everolimus (Rx)

Breast Cancer

Afinitor only

Indicated in postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole

10 mg PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Renal Cell Carcinoma

Afinitor only

Indicated for advanced renal cell carcinoma (RCC) after failure with sunitinib or sorafenib

10 mg PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Advanced Neuroendocrine Tumors

Afinitor only

Indicated for progressive neuroendocrine tumors (PNET) located in the pancreas that are not surgically resectable or are metastatic; also indicated for well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung

10 mg PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Renal Angiomyolipoma

Afinitor only

Indicated for the treatment of noncancerous kidney tumors (renal angiomyolipomas) with tuberous sclerosis complex (TSC) in patients not requiring immediate surgery

10 mg PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Subependymal Giant Cell Astrocytoma

Afinitor and Afinitor Disperz

Indicated in patients with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected

Initial dose: 4.5 mg/m² PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Partial Onset Seizures

Afinitor Disperz only

Indicated for the adjunctive treatment of patients with TSC-associated partial onset seizures

Initial dose: 5 mg/m² PO qDay consistently with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Kidney Transplant Rejection

Zortress only

Indicated for prophylaxis of organ rejection in patients with low-moderate immunologic risk

Use in combination with reduced doses of cyclosporine, as well as basiliximab and corticosteroids

Starting dose: 0.75 mg PO q12hr initially; adjust maintenance dose to achieve trough whole blood concentrations of 3-8 ng/mL target range

Initiate oral prednisone once oral medication is tolerated; further taper steroid doses on an individualized basis depending on the clinical status of patient and function of graft

Administer as soon as possible after kidney transplantation

Liver Transplant Rejection

Zortress only

Indicated for prophylaxis of allograft rejection in adult liver transplant recipients in combination with reduced doses of tacrolimus and with corticosteroids

Starting dose (30 days posttransplant): 1 mg PO q12hr initially; adjust maintenance dose to achieve trough whole blood concentrations of 3-5 ng/mL by 3 weeks after first dose of everolimus and through 12 months

Do not administer until at least 30 days post liver transplant (earlier administration associated with hepatic artery thrombosis, graft loss, and death)

Dosage Modifications

Coadministration of P-gp and CYP3A4 inhibitors

• Avoid concomitant use of P-gp and strong CYP3A4 inhibitors
• Avoid grapefruit and grapefruit juice

• Breast cancer, NET, RCC, and TSC-associated renal angiomyolipoma

  • Reduce dose to 2.5 mg qDay; may increase dose to 5 mg qDay if tolerated
  • Resume dose administered prior to inhibitor initiation, once inhibitor is discontinued for 3 days

• TSC-associated SEGA and partial-onset seizures

  • Reduce daily dose by 50%; change to every other day dosing if reduced dose is lower than the lowest available strength
  • Resume dose administered prior to inhibitor initiation, once the inhibitor is discontinued for 3 days
  • Assess trough concentrations when initiating and discontinuing inhibitor

Coadministration of P-gp and CYP3A4 inducers

• Avoid concomitant use of St John’s Wort

• Breast cancer, NET, RCC, and TSC-associated renal angiomyolipoma

  • Avoid coadministration when alternatives are available; if coadministration cannot be avoided, double daily dose ≤5 mg increments; multiple increments may be required
  • Resume dose administered prior to inducer initiation, once an inducer is discontinued for 5 days

• TSC-associated SEGA and partial-onset seizures

  • Double daily dose ≤5 mg increments; multiple increments may be required
  • Addition of another strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dosage modification
  • Assess trough concentrations when initiating and discontinuing inducer
  • Resume dose administered before starting any inducer, once all inducers are discontinued for 5 days

Noninfectious pneumonitis

• Grade 1: No dose adjustment required; initiate appropriate monitoring
• Grade 2: Withhold treatment until symptoms resolve to Grade ≤1; resume at 50% of previous dose; permanently discontinue treatment if toxicity does not resolve or improve to Grade 1 within 4 weeks
• Grade 3: Withhold treatment until symptoms resolve to Grade ≤1; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength; if toxicity recurs at Grade 3, permanently discontinue
• Grade 4: Permanently discontinue

