sirolimus (Rx)

Brand and Other Names:Rapamune
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 0.5mg
  • 1mg
  • 2mg

oral solution

  • 1mg/mL

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

Dosage Forms & Strengths

tablet

  • 0.5mg
  • 1mg
  • 2mg

oral solution

  • 1mg/mL

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)
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Interactions

Interaction Checker

and sirolimus

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            Contraindicated (3)

            • ketoconazole

              ketoconazole 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 (159)

            • 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.

            • 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.

            • amobarbital

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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • modafinil

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

            • 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.

            • oxcarbazepine

              oxcarbazepine will decrease 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.

            • 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.

            • 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.

            • 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 (180)

            • 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.

            • astragalus

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

            • clobetasone

              sirolimus will increase the level or effect of clobetasone 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 (5)

            • alvimopan

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

            • armodafinil

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

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            Adverse Effects

            >10%

            Peripheral edema, w/ corticosteroids (54-58%)

            Hypertriglyceridemia (45-57%; up to 90% when used with or following cyclosporine)

            Hypercholesterolemia (43-46%; up to 90% when used with or following cyclosporine)

            Constipation (36-38%)

            Arthralgia (25-31%)

            Thrombocytopenia (14-30%)

            Rash (10-20%)

            Hypertension (45-49%)

            Increased creatinine (39-40%)

            Abdominal pain (29-36%)

            Diarrhea (25-35%)

            Headache (34%)

            Fever (23-34%)

            Urinary tract infection (26-33%)

            Anemia (23-33%)

            Nausea (25-31%)

            Arthralgia (25-31%)

            Pain (29-33%)

            Acne (22%)

            Edema (18-20%)

            Sepsis (<20%)

            Lymphocele (<20%)

            Venous thromboembolism (<20%)

            Tachycardia (<20%)

            Stomatitis (<20%)

            Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (<20%)

            Leukopenia (<20%)

            Abnormal healing (<20%)

            Increased lactic dehydrogenase (<20%)

            Hypokalemia (<20%)

            Hypophoaphatemia (<20%)

            Hyperglycemia (<20%)

            Diabetes mellitus (<20%)

            Bone necrosis (<20%)

            Pneumonia (<20%)

            Epistaxis (<20%)

            Melanoma (<20%)

            Squamous cell carcinoma (<20%)

            Basal cell carcinoma (<20%)

            Pyelonephritis (<20%)

            Ovarian cysts (<20%)

            Menstrual disorders (amenorrhea and menorrhagia) (<20%)

            Postmarketing Reports

            Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported

            Posterior reversible encephalopathy syndrome

            Neuroendocrine carcinoma of the skin (Merkel cell carcinoma)

            Impairment of wound healing

            Embryo-fetal toxicity

            Male infertility

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            Warnings

            Black Box Warnings

            Do not use in liver or lung transplantation as safety and efficacy is not established

            Excess mortality, graft loss, and hepatic artery thrombosis have been observed in liver transplant recipients

            Bronchial anastomotic dehiscence has been observed in lung transplant recipients

            Should be prescribed only by physicians who have experience with immunosuppression in organ transplant recipients and can provide necessary follow-up and appropriate monitoring

            Increased risk of infection, lymphoma, and other malignancies due to increased immunosuppression

            Contraindications

            Hypersensitivity to sirolimus or macrolide antibiotics

            Concomitant live vaccines

            Cautions

            Increased risk of lymphoma or infections, including latent virus activation, eg, BK virus-induced nephropathy

            Fluid accumulation reported, including peripheral edema, lymphedema, pleural effusion, ascites, and pericardial effusions (including hemodynamically significant effusions and tamponade requiring intervention in children and adults), in patients receiving therapy

