temsirolimus

Absorption: IV administration results in complete bioavailability.

Distribution: Temsirolimus and sirolimus partition extensively in formed blood elements.

Metabolism/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 ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	1 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Hypersensitivity to temsirolimus, sirolimus or polysorbate 80;
Perioperative patients (may impair wound healing);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: risk for adverse reactions in older adults (especially diarrhea, edema, and pneumonia).

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypertension, venous thromboembolism

Derm: rash, abnormal wound healing

EENT: conjunctivitis

Endo: hyperglycemia

F and E: edema, hypophosphatemia

GI: ↑liver enzymes, anorexia, diarrhea, mucositis, nausea, BOWEL PERFORATION

GU: nephrotic syndrome, proteinuria, RENAL FAILURE

Hemat: anemia, leukopenia, lymphopenia, thrombocytopenia

Metab: hyperlipidemia, hypertriglyceridemia

Neuro: weakness

Resp: INTERSTITIAL LUNG DISEASE

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of strong CYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, clarithromycin, atazanavir, nelfinavir, ritonavir, ↑ levels and risk of toxicity; avoid concurrent use; if need to use CYP3A4 inhibitor, consider ↓ dose of temsirolimus.
Concurrent use of strong strong CYP3A4 inducers , including dexamethasone, phenytoin, phenobarbital, carbamazepine, rifampinor rifabutin may ↓ levels and effectiveness; avoid concurrent use; if need to use CYP3A4 inducer, consider ↑ dose of temsirolimus.
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.
↑risk of angioedema when used with ACE inhibitors or calcium channel blockers.

Drug-Natural Products:

St. John's wort may ↓ blood levels; avoid concurrent use.

Grapefruit juice may ↑ blood levels and ↑ risk of toxicity.

Route/Dosage ⬆ ⬇

IV (Adults ): 25 mg once weekly. Concurrent use of strong CYP3A4 inhibitor: 12.5 mg once weekly. Concurrent use of strong CYP3A4 inducer: 50 mg once weekly.

Availability ⬆ ⬇

(Generic available)

Solution for injection: 25 mg/mL (comes with a diluent containing polysorbate 80, polyethylene glycol 400 and dehydrated alcohol)

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) 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 creatinine, and total bilirubin. May cause ↓ serum phosphorous and potassium.
- Monitor urine protein before starting and periodically during therapy. If nephrotic syndrome occurs, discontinue temsirolimus.

Implementation ⬆ ⬇

Premedicate with IV diphenhydramine 25–50 mg (or similar antihistamine) 30 min before start of each dose of temsirolimus.

IV 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 ⬆ ⬇

Explain purpose of temsirolimus to patient.
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), or signs and symptoms of hypersensitivity reactions or infection 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.
Rep: May be teratogenic. Advise female patients of reproductive potential and male patient with partners of reproductive potential to use effective contraception during and for 3 mo after last dose of therapy. Advise females to avoid breastfeeding during and for 3 wks after last dose. May cause male and female infertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