sirolimus (Rx)

Prophylaxis of Renal Transplant Rejection

Initiate with concomitant cyclosporine and corticosteroids

Oral solution and tablets interchangeable on a mg per mg basis

Target whole blood trough concentrations: 16-24 ng/mL for the first year following transplantation; thereafter, 12-20 ng/mL

High immunologic risk

• <40 kg: 3 mg/m² loading dose
• ≥40 kg: 15 mg PO loading dose
• Maintenance: 5 mg/day PO if >40 kg and 1 mg/m²/day if <40 kg on day 2 and thereafter; obtain trough levels between days 5 and 7
• Dose adjustments: Dose should be adjusted to maintain trough concentrations within desired range based on clinical state and concomitant therapy; further dose adjustment should not be done sooner than 7-14 days following a dose adjustment
• Concomitant therapy: For the first year, following transplantation, sirolimus should be used in combination with cyclosporine and corticosteroids; cyclosporine may be initiated at 7 mg/kg/day in divided doses with the dose adjusted to achieve trough concentrations; prednisone should be given at a dose of 5 mg/day

Low-to-moderate immunologic risk

• <40 kg: 3 mg/m² loading dose
• ≥40 kg: 6 mg PO loading dose
• Maintenance: 2 mg/day PO if ≥ 40 kg and 1 mg/m²/day if <40 kg on day 2 and thereafter; obtain trough levels between days 5 and 7
• Dose adjustments: Dose should be adjusted to maintain trough concentrations within desired range based on clinical state and concomitant therapy; further dose adjustment should not be done sooner than 7-14 days following a dose adjustment
• Concomitant therapy: Following transplantation, sirolimus should be used in combination with cyclosporine and corticosteroids; may discontinue cyclosporine gradually over 4-8 weeks two to four months after transplant in patients with low immunologic risk, & sirolimus dose increased (serum concentrations of sirolimus may decrease following cyclosporine withdrawal)

Lymphangioleiomyomatosis

Indicated for treatment of lymphangioleiomyomatosis (LAM)

Initial: 2 mg/day PO x10-20 days and then measure whole blood trough level

Therapeutic drug monitoring (LAM)

• Adjust dose to maintain target concentrations between 5-15 ng/mL
• Calculate dose adjustment: New sirolimus dose = current dose x (target concentration/current concentration)
• Frequent dose adjustments based on nonsteady-state sirolimus concentrations can lead to overdosing or under dosing because sirolimus has a long half-life
• Once maintenance dose is adjusted, continue on the new maintenance dose for at least 7-14 days before further dosage adjustment with concentration monitoring
• Once a stable dose is achieved, monitor whole blood trough levels at least every 3 months

Dosage Modifications

Renal impairment

• Dose adjusment not necessary
• Adust dose of discontinue if serum creatinine increases when used in combination with cyclosporine

Hepatic impairment

• Loading dose: Dosage adjustment not required

• Maintenance dose

  • Mild-to-moderate (Child Pugh A or B): Reduce dose by 33%
  • Severe (Child Pugh C): Reduce dose by 50%

Orphan Designations

Bone sarcoma

• Sponsor: Merck; 126 E. Lincoln Avenue; Rahway, NJ 07065

Tuberous sclerosis complex

• Orphan designation for tuberous sclerosis complex-related facial angiofibromas

• Sponsors

  • OncoImmune, Inc; 333 Parkland Plaza, Suite 1000; Ann Arbor, MI 48103
  • Aucta Pharmaceuticals, LLC; 675 US Highway One; North Brunswick, New Jersey 08902
  • AI Therapeutics, Inc; 530 Old Whitfield Street; Guilford, Connecticut 06437

Uveitis

• Ophthalmic: Orphan designation for treatment of chronic/refractory anterior noninfectious uvetits afffecting the posterior segment of the eye
• Sponsor: Santen Pharmaceutical Co, Ltd; 2100 Powell Street, Suite 1600; Emeryville, California 94608

Pachyonychia congenita

• Sponsor: Santen Pharmaceutical Co, Ltd; 2100 Powell Street, Suite 1600; Emeryville, California 94608

Angiofibromas

• Orphan designation for treatment of facial angiofibromas (FA) associated with tuberous sclerosis complex (TSC)
• DSLP; 129 Hurstmere Road, Level 1, Nielsen Building; Auckland

Beta-thalassemia

• Sponsor: Rare Partners srl Impresa Sociale; 31 Corso Magenta; Milano, Italy

Pulmonary arterial hypertension

• Sponsor: Lam Therapeutics; 530 Old Whitfield Street; Guilford, Connecticut 06437

Sickle cell disease

• Sponsor: Rare Partners srl Impresa Sociale; 31 Corso Magenta Milano, Italy

Familial adenomatous polyposis

• Orphan designation for encapsulated formulation (Erapa) for treatment of familial adenomatous polyposis
• Orphan sponsor: Emtora Biosciences Inc; 16601 Blanco Road, Suite 120; San Antonio, Texas 78232

Prophylaxis of Renal Transplant Rejection

<13 years: Not recommended

≥13 years:

High Immunologic Risk

• Loading dose: <40 kg: 3 mg/m² PO
• Loading dose ≥40 kg: 15 mg PO
• Maintenance: 5 mg/day PO if >40 kg and 1 mg/m²/day if <40 kg on day 2 and thereafter; obtain trough levels between days 5 and 7
• Dose adjustments: Dose should be adjusted to maintain trough concentrations within desired range based on clinical state and concomitant therapy; further dose adjustment should not be done sooner than 7-14 days following a dose adjustment
• Concomitant therapy: For the first year, following transplantation, sirolimus should be used in combination with cyclosporine and corticosteroids; cyclosporine may be initiated at 7 mg/kg/day in divided doses with the dose adjusted to achieve trough concentrations; prednisone should be given at a dose of 5 mg/day

Low-to-moderate Immunologic risk

• Loading dose <40 kg: 3 mg/m² PO
• Loading dose ≥40 kg: 6 mg PO
• Maintenance: 2 mg/day PO if ≥ 40 kg and 1 mg/m²/day if <40 kg on day 2 and thereafter; obtain trough levels between days 5 and 7
• Dose adjustments: Dose should be adjusted to maintain trough concentrations within desired range based on clinical state and concomitant therapy; further dose adjustment should not be done sooner than 7-14 days following a dose adjustment
• Concomitant therapy: Following transplantation, sirolimus should be used in combination with cyclosporine and corticosteroids; may discontinue cyclosporine gradually over 4-8 weeks two to four months after transplant in patients with low immunologic risk, & sirolimus dose increased (serum concentrations of sirolimus may decrease following cyclosporine withdrawal)

Contraindicated (4)

• ketoconazole

  ketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.

