on findings in animal reproduction studies and on the mechanism of action, temsirolimus may cause fetal harm if administered to a pregnant woman.

Breastfeeding Considerations

It is not known if temsirolimus is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 3 weeks following the last temsirolimus dose.

Dietary Considerations

Avoid grapefruit juice (may increase the levels of the major metabolite, sirolimus).

Monitoring Parameters

CBC with differential and platelets (weekly), serum chemistries including glucose (baseline and every other week), serum cholesterol and triglycerides (baseline and periodic), liver function (baseline and periodic), renal function tests (baseline and periodic), urine protein (baseline and periodic).

Monitor for infusion reactions; monitor for signs/symptoms of infection, interstitial lung disease (or radiographic changes), hyperglycemia (excessive thirst, polyuria), bowel perforation, nephrotic syndrome, angioedema (if receiving ACE inhibitors or calcium channel blockers).

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Temsirolimus and its active metabolite, sirolimus, are targeted inhibitors of mTOR (mechanistic target of rapamycin) kinase activity. Temsirolimus (and sirolimus) bind to FKBP-12, an intracellular protein, to form a complex which inhibits mTOR signaling, halting the cell cycle at the G1 phase in tumor cells. Inhibition of mTOR blocks downstream phosphorylation of p70S6k and S6 ribosomal proteins. In renal cell carcinoma, mTOR inhibition also exhibits anti-angiogenesis activity by reducing levels of HIF-1 and HIF-2 alpha (hypoxia inducible factors) and vascular endothelial growth factor (VEGF).

Pharmacokinetics

Distribution: Vdss: 172 L

Metabolism: Hepatic; via CYP3A4 to sirolimus (primary active metabolite) and 4 minor metabolites

Half-life elimination: Temsirolimus: ~17 hours; Sirolimus: ~55 hours

Time to peak, plasma: Temsirolimus: At end of infusion; Sirolimus: 0.5 to 2 hours after temsirolimus infusion

Excretion: Feces (78%); urine (<5%)

Pricing: US

Solution (Temsirolimus Intravenous)

25 mg/mL (per mL): $1,416.00 - $1,910.95

Solution (Torisel Intravenous)

25 mg/mL (per mL): $2,219.50

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Torisel (AE, AR, AT, AU, BB, BE, BH, BR, CH, CL, CO, CY, CZ, DE, DK, EE, EG, ES, FR, GB, HK, HR, IE, IL, IS, IT, KR, KW, LT, LU, LV, MT, MY, NL, NO, PH, PL, PT, RO, SA, SE, SG, SI, SK, TH, TR, TW);
  • Torisell (CR, DO, GT, HN, NI, PA, SV)


For country abbreviations used in Lexicomp (show table)
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
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  3. Appleby L, Morrissey S, Bellmunt J, et al, “Management of Treatment-Related Toxicity With Targeted Therapies for Renal Cell Carcinoma: Evidence-Based Practice and Best Practices,” Hematol Oncol Clin North Am, 2011, 25(4):893-915. [PubMed 21763973]
  4. Atkins MB, Hidalgo M, Stadler WM, et al, “Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell Carcinoma,” J Clin Oncol, 2004, 22(5): 909-18. [PubMed 14990647]
  5. Bellmunt J, Szczylik C, Feingold J, et al, “Temsirolimus Safety Profile and Management of Toxic Effects in Patients With Advanced Renal Cell Carcinoma and Poor Prognostic Features,” Ann Oncol, 2008, 19(8):1387-92. [PubMed 18385198]
  6. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm [PubMed 6423951]
  7. Dutcher JP, de Souza P, McDermott D, et al, “Effect of Temsirolimus Versus Interferon-Alpha on Outcome of Patients With Advanced Renal Cell Carcinoma of Different Tumor Histologies,” Med Oncol, 2009, 26(2):202-9. [PubMed 19229667]
  8. Gupta S, Parsa VB, Heilbrun LK, et al, “Safety and Efficacy of Molecularly Targeted Agents in Patients With Metastatic Kidney Cancer With Renal Dysfunction,” Anticancer Drugs, 2011, 22(8):794-800. [PubMed 21799472]
  9. Hadoux J, Vignot S, and De La Motte Rouge T, “Renal Cell Carcinoma: Focus on Safety and Efficacy of Temsirolimus,” Clin Med Insights Oncol, 2010, 4:143-54. [PubMed 21234295]
  10. Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27(23):3822-3829. [PubMed 19581539]
  11. Hidalgo M, Buckner JC, Erlichman C, et al, “A Phase I and Pharmacokinetics Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients With Advanced Cancer,” Clin Cancer Res, 2006, 12(19):5755-63. [PubMed 17020981]
  12. Hudes G, Carducci M, Tomczak P, et al, “Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma,” N Engl J Med, 2007, 356(22):2271-81. [PubMed 17538086]
  13. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  14. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  15. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  16. Maroto JP, Hudes G, Dutcher JP, et al, “Drug-Related Pneumonitis in Patients With Advanced Renal Cell Carcinoma Treated With Temsirolimus,” J Clin Oncol, 2011, 29(13):1750-6. [PubMed 21444868]
  17. Oza AM, Elit L, Tsao MS, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011;29(24):3278-3285. [PubMed 21788564]
  18. Raymond E, Alexandre J, Faivre S, et al, “Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer,” J Clin Oncol, 2004, 22(12): 2336-47. [PubMed 15136596]
  19. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  20. Torisel (temsirolimus) [prescribing information]. Philadelphia, PA: Pfizer Inc; March 2018.
  21. Torisel (temsirolimus) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; December 2016.
  22. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
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