Nanoparticle albumin-bound (nab)-sirolimus is a parenteral form of sirolimus, an immunosuppressant. It is approved for treating adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor. Myelosuppression, stomatitis, and pneumonitis have been reported with nab-sirolimus.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
CAUTION: Observe and exercise usual precautions for handling, preparing, and administering hazardous drugs.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Nab-sirolimus is available as a single-dose, 100-mg lyophilized powder vial; discard any unused portion of the vial after reconstitution.
-Do not use medical devices containing silicone oil as a lubricant (e.g., syringes and IV bags) to reconstitute or administer nab-sirolimus; the formation of proteinaceous strands may occur due to the silicone oil.
Reconstitution:
-Add 20 mL of 0.9% Sodium Chloride injection to each 100-mg vial for a final vial concentration of 5 mg/mL.
-Inject the diluent slowly (over at least 1 minute) and direct the stream onto the inside wall of the vial; do not inject the diluent directly onto the powder cake or foaming may occur.
-Allow the reconstituted vial to sit for at least 5 minutes, then gently swirl and/or invert the vial slowly for at least 2 minutes until the powder is completely dissolved; do not shake the reconstituted vial or foaming may occur.
-Reconstituted vials should appear milky and homogenous without visible particulates.
-If foaming or clumping occur, let the vial stand for at least 15 minutes until foam subsides; discard the reconstituted vial if foaming or clumping persist after 1 hour.
-If particulates or settling are visible, gently invert the vial to ensure complete re-suspension prior to use; discard the reconstituted vial if precipitates are observed.
-Stability of reconstituted vials: Transfer vial contents immediately (preferred) or store vials in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 6 hours in the original carton; protect from light.
Preparation:
-Withdraw the calculated patient dose/volume from the reconstituted vial and transfer to an empty sterile PVC or polyolefin infusion bag; contents do not require further dilution.
-Discard the contents of the infusion bag if particulate matter, proteinaceous strands, or discoloration are observed.
-Storage of infusion bag: Administer contents immediately (preferred) or store in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 9 hours; protect from light. The maximum total time stored in the refrigerator (vial plus infusion bag) is 15 hours. The infusion bag may be further stored at room temperature (approximately, 25 degrees C) for up to 4 hours.
Intravenous (IV) Infusion:
-Administer the contents in the infusion bag IV over 30 minutes.
-Observe patients for signs or symptoms of hypersensitivity during and following each nab-sirolimus infusion; monitor for at least 2 hours following the completion of the first infusion and then as clinically indicated for subsequent infusions.
Increased lipase level occurred in 12% (grade 3 or 4, 6%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Stomatitis (79%; grade 3, 18%) and dry mouth/xerostomia (15%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Stomatitis typically occurred within the first 8 weeks of treatment. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher stomatitis. The term stomatitis included aphthous ulcer, mouth/oral ulceration, and esophageal ulceration.
Nausea (50%), diarrhea (47%; grade 3, 2.9%), decreased appetite/anorexia (44%), vomiting (32%; grade 3, 2.9%), abdominal pain including epigastric discomfort (29%; grade 3, 6%), constipation (24%; grade 3, 2.9%), hemorrhoids (12%), and enteritis (less than 10%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Lymphopenia/decreased lymphocyte count (82%; grade 3 or 4, 21%), anemia/decreased hemoglobin level (68%; grade 3 or 4, 6%), leukopenia/decreased leukocyte count (41%), neutropenia/decreased neutrophil count (35%), thrombocytopenia/decreased platelet count (35%), and pancytopenia (less than 10%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Obtain complete blood counts prior to initiating nab-sirolimus, every 2 months for the first year, and then every 3 months thereafter or more frequently as clinical indicated during therapy. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher myelosuppression.
Infection occurred in 59% (grade 3, 12%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Monitor patients for signs and symptoms of infection, including opportunistic infections. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe infection. The term infection included upper respiratory tract infection, urinary tract infection, sinusitis, skin infection, folliculitis, pharyngitis, nasopharyngitis, pneumonia, and vaginal infection.
Bleeding occurred in 24% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). One patient (2.9%) died following an upper GI bleed. Monitor patients for signs and symptoms of bleeding. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher bleeding. The term bleeding included epistaxis, GI bleeding, hemorrhoidal hemorrhage, mouth hemorrhage, and post procedural hemorrhage.
Fatigue occurred in 68% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Dehydration occurred in 15% (grade 3, 6%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Insomnia occurred in 21% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Blurred vision occurred in 12% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Weight loss occurred in 47% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Musculoskeletal pain occurred in 47% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). The term musculoskeletal pain included arthralgia, back pain, musculoskeletal/non-cardiac chest pain, myalgia, neck pain, and pain in extremity.
Edema occurred in 50% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). The term edema included face edema, peripheral edema, and periorbital edema.
Fever occurred in 24% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Rash (68%) and pruritus (18%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Other hypersensitivity reactions have been reported with oral sirolimus including anaphylactic reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis. Observe patients for signs or symptoms of hypersensitivity during and following each nab-sirolimus infusion; monitor for at least 2 hours following the completion of the first infusion and then as clinically indicated for subsequent infusions. Infusion rate reduction, a dose reduction, or discontinuation may be necessary in patients who develop a severe hypersensitivity reaction. The term rash included acneiform rash/dermatitis, palmar-plantar erythrodysesthesia (hand and foot syndrome), maculopapular rash, and skin exfoliation.
