Version July 2025
Note: Administer sirolimus (protein bound) in a setting where cardiopulmonary resuscitation medication and equipment are available. Refer to the Sirolimus (Conventional) monograph for dosing and information related to the oral sirolimus formulation.
Perivascular epithelioid cell tumor, malignant, locally advanced or metastatic: IV: 100 mg/m2 on days 1 and 8 every 21 days until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, mild or moderate renal impairment had no clinically significant effect on sirolimus pharmacokinetics.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST): Reduce dose to 75 mg/m2; closely monitor for increased toxicity.
Moderate impairment (total bilirubin >1.5 to 3 times ULN and any AST): Reduce dose to 56 mg/m2; closely monitor for increased toxicity.
Severe impairment: Avoid sirolimus (protein bound) use.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status. If dose reduction for toxicity is recommended in the prescribing information, the dose should be increased back to the initial or previously tolerated dose only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
|
Usual initial dose |
100 mg/m2 |
|
First dose reduction |
75 mg/m2 |
|
Second dose reduction |
56 mg/m2 |
|
Third dose reduction |
45 mg/m2 |
|
Permanently discontinue sirolimus (protein bound) if unable to tolerate 45 mg/m2. | |
|
Adverse Reaction |
Severity |
Sirolimus (Protein Bound) Dosage Modification |
|---|---|---|
|
Hematologic toxicities | ||
|
Anemia |
Grade 2 |
Withhold sirolimus (protein bound) until hemoglobin is ≥8 g/dL, then restart at the same dose level. |
|
≥ Grade 3 |
Withhold sirolimus (protein bound) until hemoglobin is ≥8 g/dL, then restart at the same dose level. If ≥ grade 3 anemia recurs, resume sirolimus (protein bound) at a reduced dose level. | |
|
Neutropenia |
Grade 2 or 3 |
Withhold sirolimus (protein bound) until ANC is ≥1,500/mm3, then restart at the same dose level. |
|
Grade 4 |
Withhold sirolimus (protein bound) until ANC is ≥1,500/mm3, then restart at a reduced dose level. | |
|
Thrombocytopenia |
Grade 2 |
Withhold sirolimus (protein bound) until platelets are >100,000/mm3, then restart at the same dose level. |
|
≥ Grade 3 |
Withhold sirolimus (protein bound) until platelets are >100,000/mm3, then restart at a reduced dose level. | |
|
Nonhematologic toxicities | ||
|
GI toxicity: Stomatitis |
Grade 2 or 3 |
Withhold sirolimus (protein bound) until ≤ grade 1, then restart at the same dose (for first occurrence). If grade 2 or 3 stomatitis recurs, restart at a reduced dose level. |
|
Grade 4 |
Permanently discontinue sirolimus (protein bound). | |
|
Hemorrhage |
Grade 2 or 3 |
Withhold sirolimus (protein bound) until ≤ grade 1, then restart at a reduced dose. If grade 2 or 3 hemorrhage recurs, permanently discontinue sirolimus (protein bound). |
|
Grade 4 |
Permanently discontinue sirolimus (protein bound). | |
|
Hyperglycemia |
≥ Grade 3 |
Withhold sirolimus (protein bound) until ≤ grade 2, then restart at a reduced dose level. |
|
Hypokalemia |
Any |
Implement potassium supplementation as clinically indicated. |
|
Grade 2 |
Withhold sirolimus (protein bound) until ≤ grade 1, then restart at the same dose level. If grade 2 hypokalemia recurs, restart at a reduced dose level. | |
|
≥ Grade 3 |
Withhold sirolimus (protein bound) until ≤ grade 1, then restart at a reduced dose level. If ≥ grade 3 hypokalemia recurs, permanently discontinue sirolimus (protein bound). | |
|
Infections |
Grade 3 |
Withhold sirolimus (protein bound) until resolved, then restart at a reduced dose level. If grade 3 infection recurs, permanently discontinue sirolimus (protein bound). |
|
Grade 4 |
Withhold sirolimus (protein bound) until resolved, then restart at a reduced dose level or permanently discontinue sirolimus (protein bound). | |
|
Infusion reaction |
Based on severity |
Reduce the infusion rate, interrupt infusion, or permanently discontinue sirolimus (protein bound) based on severity. Institute appropriate medical management as clinically indicated. |
|
Pulmonary toxicity: Interstitial lung disease (ILD)/noninfectious pneumonitis |
Grade 2 |
Withhold sirolimus (protein bound) for up to 3 weeks until ≤ grade 1, then restart at a reduced dose level. If not resolved to ≤ grade 1 within 3 weeks, permanently discontinue sirolimus (protein bound). If grade 2 ILD/noninfectious pneumonitis recurs, permanently discontinue sirolimus (protein bound). |
|
≥ Grade 3 |
Permanently discontinue sirolimus (protein bound). | |
|
Other adverse reactions |
Grade 3 |
Withhold sirolimus (protein bound) until ≤ grade 1, then restart at the same dose level. If grade 3 adverse reaction recurs, restart at a reduced dose level. |
|
Grade 4 |
