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Temsirolimus (Torisel) - Complete Drug Information

Temsirolimus and its active metabolite, sirolimus, interrupt the cellular signaling pathway in the tumor cells by inhibiting of mTOR (mechanistic target of rapamycin) kinase activity. Temsirolimus (and sirolimus) binds 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.

It is used to treat the following conditions:

Renal cell carcinoma, advanced:
- It is used in the treatment of advanced renal cell carcinoma (RCC)
Off Label Use of Temsirolimus in Adults:
- It is used in the treatment of endometrial cancer (locally advanced, recurrent, and/or metastatic)

Temsirolimus dose in Adults

For infusion reaction prophylaxis, premedicate with an H-1 antagonist (eg, diphenhydramine 25 to 50 mg IV) almost 30 minutes before infusion.

Dose in the treatment of advanced Renal cell cancer (RCC):

25 mg once weekly is given
continue until disease progression or unacceptable toxicity occurs
Dosage adjustment for concomitant CYP3A4 inhibitors/inducers:
- CYP3A4 inhibitors:
  - Avoid prescribing along with strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, telithromycin, nefazodone, protease inhibitors voriconazole)
  - if concomitant administration with a strong CYP3A4 inhibitor cannot be avoided, then reduce dose to 12.5 mg once weekly.
  - When a strong CYP3A4 inhibitor is stopped; allow ~1 week to elapse prior to adjusting the temsirolimus upward to the dose used before initiation of the CYP3A4 inhibitor.
- CYP3A4 inducers:
  - Concomitant use with strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, rifabutin, rifampin, phenobarbital, and phenytoin) should be avoided.
  - if concomitant administration with a strong CYP3A4 inducer cannot be avoided, then adjust temsirolimus dose up to 50 mg once weekly.
  - If the strong CYP3A4 enzyme inducer is stopped, reduce the temsirolimus to the dose used prior to initiation of the CYP3A4 inducer.

Dosage in the treatment of recurrent, metastatic, or locally advanced endometrial cancer:

25 mg intravenously once weekly is given
continue until disease progression or unacceptable toxicity occurs.

Temsirolimus Dose in Childrens

Not recommended for use in children

Temsirolimus (Torisel) pregnancy Risk Factor: D

If administered to a pregnant lady, it may cause fetal harm.
Reproductively-competent females are advised not to get pregnant and to use effective contraception for the duration of treatment and 3 months following the last dose of temsirolimus.
Effective birth control is recommended for male patients who have female partners with reproductive potential.
This advice applies to treatment as well as for the 3 months following the last dose of temsirolimus.

Use of Temsirolimus during breastfeeding

It is unknown if breast milk contains temsirolimus.
The manufacturer does not recommend breastfeeding during therapy or for three weeks after the last dose of temsirolimus

Temsirolimus (Torisel) dose in Renal disease:

No dosage adjustment required.

Hemodialysis:

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

Temsirolimus (Torisel) dose in Liver disease:

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

Common Side Effects of Temsirolimus (Torisel) Include:

Cardiovascular:
- Edema
- Chest Pain
Central Nervous System:
- Pain
- Headache
- Insomnia
Dermatologic:
- Skin Rash
- Pruritus
- Nail Disease
- Xeroderma
Endocrine & Metabolic:
- Increased Serum Glucose
- Increased Serum Cholesterol
- Hypertriglyceridemia
- Hypophosphatemia
- Hyperglycemia
- Hyperlipidemia
- Hypokalemia
- Weight Loss
Gastrointestinal:
- Mucositis
- Nausea
- Anorexia
- Diarrhea
- Abdominal Pain
- Constipation
- Dysgeusia
- Stomatitis
- Vomiting
Genitourinary:
- Urinary Tract Infection
Hematologic & Oncologic:
- Decreased Hemoglobin
- Lymphocytopenia
- Thrombocytopenia
- Decreased White Blood Cell Count
- Anemia
- Decreased Neutrophils
Hepatic:
- Increased Serum Alkaline Phosphatase
- Increased Serum AST
Infection:
- Infection
Neuromuscular & Skeletal:
- Weakness
- Back Pain
- Arthralgia
Renal:
- Increased Serum Creatinine
Respiratory:
- Dyspnea
- Cough
- Epistaxis
- Pharyngitis
Miscellaneous:
- Fever

Less Common Side Effects of Temsirolimus (Torisel) Include:

