Tofacitinib

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

• Recommended Evaluations and Immunization Prior to Treatment Initiation Prior to initiating tofacitinib extended-release tablets, consider performing an active and latent TB evaluation, viral hepatitis screening, a complete blood count, and updating immunizations.
• Avoid tofacitinib extended-release tablets initiation if absolute lymphocyte count <500 cells/mm 3 , an absolute neutrophil count (ANC) <1,000 cells/mm 3 or hemoglobin <9 g/dL. ( 2.1 ) Important Administration Instructions Tofacitinib extended-release tablets are not substitutable with XELJANZ (tablets and oral solution). ( 2.2 ) Switching between XELJANZ and tofacitinib extended-release tablets should be made by the healthcare provider. ( 2.2 ) Recommended Dosage Adult Patients with RA, PsA or AS Tofacitinib extended-release tablets 11 mg once daily. ( 2.3 ) Adult Patients with UC Maintenance:
• Tofacitinib extended-release tablets 11 mg once daily. Use the lowest effective dose needed to maintain response. ( 2.5 ) Dosage in Patients with Renal Impairment or Hepatic Impairment Use of tofacitinib extended-release tablets in patients with severe HI is not recommended. ( 2.3 , 2.5, 8.7 ) See full prescribing information (FPI) for recommended dosage in patients with moderate or severe RI or moderate HI. ( 2.3 , 2.5, 8.6 , 8.7 ) Dosage Modification See the full prescribing information for dosage modification by indication for patients who concomitantly use CYP2C19 and/or CYP3A4 inhibitors and patients with lymphopenia, neutropenia, or anemia. ( 2.3 , 2.5 , 7 ) 2.1 Recommended Evaluations and Immunization Prior to Treatment Initiation Prior to initiating tofacitinib extended-release tablets, consider performing the following:
• Active and latent tuberculosis (TB) infection evaluation:
• If the patient has latent TB, treat for TB prior to tofacitinib extended-release tablets treatment [see Warnings and Precautions ( 5.1 )]. Viral hepatitis screening in accordance with clinical guidelines [see Warnings and Precautions ( 5.1 )]. A complete blood count:
• Avoid initiation of tofacitinib extended-release tablets treatment in patients with a lymphocyte count less than 500 cells/mm 3 , absolute neutrophil count less than 1,000 cells/mm 3 , or hemoglobin level less than 9 g/dL [see Warnings and Precautions ( 5.9 )]. Baseline hepatic function evaluation:
• Tofacitinib extended-release tablets are not recommended for patients with severe hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology ( 12.3 )]. Update immunizations according to current immunization guidelines. The interval between live vaccinations and initiation of tofacitinib extended-release tablets should be in accordance with current vaccination guidelines regarding immunosuppressive agents [see Warnings and Precautions ( 5.10 )]. 2.2 Important Administration Instructions Tofacitinib extended-release tablets are not substitutable with XELJANZ (tablets and oral solution). Switching between XELJANZ and tofacitinib extended-release tablets should be made by the healthcare provider. Dose interruption is recommended for management of lymphopenia, neutropenia, and anemia [see Warnings and Precautions ( 5.9 ) and Adverse Reactions ( 6.1 )]. Interrupt use of tofacitinib extended-release tablets if a patient develops a serious infection until the infection is controlled [see Warnings and Precautions ( 5.1 )]. Take tofacitinib extended-release tablets with or without food [see Clinical Pharmacology ( 12.3 )]. Swallow tofacitinib extended-release tablets whole and intact. Do not crush, split, or chew the extended-release tablets [see Clinical Pharmacology ( 12.3 )]. 2.3 Recommended Dosage in
• Adults with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis Table 1 displays the recommended dosage of tofacitinib extended-release tablets for
• adults with RA, PsA, and AS [see Indication and Usage ( 1.1 , 1.2 , 1.3 )] with and without renal impairment (including those who are undergoing hemodialysis) or hepatic impairment [see Use in Specific Populations ( 8.6 , 8.7 )]. The table also displays the recommended dosage modifications for patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )], and patients with lymphopenia, neutropenia, or anemia. Table 1:
• Recommended Dosage of Tofacitinib Extended-Release Tablets in
• Adults with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis
• Adults Tofacitinib Extended-Release Tablets Patients with Normal Renal and Hepatic Function a 11 mg once daily Recommended Dosage in Patients with Renal Impairment (RI) b Mild RI (CLcr >50 and ≤80 mL/min) 11 mg once daily Moderate RI (CLcr ≥30 and ≤50 mL/min) XELJANZ tablets 5 mg once daily Severe RI (CLcr <30 mL/min) XELJANZ tablets 5 mg once daily For patients undergoing hemodialysis, administer the dose after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended after dialysis. Recommended Dosage in Patients with Hepatic Impairment (HI) Mild HI (Child-Pugh A) 11 mg once daily Moderate HI (Child-Pugh B) XELJANZ tablets 5 mg once daily Severe HI (Child-Pugh C) Use of XELJANZ tablets/tofacitinib extended-release tablets is not recommended. Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) Strong CYP2C19 inhibitor(s) 11 mg once daily Moderate CYP2C19 inhibitor(s) Moderate CYP3A4 inhibitor(s) Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) XELJANZ tablets 5 mg once daily Strong CYP3A4 inhibitor(s) Dosage Modifications for Lymphopenia, Neutropenia, or Anemia Patients with lymphocyte count less than 500 cells/mm 3 , confirmed by repeat testing Discontinue dosing. Patients with ANC less than 500 cells/mm 3 Discontinue dosing. Patients with ANC 500 to 1,000 cells/mm 3 Interrupt dosing. When ANC is greater than 1,000, resume 11 mg once daily. Patients with hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL Interrupt dosing until hemoglobin values have normalized. a Excludes patients who concomitantly use XELJANZ tablets/tofacitinib extended-release tablets with strong CYP3A4 inhibitor(s) or moderate CYP3A4 inhibitor(s) and strong CYP2C19 inhibitor(s), as well as patients with lymphocyte count less than 500 cells/mm 3 , ANC <1,000 cells/mm 3 , or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. b Tofacitinib PK was evaluated in subjects with varying degrees of renal impairment, where the severity of renal impairment was defined based on creatinine clearance (CLcr) estimated using the Cockcroft-Gault equation:
• CLcr >80 mL/min (normal renal function); >50 and ≤80 mL/min (mild renal impairment); ≥30 and ≤50 mL/min (moderate renal impairment); <30 mL/min (severe renal impairment). Switching from XELJANZ Tablets to Tofacitinib Extended-Release Tablets Patients treated with XELJANZ tablets 5 mg twice daily may be switched to tofacitinib extended-release tablets 11 mg once daily the day following the last dose of XELJANZ tablets 5 mg. 2.5 Recommended Dosage in
• Adults with Ulcerative Colitis Table 3 displays the recommended dosage of tofacitinib extended-release tablets in adult patients with ulcerative colitis (UC) [see Indications and Usage ( 1.5 )] with and without renal impairment (including those who are undergoing hemodialysis) or hepatic impairment [see Use in Specific Populations ( 8.6 , 8.7)] . Table 4 displays the recommended dosage modification for patients concomitantly using CYP2C19 and/or CYP3A4 inhibitors [see Drug Interactions ( 7 ) and Clinical Pharmacology (12.3)] , and patients with lymphopenia, neutropenia, or anemia. Table 3:
• Recommended Dosage of Tofacitinib Extended-Release Tablets in
• Adults with Ulcerative Colitis With and Without Renal Impairment or Hepatic Impairment
• Adults Tofacitinib Extended-Release Tablets Patients with Normal Renal and Hepatic Function a Maintenance:
• 11 mg once daily. Use the lowest effective dose needed to maintain response. Recommended Dosage in Patients with Renal Impairment (RI) b Mild RI (CLcr >50 and ≤80 mL/min) Same as patients with normal renal function. Moderate RI (CLcr ≥30 and ≤50 mL/min) Severe RI (CLcr <30 mL/min) Induction:
• 11 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance:
• Tofacitinib extended-release tablets is not recommended. For patients undergoing hemodialysis, administer the dose after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended after dialysis. Recommended Dosage in Patients with Hepatic Impairment (HI) Mild HI (Child-Pugh A) Same as patients with normal hepatic function. Moderate HI (Child-Pugh B) Induction:
• 11 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance:
• Tofacitinib extended-release tablets is not recommended. Severe HI (Child-Pugh C) Use of tofacitinib extended-release tablets is not recommended. a Excludes patients who concomitantly use tofacitinib extended-release tablets with strong CYP3A4 inhibitor(s) or moderate CYP3A4 inhibitor(s) and strong CYP2C19 inhibitor(s), as well as patients with lymphocyte count less than 500 cells/mm 3 , ANC <1000 cells/mm 3 , or hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL. b Tofacitinib PK was evaluated in subjects with varying degrees of renal impairment, where the severity of renal impairment was defined based on creatinine clearance (CLcr) estimated using the Cockcroft-Gault equation:
• CLcr >80 mL/min (normal renal function); CLcr >50 and ≤80 mL/min (mild renal impairment); ≥30 and ≤50 mL/min (moderate renal impairment); <30 mL/min (severe renal impairment). Table 4:
• Dosage Modifications of Tofacitinib Extended-Release Tablets Due to Drug Interactions and for Lymphopenia, Neutropenia or Anemia in
• Adults with Ulcerative Colitis
• Adults Tofacitinib Extended-Release Tablets Dosage Modifications with Concomitant Use of CYP3A4 and/or CYP2C19 Inhibitor(s) Strong CYP2C19 inhibitor(s) No dosage modification is recommended. Moderate CYP2C19 inhibitor(s) Moderate CYP3A4 inhibitor(s) Moderate CYP3A4 inhibitor(s) with strong CYP2C19 inhibitor(s) (e.g., fluconazole) Induction:
• 11 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 11 mg once daily for a maximum of 16 weeks. Discontinue 11 mg once daily after 16 weeks if adequate therapeutic response is not achieved. Maintenance:
• Tofacitinib extended-release tablets is not recommended. Strong CYP3A4 inhibitor(s) Dosage Modifications for Lymphopenia, Neutropenia, or Anemia Lymphocyte count less than 500 cells/mm 3 , confirmed by repeat testing Discontinue dosing. ANC less than 500 cells/mm 3 Discontinue dosing. ANC 500 to 1000 cells/mm 3 If taking:
• 11 mg once daily, interrupt dosing. When ANC is greater than 1,000, resume 11 mg once daily. Hemoglobin less than 8 g/dL or a decrease of more than 2 g/dL Interrupt dosing until hemoglobin values have normalized. Switching from XELJANZ Tablets to Tofacitinib Extended-Release Tablets Patients treated with XELJANZ tablets:
• 5 mg twice daily may be switched to tofacitinib extended-release tablets 11 mg once daily the day following the last dose of XELJANZ tablets 5 mg.

