Drug information of Temsirolimus

Temsirolimus


Temsirolimus is used to treat kidney cancer.

Mechanism of effect

Temsirolimus and its active metabolite, sirolimus, are targeted inhibitors of mTOR (mechanistic target of rapamycin) kinase activity. Temsirolimus (and sirolimus) bind to FKBP-12, an intracellular protein, to form a complex which inhibits mTOR signaling, halting the cell cycle at the G1 phase in tumor cells. Inhibition of mTOR blocks downstream phosphorylation of p70S6k and S6 ribosomal proteins. In renal cell carcinoma, mTOR inhibition also exhibits anti-angiogenesis activity by reducing levels of HIF-1 and HIF-2 alpha (hypoxia inducible factors) and vascular endothelial growth factor (VEGF).

Pharmacodynamic

Storage
Store intact vials at 2°C to 8°C (36°F to 46°F). Diluted solution in the vial (10 mg/mL) is stable for 24 hours at room temperature (below 25°C [77°F]). Solutions diluted for infusion (in NS) must be infused within 6 hours of preparation. Protect from light during storage, preparation, and handling.
Metabolism
Hepatic; via CYP3A4 to sirolimus (primary active metabolite) and 4 minor metabolites
Excretion
Feces (78%); urine (<5%)
Time to Peak
Temsirolimus: At end of infusion; Sirolimus: 0.5 to 2 hours after temsirolimus infusion
Half life
Temsirolimus: ~17 hours; Sirolimus: ~55 hours

Drug indications

Renal cell carcinoma, advanced: Treatment of advanced renal cell carcinoma (RCC)

Dosage

Usual Adult Dose for Renal Cell Carcinoma
25 mg IV infusion over a 30 to 60 minute period once a week
Duration of therapy: Treat until disease progression or unacceptable toxicity

Drug contraindications

Patients should not be immunized with live viral vaccines during or shortly after treatment and should avoid close contact with recently vaccinated (live vaccine) individuals

Side effects

>10%:
Cardiovascular: Edema, chest pain
Central nervous system: Pain, headache, insomnia
Dermatologic: Skin rash, pruritus, nail disease, xeroderma
Endocrine & metabolic: Increased serum glucose, increased serum cholesterol, hypertriglyceridemia, hypophosphatemia, hyperglycemia, hyperlipidemia, hypokalemia, weight loss
Gastrointestinal: Mucositis, nausea, anorexia, diarrhea, abdominal pain, constipation, dysgeusia, stomatitis, vomiting
Genitourinary: Urinary tract infection
Hematologic & oncologic: Decreased hemoglobin, lymphocytopenia, thrombocytopenia, decreased white blood cell count, anemia, decreased neutrophils
Hepatic: Increased serum alkaline phosphatase, increased serum AST
Infection: Infection (includes abscess, bronchitis, cellulitis, herpes simplex, herpes zoster)
Neuromuscular & skeletal: Weakness, back pain, arthralgia
Renal: Increased serum creatinine
Respiratory: Dyspnea, cough, epistaxis, pharyngitis
Miscellaneous: Fever
1%
 to 10%
Cardiovascular: Hypertension, venous thromboembolism (includes deep vein thrombosis and pulmonary embolism), pericardial effusion, thrombophlebitis
Central nervous system: Chills, depression, convulsions
Dermatologic: Acne vulgaris
Endocrine & metabolic: Diabetes mellitus
Gastrointestinal: Gastrointestinal hemorrhage
Hematologic & oncologic: Rectal hemorrhage
Hepatic: Hyperbilirubinemia
Infection: Sepsis, wound infection
Neuromuscular & skeletal: Myalgia
Ophthalmic: Conjunctivitis (including lacrimation disorder)
Respiratory: Rhinitis, pneumonia, upper respiratory tract infection, pleural effusion
Miscellaneous: Wound healing impairment