Cardiovascular:
- Hypertension
- Venous Thromboembolism
- Pericardial Effusion
- Thrombophlebitis
Central Nervous System:
- Chills
- Depression
- Convulsions
Dermatologic:
- Acne Vulgaris
Endocrine & Metabolic:
- Diabetes Mellitus
Gastrointestinal:
- Gastrointestinal Hemorrhage
Hematologic & Oncologic:
- Rectal Hemorrhage
Hepatic:
- Hyperbilirubinemia
Infection:
- Sepsis
- Wound Infection
Neuromuscular & Skeletal:
- Myalgia
Ophthalmic:
- Conjunctivitis
Respiratory:
- Rhinitis
- Pneumonia
- Upper Respiratory Tract Infection
- Pleural Effusion
Miscellaneous:
- Wound Healing Impairment

Contraindication to Temsirolimus Include:

Bilirubin >1.5x the upper limit of normal
History of anaphylaxis following exposure to sirolimus or temsirolimus or any portion of the formulation

Warnings and precautions

Angioedema
- Patients who have taken mTOR inhibitors along with ramipril or amlodipine have experienced angioedema.
- Monitor patients who are taking temsirolimus in combination with ACE inhibitors and calcium channel blockers for signs/symptoms that could indicate angioedema.
Suppression of bone marrow
- Anemia, neutropenia and thrombocytopenia are all possible.
- Grades 3 and 4 of hematologic toxicities are common.
Perforation of the Bowel
- There have been fatal cases of bowel perforation. These symptoms include abdominal pain, bloody stool, diarrhea, fever and metabolic acidosis.
- If you feel any abdominal pain, bloody stool or other symptoms, it is important to immediately seek medical attention.
Hyperglycemia
- During treatment, you will notice an increase in serum glucose.
- It might be necessary to initiate or modify insulin therapy and/or oral hypoglycemic treatment.
- Monitor your serum glucose during and after treatment.
- Patients with diabetes should be cautious.
Hyperlipidemia
- Patients with hyperlipidemia should be cautious.
- Increased serum lipids (cholesterol, triglycerides) may be possible.
- It might be necessary to initiate or adjust the dosage of antihyperlipidemic agent.
- At baseline, evaluate the cholesterol/triglyceride panel and every other month during treatment.
Hypersensitivity/infusion reactions
- Reports of hypersensitivity/infusion reactions, such as flushing, loss consciousness, hypotension, anaphylaxis and/or chest pain, have been made.
- Infusion reaction can occur either during the initial infusion (early on the infusion), or during subsequent infusions.
- Infusions should be made with antihistamines (H-1 antagonists) prior to use. Patients who are unable or unwilling to take antihistamine premedication must be supervised.
- Monitor throughout the infusion. You should have appropriate supportive care.
- Keep patient still for hypersensitivity reactions and do not infuse.
- You can resume treatment at a slower rate if you are able to do so.
- If H-1 antagonist is not being given as premedication, administer an IV H-2 antagonist (eg famotidine ) within 30 minutes of resuming infusion.
- Patients with severe infusion reactions should weigh the risks and benefits of continuing treatment.
- Patients with hypersensitivity to sirolimus (a metabolite), temsirolimus (a metabolite), and polysorbate 80 should be cautious.
Infection
- The treatment can lead to immunosuppression which may increase the chance of opportunistic infection and/or sepsis.
- Some cases of pneumocystis pneumonia jirovecii (PCP), have been reported.
- Concomitant use of corticosteroids and other immunosuppressive drugs may lead to the development of PCP
- Consider PCP prophylaxis for patients who are receiving concomitant immunosuppressive therapy or corticosteroid therapy.
Proteinuria
- With temsirolimus, proteinuria can be seen, as well as nephrotic syndrome.
- Monitor proteinuria at baseline, and every so often throughout therapy
- If you develop nephrotic syndrome, stop using the medication.
Toxicity in the lungs:
- Sometimes fatal, interstitial lung disease (ILD) has been diagnosed.
- Dyspnea, fever, cough, hypoxia, and/or other symptoms may be present. However, mild or asymptomatic cases are possible.
- Assess any worsening symptoms of respiratory problems immediately
- Consider stopping temsirolimus if you experience symptoms. This will allow for radiographic improvement and symptom recovery.
- Consider empiric treatment using corticosteroids or antibiotic therapy.
- Baseline radiographic chest assessment (CT scan, x-ray) takes place
- Keep checking even if you don't have any clinical symptoms.
Failure of the renal system:
- There have been cases of acute renal failure that has rapidly progressed (unrelated to the progression of disease) and patients who were not responsive to dialysis.
- Patients with renal impairment (CrCl =60mL/minute) have seen an increase in rash, infection, and dose interruptions after receiving mTOR inhibitors to treat renal cell carcinoma (Gupta 2011, 2011).
Wound healing
- It can cause impaired wound healing. Be cautious during the postoperative period.
CNS metastases/tumors
- You may be at greater risk of developing intracerebral hemorhage (may even be fatal).
Hepatic impairment
- Patients with mild hepatic impairment (bilirubin greater than 1 to 1.5x ULN, AST greater than ULN) should be cautious and reduced in dose.
- Patients with moderate-to-severe liver impairment (bilirubin >1.5x ULN) are not advised to use this medication.