Stomatitis

• Manage with topical analgesic mouth treatments (eg, benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol or phenol) with or without topical corticosteroids (eg, triamcinolone oral paste)
• Avoid using agents containing alcohol, hydrogen peroxide, iodine, and thyme derivatives in management of stomatitis which may worsen mouth ulcers
• Grade 1: No dosage adjustment required; manage with nonalcoholic or salt water (0.9%) mouthwash several times a day
• Grade 2: Withhold until improvement to ≤Grade 1; resume at same dose; if recurs at Grade 2, withhold until improvement to ≤Grade 1; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength
• Grade 3: Withhold until improvement to ≤Grade 1; resume at same dose; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength
• Grade 4: Permanently discontinue

Other nonhematologic toxicities

• Grade 1: No dosage adjustment required

• Grade 2

  • If toxicity is intolerable, withhold until improvement to Grade ≤1; resume at same dose
  • If toxicity recurs at Grade 2, withhold until improvement to Grade ≤1; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength

• Grade 3

  • Withhold until improvement to ≤Grade 1; resume at same dose; consider resuming at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength
  • If recurs at Grade 3, permanently discontinueGrade 4: Permanently discontinue
• Grade 4: Permanently discontinue

Metabolic events (eg, hyperglycemia, dyslipidemia)

• Grade 1 or 2: No dosage adjustment required
• Grade 3: Withhold until improvement to ≤Grade 2; resume at same dose; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength
• Grade 4: Discontinue treatment

Thrombocytopenia

• Grade 1 (<75,000/mm³): No dosage adjustment required
• Grade 2 (50,000-75,000/mm³): Interrupt dose until recovery at Grade ≤1; reinitiate treatment at same dose
• Grade 3 or 4 (<50,000/mm³): Interrupt dose until recovery at Grade ≤1; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength

Neutropenia

• Grade 1 or 2 (1,000-1,500/mm³): No dosage adjustment required
• Grade 3 (500-1,000/mm³): Interrupt dose until recovery at Grade ≤2; reinitiate treatment at same dose
• Grade 4 (<500/mm³): Interrupt dose until recovery at Grade ≤2; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength

Febrile neutropenia

• Grade 3 (ANC <1,000/mm³ single temperature >38.3ºC (101ºF) or a sustained temperature of ≥38ºC (100.4ºF) for >1hr): Interrupt dose until recovery at Grade ≤2 and no fever; resume at 50% of previous dose; change to every other day dosing if reduced dose is lower than the lowest available strength
• Grade 4 (Life-threatening consequences): Permanently discontinue

Therapeutic drug monitoring and dose titration

• Titrate dose to attain trough concentrations of 5-15 ng/mL
• Monitor everolimus whole blood trough concentrations
• Adjust dose using the following equation: new dose = current dose x (target concentration divided by current concentration); not exceed increments of 5 mg/dose

• Recommended timing of drug monitoring

  • Initiation, modification, and switch between Afinitor and Afinitor Disperz: 1-2 weeks
  • Initiation or discontinuation of P-gp and moderate CYP3A inhibitor, P-gp and strong CYP3A inducer, hepatic function changes: 2 weeks
  • Stable dose with change body surface area (BSA): Every 3-6 months
  • Stable dose with stable BSA: Every 6-12 months

Renal impairment

• No clinical studies were conducted in patients with decreased renal function

Hepatic impairment (Breast Cancer, NET, RCC, and TSC-Associated Renal Angiomyolipoma)

• Mild (Child Pugh class A): Decrease dose to 7.5 mg qDay; may further decreased to 5 mg qDay if not well tolerated
• Moderate (Child Pugh class B): Decrease dose to 5 mg qDay; may further decreased to 2.5 mg qDay if not well tolerated
• Severe (Child Pugh class C): Decrease dose to 2.5 mg qDay; administer only if desired benefit outweighs risk; not to exceed 2.5 mg qDay
• Adjust dose if status changes during treatment

Hepatic impairment (TSC-associated SEGA and partial-onset seizures)

• Mild-to-moderate (Child Pugh class A or B): No dosage adjustment necessary
• Severe (Child Pugh class C): 2.5 mg/m²: PO qDay

Hepatic impairment (Zortress)

• Mild (Child Pugh class A): Reduce initial daily dose by ~1/3 of the recommended daily dose
• Moderate-to-severe (Child Pugh class B or C): Reduce initial daily dose by ~1/2 of the recommended daily dose
• Further dose adjustment and/or dose titration should be made if a patient’s whole blood trough concentration of everolimus is not within the target trough concentration range of 3-8 ng/mL