Alopecia (24%), dry skin/xerosis (12%), and nail disorder (12%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Dysgeusia (32%), headache (29%), peripheral neuropathy (15%), and dizziness including vertigo (12%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). The term peripheral neuropathy included dysesthesia, hypoesthesia, and paresthesias.
Interstitial lung disease (ILD)/non-infectious pneumonitis occurred in 18% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Monitor patients for new or worsening respiratory symptoms or radiological changes that might indicate ILD or non-infectious pneumonitis. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher ILD or pneumonitis.
Cough including upper-airway cough syndrome (35%) and dyspnea (12%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Hypertension (29%; grade 3, 2.9%) and acute coronary syndrome (less than 10%) occurred in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Nephrotoxicity including increased serum creatinine level (82%) and acute kidney injury (less than 10%) occurred in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Hypertriglyceridemia/increased triglyceride level (52%) and hypercholesterolemia/increased cholesterol level (48%; grade 3 or 4, 3%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Hypoalbuminemia/decreased albumin level occurred in 35% (grade 3, 2.9%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Grade 3 or 4 hyperglycemia/increased glucose level occurred in 12% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Obtain fasting serum glucose levels prior to initiating nab-sirolimus. During therapy, monitor serum glucose levels every 3 months in non-diabetic patients (or as clinically indicated) and more frequently in patients with diabetes mellitus. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe hyperglycemia.
Hypoglycemia/decreased glucose level occurred in 15% of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Hypokalemia/decreased potassium level occurred in 44% (grade 3, 12%) of patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Obtain potassium levels prior to initiating nab-sirolimus and as clinical indicated during therapy; administer potassium supplementation as medically indicated. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher hypokalemia.
Hypomagnesemia/decreased magnesium level (42%), hyponatremia/decreased sodium level (24%; grade 3 or 4, 2.9%), hypernatremia/increased sodium level (12%), hypocalcemia/decreased calcium level (15%), and hypophosphatemia/decreased phosphate level (15%; grade 3 or 4, 9%) were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34).
Elevated hepatic enzymes including increased ALT (47%; grade 3 or 4, 2.9%), AST (32%; grade 3 or 4, 2.9%), and alkaline phosphatase (29%) levels were reported in patients with perivascular epithelioid cell tumor who received nab-sirolimus in a clinical trial (n = 34). Avoid nab-sirolimus use in patient with severe hepatic impairment. Reduce the nab-sirolimus dose in patients with mild or moderate hepatic impairment; closely monitor these patients for signs or increased nab-sirolimus toxicity.
Nab-sirolimus use is contraindicated in patients with a history of severe sirolimus, other rapamycin derivatives, or albumin hypersensitivity. Observe patients for signs or symptoms of hypersensitivity during and following each nab-sirolimus infusion; monitor for at least 2 hours following the completion of the first infusion and then as clinically indicated for subsequent infusions. Nab-sirolimus administration requires a specialized care setting that includes cardiopulmonary resuscitation medication and equipment. Infusion rate reduction, a dose reduction, or discontinuation may be necessary in patients who develop a severe hypersensitivity reaction. The nab-sirolimus product contains albumin, a derivative of human blood. As with other products derived from human blood components, there is a theoretical risk of contamination with a viral infection, including Creutzfeldt-Jakob disease (CJD), in patients receiving albumin-containing products; however, no cases of transmission of viral illness or CJD have ever been identified.
Obtain complete blood counts prior to initiating nab-sirolimus, every 2 months for the first year, and then every 3 months thereafter or more frequently as clinical indicated during therapy. Monitor patients for signs and symptoms of bleeding or infection. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher myelosuppression (e.g., anemia, neutropenia, or thrombocytopenia) or bleeding or severe infection.
Obtain potassium levels prior to initiating nab-sirolimus and as clinically indicated during therapy; administer potassium supplementation as medically indicated. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher hypokalemia.
Obtain fasting serum glucose levels prior to initiating nab-sirolimus. During therapy, monitor serum glucose levels every 3 months in non-diabetic patients (or as clinically indicated) and more frequently in patients with diabetes mellitus. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe hyperglycemia.
Monitor patients for new or worsening respiratory symptoms or radiological changes that might indicate interstitial lung disease (ILD) or non-infectious pneumonitis. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop grade 2 or higher ILD or pneumonitis.
Avoid nab-sirolimus use in patient with severe hepatic disease/impairment. Reduce the nab-sirolimus dose in patients with mild or moderate hepatic impairment; closely monitor these patients for signs of increased nab-sirolimus toxicity.
Advise patients to receive recommended immunizations prior to starting nab-sirolimus therapy; nab-sirolimus may interfere with the response to vaccines and be less effective. Vaccination with live vaccines should not be given during nab-sirolimus therapy and patients should avoid close contact with others who have received a live vaccine. Consult current vaccination guidelines for when to administer live vaccinations in patients with medication-induced immunosuppression.
Nab-sirolimus may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during nab-sirolimus therapy. Advise pregnant women of the potential fetal risk from nab-sirolimus. Oral sirolimus was embryo/fetotoxic in rats at subtherapeutic doses. A panel of experts from the 2002 European Best Practice Guidelines for Renal Transplant considered sirolimus contraindicated during pregnancy. In 2010, the National Transplantation Pregnancy Registry (NTPR) reported exposure of 12 pregnant kidney transplant recipients to sirolimus. Among 13 pregnancies, 3 spontaneous abortions occurred. One infant was born with cleft lip, cleft palate, and microtia (with concomitant exposure to mycophenolate). Another infant was born with tetralogy of Fallot. Two pregnancies in heart transplant recipients resulted in 1 spontaneous abortion and 1 live birth with facial abnormalities (exposure to sirolimus, cyclosporine, and mycophenolate at conception). Among 3 pregnancies in liver transplant recipients, 1 spontaneous abortion and 2 live births were reported. One spontaneous abortion was reported in a pancreas-kidney transplant recipient.