• levoketoconazole

  levoketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.

• mifepristone

  mifepristone increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with CYP3A substrates that have a narrow therapeutic index .

• voriconazole

  voriconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  voriconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.

Serious - Use Alternative (173)

• abametapir

  abametapir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• adagrasib

  adagrasib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a P-gp inhibitor, with sensitive P-gp substrates unless otherwise recommended in the prescribing information for these substrates.

• adalimumab

  adalimumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• adenovirus types 4 and 7 live, oral

  sirolimus decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3mo after cessation of immunosuppressive therapy.

• alefacept

  alefacept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• anakinra

  anakinra and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• anthrax vaccine

  sirolimus decreases effects of anthrax vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• antithymocyte globulin equine

  antithymocyte globulin equine and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• antithymocyte globulin rabbit

  antithymocyte globulin rabbit and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  aprepitant will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• armodafinil

  armodafinil will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• atazanavir

  atazanavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• axicabtagene ciloleucel

  sirolimus, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• azathioprine

  azathioprine and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• basiliximab

  basiliximab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• BCG vaccine live

  sirolimus decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• blinatumomab

  blinatumomab increases levels of sirolimus by decreasing metabolism. Avoid or Use Alternate Drug. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bosentan

  bosentan will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bremelanotide

  bremelanotide will decrease the level or effect of sirolimus by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexucabtagene autoleucel

  sirolimus, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• brigatinib

  brigatinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• budesonide

  budesonide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• butabarbital

  butabarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• butalbital

  butalbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• canakinumab

  canakinumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• carbamazepine

  carbamazepine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ceritinib

  ceritinib increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose.

• chloramphenicol

  chloramphenicol will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ciltacabtagene autoleucel

  sirolimus, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• cimetidine

  cimetidine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• conivaptan

  conivaptan will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cortisone

  cortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  darifenacin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dasatinib

  dasatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• dexamethasone

  dexamethasone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• DHEA, herbal

  DHEA, herbal will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diphtheria & tetanus toxoids

  sirolimus decreases effects of diphtheria & tetanus toxoids by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• diphtheria & tetanus toxoids/ acellular pertussis vaccine

  sirolimus decreases effects of diphtheria & tetanus toxoids/ acellular pertussis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine

  sirolimus decreases effects of diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• efavirenz

  efavirenz will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• enzalutamide

  enzalutamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  erdafitinib, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with erdafitinib and sensitive CYP3A4 substrates with narrow therapeutic indices. Erdafitinib may altered plasma concentrations of CYP3A4 substrates, leading to either loss of activity or increased toxicity of the substrate.
  
  erdafitinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

• erythromycin base

  erythromycin base will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• etanercept

  etanercept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• etravirine

  etravirine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• everolimus

  everolimus and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• fexinidazole

  fexinidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fluconazole

  fluconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fludrocortisone

  fludrocortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosamprenavir

  fosamprenavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fosaprepitant

  fosaprepitant will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fosphenytoin

  fosphenytoin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• glatiramer

  glatiramer and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• golimumab

  golimumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• grapefruit

  grapefruit will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• griseofulvin

  griseofulvin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• hepatitis A vaccine inactivated

  sirolimus decreases effects of hepatitis A vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis a/b vaccine

  sirolimus decreases effects of hepatitis a/b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis a/typhoid vaccine

  sirolimus decreases effects of hepatitis a/typhoid vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis b vaccine

  sirolimus decreases effects of hepatitis b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• human papillomavirus vaccine, nonavalent

  sirolimus decreases effects of human papillomavirus vaccine, nonavalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.

• human papillomavirus vaccine, quadrivalent

  sirolimus decreases effects of human papillomavirus vaccine, quadrivalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.

• hydrocortisone

  hydrocortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• hydroxychloroquine sulfate

  hydroxychloroquine sulfate and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• idecabtagene vicleucel

  sirolimus, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• idelalisib

  idelalisib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• indinavir

  indinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• infliximab

  infliximab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• influenza virus vaccine quadrivalent

  sirolimus decreases effects of influenza virus vaccine quadrivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine quadrivalent, adjuvanted

  sirolimus decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

• influenza virus vaccine quadrivalent, cell-cultured

  sirolimus decreases effects of influenza virus vaccine quadrivalent, cell-cultured by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine quadrivalent, intranasal

  sirolimus decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine trivalent

  sirolimus decreases effects of influenza virus vaccine trivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine trivalent, adjuvanted

  sirolimus decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

• isoniazid

  isoniazid will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• itraconazole

  itraconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.
  
  itraconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.

• ivosidenib

  ivosidenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• Japanese encephalitis virus vaccine

  sirolimus decreases effects of Japanese encephalitis virus vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• ketoconazole

  ketoconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lapatinib

  lapatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• larotrectinib

  larotrectinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lasmiditan

  lasmiditan increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• leflunomide

  leflunomide and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• levoketoconazole

  levoketoconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lisocabtagene maraleucel

  sirolimus, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• lonafarnib

  lonafarnib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
  
  sirolimus will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• lopinavir

  lopinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lorlatinib

  lorlatinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• lumefantrine

  lumefantrine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• marijuana

  marijuana will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• measles (rubeola) vaccine

  sirolimus decreases effects of measles (rubeola) vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• measles mumps and rubella vaccine, live

  sirolimus decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• measles, mumps, rubella and varicella vaccine, live

  sirolimus decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• meningococcal A C Y and W-135 polysaccharide vaccine combined

  sirolimus decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• methylprednisolone

  methylprednisolone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• metronidazole

  metronidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• mobocertinib

  mobocertinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• muromonab CD3

  muromonab CD3 and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• mycophenolate

  mycophenolate and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• nafcillin

  nafcillin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nefazodone

  nefazodone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  nelfinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nevirapine

  nevirapine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nifedipine

  nifedipine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nilotinib

  nilotinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nirmatrelvir

  nirmatrelvir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• olutasidenib

  olutasidenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pacritinib

  pacritinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pentobarbital

  pentobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  pexidartinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.

• phenobarbital

  phenobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenytoin

  phenytoin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• pneumococcal vaccine 13-valent

  sirolimus decreases effects of pneumococcal vaccine 13-valent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• pneumococcal vaccine heptavalent

  sirolimus decreases effects of pneumococcal vaccine heptavalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• pneumococcal vaccine polyvalent

  sirolimus decreases effects of pneumococcal vaccine polyvalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• posaconazole

  posaconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• prednisone

  prednisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pregabalin

  sirolimus, pregabalin. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration results in additive risk of developing angioedema of face, mouth, and neck. Angioedema may result in respiratory compromise.