Therapeutic drug monitoring and dosage modifications (Zortress)

• Optimally, dose adjustments should be based on trough concentrations obtained 4 or 5 days after a previous dosing change
• Recommended therapeutic range of 3- 8 ng/mL is based on an LC/MS/MS assay method; currently in clinical practice, everolimus whole blood trough concentrations may be measured by chromatographic or immunoassay methodologies
• Trough concentration <3 ng/mL: Double total daily dose using the available tablet strengths (ie, 0.25 mg, 0.5 mg, 0.75 mg)
• Trough concentration >8 ng/mL on 2 consecutive measurement: Decrease dose by 0.25 mg BID

Dosing Considerations

Do not combine the 2 dosage forms (Afinitor and Afinitor Disperz) to achieve the desired dose; use 1 dosage form or the other

Zortress only

• Limitations of use

  • Safety and efficacy has not been established in kidney transplant patients at high immunologic risk and recipients of transplanted organs other than kidney or liver
  • <18 years of age

Orphan Designations

Diffuse large B-cell lymphoma

Gastric cancer

Waldenstrom macroglobulinemia (also known as lymphoplasmacytic lymphoma)

Sponsor

• Novartis Pharmaceuticals Corporation; One Health Plaza; East Hanover, NJ 07936-1080

Tuberous Sclerosis Topical Treatment (Orphan)

Everolimus ointment

Orphan designation for topical treatment of tuberous sclerosis

Sponsor

• Aucta Pharmaceuticals, LLC; 675 US Highway One; North Brunswick, New Jersey 08902

Subependymal Giant Cell Astrocytoma

Afinitor and Afinitor Disperz

Indicated in pediatric patients (≥1 year) with tuberous sclerosis complex TSC for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected

<1 year: Safety and efficacy not established

≥1 year

• Initial dose based on body surface area with subsequent titration to attain trough concentrations of 5-15 ng/mL
• 4.5 mg/m² PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Partial-Onset Seizures

Afinitor Disperz only

Indicated for the adjunctive treatment of pediatric patients (≥2 years) with TSC-associated partial-onset seizures

<2 years: Safety and efficacy not established

≥2 years

• Initial dose: 5 mg/m² PO qDay with or without food; continue until disease progression or unacceptable toxicity (see Dosage Modifications)

Dosage Modifications

Coadministration of P-gp and CYP3A4 inhibitors

• Avoid concomitant use of P-gp and strong CYP3A4 inhibitors
• Avoid grapefruit and grapefruit juice

• TSC-associated SEGA and partial-onset seizures

  • Reduce daily dose by 50%; change to every other day dosing if reduced dose is lower than the lowest available strength
  • Resume dose administered prior to inhibitor initiation, once the inhibitor is discontinued for 3 days
  • Assess trough concentrations when initiating and discontinuing inhibitor

Coadministration of P-gp and CYP3A4 inducers

• Avoid concomitant use of St John’s Wort

• TSC-associated SEGA and partial-onset seizures

  • Double daily dose ≤5 mg increments; multiple increments may be required
  • Addition of another strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dosage modification
  • Assess trough concentrations when initiating and discontinuing inducer
  • Resume dose administered before starting any inducer, once all inducers are discontinued for 5 days

Therapeutic drug monitoring and dose titration

• Titrate dose to attain trough concentrations of 5-15 ng/mL
• Monitor everolimus whole blood trough concentrations
• Adjust dose using the following equation: new dose = current dose x (target concentration divided by current concentration); not exceed increments of 5 mg/dose

• Recommended timing of drug monitoring

  • Initiation, modification, and switch between Afinitor and Afinitor Disperz: 1-2 weeks
  • Initiation or discontinuation of P-gp and moderate CYP3A inhibitor, P-gp and strong CYP3A inducer, hepatic function changes: 2 weeks
  • Stable dose with change body surface area (BSA): Every 3-6 months
  • Stable dose with stable BSA: Every 6-12 months

Dosing Considerations

Do not combine the 2 dosage forms (Afinitor and Afinitor Disperz) to achieve the desired dose; use 1 dosage form or the other

In a randomized advanced hormone receptor positive, HER2-negative breast cancer study, no overall differences in safety or effectiveness were observed between these elderly patients and younger patients during clinical trials

