Temsirolimus

Advanced renal cell carcinoma:
Patients taking strong CYP3A4 inhibitors: Avoid use with strong CYP3A4 inhibitors. If concomitant use cannot be avoided, consider reducing the dose to 12.5 mg once weekly. The usual recommended dose may be resumed 1 week after the discontinuation of strong CYP3A4 inhibitors.

Patients taking strong CYP3A4 inducers: Avoid use with strong CYP3A4 inhibitors. If concomitant use cannot be avoided, consider reducing the dose to 50 mg once a week. The usual recommended dose may be resumed 1 week after the discontinuation of strong CYP3A4 inhibitors.

Advanced renal cell carcinoma:
Mild (bilirubin >1-1.5 x ULN or AST >ULN with bilirubin ≤ULN): Reduce dose to 15 mg once weekly. Moderate to severe (bilirubin >1.5 x ULN): Contraindicated. Recommendations on dosage adjustment in this population may vary between countries (refer to country-specific product guidelines).

Mantle cell lymphoma:
Moderate to severe: Contraindicated.

IV infusion: Dilute vial labelled as 25 mg/mL with 1.8 mL of provided diluent to make a final concentration of 10 mg/mL. Withdraw the required dose and further dilute in an infusion bag containing 250 mL of NaCl 0.9% solution. Gently invert to mix completely. Do not shake.

Hypersensitivity to temsirolimus or sirolimus. Moderate to severe hepatic impairment. Concomitant administration of live vaccines.

Patient with diabetes mellitus, hyperlipidaemia, primary CNS metastases or tumours, risk factors for skin cancer. Patients taking strong CYP3A4 inhibitors or inducers. Perioperative period. Severe renal and mild hepatic impairment. Pregnancy and lactation.

Significant: Bone marrow suppression (e.g. anaemia, neutropenia, thrombocytopenia, lymphocytopenia), hyperglycaemia or glucose intolerance, increased serum cholesterol and triglycerides; proteinuria including nephrotic syndrome; impaired wound healing, development of lymphoma and other malignancies of the skin.
Blood and lymphatic system disorders: Leucopenia, lymphopenia.
Cardiac disorders: Chest pain.
Eye disorders: Conjunctivitis.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, stomatitis, constipation, abdominal pain, gastrointestinal haemorrhage, gastritis, dysphagia, abdominal distention, aphthous stomatitis, oral pain.
General disorders and administration site conditions: Fatigue, oedema, asthenia, pyrexia, mucosal inflammation, pain, chills.
Investigations: Increased serum creatinine, AST.
Metabolism and nutrition disorders: Decreased appetite, hypocalcaemia, hypophosphataemia, hypokalaemia, dehydration.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain.
Nervous system disorders: Headache, dizziness, paraesthesia, somnolence, dysgeusia, ageusia.
Psychiatric disorders: Insomnia, depression, anxiety.
Renal and urinary disorders: UTI including cystitis.
Respiratory, thoracic and mediastinal disorders: Epistaxis, cough, pleural effusion, URTI, pharyngitis, rhinitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, dry skin, acne, nail disorder, acne.
Vascular disorders: Venous thromboembolism, thrombophlebitis, hypertension.
Potentially Fatal: Bowel perforation, interstitial lung disease (ILD), intracerebral bleeding, renal failure, infections including opportunistic infections and/or sepsis (e.g. Pneumocystis jirovecii pneumonia), hypersensitivity or infusion reactions (e.g. anaphylaxis, apnoea, dyspnoea, flushing, hypotension, chest pain, loss of consciousness).

IV/Parenteral: D

Women of childbearing potential and men with female partners of reproductive potential must use proven birth control methods during and 3 months after treatment. Discontinue breastfeeding during treatment and for 3 weeks after the last dose. Avoid excessive exposure to sunlight or artificial UV light, consider applying sunscreen or wearing protective clothing when going outdoors. Avoid close contact with those patients who have received live vaccines.

Evaluate pregnancy status in women of childbearing potential before treatment initiation. Monitor CBC with differential, platelets; blood glucose, blood cholesterol and triglycerides, LFTs and renal function, urine protein (at baseline and periodically thereafter). Perform radiographic assessment at baseline and periodically thereafter even in the absence of symptoms. Monitor for signs and symptoms of hyperglycaemia (e.g. excessive thirst, polyuria), hypersensitivity and infusion reactions, infection, ILD or radiographic changes, bowel perforation (new or worsening abdominal pain or bloody stools), nephrotic syndrome; angioedema (in patients taking concurrent ACE inhibitors or Ca channel blockers).

Increased risk of angioneurotic oedema with ACE inhibitors (e.g. ramipril) and/or Ca channel blockers (e.g. amlodipine). Increased risk of dose-limiting toxicities with sunitinib. Increased risk of cataracts with interferon-α. Increased serum concentrations with moderate CYP3A4 inhibitors (e.g. aprepitant, erythromycin, fluconazole, verapamil) and strong CYP3A4 inhibitors including protease inhibitors (e.g. nelfinavir, ritonavir), antifungals (e.g. itraconazole, ketoconazole, voriconazole), nefazodone, and P-glycoprotein inhibitors. Decreased serum concentrations with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin).
Potentially Fatal: May diminish the therapeutic effect of live vaccines. Increased risk of intracerebral bleeding with anticoagulant treatment.

Increased plasma concentration of sirolimus (active metabolite) with grapefruit and grapefruit juice. Decreased plasma concentration with St. John's wort.

Description:
Mechanism of Action: Temsirolimus, a selective mammalian target of rapamycin (mTOR) kinase inhibitor, is an antineoplastic agent. It binds with high affinity to intracellular protein (FKBP-12) to form a drug-protein complex which inhibits mTOR signalling. This inhibition suppresses proteins that regulate cell-cycle progression, thereby causing an interruption in the cell cycle at the G1 phase in tumour cells. In renal cell carcinoma, mTOR inhibition also has anti-angiogenic effects by lowering hypoxia inducible factors 1α and 2α (HIF-1α and HIF-2α) and vascular endothelial growth factor.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: At end of infusion (temsirolimus); 0.5-2 hours after infusion (sirolimus).
Metabolism: Metabolised in the liver mainly by CYP3A4 isoenzymes into sirolimus (active metabolite) and 4 minor metabolites.
Excretion: Mainly via faeces (78%); urine (approx 5%). Elimination half-life: 17.3 hours (temsirolimus); 54.6 hours (sirolimus).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6918289, Temsirolimus. https://pubchem.ncbi.nlm.nih.gov/compound/Torisel. Accessed Feb. 25, 2025.

Intact vial: Store between 2-8°C. Do not freeze. Protect from light. Diluted solution in the vial: Stable for 24 hours at room temperature (<25°C). Diluted solution for infusion: Infuse solution within 6 hours of preparation. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling administration, and disposal.

Targeted Cancer Therapy

L01EG01 - temsirolimus ; Belongs to the class of mammalian target of rapamycin (mTOR) kinase inhibitors. Used in the treatment of cancer.

Anon. Temsirolimus. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/12/2024.

Brayfield A, Cadart C (eds). Temsirolimus. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/12/2024.

Joint Formulary Committee. Temsirolimus. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/12/2024.

Temsirolimus (Accord Healthcare Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/12/2024.

Temsirolimus. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/12/2024.

Torisel 30 mg Concentrate and Solvent for Solution for Infusion (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 05/12/2024.