Angiotensin-Converting Enzyme Inhibitors, Antidiabetic Agents, Aprepitant, Baricitinib,
BCG (Intravesical), BCG (Intravesical), CarBAMazepine, Chloramphenicol (Ophthalmic),
Cladribine, Clofazimine, CloZAPine, Coccidioides immitis Skin Test, Conivaptan, CycloSPORINE (Systemic), CYP3A4 Inducers (Moderate), CYP3A4 Inducers (Strong), CYP3A4 Inhibitors (Moderate), CYP3A4 Inhibitors (Strong), Dabrafenib, Deferasirox, Deferiprone, Denosumab,
DexAMETHasone (Systemic), Dipyrone, Duvelisib, Echinacea, Enzalutamide, Erdafitinib,
Fingolimod, Fluconazole, Fosaprepitant, Fosnetupitant, Fosphenytoin, Fusidic Acid (Systemic),
Grapefruit Juice, Idelalisib, Inebilizumab, Itraconazole, Ivosidenib, Ketoconazole (Systemic),
Larotrectinib, Lasmiditan, Leflunomide, Mesalamine, MiFEPRIStone, Mitotane, Natalizumab,
Netupitant, Nivolumab, Ocrelizumab, Ozanimod, Palbociclib, P-glycoprotein/ABCB1 Inducers,
P-glycoprotein/ABCB1 Inhibitors, Phenytoin, Pidotimod, Pimecrolimus, Posaconazole, Promazine, Ranolazine, Rifamycin Derivatives, Roflumilast, Sarilumab, Siltuximab, Simeprevir,
Siponimod, Sipuleucel-T, Smallpox and Monkeypox Vaccine (Live), Stiripentol, SUNItinib,
Tacrolimus (Systemic), Tacrolimus (Topical), Tertomotide, Tocilizumab, Tofacitinib, Trastuzumab, Upadacitinib, Vaccines (Inactivated), Vaccines (Live)

Alerts

Avoid grapefruit and grapefruit juice

You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly

Call your doctor right away if you have any signs of infection like fever, chills, flu-like signs, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or a wound that will not heal

You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor

Talk with your doctor before getting any vaccines. Use of some vaccines with this medicine (temsirolimus) may either raise the chance of an infection or make the vaccine not work as well

If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar

Check your blood sugar as you have been told by your doctor

This medicine may cause high cholesterol and triglyceride levels

People taking this medicine (temsirolimus) who have brain or nervous system tumors may have a raised chance of bleeding in the brain. The chance may also be raised in people who are taking blood thinners with this medicine (temsirolimus). Sometimes, this may be deadly

Very bad and sometimes deadly holes in the GI (gastrointestinal) tract have happened with this medicine (temsirolimus

Blood clots have happened with this medicine (temsirolimus). Sometimes, these blood clots have been deadly

Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing

Points of recommendation

What do I need to tell my doctor BEFORE I take Temsirolimus
If you have a high bilirubin level or liver problems.
If you are taking sunitinib.
If you take any other drugs (prescription or OTC, natural products, vitamins). There are many drugs that interact with this medicine (temsirolimus), like certain drugs that are used for HIV, infections, or seizures.
If you are taking St. John's wort. Do not take St. John's wort with this medicine (temsirolimus). -This medicine may not work as well.
If you are breast-feeding. Do not breast-feed while you take this medicine (temsirolimus) and for 3 weeks after your last dose

If you are 65 or older, use this medicine (temsirolimus) with care. You could have more side effects

This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child

If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during treatment and for 3 months after your last dose

If you are a man and your sex partner gets pregnant while you take this medicine (temsirolimus) or within 3 months after your last dose, call your doctor right away

Use birth control to prevent pregnancy while taking this medicine (temsirolimus) and for 3 months after the last dose

This medicine may affect how wounds heal. If you have surgery, you may need to stop this medicine (temsirolimus) before surgery. Start taking it again after surgery as you are told by your doctor

Safety and efficacy have not been established in patients younger than 18 years



Pregnancy level

D

Can cause fetal harm when administered to pregnant women based on animal studies and the mechanism of action

Breast feeding warning

Data are not available regarding the presence in human milk, the effects on breastfed infants, or the effects on milk production

Ask a Pharmacist


User's questions
    No comments yet.