Contraindicated (0)

Serious - Use Alternative (167)

• adalimumab

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

• alefacept

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

• amiodarone

  amiodarone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• amobarbital

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

• anakinra

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

• anthrax vaccine

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

• antithymocyte globulin rabbit

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

• apalutamide

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

• armodafinil

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

• artemether/lumefantrine

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

• atazanavir

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

• atorvastatin

  atorvastatin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• azathioprine

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

• basiliximab

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

• BCG vaccine live

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

• bosentan

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

• bremelanotide

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

• butabarbital

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

• butalbital

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

• canakinumab

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

• carbamazepine

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

• chloramphenicol

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

• cimetidine

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

• clarithromycin

  clarithromycin will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clarithromycin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• clotrimazole

  clotrimazole will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• cobicistat

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

• conivaptan

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

• cortisone

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

• darifenacin

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

• darunavir

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

• dasatinib

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

• deferiprone

  deferiprone, everolimus. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• dexamethasone

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

• DHEA, herbal

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

• diphtheria & tetanus toxoids

  everolimus 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

  everolimus 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

  everolimus 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.

• dronedarone

  dronedarone will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• efavirenz

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

• enzalutamide

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

• erdafitinib

  erdafitinib will increase the level or effect of everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• eslicarbazepine acetate

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

• etanercept

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

• etravirine

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

• felodipine

  felodipine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• fexinidazole

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

• fluvoxamine

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

• fosamprenavir

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

• fosaprepitant

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

• fosphenytoin

  fosphenytoin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  fosphenytoin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• glatiramer

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

• golimumab

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

• grapefruit

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

• griseofulvin

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

• hepatitis A vaccine inactivated

  everolimus 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

  everolimus 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

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

• hepatitis b vaccine

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

• human papillomavirus vaccine, nonavalent

  everolimus 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

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• hydroxychloroquine sulfate

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

• idelalisib

  idelalisib will increase the level or effect of everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  indinavir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• infliximab

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

• influenza virus vaccine quadrivalent

  everolimus 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, cell-cultured

  everolimus 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

  everolimus 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

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

• isoniazid

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

• itraconazole

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

• ivosidenib

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

• Japanese encephalitis virus vaccine

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• lapatinib

  lapatinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  lapatinib will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• leflunomide

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

• levoketoconazole

  levoketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
  
  levoketoconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lopinavir

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

• loratadine

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

• lovastatin

  lovastatin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• marijuana

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

• measles (rubeola) vaccine

  everolimus 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

  everolimus 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

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

• mefloquine

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

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

  everolimus 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.

• metronidazole

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

• miconazole vaginal

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

• mifepristone

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

• mobocertinib

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

• muromonab CD3

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

• mycophenolate

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

• nafcillin

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

• nefazodone

  nefazodone will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nefazodone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nelfinavir

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

• nevirapine

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

• nicardipine

  nicardipine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nifedipine

  nifedipine will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nifedipine will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nilotinib

  nilotinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  nilotinib will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nirmatrelvir/ritonavir

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

• olutasidenib

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

• oxcarbazepine

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

• pacritinib

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

• pentobarbital

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

• pexidartinib

  pexidartinib will decrease the level or effect of everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• phenytoin

  phenytoin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  phenytoin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• pneumococcal vaccine 13-valent

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

• pneumococcal vaccine heptavalent

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

• pneumococcal vaccine polyvalent

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pregabalin

  everolimus, 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• quercetin

  quercetin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinidine

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

• quinupristin/dalfopristin

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

• rabies vaccine

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

• rabies vaccine chick embryo cell derived

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

• ranolazine

  ranolazine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• rifabutin

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

• rifampin

  rifampin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  rifampin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• rifapentine

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

• rilonacept

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

• ritonavir

  ritonavir will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ritonavir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• ropeginterferon alfa 2b

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

• rotavirus oral vaccine, live

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

• rubella vaccine

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• saquinavir

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

• secobarbital

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

• sirolimus

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

• smallpox (vaccinia) vaccine, live

  everolimus 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 everolimus 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 everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  St John's Wort will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• temsirolimus

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

• tepotinib

  tepotinib will increase the level or effect of everolimus 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

  everolimus 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

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tocilizumab

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

• tofacitinib

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

• tongkat ali

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

• topiramate

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

• travelers diarrhea and cholera vaccine inactivated

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

• tucatinib

  tucatinib will increase the level or effect of everolimus 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

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

• typhoid vaccine live

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

• ustekinumab

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

• varicella virus vaccine live

  everolimus 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 everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use of a moderate 3A4 inhibitor such as verapamil may significantly increase the plasma concentrations of everolimus following oral administration.
  
  verapamil will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Everolimus prescribing information lists indication-specific dosing recommendations.
  
  verapamil, everolimus. 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.