Counsel patients about the reproductive risk and contraception requirements during nab-sirolimus treatment. Pregnancy testing should be performed prior to starting nab-sirolimus in female patients of reproductive potential. These patients should avoid pregnancy and use effective contraception during and for 12 weeks after the last nab-sirolimus dose. Due to male-mediated teratogenicity, men with partners of reproductive potential should use effective contraception during and for 12 weeks after the last nab-sirolimus dose. There is a risk of infertility with nab-sirolimus use in male and female patients based on experience with oral sirolimus. Ovarian cysts and menstrual irregularity (e.g., amenorrhea and menorrhagia) in females and abnormal sperm production (e.g., azoospermia and oligospermia) in males have been reported following the use of an oral formulation of sirolimus. Azoospermia was reversible following the discontinuation of sirolimus in most cases.
It is not known if nab-sirolimus is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during nab-sirolimus therapy and for 2 weeks after the last dose.
For the treatment of perivascular epithelioid cell tumor (PEComa):
NOTE: Nab-sirolimus has been designated an orphan drug by the FDA for the treatment of PEComa.
-for the treatment of locally advanced unresectable or metastatic malignant PEComa:
Intravenous dosage:
Adults: 100 mg/m2 IV on days 1 and 8 repeated every 21 days until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, a dosage reduction, or permanent discontinuation may be necessary in patients who develop toxicity. The overall response rate was 39% in 31 evaluable patients with inoperable, locally advanced (15%) or metastatic (85%) PEComa who received nab-sirolimus in a phase 2 trial (the AMPECT trial); 1 patient experienced a complete response. At a median follow-up time of 2.5 years, the median duration of response was not reached (range, 5.6 to more than 47 months). At the final analysis, the median progression-free survival time was 10.6 months and the median overall survival time was 40.8 months. In this study, 12% of patients had received prior therapy.
Therapeutic Drug Monitoring:
Dosage Guidance for Treatment-Related Toxicity
Dose Adjustments
First dose reduction: 75 mg/m2 IV.
Second dose reduction: 56 mg/m2 IV.
Third dose reduction: 45 mg/m2 IV; permanently discontinue therapy in patients unable to tolerate 45 mg/m2 IV.
Bleeding
Grade 2 or 3 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less; resume therapy at a reduced dose. Permanently discontinue nab-sirolimus if the toxicity recurs.
Grade 4 toxicity: Permanently discontinue nab-sirolimus.
Hematologic Toxicity
Anemia
Grade 2 toxicity: Hold nab-sirolimus until the hemoglobin concentration is 8 g/dL or more; resume therapy at same dose level.
Grade 3 or 4 toxicity: Hold nab-sirolimus until the hemoglobin concentration is 8 g/dL or more; resume therapy at same dose level. If the toxicity recurs, resume therapy at reduced dose level.
Neutropenia
Grade 2 or 3 toxicity: Hold nab-sirolimus until the absolute neutrophil count (ANC) is 1.5 X 109 cells/L or more; resume therapy at same dose level.
Grade 4 toxicity: Hold nab-sirolimus until the ANC is 1.5 X 109 cells/L or more; resume therapy at a reduced dose level.
Thrombocytopenia
Grade 2 toxicity: Hold nab-sirolimus until the platelet count is more than 100 X 109 cells/L; resume therapy at same dose level.
Grade 3 or 4 toxicity: Hold nab-sirolimus until the platelet count is more than 100 X 109 cells/L; resume therapy at a reduced dose level.
Hyperglycemia
Grade 3 or 4 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 2 or less; resume therapy at a reduced dose level.
Hypokalemia
Grade 2 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less; resume therapy at same dose level. If the toxicity recurs, resume therapy at reduced dose level.
Grade 3 or 4 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less; resume therapy at a reduced dose level. Permanently discontinue nab-sirolimus if the toxicity recurs.
Infection
Grade 3 toxicity: Hold nab-sirolimus until the toxicity resolves; resume therapy at a reduced dose level. Permanently discontinue nab-sirolimus if the toxicity recurs.
Grade 4 toxicity: Hold nab-sirolimus until the toxicity resolves; resume therapy at a reduced dose level or permanently discontinue nab-sirolimus.
Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis
Grade 2 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less. If the toxicity resolves within 3 weeks, resume therapy at a reduced dose level and permanently discontinue nab-sirolimus if the toxicity recurs. If the toxicity does not resolve within 3 weeks, permanently discontinue nab-sirolimus.
Grade 3 or 4 toxicity: Permanently discontinue nab-sirolimus.
Stomatitis
Grade 2 or 3 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less; resume therapy at same dose level for the first occurrence. If the toxicity recurs, resume therapy at reduced dose level.
Grade 4 toxicity: Permanently discontinue nab-sirolimus.
Other Toxicity
Grade 3 toxicity: Hold nab-sirolimus until the toxicity resolves to grade 1 or less; resume therapy at same dose level. If the toxicity recurs, resume therapy at reduced dose level.
Grade 4 toxicity: Permanently discontinue nab-sirolimus.
Maximum Dosage Limits:
-Adults
100 mg/m2 IV.
-Geriatric
100 mg/m2 IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild hepatic impairment (total bilirubin level at or below the ULN and AST level more than the ULN OR total bilirubin level of 1 to 1.5 times the ULN and any AST level): Reduce the dose to 75 mg/m2 IV.
