Dosing & Uses
Dosage Forms & Strengths
Advanced Renal Cell Carcinoma
Pretreat with antihistamines (eg, diphenhydramine 25-50 mg IV 30 minutes preinfusion)
25 mg IV infusion qWeek until disease progression or unacceptable toxicity
Interrupt if ANC <1000/mm³ and/or platelets <75000/mm³ and/or Grade 3 or higher AE; restart after toxicity is reduced to at least Grade 2 at 5 mg lower dose but no lower than 15 mg
- Avoid strong CYP3A4 inducers if other therapy is availableIf coadministration with strong CYP3A4 inducer required, increase initial dose to 50 mg/week initially; base subsequent doses on serum concentration; reduce dose if strong CYP3A4 inducer is discontinued to that administered prior to initiating CYP3A4 inducer
- Avoid strong CYP3A4 inhibitors; if coadministration with strong CYP3A4 inhibitor required,reduce dose to 12.5 mg/week initially; base subsequent doses on serum concentration; if strong CYP3A4 inhibitor is discontinued; wait 1 week prior to increasing the dose to that administered prior to initiating CYP3A4 inhibitor
- Moderate to severe hepatic impairment (bilirubin >1.5 times ULN): Contraindicated
- Mild hepatic impairment: Reduce dose to 15 mg qweek
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Decreased hemoglobin (94%)
Increased alkaline phosphatase (68%)
Increased serum creatinine (57%)
Decreased lymphocyte count (53%)
Decreased platelet count (40%)
Increased AST/SGOT (38%)
Abdominal pain (21%)
Decreased potassium levels (21%)
Back pain (20%)
Urinary tract infection (15%)
Weight loss (19%)
Decreased neutrophils (19%)
Chest pain (16%)
Nail disorders (14%)
Dry skin (11%)
Hypersensitivity reaction (9%)
Increased total bilirubin (8%)
Interstitial lung disease (2%)
Bowel perforation (1%)
Bilirubin > 1.5 times the upper limit of normal
May increase risks of hypersensitivity reactions; hyperglycemia; hyperlipidemia; intracerebral hemorrhage (CNS tumor and/or on anticoagulants)
To treat hypersensitivity reactions, stop therapy and treat with an antihistamine; therapy may be restarted at physician discretion at a slower rate
Monitor for symptoms or radiographic changes of interstitial lung disease (ILD); if ILD suspected, discontinue therapy, and consider use of corticosteroids and/or antibiotics
Infections may result from immunosuppression
Bowel perforation may occur; evaluate fever, abdominal pain, bloody stools, and/or acute abdomen promptly
Renal failure, sometimes fatal, has occurred; monitor renal function at baseline and while on therapy
Due to abnormal wound healing, use caution in perioperative period
Elderly patients may be more likely to experience certain adverse reactions, including diarrhea, edema and pneumonia
Monitor throughout the infusion and appropriate supportive care should be available; interrupt infusion in all patients with severe infusion reactions and administer medical therapy
Interstitial lung disease reported, some resulting in death; prescribing information recommends baseline radiographic assessment by lung CT or chest radiograph prior to initiation
Avoid pregnancy during and for 3 months post-treatment
Consider dose modification if used concurrently with CYP3A4 inhibitors or inducers
Avoid grapefruit juice
May decrease effects of live vaccinations
Pregnancy & Lactation
Pregnancy Category: D
Lactation: not known whether distributed in breast milk, do not nurse
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Kinase inhibitor, converted to its active metabolite sirolimus that inhibits mTOR (mammalian target of rapamycin) which in turn may reduce activity/levels of several growth factors and kinases
Peak plasma: (25 mg dose) 585 ng/mL
Peak plasma time: At end of infusion (temsirolimus); 0.5-2 hr after infusion (sirolimus)
Vdss: 172 L
Metabolism: Liver; via CYP3A4 to active metabolite sirolimus and several other metabolites
Excretion: Feces (78%); urine (<5%)
Half-life: 17 hr (temsirolimus); 55 hr (sirulimus)
Inject 1.8 mL of supplied diluent to the vial (25 mg/mL). Drug vial contains an overfill of 0.2 mL (30 mg/1.2 mL). So final drug concentration=10 mg/mL for a total volume of 3 mL
Solution should be clear to slightly turbid, colorless to yellow, and free from visual particulates
Diluted solution is stable for up to 24 hr at controlled room temp
Withdraw required amount of drug from the 10 mg/mL drug solution and inject rapidly into a 250 mL NS bag/bottle (glass, polyolefin, or polyethylene)
Mix admixture by inversion of bag or bottle. Avoid excessive shaking as this may cause foaming
Use non-DEHP containers and administration sets only
An in-line polyethersulfone filter with a pore size of not greater than 5 microns is recommended
Infuse over 30-60 min. Use of infusion pump preferred
Administration of final diluted infusion solution should be completed within 6 hr from the time diluted drug solution is added to NS
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
|1||This drug is available at the lowest co-pay. Most commonly, these are generic drugs.|
|2||This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.|
|3||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.|
|4||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|5||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|6||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|NC||NOT COVERED – Drugs that are not covered by the plan.|
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.