• primidone

  primidone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• quinidine

  quinidine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rabies vaccine

  sirolimus decreases effects of rabies vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants may interfere with development of active immunity.

• rabies vaccine chick embryo cell derived

  sirolimus decreases effects of rabies vaccine chick embryo cell derived by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• rifabutin

  rifabutin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  rifampin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  rifapentine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rilonacept

  rilonacept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• ritonavir

  ritonavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b, sirolimus. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• rotavirus oral vaccine, live

  sirolimus decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• rubella vaccine

  sirolimus decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• rufinamide

  rufinamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• saquinavir

  saquinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• secobarbital

  secobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• smallpox (vaccinia) vaccine, live

  sirolimus decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• sotorasib

  sotorasib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications
  
  sotorasib will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• St John's Wort

  St John's Wort will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tacrolimus

  sirolimus and tacrolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• temsirolimus

  sirolimus and temsirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tepotinib

  tepotinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• tetanus toxoid adsorbed or fluid

  sirolimus decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• tick-borne encephalitis vaccine

  sirolimus decreases effects of tick-borne encephalitis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• tipranavir

  tipranavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tisagenlecleucel

  sirolimus, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tocilizumab

  tocilizumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tofacitinib

  sirolimus, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tongkat ali

  sirolimus and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• topiramate

  topiramate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• travelers diarrhea and cholera vaccine inactivated

  sirolimus decreases effects of travelers diarrhea and cholera vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tucatinib

  tucatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• typhoid polysaccharide vaccine

  sirolimus decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• typhoid vaccine live

  sirolimus decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• upadacitinib

  sirolimus, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.

• ustekinumab

  sirolimus and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• varicella virus vaccine live

  sirolimus decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• venetoclax

  venetoclax will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. In vitro data suggest venetoclax may inhibit P-gp substrates at therapeutic dose levels in the gut. Avoid coadministration of narrow therapeutic index P-gp substrates with venetoclax. If a narrow therapeutic index P-gp substrate must be used, it should be taken at least 6 hr before venetoclax.

• verapamil

  verapamil will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  verapamil will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  verapamil, sirolimus. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: With concomitant use of mTOR inhibitors, consider appropriate dose reductions of both medications.

• voxelotor

  voxelotor will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• yellow fever vaccine

  sirolimus decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• zafirlukast

  zafirlukast will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• zoster vaccine live

  sirolimus decreases effects of zoster vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

Monitor Closely (188)

• abrocitinib

  abrocitinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor and titrate dose of P-gp substrate appropriately.

• amikacin

  sirolimus will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amiodarone

  amiodarone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amitriptyline

  sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amobarbital

  amobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• astragalus

  sirolimus increases and astragalus decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atogepant

  sirolimus will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

  atorvastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avapritinib

  sirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axitinib

  sirolimus increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  sirolimus will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• belatacept

  belatacept and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• benazepril

  benazepril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• berotralstat

  berotralstat will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

• bosutinib

  bosutinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• brodalumab

  brodalumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• budesonide

  sirolimus will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cannabidiol

  cannabidiol will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

• captopril

  captopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• cenobamate

  cenobamate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• cholera vaccine

  sirolimus decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• clarithromycin

  clarithromycin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clotrimazole

  clotrimazole will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cobicistat

  cobicistat will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• conjugated estrogens

  sirolimus will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

  sirolimus will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cortisone

  sirolimus will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• crizotinib

  crizotinib increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.
  
  crizotinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• crofelemer

  crofelemer increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclosporine

  cyclosporine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Simultaneous coadministration significantly increases sirolimus levels; this is minimized by administering sirolimus 4 hr after cyclosporine
  
  cyclosporine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Simultaneous coadministration significantly increases sirolimus levels; this is minimized by administering sirolimus 4 hr after cyclosporine
  
  cyclosporine, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor.
  
  sirolimus increases toxicity of cyclosporine by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Elevations in serum creatinine, hemolytic uremic syndrome, TTP, and microangiopathy were observed when sirolimus used in combination with cyclosporine. Administer oral doses of sirolimus 4 hr after doses of cyclosporine.

• dabrafenib

  dabrafenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• darunavir

  darunavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• deferasirox

  deferasirox will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  sirolimus will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dengue vaccine

  sirolimus decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

• denosumab

  sirolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.

• dexamethasone

  sirolimus will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dichlorphenamide

  dichlorphenamide and sirolimus both decrease serum potassium. Use Caution/Monitor.

• digoxin

  sirolimus will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• diltiazem

  diltiazem will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• docetaxel

  sirolimus will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dronabinol

  dronabinol increases levels of sirolimus by plasma protein binding competition. Modify Therapy/Monitor Closely. Dronabinol is highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered highly protein-bound drugs. This has not been confirmed in vivo. Caution with narrow therapeutic index drugs that are highly protein bound when initiating or increasing the dose of dronabinol.

• dronedarone

  dronedarone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for sirolimus toxicity and adjust dose as needed.
  
  dronedarone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If given together, monitor for sirolimus toxicity and adjust dose as needed.

• dulaglutide

  dulaglutide, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• dupilumab

  dupilumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• duvelisib

  duvelisib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• echinacea

  sirolimus increases and echinacea decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• elacestrant

  elacestrant will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduce dose of P-gp substrates per their Prescribing Information when minimal concentration changes may lead to serious or life-threatening adverse reactions.

• elagolix

  elagolix will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  elagolix decreases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eliglustat

  eliglustat increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

• eluxadoline

  eluxadoline increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enalapril

  enalapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• encorafenib

  encorafenib, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• erythromycin base

  erythromycin base will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estradiol

  sirolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens conjugated synthetic

  sirolimus will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estropipate

  sirolimus will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felodipine

  felodipine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ferric maltol

  ferric maltol, sirolimus. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• finerenone

  sirolimus will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• fingolimod

  sirolimus increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .

• flibanserin

  flibanserin increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Increase monitoring of concentrations of drugs transported by P-gp that have a narrow therapeutic index if coadministered with flibanserin.
  
  sirolimus will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• fludrocortisone

  sirolimus will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fosinopril

  fosinopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• fosphenytoin

  fosphenytoin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• gentamicin

  sirolimus will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• glecaprevir/pibrentasvir

  glecaprevir/pibrentasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• glycerol phenylbutyrate

  glycerol phenylbutyrate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.