Moderate hepatic impairment (total bilirubin level more than 1.5 to 3 times the ULN and any AST level): Reduce the dose to 56 mg/m2 IV.
Severe hepatic impairment (total bilirubin level more than 3 times the ULN): Avoid use.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abrocitinib: (Major) Avoid concomitant use of sirolimus and abrocitinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Adagrasib: (Major) Avoid concomitant use of sirolimus and adagrasib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor.
Amiodarone: (Major) Avoid concomitant use of sirolimus and amiodarone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and amiodarone is a weak CYP3A and P-gp inhibitor.
Amlodipine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Amlodipine; Atorvastatin: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor. (Moderate) Carefully weigh the benefits of combined use of sirolimus and atorvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of atorvastatin to 10 mg/day when combined with sirolimus unless there is close monitoring of creatinine kinase and symptoms of muscle-related toxicity. However, FDA-approved labeling for sirolimus states that no clinically significant drug-drug interaction was observed with atorvastatin in drug interaction studies and the two drugs may be administered without dose adjustment.
Amlodipine; Benazepril: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor. (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Amlodipine; Celecoxib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Amlodipine; Olmesartan: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Amlodipine; Valsartan: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Amobarbital: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of sirolimus and clarithromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and clarithromycin is a strong CYP3A and P-gp inhibitor.
Angiotensin-converting enzyme inhibitors: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Apalutamide: (Major) Avoid concomitant use of sirolimus and apalutamide as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and apalutamide is a strong CYP3A and P-gp inducer.
Aprepitant, Fosaprepitant: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of aprepitant/fosaprepitant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor.
Armodafinil: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with armodafinil. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and armodafinil is a weak CYP3A inducer.
Asciminib: (Major) Avoid concomitant use of sirolimus and asciminib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and asciminib is a weak CYP3A and P-gp inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Atazanavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Atorvastatin: (Moderate) Carefully weigh the benefits of combined use of sirolimus and atorvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of atorvastatin to 10 mg/day when combined with sirolimus unless there is close monitoring of creatinine kinase and symptoms of muscle-related toxicity. However, FDA-approved labeling for sirolimus states that no clinically significant drug-drug interaction was observed with atorvastatin in drug interaction studies and the two drugs may be administered without dose adjustment.
Avacopan: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of avacopan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and avacopan is a weak CYP3A inhibitor.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Barbiturates: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Belumosudil: (Major) Avoid concomitant use of sirolimus and belumosudil. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and belumosudil is a weak CYP3A and P-gp inhibitor.
Belzutifan: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with belzutifan. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and belzutifan is a weak CYP3A inducer.
Benazepril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Berotralstat: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of berotralstat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Bexarotene: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with bexarotene. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Bicalutamide: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of bicalutamide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Bosentan: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with bosentan. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and bosentan is a moderate CYP3A inducer.
Brigatinib: (Major) Avoid concomitant use of sirolimus and brigatinib. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and brigatinib is a weak CYP3A inducer and P-gp inhibitor.
Butalbital; Acetaminophen: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Cabozantinib: (Major) Avoid concomitant use of sirolimus and cabozantinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Cannabidiol: (Major) Avoid concomitant use of sirolimus and cannabidiol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capivasertib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of capivasertib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and capivasertib is a weak CYP3A inhibitor.
Capmatinib: (Major) Avoid concomitant use of sirolimus and capmatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and capmatinib is a P-gp inhibitor.
Captopril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Carbamazepine: (Major) Avoid concomitant use of sirolimus and carbamazepine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer.
Carvedilol: (Major) Avoid concomitant use of sirolimus and carvedilol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and carvedilol is a P-gp inhibitor.
Cenobamate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with cenobamate. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and cenobamate is a moderate CYP3A inducer.
Ceritinib: (Major) Avoid concomitant use of sirolimus and ceritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Chikungunya Vaccine, Live: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Chloramphenicol: (Major) Avoid concomitant use of sirolimus and chloramphenicol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cimetidine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of cimetidine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and cimetidine is a weak CYP3A inhibitor.
Ciprofloxacin: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of ciprofloxacin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor.
Clarithromycin: (Major) Avoid concomitant use of sirolimus and clarithromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and clarithromycin is a strong CYP3A and P-gp inhibitor.
Clobazam: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with clobazam. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and clobazam is a weak CYP3A inducer.
Clofazimine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of clofazimine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and clofazimine is a weak CYP3A inhibitor.
Cobicistat: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor.
Cocaine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with cocaine is necessary. The dose of sirolimus may also need to be reduced with coadministration of cocaine. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of cocaine. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; cocaine is a weak CYP3A inhibitor.
Conivaptan: (Major) Avoid concomitant use of sirolimus and conivaptan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and conivaptan is a moderate CYP3A and P-gp inhibitor.
Crizotinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of crizotinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Avoid concomitant use of sirolimus and cyclosporine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cyclosporine is a moderate CYP3A and P-gp inhibitor.
Dabrafenib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with dabrafenib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Dalfopristin; Quinupristin: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of quinupristin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and quinupristin is a weak CYP3A inhibitor.
Danazol: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of danazol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Danicopan: (Major) Avoid concomitant use of sirolimus and danicopan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and danicopan is a P-gp inhibitor.
Daridorexant: (Major) Avoid concomitant use of sirolimus and daridorexant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and daridorexant is a weak CYP3A and P-gp inhibitor.
Darunavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Darunavir; Cobicistat: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Deferasirox: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with deferasirox. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and deferasirox is a weak CYP3A inducer.
