Usual Adult Dose for Rheumatoid Arthritis

Immediate-release tablets: 5 mg orally twice a day
Extended-release tablets: 11 mg orally once a day

Comments:

• Limitations of Use: Use of this drug in combination with biologic DMARDs or with potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.

Use: For the treatment of patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to at least 1 tumor necrosis factor (TNF) blocker

Usual Adult Dose for Psoriatic Arthritis

Immediate-release tablets: 5 mg orally twice a day
Extended-release tablets: 11 mg orally once a day

Comments:

• Limitations of Use: Use of this drug in combination with biologic DMARDs or with potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.
• This drug is used in combination with nonbiologic DMARDs in psoriatic arthritis (PsA); the efficacy of this drug as monotherapy has not been studied in PsA.

Use: For the treatment of patients with active PsA who have had an inadequate response or intolerance to at least 1 TNF blocker

Usual Adult Dose for Ankylosing Spondylitis

Immediate-release tablets: 5 mg orally twice a day
Extended-release tablets: 11 mg orally once a day

Comments:

• Limitations of Use: Use of this drug in combination with biologic DMARDs or potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.

Use: For the treatment of patients with active ankylosing spondylitis who have had an inadequate response or intolerance to at least 1 TNF blocker

Usual Adult Dose for Ulcerative Colitis

Immediate-Release Tablets:

• Induction: 10 mg orally twice a day for at least 8 weeks
• Maintenance: 5 mg orally twice a day

Extended-Release Tablets:

• Induction: 22 mg orally once a day for at least 8 weeks
• Maintenance: 11 mg orally once a day

Comments:

• Limitations of Use: Use of this drug in combination with biological therapies for ulcerative colitis or with potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.
• Induction: Patients should be evaluated and transitioned to maintenance therapy depending on therapeutic response.
• If needed, 10 mg orally twice a day (immediate-release tablets) or 22 mg orally once a day (extended-release tablets) should be continued for up to 16 weeks; if adequate therapeutic response is not achieved after 16 weeks, the induction dosage should be discontinued.
• Maintenance: For patients with loss of response during maintenance therapy, a dosage of 10 mg orally twice a day (immediate-release tablets) or 22 mg orally once a day (extended-release tablets) may be considered and limited to the shorted duration, with careful consideration of the risks/benefits for the individual patient; the lowest effective dose needed to maintain response should be used.

Use: For the treatment of patients with moderately to severely active ulcerative colitis who have an inadequate response or intolerance to at least 1 TNF blocker

Usual Pediatric Dose for Juvenile Idiopathic Arthritis

2 Years or Older:
Immediate-release oral solution:

• Weight 10 to less than 20 kg: 3.2 mg orally twice a day
• Weight 20 to less than 40 kg: 4 mg orally twice a day
• Weight at least 40 kg: 5 mg orally twice a day

Immediate-release tablets:

• Weight at least 40 kg: 5 mg orally twice a day

Comments:

• Limitations of Use: Use of this drug in combination with biologic DMARDs or with potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended.
• Patients weighing at least 40 kg may be switched from the oral solution to the tablets.

Use: For the treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients who have had an inadequate response or intolerance to at least 1 TNF blocker

Renal Dose Adjustments

MILD RENAL DYSFUNCTION: No adjustment recommended.

MODERATE OR SEVERE RENAL DYSFUNCTION:
Patients with RA, PsA, and Ankylosing Spondylitis:

• Immediate-release tablets: 5 mg orally once a day
• Extended-release tablets: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with Ulcerative Colitis:

• Immediate-release tablets:
• If taking 10 mg orally twice a day: Dose should be reduced to 5 mg orally twice a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.
• Extended-release tablets:
• If taking 22 mg orally once a day: Dose should be reduced to 11 mg orally once a day.
• If taking 11 mg orally once a day: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with pcJIA:

• Immediate-release oral solution/tablets:
• If taking 3.2 mg orally twice a day: Dose should be reduced to 3.2 mg orally once a day.
• If taking 4 mg orally twice a day: Dose should be reduced to 4 mg orally once a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.