• haemophilus influenzae type b vaccine

  sirolimus decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• hydrocortisone

  sirolimus will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ifosfamide

  ifosfamide, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with ifosfamide may increase the risk of immunosuppression and myelosuppression.

• iloperidone

  iloperidone increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• indinavir

  indinavir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• influenza virus vaccine quadrivalent, recombinant

  sirolimus decreases effects of influenza virus vaccine quadrivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.

• influenza virus vaccine trivalent, recombinant

  sirolimus decreases effects of influenza virus vaccine trivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.

• irinotecan liposomal

  sirolimus will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• isavuconazonium sulfate

  sirolimus will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isavuconazonium sulfate will increase the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Isavuconazonium sulfate, an inhibitor of P-gp and CYP3A4, may increase the effects or levels of sensitive P-gp or CYP3A4 substrates, which may require dose adjustment.
  
  sirolimus and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
  
  istradefylline will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• ivacaftor

  ivacaftor increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ivermectin

  sirolimus will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ixekizumab

  ixekizumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• ketoconazole

  ketoconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lapatinib

  lapatinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lemborexant

  sirolimus will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

• letermovir

  letermovir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor sirolimus plasma concentrations during treatment and after discontinuation of letemovir and adjust dose of sirolimus accordingly. When letermovir is coadministered with cyclosporine, sirolimus is recommended to be taken 4 hr after cyclosporine oral (MODIFIED) administration. Higher doses of sirolimus are needed to maintain the recommended sirolimus trough concentration ranges if cyclosporine is discontinued from combination therapy.

• levoketoconazole

  levoketoconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lisinopril

  lisinopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• lomitapide

  sirolimus increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
  
  lomitapide increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

• lomustine

  lomustine, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with lomustine may increase the risk of immunosuppression and myelosuppression.

• lonafarnib

  lonafarnib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

• loperamide

  sirolimus will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• loratadine

  loratadine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lovastatin

  lovastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• maitake

  sirolimus increases and maitake decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• maraviroc

  sirolimus will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• mechlorethamine

  mechlorethamine, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with mechlorethamine may increase the risk of immunosuppression and myelosuppression.

• meningococcal group B vaccine

  sirolimus decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.

• mercaptopurine

  mercaptopurine and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• mestranol

  sirolimus will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metformin

  sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methotrexate

  methotrexate and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.

• methylprednisolone

  sirolimus will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metoclopramide intranasal

  metoclopramide intranasal will increase the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Metoclopramide may increase the absorption of sirolimus. Monitor therapeutic drug concentrations and adjust the dose as needed.

• micafungin

  micafungin increases levels of sirolimus by unspecified interaction mechanism. Use Caution/Monitor.

• midazolam intranasal

  sirolimus will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• mitotane

  mitotane decreases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• moexipril

  moexipril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• nefazodone

  nefazodone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nelfinavir

  sirolimus will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neomycin PO

  sirolimus will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nicardipine

  nicardipine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  nifedipine will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nilotinib

  nilotinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ocrelizumab

  sirolimus and ocrelizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration of ocrelizumab with immunosuppressants may increase the risk of immunosuppression.

• ofatumumab SC

  ofatumumab SC, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

• olaparib

  sirolimus and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity.

• omaveloxolone

  omaveloxolone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.

• oritavancin

  oritavancin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP3A4 inducer; caution if coadministered with CYP3A4 substrates that have a narrow therapeutic index

• ozanimod

  ozanimod, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration with immunosuppressive therapies may increase the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs in order to avoid unintended additive immunosuppressive effects.

• paclitaxel

  sirolimus will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paclitaxel protein bound

  sirolimus will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• palbociclib

  palbociclib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib

• paliperidone

  sirolimus will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paromomycin

  sirolimus will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• perindopril

  perindopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• phenobarbital

  phenobarbital will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• phenytoin

  phenytoin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• pitolisant

  pitolisant will decrease the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

• poliovirus vaccine inactivated

  sirolimus decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• ponatinib

  ponatinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• ponesimod

  ponesimod and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• posaconazole

  sirolimus will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisolone

  sirolimus will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

  sirolimus will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quercetin

  quercetin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quinapril

  quinapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• ramipril

  ramipril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• ranolazine

  ranolazine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ribociclib

  ribociclib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

• rifampin

  rifampin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• risperidone

  sirolimus will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ritonavir

  ritonavir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rolapitant

  rolapitant will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Oral rolapitant (P-gp inhibitor) may increase plasma concentrations of P-gp substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of P-gp substrates and rolapitant can not be avoided.

• rucaparib

  rucaparib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• saquinavir

  sirolimus will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sarecycline

  sarecycline will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• sarilumab

  sarilumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

• secukinumab

  secukinumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• silodosin

  sirolimus will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siltuximab

  siltuximab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

• simvastatin

  simvastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siponimod

  siponimod and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• sipuleucel-T

  sirolimus decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.

• sofosbuvir/velpatasvir

  sofosbuvir/velpatasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Closely monitor P-gp substrates, particularly those with a narrow therapeutic index. Modify dose if needed.
  
  sofosbuvir/velpatasvir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

• spironolactone

  spironolactone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. sirolimus dose may need to be adjusted

• St John's Wort

  St John's Wort will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• stiripentol

  stiripentol, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

• streptomycin

  sirolimus will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tacrolimus

  sirolimus will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tazemetostat

  tazemetostat will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  sirolimus will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teclistamab

  teclistamab will increase the level or effect of sirolimus by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  tecovirimat will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• teduglutide

  teduglutide increases levels of sirolimus by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

• telotristat ethyl

  telotristat ethyl will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

• tenofovir DF

  sirolimus, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
  
  sirolimus increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

• tinidazole

  sirolimus will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  tipranavir, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Sirolimus levels may incr or decr, due to contradictory effects of tipranavir on hepatic CYP3A4 and P glycoprotein.

• tobramycin

  sirolimus will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tolvaptan

  sirolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  tolvaptan will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• trandolapril

  trandolapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• trastuzumab

  trastuzumab, sirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

• trastuzumab deruxtecan

  trastuzumab deruxtecan, sirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

• trazodone

  trazodone will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• trofinetide

  trofinetide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• tucatinib

  tucatinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• ublituximab

  ublituximab and sirolimus both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered

• ustekinumab

  ustekinumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• vemurafenib

  vemurafenib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vinblastine

  sirolimus will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine

  sirolimus will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine liposomal

  sirolimus will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• voclosporin

  voclosporin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.