Quoted from the official label, section “Dosage & Administration”.

Other warnings

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

Quoted from the official label, section “Overdosage”.

Use in children

The safety and effectiveness of tofacitinib extended-release tablets in pediatric patients have not been established.

Quoted from the official label, section “Pediatric Use”.

Use in older people

• Of the 3,315
• adults who were enrolled in clinical trials with RA (Studies RA-I to V), a total of 505 patients were 65 years of age and older, including 71 patients 75 years and older.
• The frequency of serious infection among XELJANZ tablets-treated patients 65 years of age and older was higher than among those
• adults under the age of 65.
• Of the 1,156 XELJANZ tablet-treated patients in clinical trials of patients with UC, a total of 77 patients (7%) were 65 years of age or older.
• Clinical studies of tofacitinib in patients with UC did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger adult patients.
• Of the 783 XELJANZ tablet-treated patients in clinical trials of patients with PsA, a total of 72 (9.2%) patients were 65 years of age and older, including 2 (0.3%) patients 75 years and older.
• These clinical studies did not include sufficient numbers of patients aged 65 years and older with PsA to determine if they respond differently from younger adult patients.
• Of the 420 XELJANZ tablet-treated patients in clinical trials of patients with AS, a total of 12 (2.9%) patients were 65 years of age and older, including 1 (0.2%) patient 75 years and older.
• These clinical studies did not include sufficient numbers of patients aged 65 years and older with AS to determine if they respond differently from younger adult patients.

Quoted from the official label, section “Geriatric Use”.