Delavirdine: (Major) Avoid concomitant use of sirolimus and delavirdine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with dexamethasone. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
Dextromethorphan; Quinidine: (Major) Avoid concomitant use of sirolimus and quinidine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and quinidine is a P-gp inhibitor.
Diltiazem: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of diltiazem. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor.
Dronedarone: (Major) Avoid concomitant use of sirolimus and dronedarone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and dronedarone is a moderate CYP3A and P-gp inhibitor.
Duvelisib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of duvelisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with efavirenz. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with efavirenz. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with efavirenz. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Elacestrant: (Major) Avoid concomitant use of sirolimus and elacestrant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elagolix: (Major) Avoid concomitant use of sirolimus and elagolix. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of sirolimus and elagolix. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor.
Elbasvir; Grazoprevir: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of grazoprevir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and grazoprevir is a weak CYP3A inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Major) Avoid concomitant use of sirolimus and ivacaftor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ivacaftor is a weak CYP3A and P-gp inhibitor.
Eliglustat: (Major) Avoid concomitant use of sirolimus and eliglustat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and eliglustat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of sirolimus and cobicistat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and cobicistat is a strong CYP3A and P-gp inhibitor.
Enalapril, Enalaprilat: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Enasidenib: (Major) Avoid concomitant use of sirolimus and enasidenib. Concurrent use may alter sirolimus exposure and decrease its efficacy or increase the risk of adverse effects. Sirolimus is a P-gp and CYP3A substrate and enasidenib is a P-gp inhibitor and weak CYP3A inducer. The net effect on sirolimus exposure is unknown.
Encorafenib: (Major) Avoid concomitant use of sirolimus and encorafenib as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Major) Avoid concomitant use of sirolimus and enzalutamide as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and enzalutamide is a strong CYP3A inducer.
Erdafitinib: (Major) Avoid concomitant use of sirolimus and erdafitinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Erythromycin: (Major) Avoid concomitant use of sirolimus and erythromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and erythromycin is a moderate CYP3A and P-gp inhibitor.
Eslicarbazepine: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with eslicarbazepine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Etravirine: (Major) Avoid concomitant use of sirolimus and etravirine. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and etravirine is a weak CYP3A inducer and P-gp inhibitor.
Ezetimibe; Simvastatin: (Major) Guidelines recommend avoiding coadministration of simvastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Fedratinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of fedratinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Fexinidazole: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of fexinidazole. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and fexinidazole is a moderate CYP3A inhibitor.
Flibanserin: (Major) Avoid concomitant use of sirolimus and flibanserin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and flibanserin is a P-gp inhibitor.
Fluconazole: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of fluconazole. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Fluvastatin: (Moderate) Carefully weigh the benefits of combined use of sirolimus and fluvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of fluvastatin to 40 mg/day if combined with sirolimus.
Fluvoxamine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of fluvoxamine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor.
Fosamprenavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Fosinopril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Fosphenytoin: (Major) Avoid concomitant use of sirolimus and phenytoin/fosphenytoin as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and phenytoin/fosphenytoin is a strong CYP3A and P-gp inducer.
Fostamatinib: (Major) Avoid concomitant use of sirolimus and fostamatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and fostamatinib is a weak CYP3A and P-gp inhibitor.
Futibatinib: (Major) Avoid concomitant use of sirolimus and futibatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and futibatinib is a P-gp inhibitor.
Gilteritinib: (Major) Avoid concomitant use of sirolimus and gilteritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Major) Avoid concomitant use of sirolimus and glecaprevir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and glecaprevir is a P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and pibrentasvir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and pibrentasvir is a P-gp inhibitor.
Glycerol Phenylbutyrate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with glycerol phenylbutyrate. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Ibrutinib: (Major) Avoid concomitant use of sirolimus and ibrutinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and ibrutinib is a P-gp inhibitor.
Idelalisib: (Major) Avoid concomitant use of sirolimus and idelalisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Imatinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of imatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Indinavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Isavuconazonium: (Major) Avoid concomitant use of sirolimus and isavuconazonium. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and isavuconazonium is a moderate CYP3A and P-gp inhibitor.
Isoniazid, INH: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of isoniazid. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and isoniazid is a weak CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concomitant use of sirolimus and rifampin as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and rifampin is a strong CYP3A and P-gp inducer. (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of isoniazid. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and isoniazid is a weak CYP3A inhibitor.
Isoniazid, INH; Rifampin: (Major) Avoid concomitant use of sirolimus and rifampin as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and rifampin is a strong CYP3A and P-gp inducer. (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of isoniazid. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and isoniazid is a weak CYP3A inhibitor.
Istradefylline: (Major) Avoid concomitant use of sirolimus and istradefylline. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and istradefylline is a weak CYP3A and P-gp inhibitor.
Itraconazole: (Major) Avoid concomitant use of sirolimus and itraconazole. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and itraconazole is a strong CYP3A and P-gp inhibitor.
Ivacaftor: (Major) Avoid concomitant use of sirolimus and ivacaftor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ivacaftor is a weak CYP3A and P-gp inhibitor.
Ivosidenib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with ivosidenib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and ivosidenib is a weak CYP3A inducer.
Ketoconazole: (Major) Avoid concomitant use of sirolimus and ketoconazole. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ketoconazole is a strong CYP3A and P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of sirolimus and clarithromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and clarithromycin is a strong CYP3A and P-gp inhibitor.
Lapatinib: (Major) Avoid concomitant use of sirolimus and lapatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and lapatinib is a weak CYP3A and P-gp inhibitor.
Larotrectinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of larotrectinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and larotrectinib is a weak CYP3A inhibitor.
Lasmiditan: (Major) Avoid concomitant use of sirolimus and lasmiditan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Major) Avoid concomitant use of sirolimus and ledipasvir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and ledipasvir is a P-gp inhibitor.
Lefamulin: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of lefamulin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and lefamulin is a moderate CYP3A inhibitor.
Lenacapavir: (Major) Avoid concomitant use of sirolimus and lenacapavir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and lenacapavir is a moderate CYP3A and P-gp inhibitor.
Letermovir: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of letermovir. Avoid the use of nab-sirolimus with letermovir plus cyclosporine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor; combination letermovir plus cyclosporine has a net effect similar to that of a strong CYP3A inhibitor.
Levamlodipine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Levoketoconazole: (Major) Avoid concomitant use of sirolimus and ketoconazole. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ketoconazole is a strong CYP3A and P-gp inhibitor.
Lisinopril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Live Vaccines: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Lomitapide: (Major) Avoid concomitant use of sirolimus and lomitapide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lomitapide is a P-gp inhibitor.
Lonafarnib: (Major) Avoid concomitant use of sirolimus and lonafarnib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and lonafarnib is a strong CYP3A and P-gp inhibitor.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Lorlatinib: (Major) Avoid concomitant use of sirolimus and lorlatinib as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and lorlatinib is a moderate CYP3A and P-gp inducer.
Lovastatin: (Major) Guidelines recommend avoiding coadministration of lovastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of sirolimus and ivacaftor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ivacaftor is a weak CYP3A and P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and lumacaftor; ivacaftor as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and lumacaftor is a strong CYP3A and P-gp inducer.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of sirolimus and lumacaftor; ivacaftor as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and lumacaftor is a strong CYP3A and P-gp inducer.
Maribavir: (Major) Avoid concomitant use of sirolimus and maribavir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and maribavir is a weak CYP3A and P-gp inhibitor.
Mavacamten: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with mavacamten. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Mefloquine: (Major) Avoid concomitant use of sirolimus and mefloquine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and mefloquine is a P-gp inhibitor.
Meropenem: (Major) Avoid concomitant use of sirolimus and meropenem as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
Meropenem; Vaborbactam: (Major) Avoid concomitant use of sirolimus and meropenem as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and meropenem is a weak CYP3A and P-gp inducer.
Methohexital: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Micafungin: (Moderate) Monitor for an increase in sirolimus-related adverse effects and adjust sirolimus dosage as appropriate based on response if concomitant use with micafungin is required. Concomitant use has been observed to increase sirolimus overall exposure by 21% without an effect on sirolimus peak.
Mifepristone: (Contraindicated) Concomitant use of sirolimus and mifepristone is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Mitapivat: (Major) Avoid concomitant use of sirolimus and mitapivat. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and mitapivat is a weak CYP3A inducer and P-gp inhibitor.
Mitotane: (Major) Avoid concomitant use of sirolimus and mitotane as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and mitotane is a strong CYP3A inducer.
Mobocertinib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with mobocertinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and mobocertinib is a weak CYP3A inducer.
Modafinil: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with modafinil. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and modafinil is a weak CYP3A inducer.
Moexipril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Nafcillin: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with nafcillin. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and nafcillin is a moderate CYP3A inducer.
Natalizumab: (Major) The concomitant use of natalizumab and immunosuppressives may further increase the risk of infections, including progressive multifocal leukoencephalopathy (PML), over the risk observed with use of natalizumab alone. Prior treatment with an immunosuppressant is also a risk factor for PML. The safety and efficacy of natalizumab in combination with immunosuppressants has not been evaluated. Multiple sclerosis (MS) patients receiving chronic immunosuppressant therapy should not ordinarily be treated with natalizumab. Also, natalizumab for Crohn's disease should not be used in combination with sirolimus.
Nefazodone: (Major) Avoid concomitant use of sirolimus and nefazodone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Neratinib: (Major) Avoid concomitant use of sirolimus and neratinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and neratinib is a P-gp inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of netupitant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nevirapine: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with nevirapine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nicardipine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of nicardipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and nicardipine is a weak CYP3A inhibitor.
Nilotinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of nilotinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. (Major) Before prescribing ritonavir-boosted nirmatrelvir for a patient receiving sirolimus, the patient's specialist provider(s) should be consulted, given the significant drug-drug interaction potential and because close monitoring may not be feasible. If this is not feasible, consider an alternative COVID-19 therapy. Coadministration may increase sirolimus exposure resulting in increased toxicity. Sirolimus is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Nirogacestat: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of nirogacestat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Odevixibat: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with odevixibat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Olutasidenib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with olutasidenib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and olutasidenib is a weak CYP3A inducer.
Omaveloxolone: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with omaveloxolone. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and omaveloxolone is a weak CYP3A inducer.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with rifabutin. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Oritavancin: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with oritavancin. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and oritavancin is a weak CYP3A inducer.
Osilodrostat: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of osilodrostat. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and osilodrostat is a weak CYP3A inhibitor.
Osimertinib: (Major) Avoid concomitant use of sirolimus and osimertinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and osimertinib is a P-gp inhibitor.
Oxcarbazepine: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with oxcarbazepine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and oxcarbazepine is a weak CYP3A inducer.
Pacritinib: (Major) Avoid concomitant use of sirolimus and pacritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and pacritinib is a weak CYP3A and P-gp inhibitor.
Palbociclib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of palbociclib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and palbociclib is a weak CYP3A inhibitor.