• zoster vaccine recombinant

  sirolimus decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.

Minor (9)

• acetazolamide

  acetazolamide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alvimopan

  sirolimus will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• armodafinil

  sirolimus will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fexofenadine

  sirolimus will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• loratadine

  sirolimus will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• ruxolitinib

  sirolimus will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  sirolimus will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• abrocitinib

  Monitor Closely (1)abrocitinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor and titrate dose of P-gp substrate appropriately.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• adagrasib

  Serious - Use Alternative (1)adagrasib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a P-gp inhibitor, with sensitive P-gp substrates unless otherwise recommended in the prescribing information for these substrates.

• adalimumab

  Serious - Use Alternative (1)adalimumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• adenovirus types 4 and 7 live, oral

  Serious - Use Alternative (1)sirolimus decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3mo after cessation of immunosuppressive therapy.

• alefacept

  Serious - Use Alternative (1)alefacept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• alvimopan

  Minor (1)sirolimus will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• amikacin

  Monitor Closely (1)sirolimus will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amitriptyline

  Monitor Closely (1)sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amobarbital

  Monitor Closely (1)amobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• anakinra

  Serious - Use Alternative (1)anakinra and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anthrax vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of anthrax vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• antithymocyte globulin equine

  Serious - Use Alternative (1)antithymocyte globulin equine and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• antithymocyte globulin rabbit

  Serious - Use Alternative (1)antithymocyte globulin rabbit and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  Serious - Use Alternative (1)aprepitant will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• armodafinil

  Serious - Use Alternative (1)armodafinil will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)sirolimus will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• artemether/lumefantrine

  Serious - Use Alternative (1)artemether/lumefantrine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• astragalus

  Monitor Closely (1)sirolimus increases and astragalus decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atazanavir

  Serious - Use Alternative (1)atazanavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• atogepant

  Monitor Closely (1)sirolimus will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)atorvastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avapritinib

  Monitor Closely (1)sirolimus will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axicabtagene ciloleucel

  Serious - Use Alternative (1)sirolimus, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• axitinib

  Monitor Closely (1)sirolimus increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azathioprine

  Serious - Use Alternative (1)azathioprine and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• basiliximab

  Serious - Use Alternative (1)basiliximab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• bazedoxifene/conjugated estrogens

  Monitor Closely (1)sirolimus will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• BCG vaccine live

  Serious - Use Alternative (1)sirolimus decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• belatacept

  Monitor Closely (1)belatacept and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• benazepril

  Monitor Closely (1)benazepril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• berotralstat

  Monitor Closely (1)berotralstat will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

• blinatumomab

  Serious - Use Alternative (1)blinatumomab increases levels of sirolimus by decreasing metabolism. Avoid or Use Alternate Drug. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bosentan

  Serious - Use Alternative (1)bosentan will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bosutinib

  Monitor Closely (1)bosutinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of sirolimus by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexucabtagene autoleucel

  Serious - Use Alternative (1)sirolimus, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• brigatinib

  Serious - Use Alternative (1)brigatinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• brodalumab

  Monitor Closely (1)brodalumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• budesonide

  Monitor Closely (1)sirolimus will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)budesonide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• butabarbital

  Serious - Use Alternative (1)butabarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• butalbital

  Serious - Use Alternative (1)butalbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• canakinumab

  Serious - Use Alternative (1)canakinumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• cannabidiol

  Monitor Closely (1)cannabidiol will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Therapeutic drug monitoring and dose reduction of P-gp substrates should be considered when given orally and concurrently with cannabidiol

• captopril

  Monitor Closely (1)captopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• carbamazepine

  Serious - Use Alternative (1)carbamazepine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cenobamate

  Monitor Closely (1)cenobamate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Serious - Use Alternative (1)ceritinib increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cholera vaccine

  Monitor Closely (1)sirolimus decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• ciltacabtagene autoleucel

  Serious - Use Alternative (1)sirolimus, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• cimetidine

  Serious - Use Alternative (1)cimetidine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)clarithromycin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clotrimazole

  Monitor Closely (1)clotrimazole will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cobicistat

  Monitor Closely (1)cobicistat will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• conivaptan

  Serious - Use Alternative (1)conivaptan will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• conjugated estrogens

  Monitor Closely (1)sirolimus will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (1)sirolimus will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cortisone

  Monitor Closely (1)sirolimus will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)cortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• crizotinib

  Monitor Closely (2)crizotinib increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.
  
  crizotinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (4)cyclosporine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Simultaneous coadministration significantly increases sirolimus levels; this is minimized by administering sirolimus 4 hr after cyclosporine
  
  cyclosporine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Simultaneous coadministration significantly increases sirolimus levels; this is minimized by administering sirolimus 4 hr after cyclosporine
  
  cyclosporine, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor.
  
  sirolimus increases toxicity of cyclosporine by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Elevations in serum creatinine, hemolytic uremic syndrome, TTP, and microangiopathy were observed when sirolimus used in combination with cyclosporine. Administer oral doses of sirolimus 4 hr after doses of cyclosporine.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• darifenacin

  Serious - Use Alternative (1)darifenacin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dasatinib

  Serious - Use Alternative (1)dasatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deflazacort

  Monitor Closely (1)sirolimus will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dengue vaccine

  Monitor Closely (1)sirolimus decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

• denosumab

  Monitor Closely (1)sirolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.

• dexamethasone

  Monitor Closely (1)sirolimus will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)dexamethasone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• DHEA, herbal

  Serious - Use Alternative (1)DHEA, herbal will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and sirolimus both decrease serum potassium. Use Caution/Monitor.

• digoxin

  Monitor Closely (1)sirolimus will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diphtheria & tetanus toxoids

  Serious - Use Alternative (1)sirolimus decreases effects of diphtheria & tetanus toxoids by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• diphtheria & tetanus toxoids/ acellular pertussis vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of diphtheria & tetanus toxoids/ acellular pertussis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• docetaxel

  Monitor Closely (1)sirolimus will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dronabinol

  Monitor Closely (1)dronabinol increases levels of sirolimus by plasma protein binding competition. Modify Therapy/Monitor Closely. Dronabinol is highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered highly protein-bound drugs. This has not been confirmed in vivo. Caution with narrow therapeutic index drugs that are highly protein bound when initiating or increasing the dose of dronabinol.

• dronedarone

  Monitor Closely (2)dronedarone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for sirolimus toxicity and adjust dose as needed.
  
  dronedarone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If given together, monitor for sirolimus toxicity and adjust dose as needed.