• voriconazole

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

• voxelotor

  voxelotor will increase the level or effect of everolimus 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

  everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• zoster vaccine live

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

Monitor Closely (90)

• astragalus

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

• belatacept

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

• belzutifan

  belzutifan will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benazepril

  benazepril, everolimus. 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
  
  berotralstat will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

• betrixaban

  everolimus increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

• cannabidiol

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

• cholera vaccine

  everolimus 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.

• crizotinib

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

• cyclosporine

  cyclosporine will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Everolimus is a CYP3A4 and P-gp substrate. Prescribing information for coadministration with cyclosporine (a CYP3A4 and P-gp strong inhibitor) depends on everolimus indication and brand. Avoid coadministration if used for renal cell carcinoma (Afinitor). If used for kidney transplant immunosuppression (Zortress), reduce cyclosporine dose and use target serum concentration to reduce nephrotoxicity.

• dabrafenib

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

• deferasirox

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

• dengue vaccine

  everolimus 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

  everolimus, 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.

• dichlorphenamide

  dichlorphenamide and everolimus both decrease serum potassium. Use Caution/Monitor.
  
  dichlorphenamide, everolimus. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• diltiazem

  diltiazem will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is based on indication. In breast cancer, PNET, renal cell cancer, or renal angiomyolipoma w/ TSC patents, decrease everolimus dose to 2.5-5 mg/day; decrease everolimus dose 50% and monitor levels in SEGA patients.

• duvelisib

  duvelisib will increase the level or effect of everolimus 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

  everolimus 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  elagolix decreases levels of everolimus 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 everolimus 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.

• elranatamab

  elranatamab will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

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

• enalapril

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

• encorafenib

  encorafenib, everolimus. 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.

• epcoritamab

  epcoritamab, everolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• fedratinib

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

• ferric maltol

  ferric maltol, everolimus. 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).

• fingolimod

  everolimus 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. .

• fosinopril

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

• glecaprevir/pibrentasvir

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

• glofitamab

  glofitamab, everolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• glycerol phenylbutyrate

  glycerol phenylbutyrate will decrease the level or effect of everolimus 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

  everolimus 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.

• influenza virus vaccine quadrivalent, recombinant

  everolimus 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

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

• isavuconazonium sulfate

  isavuconazonium sulfate will increase the level or effect of everolimus 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.

• istradefylline

  istradefylline will increase the level or effect of everolimus 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 everolimus 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 everolimus 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.

• lenacapavir

  lenacapavir will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  letermovir increases levels of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lisinopril

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

• lonafarnib

  lonafarnib will increase the level or effect of everolimus 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.

• lonapegsomatropin

  lonapegsomatropin decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• lorlatinib

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

• maitake

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

• mercaptopurine

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

• metformin

  everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• mitotane

  mitotane decreases levels of everolimus 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, everolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

• ofatumumab SC

  ofatumumab SC, everolimus. 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.

• omaveloxolone

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

• palbociclib

  palbociclib will increase the level or effect of everolimus 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

• perindopril

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

• pirtobrutinib

  pirtobrutinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.

• pitolisant

  pitolisant will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

• poliovirus vaccine inactivated

  everolimus 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quinapril

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

• ramipril

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

• ribociclib

  ribociclib will increase the level or effect of everolimus 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.

• ritlecitinib

  ritlecitinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP3A4 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP3A substrates.

• rucaparib

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

• sarecycline

  sarecycline will increase the level or effect of everolimus 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.

• siponimod

  siponimod and everolimus 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

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

• sofosbuvir/velpatasvir

  sofosbuvir/velpatasvir will increase the level or effect of everolimus 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 everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

• somapacitan

  somapacitan decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• somatrogon

  somatrogon decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• somatropin

  somatropin decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• stiripentol

  stiripentol, everolimus. 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 everolimus 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.