            Not for liver or lung transplant

            Impaired or delayed wound healing reported in patients receiving therapy, including lymphocele and wound dehiscence mTOR inhibitors such as sirolimus have been shown in vitro to inhibit production of certain growth factors that may affect angiogenesis, fibroblast proliferation, and vascular permeability; lymphocele, a known surgical complication of renal transplantation, reported to occur significantly more often in dose-related fashion in patients receiving therapy; appropriate measures should be considered to minimize complications; patients with body mass index (BMI) >30 kg/m² may be at increased risk of abnormal wound healing based on data from medical literature

            Exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor

            Progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported; commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia

            Based on animal studies and mechanism of action, therapy may cause fetal harm when administered to a pregnant woman; in animal studies, mTOR inhibitors caused embryo- fetal toxicity when administered during period of organogenesis at maternal exposures that were equal to or less than human exposures at recommended lowest starting dose; advise pregnant women of potential risk to a fetus; advise women of childbearing potential to avoid becoming pregnant and to use effective contraception while on therapy and for 12 weeks after ending treatment

            Associated with development of angioedema; concomitant use of other drugs known to cause angioedema, such as angiotensin-converting enzyme (ACE) inhibitors, may increase risk of developing angioedema; elevated sirolimus levels (with/without concomitant ACE inhibitors) may potentiate angioedema; in some cases, angioedema has resolved upon discontinuation or therapy dose reduction

            Any patient receiving therapy should be monitored for hyperlipidemia; if detected, interventions such as diet, exercise, and lipid-lowering agents should be initiated as outlined by National Cholesterol Education Program guidelines

            Hyperlipidemia: In clinical trials of patients receiving sirolimus plus cyclosporine or after cyclosporine withdrawal, up to 90% of patients required treatment for hyperlipidemia and hypercholesterolemia with anti-lipid therapy; despite antilipid management, up to 50% of patients had fasting serum cholesterol levels >240 mg/dL and triglycerides above recommended target levels

            Consult lab regarding type of assay for drug monitoring; whole blood concentrations are being measured by various chromatographic and immunoassay methodologies; sample concentration values from different assays may not be interchangeable

            Cases of interstitial lung disease [ILD] (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis), some fatal, with no identified infectious etiology have occurred in patients receiving immunosuppressive regimens including sirolimus; in some cases, was reported with pulmonary hypertension (including pulmonary arterial hypertension as a secondary event; in some cases, the ILD has resolved upon discontinuation or dose reduction; risk may be increased as trough sirolimus concentration increases

            Safety and efficacy of de novo use of sirolimus without cyclosporine is not established in renal transplant patients; in a multicenter clinical study significantly higher acute rejection rates and numerically higher death rates compared to patients treated with cyclosporine, MMF, steroids, and IL-2 receptor antagonist reported; a benefit, in terms of better renal function, was not apparent in the treatment arm with de novo use of sirolimus without cyclosporine

            Drug interaction overview

            • Coadministration with live virus vaccines is contraindicated (see Black Box Warnings)
            • CYP3A4 inhibitors (including grapefruit juice) may increase whole blood levels
            • Coadministration of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (eg, rifampin or rifabutin) not recommended
            • Concomitant use with a calcineurin inhibitor (eg, cyclosporine, tacrolimus, sirolimus) may increase risk of calcineurin inhibitor-induced hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, pancytopenia, or neutropenia
            • Live vaccines should be avoided during treatment; live vaccines may include, but are not limited to, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid; immunosuppressants may affect response to vaccination; during treatment, vaccination may be less effective
            • Renal function should be closely monitored during the coadministration with cyclosporine, because long-term administration of the combination has been associated with deterioration of renal function; appropriate adjustment of immunosuppressive regimen, including discontinuation of therapy and/or cyclosporine, should be considered in patients with elevated or increasing serum creatinine levels; in patients at low- to moderate-immunologic risk, continuation of combination therapy with cyclosporine beyond 4 months following transplantation should only be considered when benefits outweigh risks of this combination for individual patients; exercise caution when using agents (eg, aminoglycosides and amphotericin B) that are known to have a deleterious effect on renal function; in patients with delayed graft function, therapy may delay recovery of renal function
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            Pregnancy & Lactation