• dulaglutide

  Monitor Closely (1)dulaglutide, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• dupilumab

  Monitor Closely (1)dupilumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• echinacea

  Monitor Closely (1)sirolimus increases and echinacea decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• efavirenz

  Serious - Use Alternative (1)efavirenz will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• elacestrant

  Monitor Closely (1)elacestrant will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduce dose of P-gp substrates per their Prescribing Information when minimal concentration changes may lead to serious or life-threatening adverse reactions.

• elagolix

  Monitor Closely (2)elagolix will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  elagolix decreases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eliglustat

  Monitor Closely (1)eliglustat increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

• eluxadoline

  Monitor Closely (1)eluxadoline increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enalapril

  Monitor Closely (1)enalapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• encorafenib

  Monitor Closely (1)encorafenib, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enzalutamide

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  Serious - Use Alternative (2)erdafitinib, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with erdafitinib and sensitive CYP3A4 substrates with narrow therapeutic indices. Erdafitinib may altered plasma concentrations of CYP3A4 substrates, leading to either loss of activity or increased toxicity of the substrate.
  
  erdafitinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin base will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  Serious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• estradiol

  Monitor Closely (1)sirolimus will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)sirolimus will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)sirolimus will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• etanercept

  Serious - Use Alternative (1)etanercept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• etravirine

  Serious - Use Alternative (1)etravirine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• everolimus

  Serious - Use Alternative (1)everolimus and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felodipine

  Monitor Closely (1)felodipine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ferric maltol

  Monitor Closely (1)ferric maltol, sirolimus. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fexofenadine

  Minor (1)sirolimus will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• finerenone

  Monitor Closely (1)sirolimus will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• fingolimod

  Monitor Closely (1)sirolimus increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .

• flibanserin

  Monitor Closely (2)sirolimus will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
  
  flibanserin increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Increase monitoring of concentrations of drugs transported by P-gp that have a narrow therapeutic index if coadministered with flibanserin.

• fluconazole

  Serious - Use Alternative (1)fluconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fludrocortisone

  Monitor Closely (1)sirolimus will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)fludrocortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosamprenavir

  Serious - Use Alternative (1)fosamprenavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fosaprepitant

  Serious - Use Alternative (1)fosaprepitant will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fosinopril

  Monitor Closely (1)fosinopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• fosphenytoin

  Monitor Closely (1)fosphenytoin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• gentamicin

  Monitor Closely (1)sirolimus will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• glatiramer

  Serious - Use Alternative (1)glatiramer and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• glycerol phenylbutyrate

  Monitor Closely (1)glycerol phenylbutyrate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.

• golimumab

  Serious - Use Alternative (1)golimumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• grapefruit

  Serious - Use Alternative (1)grapefruit will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• griseofulvin

  Serious - Use Alternative (1)griseofulvin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• haemophilus influenzae type b vaccine

  Monitor Closely (1)sirolimus decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• hepatitis A vaccine inactivated

  Serious - Use Alternative (1)sirolimus decreases effects of hepatitis A vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis a/b vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of hepatitis a/b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis a/typhoid vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of hepatitis a/typhoid vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• hepatitis b vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of hepatitis b vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• human papillomavirus vaccine, nonavalent

  Serious - Use Alternative (1)sirolimus decreases effects of human papillomavirus vaccine, nonavalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.

• human papillomavirus vaccine, quadrivalent

  Serious - Use Alternative (1)sirolimus decreases effects of human papillomavirus vaccine, quadrivalent by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune responses to vaccines.

• hydrocortisone

  Monitor Closely (1)sirolimus will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)hydrocortisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• idecabtagene vicleucel

  Serious - Use Alternative (1)sirolimus, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• ifosfamide

  Monitor Closely (1)ifosfamide, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with ifosfamide may increase the risk of immunosuppression and myelosuppression.

• iloperidone

  Monitor Closely (1)iloperidone increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)indinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• infliximab

  Serious - Use Alternative (1)infliximab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• influenza virus vaccine quadrivalent

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine quadrivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine quadrivalent, adjuvanted

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

• influenza virus vaccine quadrivalent, cell-cultured

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine quadrivalent, cell-cultured by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine quadrivalent, intranasal

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine quadrivalent, recombinant

  Monitor Closely (1)sirolimus decreases effects of influenza virus vaccine quadrivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.

• influenza virus vaccine trivalent

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine trivalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• influenza virus vaccine trivalent, adjuvanted

  Serious - Use Alternative (1)sirolimus decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

• influenza virus vaccine trivalent, recombinant

  Monitor Closely (1)sirolimus decreases effects of influenza virus vaccine trivalent, recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immune response to vaccine may be decreased in immunocompromised individuals.

• irinotecan liposomal

  Monitor Closely (1)sirolimus will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• isavuconazonium sulfate

  Monitor Closely (3)sirolimus will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isavuconazonium sulfate will increase the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Isavuconazonium sulfate, an inhibitor of P-gp and CYP3A4, may increase the effects or levels of sensitive P-gp or CYP3A4 substrates, which may require dose adjustment.
  
  sirolimus and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.

• isoniazid

  Serious - Use Alternative (1)isoniazid will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• istradefylline

  Monitor Closely (2)istradefylline will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
  
  istradefylline will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

  Serious - Use Alternative (2)itraconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.
  
  itraconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole treatment.

• ivacaftor

  Monitor Closely (1)ivacaftor increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ivermectin

  Monitor Closely (1)sirolimus will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixekizumab

  Monitor Closely (1)ixekizumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• Japanese encephalitis virus vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of Japanese encephalitis virus vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• ketoconazole

  Contraindicated (1)ketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.Monitor Closely (1)ketoconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ketoconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lapatinib

  Monitor Closely (1)lapatinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)lapatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• larotrectinib

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lasmiditan

  Serious - Use Alternative (1)lasmiditan increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• leflunomide

  Serious - Use Alternative (1)leflunomide and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• lemborexant

  Monitor Closely (1)sirolimus will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

• letermovir

  Monitor Closely (1)letermovir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor sirolimus plasma concentrations during treatment and after discontinuation of letemovir and adjust dose of sirolimus accordingly. When letermovir is coadministered with cyclosporine, sirolimus is recommended to be taken 4 hr after cyclosporine oral (MODIFIED) administration. Higher doses of sirolimus are needed to maintain the recommended sirolimus trough concentration ranges if cyclosporine is discontinued from combination therapy.

