temsirolimus


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temsirolimus

(tem-si-ro-li-mus) ,

Torisel

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

Advanced renal cell carcinoma.

Action

Binds to an intracellular protein. The resultant complex inhibits an enzyme, mTOR (mammalian target of rapamycin). Inhibition of this enzyme arrests cell growth in the G1 phase.

Therapeutic effects

Decreased spread of renal cell carcinoma.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Temsirolimus and sirolimus partition extensively in formed blood elements.
Metabolism and Excretion: Mostly metabolized by the liver to sirolimus, an active metabolite Primarily eliminated in feces.
Half-life: Temsirolimus—17.3 hr; sirolimus—54.6 hr.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownend of infusion1 wk

Contraindications/Precautions

Contraindicated in: Obstetric / Lactation: Pregnancy and lactation.
Use Cautiously in: Hypersensitivity to temsirolimus, sirolimus or polysorbate 80; Perioperative patients (may impair wound healing); Geriatric: ↑ risk for adverse reactions (especially diarrhea, edema, and pneumonia); Obstetric: Patients which child-bearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • weakness (most frequent)

Ear, Eye, Nose, Throat

  • conjunctivitis

Cardiovascular

  • edema (most frequent)
  • hypertension
  • venous thromboembolism

Respiratory

  • interstitial lung disease (life-threatening)

Gastrointestinal

  • bowel perforation (life-threatening)
  • anorexia (most frequent)
  • diarrhea (most frequent)
  • ↑ liver enzymes (most frequent)
  • mucositis (most frequent)
  • nausea (most frequent)

Genitourinary

  • renal failure (life-threatening)

Dermatologic

  • rash (most frequent)
  • abnormal wound healing

Endocrinologic

  • hyperglycemia (most frequent)

Fluid and Electrolyte

  • edema (most frequent)
  • hypophosphatemia (most frequent)

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • lymphopenia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • hyperlipidemia (most frequent)
  • hypertriglyceridemia (most frequent)

Miscellaneous

  • hypersensitivity reactions including anaphylaxis
  • ↑ risk of infections

Interactions

Drug-Drug interaction

Concurrent use of strong CYP3A4 enzyme inhibitors including ketoconazole, itraconozole, voriconazole, clarithromycin, telithromycin, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir ↑ blood levels and ↑ risk of toxicity; consider ↓ dose to 12.5 mg weekly.Concurrent use of strong inducers of the CYP 3A4 enzyme system including dexamethasone, phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin or rifampacin may ↓ blood levels and ↓ efficacy; consider ↑ dose to 50 mg weekly.Concurrent use with sunitinib ↑ risk of toxicity (rash, gout, cellulitis).May ↓ antibody response to and ↑ risk of adverse reactions from live virus vaccines ; avoid current use.St. John's wort may ↓ blood levels; avoid concurrent use.Grapefruit juice may ↑ blood levels and ↑ risk of toxicity.

Route/Dosage

Intravenous (Adults) 25 mg once weekly; dose modification is required for bone marrow toxicity or concurrent use of agents affecting the CYP 3A4 enzyme system (pre-treatment with antihistamine is recommended).

Availability

Concentrated solution for IV infusion (must be diluted): 25 mg/mL (comes with a diluent containing polysorbate 80, polyethylene glycol 400 and dehydrated alcohol)

Nursing implications

Nursing assessment

  • Assess for signs of hypersensitivity reactions (anaphylaxis, dyspnea, flushing, chest pain) during administration. If reaction occurs, stop infusion and observe patient for at least 30–60 min. May resume treatment with administration of an antihistamine (if not previously administered) and/or an H2 antagonist (such as IV famotidine 20 mg or IV ranitidine 50 mg) 30 min before restarting temsirolimus. Infuse at a slower rate over 60 min.
  • Monitor for signs of infection, including opportunistic infection (sore throat; appearance of sputum, urine, stool; vital signs) during therapy.
  • Monitor for signs of interstitial lung disease (dyspnea, cough, hypoxia, fever). CAT scan or chest x-ray should be done prior to and periodically during therapy to monitor lung status. If clinically significant symptoms occur, discontinuation of therapy and/or treatment with corticosteroids and/or antibiotics may be required.
  • Lab Test Considerations: Monitor CBC and platelet count prior to and during therapy. May cause ↓ ANC and platelets. Hold dose if ANC <1000/mm3, platelet count <75,000/mm3, or adverse reactions grade 3 or greater. Once toxicities have resolved to grade 2 or less, may restart temsirolimus at a dose decreased by 5 mg/wk to a dose no lower than 15 mg/wk. May cause ↓hemoglobin, lymphocytes, and leukocytes.
    • Monitor serum glucose prior to and periodically during therapy. May cause ↑ serum glucose requiring increase in dose of or initiation of insulin or oral hypoglycemia agent therapy.
    • Monitor serum cholesterol and triglycerides prior to and during therapy. May cause increase requiring initiation or increase in dose of lipid lowering agents.
    • Monitor liver enzymes prior to and during therapy. May cause ↑ AST, alkaline phosphatase, serum creatine, and total bilirubin. May cause ↓ serum phosphorous and potassium.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Premedicate with IV diphenhydramine 25–50 mg (or similar antihistamine) 30 min before start of each dose of temsirolimus.
  • Intravenous Administration
  • Diluent: Inject 1.8 mL of diluent for Torisel into temsirolimus vial for a concentration of 10 mg/mL. Concentration: Vial contains an overfill and total volume will be 3 mL of 10 mg/mL solution. Mix well by inversion of vial. Allow sufficient time for air bubbles to subside. Solution should be clear to slightly turbid, colorless to yellow, and free from visual particles. Store undiluted solution in refrigerator and protect from light during storage and preparation. Diluted solution is stable for 24 hr at room temperature. Withdraw required amount of temsirolimus 10 mg/mL solution and inject rapidly into 250 mL container (glass, polyolefin, or polyethylene) of 0.9% NaCl. Mix by inversion; avoid excessive shaking to prevent foaming. Administer with non-DEHP (di-(2–ethylhexyl) phthalate tubing and an in-line filter with pore size of not >5 microns.
  • Rate: Administer over 30–60 min using an infusion pump to ensure accurate delivery. Complete infusion within 6 hrs of mixture with 0.9% NaCl.
  • Y-Site Incompatibility: Do not mix in solution or administer via Y-site with other solutions or medications.

Patient/Family Teaching

  • Advise patient to notify health care professional immediately if any new or worsening abdominal pain or blood in stools occur or if signs of bowel perforation (fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea) occur.
  • Advise patient to avoid drinking grapefruit juice while taking temsirolimus.
  • Advise patients to notify health care professional if excessive thirst or volume or frequency of urination and diabetic patients to closely monitor glucose.
  • Inform patient of the increased risk for intracerebral bleeding with temsirolimus.
  • Advise patient to consult health care professional prior to taking any Rx, OTC, or herbal products, especially St. John's Wort.
  • Instruct patient not to receive any vaccinations without advice of health care professional and to avoid contact with persons who have received live vaccines during therapy.
  • Advise female patients to avoid becoming pregnant during and for 3 mo after therapy. Men with partners of child-bearing potential should use reliable contraception throughout therapy and for 3 mo after last dose of temsirolimus.

Evaluation/Desired Outcomes

  • Decreased spread of renal cell carcinoma.

temsirolimus

A specific inhibitor of the mammalian target of RAPAMYCIN KINASE. It is capable of inhibiting angiogenesis and has been used to treat advanced cases of renal cell carcinoma. It has been found more effective than interferon alpha in prolonging survival.
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