sirolimus protein bound

Action and Spectrum

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Pancytopenia (<10%) 

Acute coronary syndrome (<10%) 

Enteritis (<10%) 

Acute kidney injury (AKI) (<10%) 

Grades 3-4; General 

• Dehydration (6%) 
• Vomiting (2.9%) 
• Fatigue (2.9%) 
• Musculoskeletal pain (2.9%) 
• Hemorrhage (2.9%) 
• Abdominal pain (6%) 
• Diarrhea (2.9%) 
• Constipation (2.9%) 
• Edema (2.9%) 
• Hypertension (2.9%) 
• Insomnia (2.9%) 

Grades 3-4; Laboratory abnormalities 

• Increased lipase (6%) 
• Decreased albumin (2.9%) 
• Increased AST/ALT (2.9%) 
• Decreased phosphate (9%) 
• Increased cholesterol (3%) 
• Increased AST/ALT (2.9%) 

>10% 

all grades, General 

• Fatigue (68%) 
• Edema (50%) 
• Diarrhea (47%) 
• Musculoskeletal pain (47%) 
• Cough (35%) 
• Dysgeusia (32%) 
• Headache (29%) 
• Constipation (24%) 
• Hemorrhage (24%) 
• Pneumonitis (18%) 
• Dehydration (15%) 
• Hemorrhoids (12%) 
• Nail disorder (12%) 
• Dyspnea (12%) 
• Stomatitis (79%) 
• Infections (59%) 
• Nausea (50%) 
• Weight decreased (47%) 
• Decrease appetite (44%) 
• Vomiting (32%) 
• Abdominal pain (29%) 
• Hypertension (29%) 
• Pyrexia (24%) 
• Insomnia (21%) 
• Dry mouth (15%) 
• Peripheral neuropathy (15%) 
• Dry skin (12%) 
• Dizziness (12%) 
• Vision blurred (12%) 

all grades, Laboratory abnormalities 

• Increased creatinine (82%) 
• Increased triglycerides (52%) 
• Increased ALT (47%) 
• Decreased magnesium (42%) 
• Decreased neutrophils (35%) 
• Decreased albumin (35%) 
• Increased phosphatase (29%) 
• Decreased calcium (15%) 
• Decreased phosphate (15%) 
• Increased glucose (12%) 
• Decreased lymphocytes (82%) 
• Decreased hemoglobin (68%) 
• Increased cholesterol (48%) 
• Decreased potassium (44%) 
• Decreased leukocytes (41%) 
• Decreased platelets (35%) 
• Increased AST (32%) 
• Decreased sodium (24%) 
• Decreased glucose (15%) 
• Increased lipase (12%) 
• Increased sodium (12%) 

Grades 3-4, General 

• Infections (12%) 
• Stomatitis (18%) 

Grades 3-4, Laboratory abnormalities 

• Decreased potassium (12%) 
• Decreased lymphocytes (21%) 
• Increased glucose (12%) 

Black Box Warning

Black Box Warning: 

There is currently no specific black box warning associated with sirolimus protein bound. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: sirolimus should not be used in individuals who have a known hypersensitivity or allergic reaction to sirolimus or any of its components. 
• Pregnancy: sirolimus may cause harm to the developing fetus. It is contraindicated during pregnancy, and alternative treatment options should be considered. 
• Breastfeeding: It is not recommended to use while using sirolimus, as it may pass into breast milk and harm the nursing infant. 
• Active Infections: sirolimus may suppress the immune system, increasing the risk of infections. It should be used under caution or avoided in individuals with active, severe, or uncontrolled infections.

Caution: 

• Immunosuppression: sirolimus protein-bound may suppress the immune system, increasing the risk of infections. Close monitoring for signs of infection is important, and caution should be exercised in individuals with a history of recurrent or chronic infections. 
• Renal Impairment: sirolimus is primarily metabolized by the kidneys, so caution is advised in individuals with renal impairment. Dose adjustments are necessary in these patients to prevent drug accumulation and potential toxicity. 
• Hepatic Impairment: sirolimus is metabolized in the liver, so caution is recommended in individuals with hepatic impairment. Close monitoring of liver function is important, and dose adjustments may be needed. 
• Hyperlipidemia: sirolimus can cause elevations in cholesterol and triglyceride levels. Individuals with pre-existing hyperlipidemia should be closely monitored, and lipid-lowering therapy may be necessary. 
• Interactions with Other Medications: sirolimus can interact with other medications, including those that affect liver enzymes or have immunosuppressive effects. 