Permanently discontinue sirolimus (protein bound). | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Edema (50%), hypertension (29%)
Dermatologic: Alopecia (24%), nail disease (12%), pruritus (18%), skin rash (68%), xeroderma (12%)
Endocrine & metabolic: Decreased serum albumin (35%), decreased serum calcium (15%), decreased serum glucose (15%), decreased serum magnesium (42%), decreased serum phosphate (15%), decreased serum sodium (24%), dehydration (15%; severe dehydration: 6%), hyperglycemia (12%), hypokalemia (44%), increased serum cholesterol (48%), increased serum sodium (12%), increased serum triglycerides (52%), weight loss (47%)
Gastrointestinal: Abdominal pain (29%; severe abdominal pain: 6%), constipation (24%), decreased appetite (44%), diarrhea (47%; grade 3: 3%), dysgeusia (32%), hemorrhoids (12%), increased serum lipase (12%), nausea (50%), stomatitis (79%; grade 3: 18%), vomiting (32%; grade 3: 3%), xerostomia (15%)
Hematologic & oncologic: Anemia (68%; grades 3: 6%), decreased white blood cell count (41%), hemorrhage (24%; grades ≥3: 3%), lymphocytopenia (82%; grades 3/4: 21%), neutropenia (35%), thrombocytopenia (35%)
Hepatic: Increased serum alanine aminotransferase (47%), increased serum alkaline phosphatase (29%), increased serum aspartate aminotransferase (32%)
Infection: Infection (59%; including urinary tract infection, upper respiratory infection, and sinusitis), serious infection (12%; including abdominal infection, pneumonia, and skin infection)
Nervous system: Dizziness (12%), fatigue (68%), headache (29%), insomnia (21%), peripheral neuropathy (15%)
Neuromuscular & skeletal: Musculoskeletal pain (47%)
Otic: Blurred vision (12%)
Renal: Increased serum creatinine (82%)
Respiratory: Cough (35%), dyspnea (12%), interstitial pulmonary disease (≤18%), pneumonitis (≤18%)
Miscellaneous: Fever (24%)
1% to 10%:
Cardiovascular: Acute coronary syndrome (<10%), edema (<10%)
Gastrointestinal: Enteritis (<10%)
Hematologic & oncologic: Pancytopenia (<10%), upper gastrointestinal hemorrhage (6%)
Renal: Acute kidney injury (<10%)
Frequency not defined:
Dermatologic: Acneiform eruption (dermatitis)
Genitourinary: Cystitis (noninfective)
History of severe hypersensitivity to sirolimus, other rapamycin derivatives, albumin, or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Sirolimus (protein bound) may cause hematologic toxicity, including anemia, thrombocytopenia, and neutropenia. Grade 3 anemia was observed.
• GI toxicity: Stomatitis, including mouth ulcers and oral mucositis, occurred in a majority of patients treated with sirolimus (protein bound), including grade 3 stomatitis. Stomatitis was mostly first reported within 8 weeks of treatment.
• Hemorrhage: Sirolimus (protein bound) can cause serious and sometimes fatal hemorrhage; hemorrhage was reported in almost one-fourth of patients.
• Hyperglycemia: Sirolimus (protein bound) is associated with hyperglycemia, most commonly reported as grade 3 hyperglycemia.
• Hypersensitivity: Sirolimus (protein bound) may cause hypersensitivity reactions. Conventional sirolimus (the oral formulation) is associated with hypersensitivity reactions including anaphylactic, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis. Sirolimus (protein bound) contains albumin, which is associated with hypersensitivity reactions including anaphylaxis. Administer sirolimus (protein bound) in a setting where cardiopulmonary resuscitation medication and equipment are available.
• Hypokalemia: Sirolimus (protein bound) can cause hypokalemia; grade 3 hypokalemia has been observed.
• Infection: Sirolimus (protein bound) can cause infections. Infections commonly reported included urinary tract infections (UTIs), upper respiratory tract infections, and sinusitis. Grade 3 infections were observed, including cases of grade 3 UTI, pneumonia, skin, and abdominal infections.
• Pulmonary toxicity: Sirolimus (protein bound) may cause interstitial lung disease (ILD)/noninfectious pneumonitis. All cases of ILD/noninfectious pneumonitis were grades 1 or 2.
Concurrent drug therapy issues:
• Vaccination: Sirolimus (protein bound) has not been studied in conjunction with immunization. Immunization during sirolimus (protein bound) treatment may be ineffective. Prior to initiating sirolimus (protein bound), if possible, update immunizations according to immunization guidelines. Immunization with live vaccines is not recommended during sirolimus (protein bound) treatment. Patients receiving sirolimus (protein bound) should avoid close contact with individuals who have received live vaccines. The interval between live vaccinations and sirolimus (protein bound) initiation should be in accordance with current vaccination guidelines for patients on immunosuppressive therapies.