Liver Dose Adjustments

MILD LIVER DYSFUNCTION: No adjustment recommended.

MODERATE LIVER DYSFUNCTION:
Patients with RA, PsA, and Ankylosing Spondylitis:

• Immediate-release tablets: 5 mg orally once a day
• Extended-release tablets: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with Ulcerative Colitis:

• Immediate-release tablets:
• If taking 10 mg orally twice a day: Dose should be reduced to 5 mg orally twice a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.
• Extended-release tablets:
• If taking 22 mg orally once a day: Dose should be reduced to 11 mg orally once a day.
• If taking 11 mg orally once a day: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with pcJIA:

• Immediate-release oral solution/tablets:
• If taking 3.2 mg orally twice a day: Dose should be reduced to 3.2 mg orally once a day.
• If taking 4 mg orally twice a day: Dose should be reduced to 4 mg orally once a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.

SEVERE LIVER DYSFUNCTION: Not recommended.

Dose Adjustments

Switching from Immediate-Release Tablets to Extended-Release Tablets:

• Patients treated with immediate-release tablets 5 mg orally twice a day may be switched to extended-release tablets 11 mg orally once a day the day after the last dose of immediate-release tablets 5 mg.
• Patients treated with immediate-release tablets 10 mg orally twice a day may be switched to extended-release tablets 22 mg orally once a day the day after the last dose of immediate-release tablets 10 mg.

PATIENTS WITH RA, PsA, AND ANKYLOSING SPONDYLITIS:
Coadministration with strong CYP450 3A4 inhibitors (e.g., ketoconazole), or a moderate CYP450 3A4 inhibitor(s) with a strong CYP450 2C19 inhibitor(s) (e.g., fluconazole):

• Immediate-release tablets: 5 mg orally once a day
• Extended-release tablets: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Lymphocyte count less than 500 cells/mm3, confirmed by repeat testing: Dosing should be discontinued.

Absolute neutrophil count (ANC) 500 to 1000 cells/mm3:

• Immediate-release tablets: Dosing should be interrupted; when ANC is greater than 1000 cells/mm3, dosing should resume at 5 mg orally twice a day.
• Extended-release tablets: Dosing should be interrupted; when ANC is greater than 1000 cells/mm3, dosing should resume at 11 mg orally once a day.

ANC less than 500 cells/mm3: Dosing should be discontinued.

Hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL: Dosing should be interrupted until hemoglobin values have normalized.

PATIENTS WITH ULCERATIVE COLITIS:
Coadministration with strong CYP450 3A4 inhibitors (e.g., ketoconazole), or a moderate CYP450 3A4 inhibitor(s) with a strong CYP450 2C19 inhibitor(s) (e.g., fluconazole):

• Immediate-release tablets:
• If taking 10 mg orally twice a day: Dose should be reduced to 5 mg orally twice a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.
• Extended-release tablets:
• If taking 22 mg orally once a day: Dose should be reduced to 11 mg orally once a day.
• If taking 11 mg orally once a day: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Lymphocyte count less than 500 cells/mm3, confirmed by repeat testing: Dosing should be discontinued.

ANC 500 to 1000 cells/mm3:

• Immediate-release tablets:
• If taking 10 mg orally twice a day: Dose should be reduced to 5 mg orally twice a day; when ANC is greater than 1000 cells/mm3, dose should increase to 10 mg orally twice a day, based on clinical response.
• If taking 5 mg orally twice a day: Dosing should be interrupted; when ANC is greater than 1000 cells/mm3, dosing should resume at 5 mg orally twice a day.
• Extended-release tablets:
• If taking 22 mg orally once a day: Dose should be reduced to 11 mg orally once a day; when ANC is greater than 1000 cells/mm3, dose should increase to 22 mg orally once a day, based on clinical response.
• If taking 11 mg orally once a day: Dosing should be interrupted; when ANC is greater than 1000 cells/mm3, dosing should resume at 11 mg orally once a day.