• tacrolimus

  tacrolimus and everolimus both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. If used for liver transplant immunosuppression (Zortress), reduce tacrolimus dose and use target serum concentration to reduce nephrotoxicity.

• talquetamab

  talquetamab will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• tazemetostat

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

• teclistamab

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

• tecovirimat

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

• telotristat ethyl

  telotristat ethyl will decrease the level or effect of everolimus 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.

• trandolapril

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

• trastuzumab

  trastuzumab, everolimus. 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, everolimus. 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• trofinetide

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

• tucatinib

  tucatinib will increase the level or effect of everolimus 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.

• turmeric

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

• ustekinumab

  ustekinumab, everolimus. 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• verapamil

  everolimus will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Everolimus prescribing information lists indication-specific dosing recommendations.

• voclosporin

  voclosporin, everolimus. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• zoster vaccine recombinant

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

Minor (4)

• acetazolamide

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

• anastrozole

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

• cyclophosphamide

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

• larotrectinib

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

• acetazolamide

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

• adalimumab

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

• alefacept

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

• amiodarone

  Serious - Use Alternative (1)amiodarone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• amobarbital

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

• anakinra

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

• anastrozole

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

• anthrax vaccine

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

• antithymocyte globulin equine

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

• antithymocyte globulin rabbit

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

• apalutamide

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

• aprepitant

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

• armodafinil

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

• artemether/lumefantrine

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

• astragalus

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

• atazanavir

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

• atorvastatin

  Serious - Use Alternative (1)atorvastatin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• azathioprine

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

• basiliximab

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

• BCG vaccine live

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

• belatacept

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

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benazepril

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

• berotralstat

  Monitor Closely (2)berotralstat will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
  
  berotralstat will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

• betrixaban

  Monitor Closely (1)everolimus increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

• bosentan

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

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of everolimus 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

  Serious - Use Alternative (1)brigatinib will decrease the level or effect of everolimus 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

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

• butabarbital

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

• butalbital

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

• canakinumab

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

• cannabidiol

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

• captopril

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

• carbamazepine

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

• cenobamate

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

• chloramphenicol

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

• cholera vaccine

  Monitor Closely (1)everolimus 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.

• cimetidine

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

• clarithromycin

  Serious - Use Alternative (2)clarithromycin will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  clarithromycin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• clotrimazole

  Serious - Use Alternative (1)clotrimazole will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• cobicistat

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

• conivaptan

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

• cortisone

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

• crizotinib

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

• cyclophosphamide

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

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Everolimus is a CYP3A4 and P-gp substrate. Prescribing information for coadministration with cyclosporine (a CYP3A4 and P-gp strong inhibitor) depends on everolimus indication and brand. Avoid coadministration if used for renal cell carcinoma (Afinitor). If used for kidney transplant immunosuppression (Zortress), reduce cyclosporine dose and use target serum concentration to reduce nephrotoxicity.

• dabrafenib

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

• darifenacin

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

• darunavir

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

• dasatinib

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

• deferasirox

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

• deferiprone

  Serious - Use Alternative (1)deferiprone, everolimus. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• dengue vaccine

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

• denosumab

  Monitor Closely (1)everolimus, 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

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

• DHEA, herbal

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

• dichlorphenamide

  Monitor Closely (2)dichlorphenamide and everolimus both decrease serum potassium. Use Caution/Monitor.
  
  dichlorphenamide, everolimus. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is based on indication. In breast cancer, PNET, renal cell cancer, or renal angiomyolipoma w/ TSC patents, decrease everolimus dose to 2.5-5 mg/day; decrease everolimus dose 50% and monitor levels in SEGA patients.

• diphtheria & tetanus toxoids

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

• diphtheria & tetanus toxoids/ acellular pertussis vaccine

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

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

  Serious - Use Alternative (1)everolimus 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.

• dronedarone

  Serious - Use Alternative (2)dronedarone will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• duvelisib

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

• echinacea

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

• efavirenz

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

• elagolix

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

• eliglustat

  Monitor Closely (1)eliglustat increases levels of everolimus 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.