Temsirolimus: Drug Interaction

Risk Factor C (Monitor therapy)
Angiotensin-Converting Enzyme Inhibitors	Temsirolimus may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Dexamethasone (Systemic)	May decrease serum concentrations of the active metabolite(s) of Temsirolimus.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
CarBAMazepine	May decrease the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are also likely to be decreased (and maybe to an even greater degree). Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as carbamazepine; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered.
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.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Temsirolimus. Management: Consider increasing the dose of temsirolimus to 50 mg IV/week (from 25 mg IV/week) if a concomitant CYP3A4 strong inducer is necessary.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors whenever possible. If combined, decrease temsirolimus dose to 12.5 mg per week and monitor patients for increased temsirolimus effects and toxicities.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
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.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Fluconazole	May increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to fluconazole. Monitor sirolimus concentrations in all patients receiving fluconazole or any systemic azole antifungal.
Fosphenytoin	May decrease the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are also likely to be decreased (and maybe to an even greater degree). Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as phenytoin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered.
Ketoconazole (Systemic)	May increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Temsirolimus dose adjustments will likely be needed when starting/stopping/changing ketoconazole. Clinical data suggest temsirolimus (adult) dose reductions of around 50% should be considered, but specific guidelines are lacking.
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Phenytoin	May decrease the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are also likely to be decreased (and maybe to an even greater degree). Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as phenytoin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered.
Posaconazole	May increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to posaconazole. Monitor sirolimus concentrations in all patients receiving posaconazole or any systemic azole antifungal.
Protease Inhibitors	May enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.
Rifamycin Derivatives	May decrease the serum concentration of Temsirolimus. Rifamycins will likely cause an even greater decrease in the concentration of the active metabolite sirolimus. Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as rifampin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Grapefruit Juice	May increase the serum concentration of Temsirolimus.
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Itraconazole	May increase serum concentrations of the active metabolite(s) of Temsirolimus.
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
SUNItinib	Temsirolimus may enhance the adverse/toxic effect of SUNItinib.
Tacrolimus (Systemic)	May enhance the adverse/toxic effect of Temsirolimus. Temsirolimus may enhance the adverse/toxic effect of Tacrolimus (Systemic). Temsirolimus may decrease the serum concentration of Tacrolimus (Systemic).
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Temsirolimus. Temsirolimus may enhance the adverse/toxic effect of Tacrolimus (Topical).
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitor:

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 following :
infusion reactions
signs/symptoms of infection
interstitial lung disease (or radiographic changes)
hyperglycemia (excessive thirst, polyuria)
bowel perforation
nephrotic syndrome
angioedema in patients receiving ACE inhibitors or calcium channel blockers)

How to administer Temsirolimus (Torisel)?

Use an infusion pump to infuse intravenously for between 30 and 60 minutes
Use non-PVC, polyethylene-lined nonDEHP administration tubing. If PVC-containing administration sets must be used, they should not contain DEHP.
Use an inline polyethersulfone filtre =5 micron
If the set doesn't have an inline filter, you should add a polyethersulfone filter end filter (0.2-2.5 micron).
Do not combine an inline filter with an end filter
Before infusion, premedicate with an H-1 inhibitor (eg diphenhydramine 25-50 mg IV) for at least 30 minutes.
During infusion, monitor
Withhold infusion to prevent hypersensitivity/infusion reaction
Monitor for between 30 and 60 minutes
You may resume infusion at a lower rate (over 60 mins) at your discretion after 30 minutes of administration of a histamine antagonist and/or histamine 2 antagonist (eg famotidine, ranitidine).
Administration should be completed within six hours of the admixture.

Mechanism of action of Temsirolimus (Torisel):

Temsirolimus (and its active metabolite sirolimus) interrupts the cellular signaling pathway of tumor cells by inducing mTOR (mechanistic Target of Rapamycin) kinase activation.
Temsirolimus and sirolimus bind to FKBP-12, an intracellular proteins, to form a complex that inhibits mTOR signaling. This stops the cell cycle from the G1 phase in cancer cells.
The inhibition of mTOR prevents downstream phosphorylation for p70S6k or S6 ribosomal protein phosphatases.
mTOR inhibition is also effective in renal cell carcinoma by reducing HIF-1 and HIF-2 beta (hypoxia-inducible factor) levels and vascular endothelial grow factor (VEGF).

Distribution: V :