Pazopanib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of pazopanib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and pazopanib is a weak CYP3A inhibitor.
Pentobarbital: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Perindopril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Perindopril; Amlodipine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor. (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Pexidartinib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with pexidartinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Phenobarbital: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Phentermine; Topiramate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with topiramate. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and topiramate is a weak CYP3A inducer.
Phenytoin: (Major) Avoid concomitant use of sirolimus and phenytoin/fosphenytoin as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and phenytoin/fosphenytoin is a strong CYP3A and P-gp inducer.
Pirtobrutinib: (Major) Avoid concomitant use of sirolimus and pirtobrutinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and pirtobrutinib is a weak CYP3A and P-gp inhibitor.
Pitavastatin: (Major) Guidelines recommend avoiding coadministration of pitavastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Pitolisant: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with pitolisant. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and pitolisant is a weak CYP3A inducer.
Posaconazole: (Contraindicated) Coadministration of posaconazole and sirolimus is contraindicated. Concomitant use has been observed to increase overall sirolimus exposure by approximately 9-fold which may increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Pravastatin: (Moderate) Carefully weigh the benefits of combined use of sirolimus and pravastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of pravastatin to 40 mg/day if combined with sirolimus.
Pretomanid: (Major) Avoid concomitant use of sirolimus and pretomanid. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and pretomanid is a P-gp inhibitor.
Primidone: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Propafenone: (Major) Avoid concomitant use of sirolimus and propafenone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and propafenone is a P-gp inhibitor.
Protease inhibitors: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Quinapril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Quinidine: (Major) Avoid concomitant use of sirolimus and quinidine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and quinidine is a P-gp inhibitor.
Quinine: (Major) Avoid concomitant use of sirolimus and quinine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and quinine is a weak CYP3A and P-gp inhibitor.
Ramipril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Ranolazine: (Major) Avoid concomitant use of sirolimus and ranolazine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ranolazine is a weak CYP3A and P-gp inhibitor.
Repotrectinib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with repotrectinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer.
Ribociclib: (Major) Avoid concomitant use of sirolimus and ribociclib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Major) Avoid concomitant use of sirolimus and ribociclib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifabutin: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with rifabutin. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Rifampin: (Major) Avoid concomitant use of sirolimus and rifampin as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and rifampin is a strong CYP3A and P-gp inducer.
Rifapentine: (Major) Avoid concomitant use of sirolimus and rifapentine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ritlecitinib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of ritlecitinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Rolapitant: (Major) Avoid concomitant use of sirolimus and rolapitant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and rolapitant is a P-gp inhibitor.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Rucaparib: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of rucaparib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and rucaparib is a weak CYP3A inhibitor.
Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as sirolimus, may occur during concurrent use with rufinamide.
Saquinavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Sarecycline: (Major) Avoid concomitant use of sirolimus and sarecycline. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and sarecycline is a P-gp inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid concomitant use of sirolimus and barbiturates as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and barbiturates are strong CYP3A and P-gp inducers.
Selpercatinib: (Major) Avoid concomitant use of sirolimus and selpercatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and selpercatinib is a weak CYP3A and P-gp inhibitor.
Simvastatin: (Major) Guidelines recommend avoiding coadministration of simvastatin with sirolimus due to the potential for increased risk of myopathy/rhabdomyolysis. Consider use of an alternative statin such as atorvastatin, fluvastatin, pravastatin, or rosuvastatin with dose limitations in patients receiving sirolimus.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid concomitant use of sirolimus and taurursodiol. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and taurursodiol is a weak CYP3A inducer and P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Major) Avoid concomitant use of sirolimus and velpatasvir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of sirolimus and velpatasvir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and velpatasvir is a P-gp inhibitor. (Major) Avoid concomitant use of sirolimus and voxilaprevir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and voxilaprevir is a P-gp inhibitor.
Sorafenib: (Major) Avoid concomitant use of sirolimus and sorafenib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and sorafenib is a P-gp inhibitor.
Sotorasib: (Major) Avoid concomitant use of sirolimus and sotorasib. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and sotorasib is a moderate CYP3A inducer and P-gp inhibitor.
Sparsentan: (Major) Avoid concomitant use of sirolimus and sparsentan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and sparsentan is a P-gp inhibitor.
Spironolactone: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of spironolactone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of spironolactone. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of sirolimus and St. John's wort as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and St. John's wort is a strong CYP3A and P-gp inducer.
Stiripentol: (Major) Avoid concomitant use of sirolimus and stiripentol. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and stiripentol is a weak CYP3A inducer and P-gp inhibitor.
Streptogramins: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of quinupristin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and quinupristin is a weak CYP3A inhibitor.
Tacrolimus: (Moderate) The concomitant use of sirolimus with a calcineurin inhibitor, such as tacrolimus, may increase the risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy. In addition to a potential increased risk of thrombotic microangiopathy, sirolimus may decrease the blood concentration of tacrolimus.
Tazemetostat: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with tazemostat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and tazemostat is a weak CYP3A inducer.
Tecovirimat: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with tecovirimat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and tecovirimat is a weak CYP3A inducer.
Teduglutide: (Moderate) Teduglutide may increase absorption of sirolimus because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of sirolimus is recommended.
Telmisartan; Amlodipine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of amlodipine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and amlodipine is a weak CYP3A inhibitor.
Telotristat Ethyl: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with telotristat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and telotristat is a weak CYP3A inducer.
