temsirolimus

Contraindicated in:

Bilirubin >1.5 times upper limit of normal (ULN);
OB: Pregnancy;
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, DEEP VEIN THROMBOSIS, hypertension

Derm: rash, abnormal wound healing

EENT: conjunctivitis

Endo: hyperglycemia

F and E: 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 (ILD), PULMONARY EMBOLISM

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, clarithromycin, atazanavir, nelfinavir, and ritonavir, may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use unavoidable, consider ↓ temsirolimus dose.
Strong CYP3A4 inducers, including dexamethasone, phenytoin, phenobarbital, carbamazepine, rifampin, and rifabutin, may ↓ levels and effectiveness; avoid concurrent use; if concurrent use unavoidable, consider ↑ temsirolimus dose.
Sunitinib may ↑ 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 ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and ↑ risk of toxicity.

Availability ⬆ ⬇

(Generic available)

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

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.

Hepatic Impairment

IV (Adults ): Mild hepatic impairment (bilirubin >1–1.5 times ULN or AST >ULN with bilirubin <ULN): 15 mg once weekly.

US Brand Names ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors, kinase inhibitors

Pharmacokinetics ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of temsirolimus to patient. Do not stop receiving drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes. .
Emphasize the importance of follow-up examination to monitor progress and side effects.
Instruct patient to immediately report signs and symptoms of a hypersensitivity or infusion reaction, including swelling of face, lips, tongue, or throat; wheezing; difficulty breathing; flushing; and chest pain.
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 notify health care professional immediately of symptoms of lung problems such as difficulty breathing, cough, fever.
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. Advise patients with diabetes to closely monitor glucose.
Inform patient of the ↑ 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 cause fetal harm. Advise women of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose of therapy. Advise women to avoid breastfeeding during therapy and for 3 wk after last dose. May cause male and female infertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