Side effects

• The following clinically significant adverse reactions are described elsewhere in the labeling:
• Serious Infections [see Warnings and Precautions ( 5.1 )] Increased Risk of Mortality [see Warnings and Precautions ( 5.2 )] Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions ( 5.3 )] Major Adverse Cardiovascular Events [see Warnings and Precautions ( 5.4 )] Thrombosis [see Warnings and Precautions ( 5.5 )] Gastrointestinal Perforations [see Warnings and Precautions ( 5.6 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Hypoglycemia in Patients with Diabetes [see Warnings and Precautions ( 5.8 )] Laboratory Abnormalities [see Warnings and Precautions ( 5.9 )] Most common adverse reactions are:
• RA, PsA, and AS:
• Reported in ≥2% of adult patients treated with XELJANZ tablets monotherapy or in combination with DMARDs:
• upper respiratory tract infection (URI), nasopharyngitis, diarrhea, and headache.
• ( 6.1 ) UC:
• Reported in ≥ 5% of adult patients treated with either XELJANZ tablets and ≥1% greater than reported in patients treated with placebo:
• nasopharyngitis, elevated cholesterol levels, headache, URI, increased blood creatine phosphokinase, rash, diarrhea, and herpes zoster.
• ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
• 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.
• The clinical studies described in this subsection were conducted using XELJANZ tablets (referred to as “XELJANZ” in this subsection of labeling).
• Adverse Reactions in
• Adults with Rheumatoid Arthritis In RA Safety Study 1, 1,455
• adults were treated with XELJANZ 5 mg twice daily, 1,456
• adults were treated with 10 mg twice daily, and 1,451
• adults were treated with a TNF blocker for a median of 4 years [see Clinical Studies (14.6)].
• A dosage of XELJANZ 10 mg twice daily is not recommended for the treatment of RA because of increased risks [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5 )].
• For the treatment of
• adults with moderately to severely active RA [see Indications and Usage ( 1.1 )], the recommended dosage of XELJANZ is 5 mg twice daily and the recommended dosage for tofacitinib extended-release tablets are 11 mg once daily.
• The safety of XELJANZ was also evaluated in two Phase 2 and five Phase 3 double-blind, placebo-controlled, multicenter trials in patients with RA.
• In these trials,
• adults were randomized to receive:
• XELJANZ (monotherapy) 5 mg twice daily (292 patients) or 10 mg twice daily (306 patients), In combination with DMARDs (including methotrexate), XELJANZ 5 mg twice daily (1,044 patients) or 10 mg twice daily (1,043 patients and Placebo (809 patients).
• All seven trials included provisions for patients taking placebo to receive treatment with XELJANZ at Month 3 or Month 6 either by patient response (based on uncontrolled disease activity) or by design, so that adverse events cannot always be unambiguously attributed to a given treatment.
• Therefore, some analyses that follow include patients who changed treatment by design or by patient response from placebo to XELJANZ in both the placebo and XELJANZ group of a given interval.
• Comparisons between placebo and XELJANZ groups were based on the first 3 months of exposure, and comparisons between XELJANZ 5 mg twice daily and XELJANZ 10 mg twice daily were based on the first 12 months of exposure.
• The long-term safety population includes all
• adults with RA who participated in a double-blind, placebo-controlled trial (including earlier development phase studies) and then participated in one of two long-term safety studies.
• The design of the long-term safety studies allowed for modification of XELJANZ doses according to clinical judgment.
• This limits the interpretation of the long-term safety data with respect to dose.
• The most common serious adverse reactions were serious infections [see Warnings and Precautions ( 5.1 )].
• The proportion of patients who discontinued treatment due to any adverse reaction during the 0 to 3 months exposure in the double-blind, placebo-controlled trials was 4% for XELJANZ-treated patients and 3% for placebo-treated patients.
• Overall Infections In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, the overall frequency of infections was 20% and 22% in the XELJANZ 5 mg twice daily and XELJANZ 10 mg twice daily groups, respectively, and 18% in the placebo group.
• The most commonly reported infections with XELJANZ were upper respiratory tract infections, nasopharyngitis, and urinary tract infections (4%, 3%, and 2% of patients, respectively).