ANC less than 500 cells/mm3: Dosing should be discontinued.

Hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL: Dosing should be interrupted until hemoglobin values have normalized.

PATIENTS WITH pcJIA:
Coadministration with strong CYP450 3A4 inhibitors (e.g., ketoconazole), or a moderate CYP450 3A4 inhibitor(s) with a strong CYP450 2C19 inhibitor(s) (e.g., fluconazole):

• Immediate-release oral solution/tablets:
• If taking 3.2 mg orally twice a day: Dose should be reduced to 3.2 mg orally once a day.
• If taking 4 mg orally twice a day: Dose should be reduced to 4 mg orally once a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.

Lymphocyte count less than 500 cells/mm3, confirmed by repeat testing: Dosing should be discontinued.

ANC 500 to 1000 cells/mm3: Dosing should be interrupted until ANC is greater than 1000 cells/mm3.

ANC less than 500 cells/mm3: Dosing should be discontinued.

Hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL: Dosing should be interrupted until hemoglobin values have normalized.

Precautions

US BOXED WARNINGS:

• SERIOUS INFECTIONS: Patients treated with this drug are at increased risk for developing serious infections that may lead to hospitalization or death; most patients who developed these infections were taking concomitant immunosuppressants (e.g., methotrexate, corticosteroids). If a serious infection develops, therapy should be interrupted until the infection is controlled. Reported infections include: active tuberculosis (TB), which may present with pulmonary/extrapulmonary disease; invasive fungal infections (including cryptococcosis, pneumocystosis);.and bacterial, viral (including herpes zoster) and other infections (due to opportunistic pathogens). Patients should be tested for latent TB before starting this drug and during therapy; treatment for latent infection should be started prior to therapy. Patients with invasive fungal infections may present with disseminated, rather than localized, disease. The risks and benefits of this drug should be carefully considered before starting therapy in patients with chronic/recurrent infection. Patients should be closely monitored for signs/symptoms of infection during and after therapy, including the possible development of TB in patients who tested negative for latent TB infection before starting therapy.
• MORTALITY: A large, randomized, postmarketing safety study in RA patients 50 years and older with at least 1 cardiovascular (CV) risk factor compared this drug (5 or 10 mg twice a day) to TNF blockers; a higher rate of all-cause mortality (including sudden CV death) was observed with this drug (5 or 10 mg twice a day). An immediate-release formulation dosage of 10 mg twice a day (or extended-release formulation dosage of 22 mg once a day) is not recommended for the treatment of RA or PsA.
• MALIGNANCIES: Malignancies (including lymphomas, solid tumors) have been reported with this drug and other JAK inhibitors used to treat inflammatory conditions; in RA patients, a higher rate of malignancies (excluding nonmelanoma skin cancer) was observed with this drug (5 or 10 mg twice a day) compared with TNF blockers. Lymphomas and lung cancers were observed at a higher rate in RA patients treated with this drug (5 or 10 mg twice a day) compared to those treated with TNF blockers; patients who are current/past smokers are at additional increased risk. Epstein Barr Virus-associated posttransplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with this drug and concomitant immunosuppressive medications.
• MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE): RA patients 50 years and older with at least 1 CV risk factor, treated with this drug (5 or 10 mg twice a day), had a higher rate of MACE (defined as CV death, myocardial infarction, and stroke), compared with TNF blockers; patients who are current/past smokers are at additional increased risk. This drug should be discontinued in patients who have had a myocardial infarction or stroke.
• THROMBOSIS: Thrombosis (including pulmonary embolism, deep venous thrombosis, and arterial thrombosis) has occurred in patients treated with this drug and other JAK inhibitors used to treat inflammatory conditions; many of these events were serious and some resulted in death. RA patients 50 years and older with at least 1 CV risk factor treated with this drug (5 or 10 mg twice a day) had an observed increase in incidence of these events compared to TNF blockers. This drug should be avoided in patients at risk. Patients with symptoms of thrombosis should discontinue this drug and be promptly evaluated.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in pcJIA patients younger than 2 years. Safety and efficacy of the extended-release formulation or for indications other than pcJIA have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