• levoketoconazole

  Contraindicated (1)levoketoconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.Monitor Closely (1)levoketoconazole will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)levoketoconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lisinopril

  Monitor Closely (1)lisinopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• lisocabtagene maraleucel

  Serious - Use Alternative (1)sirolimus, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• lomitapide

  Monitor Closely (2)sirolimus increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
  
  lomitapide increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

• lomustine

  Monitor Closely (1)lomustine, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with lomustine may increase the risk of immunosuppression and myelosuppression.

• lonafarnib

  Monitor Closely (1)lonafarnib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.Serious - Use Alternative (2)lonafarnib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
  
  sirolimus will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loperamide

  Monitor Closely (1)sirolimus will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lopinavir

  Serious - Use Alternative (1)lopinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• loratadine

  Monitor Closely (1)loratadine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)sirolimus will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• lorlatinib

  Serious - Use Alternative (1)lorlatinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.

• lovastatin

  Monitor Closely (1)lovastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• lumefantrine

  Serious - Use Alternative (1)lumefantrine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• maitake

  Monitor Closely (1)sirolimus increases and maitake decreases immunosuppressive effects; risk of infection. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• maraviroc

  Monitor Closely (1)sirolimus will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• marijuana

  Serious - Use Alternative (1)marijuana will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• measles (rubeola) vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of measles (rubeola) vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• measles mumps and rubella vaccine, live

  Serious - Use Alternative (1)sirolimus decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• measles, mumps, rubella and varicella vaccine, live

  Serious - Use Alternative (1)sirolimus decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• mechlorethamine

  Monitor Closely (1)mechlorethamine, sirolimus. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with mechlorethamine may increase the risk of immunosuppression and myelosuppression.

• meningococcal A C Y and W-135 polysaccharide vaccine combined

  Serious - Use Alternative (1)sirolimus decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• meningococcal group B vaccine

  Monitor Closely (1)sirolimus decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.

• mercaptopurine

  Monitor Closely (1)mercaptopurine and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• mestranol

  Monitor Closely (1)sirolimus will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metformin

  Monitor Closely (1)sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methotrexate

  Monitor Closely (1)methotrexate and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Combination may increase risk of myelosuppression.

• methylprednisolone

  Monitor Closely (1)sirolimus will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)methylprednisolone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• metoclopramide intranasal

  Monitor Closely (1)metoclopramide intranasal will increase the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Metoclopramide may increase the absorption of sirolimus. Monitor therapeutic drug concentrations and adjust the dose as needed.

• metronidazole

  Serious - Use Alternative (1)metronidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• micafungin

  Monitor Closely (1)micafungin increases levels of sirolimus by unspecified interaction mechanism. Use Caution/Monitor.

• miconazole vaginal

  Serious - Use Alternative (1)miconazole vaginal will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• midazolam intranasal

  Monitor Closely (1)sirolimus will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• mifepristone

  Contraindicated (1)mifepristone increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with CYP3A substrates that have a narrow therapeutic index .

• mitotane

  Monitor Closely (1)mitotane decreases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• moexipril

  Monitor Closely (1)moexipril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• muromonab CD3

  Serious - Use Alternative (1)muromonab CD3 and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• mycophenolate

  Serious - Use Alternative (1)mycophenolate and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• nafcillin

  Serious - Use Alternative (1)nafcillin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nefazodone

  Monitor Closely (1)nefazodone will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  Monitor Closely (1)sirolimus will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nelfinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• neomycin PO

  Monitor Closely (1)sirolimus will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nevirapine

  Serious - Use Alternative (1)nevirapine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)nifedipine will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nifedipine will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nilotinib

  Monitor Closely (1)nilotinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nilotinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nirmatrelvir

  Serious - Use Alternative (1)nirmatrelvir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nirmatrelvir/ritonavir

  Serious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ocrelizumab

  Monitor Closely (1)sirolimus and ocrelizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration of ocrelizumab with immunosuppressants may increase the risk of immunosuppression.

• ofatumumab SC

  Monitor Closely (1)ofatumumab SC, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

• olaparib

  Monitor Closely (1)sirolimus and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity.

• olutasidenib

  Serious - Use Alternative (1)olutasidenib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• omaveloxolone

  Monitor Closely (1)omaveloxolone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.

• oritavancin

  Monitor Closely (1)oritavancin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP3A4 inducer; caution if coadministered with CYP3A4 substrates that have a narrow therapeutic index

• oxcarbazepine

  Serious - Use Alternative (1)oxcarbazepine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ozanimod

  Monitor Closely (1)ozanimod, sirolimus. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration with immunosuppressive therapies may increase the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs in order to avoid unintended additive immunosuppressive effects.

• paclitaxel

  Monitor Closely (1)sirolimus will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paclitaxel protein bound

  Monitor Closely (1)sirolimus will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• pacritinib

  Serious - Use Alternative (1)pacritinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• palbociclib

  Monitor Closely (1)palbociclib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib

• paliperidone

  Monitor Closely (1)sirolimus will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• paromomycin

  Monitor Closely (1)sirolimus will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• pentobarbital

  Serious - Use Alternative (1)pentobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• perindopril

  Monitor Closely (1)perindopril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• pexidartinib

  Serious - Use Alternative (1)pexidartinib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.

• phenobarbital

  Monitor Closely (1)phenobarbital will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenytoin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• pitolisant

  Monitor Closely (1)pitolisant will decrease the level or effect of sirolimus by Other (see comment). Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

• pneumococcal vaccine 13-valent

  Serious - Use Alternative (1)sirolimus decreases effects of pneumococcal vaccine 13-valent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• pneumococcal vaccine heptavalent

  Serious - Use Alternative (1)sirolimus decreases effects of pneumococcal vaccine heptavalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• pneumococcal vaccine polyvalent

  Serious - Use Alternative (1)sirolimus decreases effects of pneumococcal vaccine polyvalent by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• poliovirus vaccine inactivated

  Monitor Closely (1)sirolimus decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• ponatinib

  Monitor Closely (1)ponatinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• ponesimod

  Monitor Closely (1)ponesimod and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• posaconazole

  Monitor Closely (1)sirolimus will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)posaconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• prednisolone

  Monitor Closely (1)sirolimus will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

  Monitor Closely (1)sirolimus will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)prednisone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pregabalin

  Serious - Use Alternative (1)sirolimus, pregabalin. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration results in additive risk of developing angioedema of face, mouth, and neck. Angioedema may result in respiratory compromise.