Dosage form specific issues:
• Albumin: Sirolimus (protein bound) contains albumin, which confers a remote risk of viral disease transmission and a remote theoretical risk of transmission of Creutzfeldt-Jakob disease.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Intravenous [preservative free]:
Fyarro: 100 mg (1 ea) [contains albumin human]
No
Suspension (reconstituted) (Fyarro Intravenous)
100 mg (per each): $9,574.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Fyarro is available through specialty pharmacies and distributors. Information regarding access is available from the manufacturer's assistance program at https://aadiassist.com/Content/fyarro-fact-sheet.pdf or at 1-855-223-4482.
IV: Infuse over 30 minutes. Administer sirolimus (protein bound) in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor closely for hypersensitivity/infusion reactions during and after infusion (monitor for at least 2 hours after the first infusion and as clinically necessary for subsequent infusions).
This medication is not on the NIOSH (2024) list; however, it meets the criteria for a hazardous drug. Sirolimus (protein bound) contains manufacturer's special handling information and is a hazardous drug (per product labeling).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Perivascular epithelioid cell tumor, malignant, locally advanced or metastatic: Treatment of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa) in adults.
Sirolimus (protein bound) may be confused with everolimus, sirolimus (conventional), sirolimus (topical), tacrolimus, temsirolimus.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; immunosuppressant agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major), P-glycoprotein (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Sirolimus Products may increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Atazanavir: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Bulevirtide: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
CYP3A4 Inducers (Weak): May decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
CYP3A4 Inhibitors (Weak): May increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Elacestrant: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Futibatinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Gepotidacin: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Gilteritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Givinostat: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Maribavir: May increase serum concentration of Sirolimus Products. Risk C: Monitor
Micafungin: May increase serum concentration of Sirolimus Products. Risk C: Monitor
Milk Thistle: May increase serum concentration of Sirolimus Products. Risk C: Monitor
Mitapivat: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Pacritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sotagliflozin: May decrease serum concentration of Sirolimus (Protein Bound). Sotagliflozin may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sparsentan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Spironolactone: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tacrolimus (Systemic): May increase adverse/toxic effects of Sirolimus Products. Sirolimus Products may increase adverse/toxic effects of Tacrolimus (Systemic). Sirolimus Products may decrease serum concentration of Tacrolimus (Systemic). Risk X: Avoid
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Treosulfan: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Trofinetide: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Venetoclax: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if possible. If combined use is unavoidable, administer the P-gp substrate at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider Therapy Modification
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
Xanomeline: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Grapefruit or grapefruit juice may increase serum sirolimus concentrations. Management: Avoid grapefruit and grapefruit juice.
Verify pregnancy status prior to treatment. Patients who could become pregnant should use effective contraception during therapy and for 12 weeks after the last sirolimus (protein bound) dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 12 weeks after the last dose of sirolimus (protein bound).
Sirolimus may impair fertility. Ovarian cysts, amenorrhea, menorrhagia, azoospermia, or oligospermia have been observed following use of conventional sirolimus (oral formulation).
Also refer to sirolimus (conventional) for additional information.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to sirolimus (protein bound) may cause fetal harm. Adverse events were observed in animal reproduction studies following use of conventional sirolimus (oral formulation) at doses equivalent to or less than the recommended equivalent human starting dose.
Also refer to sirolimus (conventional) for additional information.
It is not known if sirolimus is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks after the last sirolimus (protein bound) dose.
Avoid grapefruit and grapefruit juice.
CBC with differential at baseline and every 2 months for the first year, then every 3 months thereafter; more frequently if clinically indicated. Potassium levels at baseline and periodically. Monitor fasting serum glucose at baseline; during treatment, monitor serum glucose every 3 months (or as clinically indicated) in patients without diabetes; monitor more frequently in patients with diabetes. Verify pregnancy status prior to treatment (in patients who can become pregnant). Monitor for signs/symptoms of hemorrhage, hyperglycemia, infections (including opportunistic infections), pulmonary toxicity, and/or stomatitis. Monitor closely during and after infusion for hypersensitivity/infusion reactions (monitor for at least 2 hours after the first infusion and as clinically necessary for subsequent infusions).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Sirolimus (protein bound) is an albumin-bound nanoparticle sirolimus formulation that inhibits mammalian (mechanistic) target of rapamycin (mTOR) (Wagner 2021). mTOR controls key cellular processes such as cell survival, growth, and proliferation, and is commonly dysregulated in several human cancers. In cells, sirolimus forms an immunosuppressive complex, sirolimus-FKBP-12 complex, which binds to and inhibits activation of the mTOR complex 1 (mTORC1). Inhibition of mTOR by sirolimus reduces cell proliferation, angiogenesis, and glucose uptake. In preclinical models, IV administration of nanoparticle protein bound sirolimus has demonstrated higher intratumor accumulation, greater mTOR inhibition, and higher tumor growth inhibition compared to oral mTOR inhibitors (Wagner 2021).
Protein binding: >99%, primarily to serum albumin.
Metabolism: Hepatic, via CYP3A4.
Half-life elimination: ~59 hours.
Excretion: Oral: Feces (91%), Urine (2%).