Comorbidities: 

• Renal Dysfunction: sirolimus protein-bound may affect kidney function, and individuals with pre-existing renal impairment or diseases such as chronic kidney disease should be monitored closely. 
• Hepatic Dysfunction: sirolimus protein-bound is metabolized in the liver, so individuals with liver diseases or impaired liver function may require dose adjustments or careful monitoring. 
• Hyperlipidemia: sirolimus protein-bound has been associated with elevated cholesterol and triglyceride levels. Individuals with pre-existing hyperlipidemia or a history of lipid disorders may require monitoring and management of their lipid levels. 
• Diabetes: sirolimus protein-bound may have an impact on glucose metabolism and can increase the risk of hyperglycemia or worsen existing diabetes. Close monitoring of blood glucose levels is important in individuals with diabetes or those at risk of developing diabetes. 
• Infections: sirolimus protein-bound can suppress the immune system, increasing the risk of infections. Individuals with a history of recurrent or chronic infections should be closely monitored and appropriate preventive measures should be taken. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

sirolimus protein-bound, also known as temsirolimus, is a targeted anticancer medication that belongs to a class of drugs called mTOR inhibitors. Its mechanism of action involves inhibiting the activity of mammalian target of rapamycin (mTOR). 

mTOR is a regulator of cell growth, proliferation, and survival. By inhibiting mTOR, sirolimus protein-bound disrupts the signaling pathways involved in cell division and growth, particularly in cancer cells. This interference with mTOR signaling inhibits the translation of messenger RNA (mRNA) into proteins that are necessary for cell cycle progression and cell proliferation.  

Pharmacodynamics: 

• Inhibition of mTOR: sirolimus protein bound disrupts the mTOR signaling pathway, which plays a crucial role in cell growth, proliferation, and survival. By blocking mTOR, sirolimus protein bound inhibits the translation of mRNA into proteins that are necessary for cell cycle progression and cell growth. 
• Suppression of angiogenesis: sirolimus protein bound interferes with angiogenesis that supply nutrients to tumors. It reduces the production of vascular endothelial growth factor (VEGF), a protein that promotes angiogenesis. By suppressing angiogenesis, sirolimus protein bound limits the blood supply to tumors, potentially inhibiting their growth. 
• Induction of apoptosis: sirolimus protein bound can induce programmed cell death. It triggers a cascade of events within cells that ultimately leads to their self-destruction. This apoptotic effect contributes to the elimination of cancer cells and the inhibition of tumor growth. 
• Immunomodulation: sirolimus protein bound can modulate the immune response, particularly by affecting the function of T cells. It may inhibit the activation and proliferation of T cells, which can have both immunosuppressive and antitumor effects. 

Pharmacokinetics: 

Absorption 

sirolimus protein bound is administered intravenously, ensuring complete and rapid absorption into the systemic circulation. 

Distribution 

sirolimus protein bound has a large volume of distribution, indicating extensive tissue distribution. It extensively binds to plasma proteins, mainly albumin and alpha-1 acid glycoprotein. 

Metabolism 

sirolimus protein bound undergoes metabolism in the liver by cytochrome P450 enzyme system, specifically CYP3A4. The major metabolite formed is sirolimus acid, which exhibits similar pharmacological activity to the parent drug. 

Elimination and excretion 

sirolimus protein bound and its metabolites are eliminated through the feces. 

Adminstartion

Administration: 

sirolimus protein bound (temsirolimus) is administered intravenously under the supervision of a healthcare professional. The administration typically involves diluting the medication in a compatible intravenous solution and administering it as a slow infusion over a specific duration prescribed by the healthcare provider.

The infusion rate and duration may vary depending on the specific indication being treated. The administration of sirolimus protein bound should be carried out in a controlled clinical setting equipped to handle any potential infusion-related reactions or adverse effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sirolimus protein bound 

Pronounced: (sih-roh-LYE-mus proh-teen bound)  

Why do we use sirolimus protein bound? 

sirolimus protein bound (temsirolimus) is used for the treatment of certain types of cancer. Its primary used in the treatment of advanced renal cell carcinoma and relapsed or refractory mantle cell lymphoma (a type of non-Hodgkin’s lymphoma). 

In advanced renal cell carcinoma, sirolimus protein bound is used as a single or in combination with other anticancer medications to slow down the growth and spread of cancer cells. It helps to inhibit the activity of a protein called mTOR (mammalian target of rapamycin), which plays a role in the abnormal growth of cancer cells. 

In relapsed or refractory mantle cell lymphoma, sirolimus protein bound is used as a single agent to treat patients who are not responded to or have relapsed following other treatments.