• elranatamab

  Monitor Closely (1)elranatamab will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

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

• enalapril

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

• encorafenib

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

• enzalutamide

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

• epcoritamab

  Monitor Closely (1)epcoritamab, everolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• erdafitinib

  Serious - Use Alternative (1)erdafitinib will increase the level or effect of everolimus 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

  Serious - Use Alternative (2)erythromycin base will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin ethylsuccinate

  Serious - Use Alternative (2)erythromycin ethylsuccinate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin lactobionate

  Serious - Use Alternative (2)erythromycin lactobionate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• erythromycin stearate

  Serious - Use Alternative (2)erythromycin stearate will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• eslicarbazepine acetate

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

• etanercept

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

• etravirine

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

• fedratinib

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

• felodipine

  Serious - Use Alternative (1)felodipine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• ferric maltol

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

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of everolimus 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.

• fingolimod

  Monitor Closely (1)everolimus 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. .

• fluconazole

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

• fluvoxamine

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

• fosamprenavir

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

• fosaprepitant

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

• fosinopril

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

• fosphenytoin

  Serious - Use Alternative (2)fosphenytoin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  fosphenytoin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• glatiramer

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

• glecaprevir/pibrentasvir

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

• glofitamab

  Monitor Closely (1)glofitamab, everolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• glycerol phenylbutyrate

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

• golimumab

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

• grapefruit

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

• griseofulvin

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

• haemophilus influenzae type b vaccine

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

• hepatitis A vaccine inactivated

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

• hepatitis a/b vaccine

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

• hepatitis a/typhoid vaccine

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

• hepatitis b vaccine

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

• human papillomavirus vaccine, nonavalent

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

• human papillomavirus vaccine, quadrivalent

  Serious - Use Alternative (1)everolimus 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

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

• hydroxychloroquine sulfate

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

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of everolimus 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

  Serious - Use Alternative (2)indinavir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
  
  indinavir will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• infliximab

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

• influenza virus vaccine quadrivalent

  Serious - Use Alternative (1)everolimus 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, cell-cultured

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

• influenza virus vaccine quadrivalent, intranasal

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

• influenza virus vaccine quadrivalent, recombinant

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

• influenza virus vaccine trivalent

  Serious - Use Alternative (1)everolimus 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, recombinant

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

• isavuconazonium sulfate

  Monitor Closely (1)isavuconazonium sulfate will increase the level or effect of everolimus 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.

• isoniazid

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

• istradefylline

  Monitor Closely (2)istradefylline will increase the level or effect of everolimus 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 everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

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

• ivacaftor

  Monitor Closely (1)ivacaftor increases levels of everolimus 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.

• ivosidenib

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

• Japanese encephalitis virus vaccine

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

• ketoconazole

  Serious - Use Alternative (2)ketoconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• lapatinib

  Serious - Use Alternative (2)lapatinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  lapatinib will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• larotrectinib

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

• leflunomide

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

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

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

• levoketoconazole

  Serious - Use Alternative (2)levoketoconazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  levoketoconazole will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• lisinopril

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

• lonafarnib

  Monitor Closely (1)lonafarnib will increase the level or effect of everolimus 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.

• lonapegsomatropin

  Monitor Closely (1)lonapegsomatropin decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• lopinavir

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

• loratadine

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

• lorlatinib

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

• lovastatin

  Serious - Use Alternative (1)lovastatin will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• lumacaftor/ivacaftor

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

• lumefantrine

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

• maitake

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

• marijuana

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

• measles (rubeola) vaccine

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

• measles mumps and rubella vaccine, live

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

• measles, mumps, rubella and varicella vaccine, live

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

• mefloquine

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

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

  Serious - Use Alternative (1)everolimus 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.

• mercaptopurine

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

• metformin

  Monitor Closely (1)everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• metronidazole

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

• miconazole vaginal

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

• mifepristone

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

• mitotane

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

• mobocertinib

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

• moexipril

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

• muromonab CD3

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

• mycophenolate

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

• nafcillin

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

• nefazodone

  Serious - Use Alternative (2)nefazodone will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nefazodone will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nelfinavir

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

• nevirapine

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

• nicardipine

  Serious - Use Alternative (1)nicardipine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nifedipine

  Serious - Use Alternative (2)nifedipine will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
  
  nifedipine will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nilotinib

  Serious - Use Alternative (2)nilotinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  nilotinib will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• nirmatrelvir/ritonavir

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

• ofatumumab SC

  Monitor Closely (1)ofatumumab SC, everolimus. 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.