• primidone

  Serious - Use Alternative (1)primidone will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• quercetin

  Monitor Closely (1)quercetin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)quinapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• quinidine

  Serious - Use Alternative (1)quinidine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinupristin/dalfopristin

  Serious - Use Alternative (1)quinupristin/dalfopristin will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rabies vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of rabies vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants may interfere with development of active immunity.

• rabies vaccine chick embryo cell derived

  Serious - Use Alternative (1)sirolimus decreases effects of rabies vaccine chick embryo cell derived by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• ramipril

  Monitor Closely (1)ramipril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• ranolazine

  Monitor Closely (1)ranolazine will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)rifampin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  Serious - Use Alternative (1)rifapentine will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rilonacept

  Serious - Use Alternative (1)rilonacept and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• risperidone

  Monitor Closely (1)sirolimus will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ritonavir

  Monitor Closely (1)ritonavir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)ritonavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Oral rolapitant (P-gp inhibitor) may increase plasma concentrations of P-gp substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of P-gp substrates and rolapitant can not be avoided.

• ropeginterferon alfa 2b

  Serious - Use Alternative (1)ropeginterferon alfa 2b, sirolimus. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• rotavirus oral vaccine, live

  Serious - Use Alternative (1)sirolimus decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• rubella vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• rufinamide

  Serious - Use Alternative (1)rufinamide will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ruxolitinib

  Minor (1)sirolimus will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)sirolimus will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• saquinavir

  Monitor Closely (1)sirolimus will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)saquinavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sarecycline

  Monitor Closely (1)sarecycline will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• sarilumab

  Monitor Closely (1)sarilumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

• secobarbital

  Serious - Use Alternative (1)secobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• secukinumab

  Monitor Closely (1)secukinumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• silodosin

  Monitor Closely (1)sirolimus will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siltuximab

  Monitor Closely (1)siltuximab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

• simvastatin

  Monitor Closely (1)simvastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siponimod

  Monitor Closely (1)siponimod and sirolimus both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• sipuleucel-T

  Monitor Closely (1)sirolimus decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.

• smallpox (vaccinia) vaccine, live

  Serious - Use Alternative (1)sirolimus decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• sofosbuvir/velpatasvir

  Monitor Closely (2)sofosbuvir/velpatasvir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.
  
  sofosbuvir/velpatasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Closely monitor P-gp substrates, particularly those with a narrow therapeutic index. Modify dose if needed.

• sotorasib

  Serious - Use Alternative (2)sotorasib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications
  
  sotorasib will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• spironolactone

  Monitor Closely (1)spironolactone will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. sirolimus dose may need to be adjusted

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (2)stiripentol, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

• streptomycin

  Monitor Closely (1)sirolimus will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tacrolimus

  Monitor Closely (1)sirolimus will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)sirolimus and tacrolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tazemetostat

  Monitor Closely (2)tazemetostat will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  sirolimus will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teclistamab

  Monitor Closely (1)teclistamab will increase the level or effect of sirolimus by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• teduglutide

  Monitor Closely (1)teduglutide increases levels of sirolimus by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

• telotristat ethyl

  Monitor Closely (1)telotristat ethyl will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

• temsirolimus

  Serious - Use Alternative (1)sirolimus and temsirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tenofovir DF

  Monitor Closely (2)sirolimus, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
  
  sirolimus increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

• tepotinib

  Serious - Use Alternative (1)tepotinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• tetanus toxoid adsorbed or fluid

  Serious - Use Alternative (1)sirolimus decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• tick-borne encephalitis vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of tick-borne encephalitis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• tinidazole

  Monitor Closely (1)sirolimus will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Sirolimus levels may incr or decr, due to contradictory effects of tipranavir on hepatic CYP3A4 and P glycoprotein.Serious - Use Alternative (1)tipranavir will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tisagenlecleucel

  Serious - Use Alternative (1)sirolimus, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tobramycin

  Monitor Closely (1)sirolimus will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tocilizumab

  Serious - Use Alternative (1)tocilizumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tofacitinib

  Serious - Use Alternative (1)sirolimus, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• tolvaptan

  Monitor Closely (2)sirolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  tolvaptan will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tongkat ali

  Serious - Use Alternative (1)sirolimus and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• topiramate

  Serious - Use Alternative (1)topiramate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trandolapril

  Monitor Closely (1)trandolapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• trastuzumab

  Monitor Closely (1)trastuzumab, sirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

• trastuzumab deruxtecan

  Monitor Closely (1)trastuzumab deruxtecan, sirolimus. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.

• travelers diarrhea and cholera vaccine inactivated

  Serious - Use Alternative (1)sirolimus decreases effects of travelers diarrhea and cholera vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• trazodone

  Monitor Closely (1)trazodone will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  Serious - Use Alternative (1)triamcinolone acetonide injectable suspension will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trofinetide

  Monitor Closely (1)trofinetide will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• typhoid polysaccharide vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• typhoid vaccine live

  Serious - Use Alternative (1)sirolimus decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• ublituximab

  Monitor Closely (1)ublituximab and sirolimus both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered

• upadacitinib

  Serious - Use Alternative (1)sirolimus, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.

• ustekinumab

  Monitor Closely (1)ustekinumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.Serious - Use Alternative (1)sirolimus and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

• varicella virus vaccine live

  Serious - Use Alternative (1)sirolimus decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• vemurafenib

  Monitor Closely (1)vemurafenib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• venetoclax

  Serious - Use Alternative (1)venetoclax will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. In vitro data suggest venetoclax may inhibit P-gp substrates at therapeutic dose levels in the gut. Avoid coadministration of narrow therapeutic index P-gp substrates with venetoclax. If a narrow therapeutic index P-gp substrate must be used, it should be taken at least 6 hr before venetoclax.

• verapamil

  Serious - Use Alternative (3)verapamil will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  verapamil will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  verapamil, sirolimus. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: With concomitant use of mTOR inhibitors, consider appropriate dose reductions of both medications.

• vinblastine

  Monitor Closely (1)sirolimus will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine

  Monitor Closely (1)sirolimus will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine liposomal

  Monitor Closely (1)sirolimus will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• voclosporin

  Monitor Closely (1)voclosporin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.

• voriconazole

  Contraindicated (2)voriconazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  voriconazole increases levels of sirolimus by decreasing metabolism. Contraindicated.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• yellow fever vaccine

  Serious - Use Alternative (1)sirolimus decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• zafirlukast

  Serious - Use Alternative (1)zafirlukast will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• zoster vaccine live

  Serious - Use Alternative (1)sirolimus decreases effects of zoster vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.

• zoster vaccine recombinant

  Monitor Closely (1)sirolimus decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.