            Pregnancy

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

            Animal studies

            • Reproductive studies in animals have demonstrated that sirolimus showed embryo/fetotoxicity manifested as mortality and reduced fetal weights (with associated delays in skeletal ossification) in rats when given doses ~0.2-0.5 the human dose

            Contraception

            • Females should not be pregnant or become pregnant while receiving sirolimus
            • Females of reproductive potential are recommended to use highly effective contraception methods during treatment and for 12 weeks after treatment has been stopped

            Infertility

            • Based on clinical findings and findings in animals, male and female fertility may be compromised by the treatment; ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) reported in females; azoospermia reported in males and has been reversible upon discontinuation in most cases

            Lactation

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

            Sirolimus is excreted in trace amounts in milk of lactating rats Because many drugs are excreted in human milk, and because of the potential for adverse reactions in nursing infants from sirolimus, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Inhibits T-cell activation and proliferation and inhibits antibody production that occurs in response to antigenic and cytokine stimulation; inhibits T- cell proliferation by inhibiting progression from the G1 to the S phase of the cell cycle

            Lymphangioleiomyomatosis

            • Lymphangioleiomyomatosis involves lung tissue infiltration with smooth muscle-like cells that harbor inactivating mutations of the tuberous sclerosis complex (TSC) gene (LAM cells)
            • Loss of TSC gene function activates the mTOR signaling pathway, resulting in cellular proliferation and release of lymphangiogenic growth factors
            • Sirolimus inhibits the activated mTOR pathway and thus the proliferation of LAM cells

            Absorption

            Bioavailability: 14% (oral solution); 41% (tablet)

            Peak Plasma Time: 1-3 hr (oral solution); 1-6 hr (tablet)

            Distribution

            Protein Bound: 92%

            Vd:12 L/kg

            Metabolism

            CYP3A4

            Elimination

            Half-Life: 2.5 days

            Excretion: feces (91%)

            Pharmacogenomics

            Rapamycins form complexes with an intracellular immunophillin (FKBP), which bind to a kinase called the mammalian target of rapamycin (mTOR)

            Intrinsic rapamycin resistance may be caused by genetic mutations identified for FKBP and mTOR genes

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            Administration

            Instructions

            Take consistently either with or without food

            Take 4 hr after cyclosporine

            Renal transplantation: Not to exceed 40 mg/day

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            sirolimus oral
            -
            0.5 mg tablet
            sirolimus oral
            -
            1 mg tablet
            sirolimus oral
            -
            2 mg tablet
            sirolimus oral
            -
            1 mg/mL solution
            sirolimus oral
            -
            1 mg/mL solution
            sirolimus oral
            -
            2 mg tablet
            sirolimus oral
            -
            0.5 mg tablet
            sirolimus oral
            -
            1 mg/mL solution
            sirolimus oral
            -
            1 mg/mL solution
            sirolimus oral
            -
            1 mg tablet
            Rapamune oral
            -
            1 mg/mL solution
            Rapamune oral
            -
            2 mg tablet
            Rapamune oral
            -
            1 mg tablet
            Rapamune oral
            -
            0.5 mg tablet
            Rapamune oral
            -
            1 mg/mL solution

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            sirolimus oral

            SIROLIMUS - ORAL

            (sir-OH-li-mus)

            COMMON BRAND NAME(S): Rapamune

            WARNING: Sirolimus lowers the body's ability to fight an infection/disease (immunosuppression). This may increase your risk of developing an infection or certain types of cancer (such as skin cancer, lymphoma). To reduce the risk of these serious side effects, take this medication at the lowest effective dose as directed by your doctor. Keep all medical and laboratory appointments.Tell your doctor right away if you develop any of the following: unusual skin changes, change in the appearance/size of moles, unusual growths/lumps, swollen glands, night sweats, unexplained weight loss, signs of infection (such as sore throat that doesn't go away, fever).Sirolimus is not recommended for the prevention of rejection of liver or lung transplants because it has rarely caused very serious (possibly fatal) liver/lung problems in those cases.