• Serious Infections:
• In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, serious infections were reported in 1 patient (0.5 events per 100 patient-years) who received placebo and 11 patients (1.7 events per 100 patient-years) who received XELJANZ 5 mg or 10 mg twice daily.
• The rate difference between treatment groups (and the corresponding 95% confidence interval) was 1.1 (- 0.4, 2.5) events per 100 patient-years for the combined XELJANZ 5 mg twice daily and 10 mg twice daily group minus placebo.
• In the seven placebo-controlled trials, during the 0 to 12 months exposure, serious infections were reported in 34 patients (2.7 events per 100 patient-years) who received XELJANZ 5 mg twice daily and 33 patients (2.7 events per 100 patient-years) who received XELJANZ 10 mg twice daily.
• The rate difference between XELJANZ doses (and the corresponding 95% confidence interval) was -0.1 (-1.3, 1.2) events per 100 patient-years for XELJANZ 10 mg twice daily minus XELJANZ 5 mg twice daily.
• The most common serious infections included pneumonia, cellulitis, herpes zoster, and urinary tract infection [see Warnings and Precautions ( 5.1 )].
• Tuberculosis:
• In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, tuberculosis (TB) was not reported in patients who received placebo, XELJANZ 5 mg twice daily, or XELJANZ 10 mg twice daily.
• In the seven placebo-controlled trials, during the 0 to 12 months exposure, TB was reported in 0 patients who received XELJANZ 5 mg twice daily and 6 patients (0.5 events per 100 patient-years) who received XELJANZ 10 mg twice daily.
• The rate difference between XELJANZ doses (and the corresponding 95% confidence interval) was 0.5 (0.1, 0.9) events per 100 patient-years for XELJANZ 10 mg twice daily minus XELJANZ 5 mg twice daily.
• Cases of disseminated TB were also reported.
• The median XELJANZ exposure prior to diagnosis of TB was 10 months (range from 152 to 960 days) [see Warnings and Precautions ( 5.1 )].
• Opportunistic Infections (excluding tuberculosis):
• In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, opportunistic infections were not reported in patients who received placebo, XELJANZ 5 mg twice daily, or XELJANZ 10 mg twice daily.
• In the seven placebo-controlled trials, during the 0 to 12 months exposure, opportunistic infections were reported in 4 patients (0.3 events per 100 patient-years) who received XELJANZ 5 mg twice daily and 4 patients (0.3 events per 100 patient-years) who received XELJANZ 10 mg twice daily.
• The rate difference between XELJANZ doses (and the corresponding 95% confidence interval) was 0 (-0.5, 0.5) events per 100 patient-years for XELJANZ 10 mg twice daily minus XELJANZ 5 mg twice daily.
• The median XELJANZ exposure prior to diagnosis of an opportunistic infection was 8 months (range from 41 to 698 days) [see Warnings and Precautions ( 5.1 )].
• Malignancies In the seven placebo-controlled trials in patients with RA, during the 0 to 3 months exposure, malignancies excluding NMSC were reported in 0 patients who received placebo and 2 patients (0.3 events per 100 patient-years) who received either XELJANZ 5 mg or 10 mg twice daily.
• The rate difference between treatment groups (and the corresponding 95% confidence interval) was 0.3 (-0.1, 0.7) events per 100 patient-years for the combined XELJANZ 5 mg and 10 mg twice daily group minus placebo.
• In the seven placebo-controlled trials, during the 0 to 12 months exposure, malignancies excluding NMSC were reported in 5 patients (0.4 events per 100 patient-years) who received XELJANZ 5 mg twice daily and 7 patients (0.6 events per 100 patient-years) who received XELJANZ 10 mg twice daily.
• The rate difference between XELJANZ doses (and the corresponding 95% confidence interval) was 0.2 (-0.4, 0.7) events per 100 patient-years for XELJANZ 10 mg twice daily minus XELJANZ 5 mg twice daily.
• One of these malignancies was a case of lymphoma that occurred during the 0-to-12-month period in a patient treated with XELJANZ 10 mg twice daily.
• The most common types of malignancy, including malignancies observed during the long-term extension in XELJANZ-treated patients, were lung and breast cancer, followed by gastric, colorectal, renal cell, prostate cancer, lymphoma, and malignant melanoma [see Warnings and Precautions ( 5.3 )].
• Laboratory Abnormalities Lymphopenia:
