Temsirolimus: uses, dosing, side effects & brands

The following serious adverse reactions have been associated with TORISEL in clinical trials and are discussed in greater detail in other sections of the label [see Warnings and Precautions (5) ] . • Hypersensitivity/Infusion Reactions [see Warnings and Precautions (5.1) ] • Hepatic Impairment [see Warnings and Precautions (5.2) ] • Hyperglycemia/Glucose Intolerance [see Warnings and Precautions (5.3) ] • Infections [see Warnings and Precautions (5.4) ] • Interstitial Lung Disease [see Warnings and Precautions (5.5) ] • Hyperlipidemia [see Warnings and Precautions (5.6) ] • Bowel Perforation [see Warnings and Precautions (5.7) ] • Renal Failure [see Warnings and Precautions (5.8) ] • Wound Healing Complications [see Warnings and Precautions (5.9) ] • Intracerebral Hemorrhage [see Warnings and Precautions (5.10) ] The most common (≥30%) adverse reactions observed with TORISEL are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common (≥30%) laboratory abnormalities observed with TORISEL are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, lymphopenia, elevated alkaline phosphatase, elevated serum creatinine, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia. The most common adverse reactions (incidence ≥30%) are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities (incidence ≥30%) are…

TORISEL is contraindicated in patients with bilirubin >1.5×ULN [see Warnings and Precautions (5.2) ] . TORISEL is contraindicated in patients with bilirubin > 1.5×ULN. ( 4 )

Strong inducers of CYP3A4/5 and inhibitors of CYP3A4 may affect concentrations of the primary metabolite of TORISEL. If alternatives cannot be used, dose modifications of TORISEL are recommended. ( 7.1 , 7.2 , 7.3 ) 7.1 Agents Inducing CYP3A Metabolism Co-administration of TORISEL with rifampin, a potent CYP3A4/5 inducer, had no significant effect on temsirolimus C max (maximum concentration) and AUC (area under the concentration versus the time curve) after intravenous administration, but decreased sirolimus C max by 65% and AUC by 56% compared to TORISEL treatment alone. If alternative treatment cannot be administered, a dose adjustment should be considered [see Dosage and Administration (2.4) ] . 7.2 Agents Inhibiting CYP3A Metabolism Co-administration of TORISEL with ketoconazole, a potent CYP3A4 inhibitor, had no significant effect on temsirolimus C max or AUC; however, sirolimus AUC increased 3.1-fold, and C max increased 2.2-fold compared to TORISEL alone. If alternative treatment cannot be administered, a dose adjustment should be considered [see Dosage and Administration (2.4) ] . 7.3 Angioedema with ACE inhibitors and Calcium Channel Blockers Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with ramipril and/or amlodipine. Monitor patients for signs and symptoms of angioedema when temsirolimus is given concomitantly with angiotensin converting enzyme (ACE) inhibitors (e.g., ramipril) or calcium channel blockers (CCB) (e.g., amlodipine). Drug Interactions Effect of Temsirolimus on CYP2D6 or CYP3A The concentration of desipramine, a CYP2D6 substrate, was unaffected when 25 mg of temsirolimus was co-administered. No clinically significant effect is anticipated when 25 mg of temsirolimus is co-administered with agents that are metabolized by CYP2D6 or CYP3A.