            USES: Sirolimus is used with other medications to prevent rejection of a kidney transplant. This medication belongs to a class of drugs known as immunosuppressants. It works by weakening your body's defense system (immune system) to help your body accept the new organ as if it were your own.Sirolimus may also be used to treat a certain lung disease (lymphangioleiomyomatosis-LAM).

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking sirolimus and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually once daily. Swallow this medication whole. Do not crush, chew, or split the tablets. If you have nausea or an upset stomach, you may take this medication with food. However, it is important to choose one way (with food or without food) and take this medication the same way with every dose. Consult your doctor or pharmacist for more details.The dosage is based on your weight, medical condition, laboratory tests (such as sirolimus trough levels), and response to treatment.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Also, do not stop taking this medication without consulting your doctor.If you are also taking cyclosporine, take sirolimus 4 hours after your cyclosporine dose. Consult your pharmacist for more information.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.If you are taking this medication to treat LAM, tell your doctor if your condition worsens.

            SIDE EFFECTS: See also Warning section.Diarrhea, joint pain, shaking, acne, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, yellowing eyes/skin, dark urine, muscle pain/cramps, bone pain, increased thirst/hunger, frequent urination, hearing problems (such as hearing loss, ringing in the ears), unusual tiredness, fast/slow/irregular heartbeat, easy bruising/bleeding, mental/mood changes, swelling ankles/feet, severe headache, dizziness, stomach/abdominal pain, missed/heavy/painful periods, signs of kidney problems (such as change in the amount of urine, frothy urine), pain/redness/swelling of arms or legs, swelling abdomen.Get medical help right away if you have any very serious side effects, including: chest pain, shortness of breath.This medication may increase your risk of getting a rare but very serious (possibly fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if you have any of these side effects: clumsiness, loss of coordination/balance, weakness, sudden change in your thinking (such as confusion, difficulty concentrating, memory loss), difficulty talking/walking, seizure, vision changes.Sirolimus may slow wound healing after surgery. Tell your doctor right away if you have signs that your surgery wound is not healing well (such as redness, swelling, pain). The risk of poor wound healing is higher if you are obese.Sirolimus may cause your cholesterol/triglycerides to increase. You may be required to have your cholesterol/triglycerides checked periodically and/or take another medication to control your cholesterol/triglycerides.Sirolimus can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Get medical help right away if you develop any rash.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking sirolimus, tell your doctor or pharmacist if you are allergic to it; or to temsirolimus; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, high cholesterol/triglyceride levels, cancer, any recent/current infections.Sirolimus can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).This medication may increase your risk of developing skin cancer. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication can affect fertility in males. Ask your doctor for more details.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while taking sirolimus. Sirolimus may harm an unborn baby. Ask about reliable forms of birth control while using this medication and for 12 weeks after stopping treatment. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.This medication may pass into breast milk and may have undesirable effects on a nursing infant. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: ACE inhibitors (such as benazepril, lisinopril), other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab, tacrolimus).Other medications can affect the removal of sirolimus from your body, which may affect how sirolimus works. Examples include azole antifungals (such as itraconazole, ketoconazole, voriconazole), enzalutamide, macrolide antibiotics (such as clarithromycin, erythromycin), mifepristone, HIV and HCV protease inhibitors (such as indinavir, ritonavir, telaprevir), rifamycins (such as rifampin, rifabutin), St. John's wort, among others.Sirolimus is very similar to temsirolimus. Do not use medications containing temsirolimus while using sirolimus.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Laboratory and/or medical tests (such as kidney/liver function, cholesterol/triglyceride levels, urine tests for protein, sirolimus trough level) will be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.If you had an organ transplant, attend a transplant education class or support group to learn more about the signs of organ rejection such as a feeling of being ill, fever, or tenderness/pain around the transplanted organ. Tell your doctor right away if you notice any of these signs.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

            Information last revised September 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.