• olutasidenib

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

• omaveloxolone

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

• oxcarbazepine

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

• pacritinib

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

• palbociclib

  Monitor Closely (1)palbociclib will increase the level or effect of everolimus 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

• pentobarbital

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

• perindopril

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

• pexidartinib

  Serious - Use Alternative (1)pexidartinib will decrease the level or effect of everolimus 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

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
  
  phenobarbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenytoin

  Serious - Use Alternative (2)phenytoin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  phenytoin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• pirtobrutinib

  Monitor Closely (1)pirtobrutinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.

• pitolisant

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

• pneumococcal vaccine 13-valent

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

• pneumococcal vaccine heptavalent

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

• pneumococcal vaccine polyvalent

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

• poliovirus vaccine inactivated

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

• ponatinib

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

• posaconazole

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

• pregabalin

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

• primidone

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

• quercetin

  Serious - Use Alternative (1)quercetin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinapril

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

• quinidine

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

• quinupristin/dalfopristin

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

• rabies vaccine

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

• rabies vaccine chick embryo cell derived

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

• ramipril

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

• ranolazine

  Serious - Use Alternative (1)ranolazine will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• ribociclib

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

• rifabutin

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

• rifampin

  Serious - Use Alternative (2)rifampin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  rifampin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• rifapentine

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

• rilonacept

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

• ritlecitinib

  Monitor Closely (1)ritlecitinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP3A4 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP3A substrates.

• ritonavir

  Serious - Use Alternative (2)ritonavir will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ritonavir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• ropeginterferon alfa 2b

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

• rotavirus oral vaccine, live

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

• rubella vaccine

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

• rucaparib

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

• rufinamide

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

• saquinavir

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

• sarecycline

  Monitor Closely (1)sarecycline will increase the level or effect of everolimus 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.

• secobarbital

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

• siponimod

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

• sipuleucel-T

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

• sirolimus

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

• smallpox (vaccinia) vaccine, live

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

• sofosbuvir/velpatasvir

  Monitor Closely (2)sofosbuvir/velpatasvir increases levels of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.
  
  sofosbuvir/velpatasvir will increase the level or effect of everolimus 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.

• somapacitan

  Monitor Closely (1)somapacitan decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• somatrogon

  Monitor Closely (1)somatrogon decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• somatropin

  Monitor Closely (1)somatropin decreases effects of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

• sotorasib

  Serious - Use Alternative (2)sotorasib will decrease the level or effect of everolimus 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 everolimus 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

  Serious - Use Alternative (2)St John's Wort will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  St John's Wort will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• stiripentol

  Monitor Closely (2)stiripentol, everolimus. 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 everolimus 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.

• tacrolimus

  Monitor Closely (1)tacrolimus and everolimus both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. If used for liver transplant immunosuppression (Zortress), reduce tacrolimus dose and use target serum concentration to reduce nephrotoxicity.

• talquetamab

  Monitor Closely (1)talquetamab will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• tazemetostat

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

• teclistamab

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

• tecovirimat

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

• telotristat ethyl

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

• temsirolimus

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

• tepotinib

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

• tetanus toxoid adsorbed or fluid

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

• tick-borne encephalitis vaccine

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

• tipranavir

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

• tocilizumab

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

• tofacitinib

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

• tongkat ali

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

• topiramate

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

• trandolapril

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

• trastuzumab

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

• trastuzumab deruxtecan

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

• travelers diarrhea and cholera vaccine inactivated

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

• trazodone

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

• trofinetide

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

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of everolimus 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.

• turmeric

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

• typhoid polysaccharide vaccine

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

• typhoid vaccine live

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

• ustekinumab

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

• varicella virus vaccine live

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

• vemurafenib

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

• venetoclax

  Serious - Use Alternative (1)venetoclax will increase the level or effect of everolimus 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

  Monitor Closely (1)everolimus will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Everolimus prescribing information lists indication-specific dosing recommendations.Serious - Use Alternative (3)verapamil will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use of a moderate 3A4 inhibitor such as verapamil may significantly increase the plasma concentrations of everolimus following oral administration.
  
  verapamil will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Everolimus prescribing information lists indication-specific dosing recommendations.
  
  verapamil, everolimus. 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.

• voclosporin

  Monitor Closely (1)voclosporin, everolimus. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• voriconazole

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

• voxelotor

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

• yellow fever vaccine

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

• zafirlukast

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

• zoster vaccine live

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

• zoster vaccine recombinant

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