Temsirolimus: (Contraindicated) Do not use sirolimus concomitantly with temsirolimus. Temsirolimus is extensively metabolized in the liver primarily by cytochrome P450 3A4, but also by P-glycoprotein (P-gp). Five metabolites are formed, but sirolimus is the principal and active metabolite; the remainder of the metabolites account for less than 10% of radioactivity in plasma. Residual sirolimus concentrations are present up to a week after temsirolimus administration.
Tepotinib: (Major) Avoid concomitant use of sirolimus and tepotinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tezacaftor; Ivacaftor: (Major) Avoid concomitant use of sirolimus and ivacaftor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ivacaftor is a weak CYP3A and P-gp inhibitor.
Ticagrelor: (Major) Avoid concomitant use of sirolimus and ticagrelor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and ticagrelor is a weak CYP3A and P-gp inhibitor.
Tipranavir: (Major) Avoid concomitant use of sirolimus and protease inhibitors; a sirolimus dosage reduction may be considered if concomitant use is necessary. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects.
Tofacitinib: (Major) Concomitant use of tofacitinib with potent immunosuppressants, such as sirolimus, is not recommended; coadministration may result in additive immunosuppression and increased risk of infection. Combined use of multiple-dose tofacitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
Topiramate: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with topiramate. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and topiramate is a weak CYP3A inducer.
Trandolapril: (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Trandolapril; Verapamil: (Major) Avoid concomitant use of sirolimus and verapamil. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and verapamil is a moderate CYP3A and P-gp inhibitor. (Moderate) Sirolimus has been associated with the development of angioedema. The use of sirolimus with other drugs known to cause angioedema, such as angiotensin-converting enzyme inhibitors may increase the risk of developing angioedema. Patients should be monitored for angioedema if any of these drugs are coadministered with sirolimus.
Trofinetide: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of trofinetide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Major) Avoid concomitant use of sirolimus and tucatinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and tucatinib is a strong CYP3A and P-gp inhibitor.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Upadacitinib: (Major) Avoid use of upadacitinib in combination with potent immunosuppressants such as sirolimus. A risk of added immunosuppression exists when upadacitinib is coadministered with potent immunosuppressives. Combined use of multiple-dose upadacitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Vemurafenib: (Major) Avoid concomitant use of sirolimus and vemurafenib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and vemurafenib is a P-gp inhibitor.
Venetoclax: (Major) Avoid concomitant use of sirolimus and venetoclax. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and venetoclax is a P-gp inhibitor.
Verapamil: (Major) Avoid concomitant use of sirolimus and verapamil. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and verapamil is a moderate CYP3A and P-gp inhibitor.
Viloxazine: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of viloxazine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and viloxazine is a weak CYP3A inhibitor.
Voclosporin: (Major) Avoid concomitant use of sirolimus and voclosporin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of vonoprazan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of vonoprazan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of sirolimus and clarithromycin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and clarithromycin is a strong CYP3A and P-gp inhibitor. (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of vonoprazan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Contraindicated) Concomitant use of voriconazole with sirolimus is contraindicated; use may increase sirolimus exposure and risk for adverse effects. Sirolimus is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration has been observed to increase sirolimus peak and overall exposure by 7- and 11-fold, respectively
Voxelotor: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of voxelotor. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines to sirolimus recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving sirolimus. At least 2 weeks before initiation of sirolimus therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Sirolimus recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Zafirlukast: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of zafirlukast. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and zafirlukast is a weak CYP3A inhibitor.
Zanubrutinib: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with zanubrutinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and zanubrutinib is a weak CYP3A inducer.
Zonisamide: (Major) Avoid concomitant use of sirolimus and zonisamide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and zonisamide is a P-gp inhibitor.
Nanoparticle albumin-bound (nab)-sirolimus is an immunosuppressant that inhibits the mechanistic target of rapamycin kinase (mTOR), a protein that is downstream of the PI3K/AKT pathway, which prevents tumor cell survival, growth, and proliferation. Sirolimus works by binding to the immunophilin, FK Binding Protein-12 (FKBP-12) inhibiting the activation of mTOR complex 1. In mice, IV administration of sirolimus resulted in a higher tumor accumulation of sirolimus, inhibition of an mTOR target in the tumor, and tumor growth inhibition compared with an oral formulation of sirolimus at the same weekly dose.
Nanoparticle albumin-bound (nab)-sirolimus is administered intravenously. It is more than 99% bound to serum albumin in vitro. The mean elimination half-life of nab-sirolimus is 59 hours (coefficient of variation, 41%). Nab-sirolimus is metabolized in the liver via CYP3A4. In human subjects who received a single dose of radiolabeled nab-sirolimus, 91% of the radioactivity was recovered in the feces and 2% of the radioactivity was recovered in the urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
Sirolimus is a substrate of CYP3A4 and P-glycoprotein (P-gp).
-Route-Specific Pharmacokinetics
Intravenous Route
Following administration of nab-sirolimus at the recommended dosage, the estimated mean Cmax and AUC(0-inf) values of sirolimus were 2,590 nanograms/mL (coefficient of variation (CV), 30%) and 22,100 nanograms X hour/mL (CV, 50%), respectively, in patients with advanced solid tumors.
-Special Populations
Renal Impairment
Mild or moderate renal impairment (creatinine clearance, 30 to 89 mL/min) did not have a clinically significant impact on the pharmacokinetic values of sirolimus. Nab-sirolimus use has not been evaluated in patients with severe renal impairment.
Geriatric
Age (range, 18 to 78 years) did not have a clinically significant impact on the pharmacokinetic values of sirolimus.
Gender Differences
Sex did not have a clinically significant impact on the pharmacokinetic values of sirolimus.