HEMODIALYSIS:
Patients with RA, PsA, and Ankylosing Spondylitis:

• Immediate-release tablets: 5 mg orally once a day
• Extended-release tablets: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with Ulcerative Colitis:

• Immediate-release tablets:
• If taking 10 mg orally twice a day: Dose should be reduced to 5 mg orally twice a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.
• Extended-release tablets:
• If taking 22 mg orally once a day: Dose should be reduced to 11 mg orally once a day.
• If taking 11 mg orally once a day: Dose should be reduced to immediate-release tablets 5 mg orally once a day.

Patients with pcJIA:

• Immediate-release oral solution/tablets:
• If taking 3.2 mg orally twice a day: Dose should be reduced to 3.2 mg orally once a day.
• If taking 4 mg orally twice a day: Dose should be reduced to 4 mg orally once a day.
• If taking 5 mg orally twice a day: Dose should be reduced to 5 mg orally once a day.

Comments:

• For patients undergoing hemodialysis, dose should be administered after the dialysis session on dialysis days; if a dose was taken before the dialysis procedure, supplemental doses are not recommended in patients after dialysis.

Other Comments

Administration advice:

• The extended-release tablets are not interchangeable or substitutable with the oral solution.
• Changes between the immediate-release tablets and extended-release tablets should be made by the health care provider.
• Do not start this drug in patients with an absolute lymphocyte count less than 500 cells/mm3, an ANC less than 1000 cells/mm3, or a hemoglobin level less than 9 g/dL.
• Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia.
• Interrupt use of this drug if a patient develops a serious infection until the infection is controlled.
• Administer this drug with or without food.
• Swallow the extended-release tablets whole and intact; do not crush, split, or chew.
• Administer the oral solution using the included press-in bottle adapter and oral dosing syringe.
• Use the oral solution within 60 days of opening the bottle; after 60 days, discard remaining oral solution.

Storage requirements:

• Oral solution: Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).
• Store in original bottle and carton to protect from light.
• Discard remaining oral solution 60 days after opening the bottle.
• Tablets: Store at 20C to 25C (68F to 77F); do not repackage.

Monitoring:

• Hematologic: Lymphocyte counts (at baseline and every 3 months thereafter); neutrophil counts and hemoglobin (at baseline, after 4 to 8 weeks of therapy, and every 3 months thereafter)
• Hepatic: Liver tests (routinely)
• Infections/Infestations: For signs/symptoms of infection (during and after therapy); for latent/active TB infection (before and per applicable guidelines during therapy); for signs/symptoms of TB (during therapy); for viral hepatitis (before starting therapy)
• Metabolic: Lipid parameters (about 4 to 8 weeks after starting therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Do not start taking this drug if you have an active infection; contact health care provider immediately during therapy if symptoms suggesting infection develop (to ensure rapid evaluation and appropriate treatment).
• Be alert for signs/symptoms of cardiovascular events, especially if you are a current/past smoker or have other cardiovascular risk factors.
• Stop taking this drug and call health care provider at once if any symptoms of thrombosis (sudden shortness of breath, chest pain worsened with breathing, swelling of leg/arm, leg pain/tenderness, red/discolored skin in the affected leg/arm) develop.
• Stop taking this drug and call health care provider at once if any symptoms of allergic reactions develop during therapy.
• Patients of childbearing potential: Inform prescriber of known/suspected pregnancy; if this drug has been taken during pregnancy, contact the registry for pregnant women to enroll.
• Do not breastfeed during therapy and for at least 18 hours after the last dose of the immediate-release tablets/oral solution or 36 hours after the last dose of the extended-release tablets.
• If taking the extended-release tablets: An inert tablet shell may be noticed in the stool or via colostomy; the active medication has already been absorbed by the time you see the inert tablet shell.

Frequently asked questions

• What are the new drugs for the treatment of rheumatoid arthritis (RA)?
• Is Xeljanz an immunosuppressant?
• Who makes Xeljanz and where is it made?