• In the placebo-controlled clinical trials in patients with RA, confirmed decreases in absolute lymphocyte counts below 500 cells/mm 3 occurred in 0.04% of patients for the XELJANZ 5 mg twice daily and 10 mg twice daily groups combined during the first 3 months of exposure.
• Confirmed lymphocyte counts less than 500 cells/mm 3 were associated with an increased incidence of treated and serious infections [see Warnings and Precautions ( 5.9 )].
• Neutropenia:
• In the placebo-controlled clinical trials in patients with RA, confirmed decreases in ANC below 1,000 cells/mm 3 occurred in 0.07% of patients for the XELJANZ 5 mg twice daily and 10 mg twice daily groups combined during the first 3 months of exposure.
• There were no confirmed decreases in ANC below 500 cells/mm 3 observed in any treatment group.
• There was no clear relationship between neutropenia and the occurrence of serious infections.
• In the long-term safety population, the pattern and incidence of confirmed decreases in ANC remained consistent with what was seen in the placebo-controlled clinical trials [see Warnings and Precautions ( 5.9 )].
• Liver Enzyme Elevations:
• Confirmed increases in liver enzymes greater than 3 times the upper limit of normal (3x ULN) were observed in patients with RA treated with XELJANZ.
• In patients experiencing liver enzyme elevation, modification of treatment regimen, such as reduction in the dose of concomitant DMARD, interruption of XELJANZ, or reduction in XELJANZ dosage, resulted in decrease or normalization of liver enzymes.
• In the placebo-controlled monotherapy trials (0 to 3 months), no differences in the incidence of ALT or AST elevations were observed between the placebo, and XELJANZ 5 mg, and 10 mg twice daily groups.
• In the placebo-controlled background DMARD trials (0 to 3 months), ALT elevations greater than 3x ULN were observed in 1.0%, 1.3% and 1.2% of patients who received placebo, XELJANZ 5 mg, and 10 mg twice daily, respectively.
• In these trials, AST elevations greater than 3x ULN were observed in 0.6%, 0.5% and 0.4% of patients who received placebo, XELJANZ 5 mg, and 10 mg twice daily, respectively.
• One case of drug-induced liver injury was reported in a patient treated with XELJANZ 10 mg twice daily for approximately 2.5 months.
• The patient developed symptomatic elevations of AST and ALT greater than 3x ULN and bilirubin elevations greater than 2x ULN, which required hospitalizations and a liver biopsy.
• Lipid Elevations:
• In the placebo-controlled clinical trials in patients with RA, dose-related elevations in lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) were observed at one month of exposure and remained stable thereafter.
• Changes in lipid parameters during the first 3 months of exposure in the placebo-controlled clinical trials are summarized below:
• Mean LDL cholesterol increased by 15% in the XELJANZ 5 mg twice daily arm and 19% in the XELJANZ 10 mg twice daily arm.
• Mean HDL cholesterol increased by 10% in the XELJANZ 5 mg twice daily arm and 12% in the XELJANZ 10 mg twice daily arm.
• Mean LDL/HDL ratios were essentially unchanged in XELJANZ-treated patients.
• In a placebo-controlled clinical trial, elevations in LDL cholesterol and ApoB decreased to pretreatment levels in response to statin therapy.
• In the long-term safety population, elevations in lipid parameters remained consistent with what was seen in the placebo-controlled clinical trials.
• Serum Creatinine Elevations:
• In the placebo-controlled clinical trials in patients with RA, dose-related elevations in serum creatinine were observed with XELJANZ treatment.
• The mean increase in serum creatinine was <0.1 mg/dL in the 12-month pooled safety analysis; however, with increasing duration of exposure in the long-term extensions, up to 2% of patients were discontinued from XELJANZ treatment due to the protocol-specified discontinuation criterion of an increase in creatinine by more than 50% of baseline.
• The clinical significance of the observed serum creatinine elevations is unknown.
• Common Adverse Reactions Table 5 displays adverse reactions that occurred in 2% or more of patients on XELJANZ 5 mg or 10 mg twice daily and at least 1% greater than in XELJANZ-treated patients that observed in placebo-treated patients with or without DMARD in the RA trials.
• Table 5:
• Common Adverse Reactions* in Clinical Trials of XELJANZ for the Treatment of Rheumatoid Arthritis in
• Adults With or Without Concomitant DMARDs (0 to 3 Months) Preferred Term Placebo XELJANZ 5 mg Twice Daily XELJANZ 10 mg Twice Daily** N = 809 (%) N = 1,336 (%) N = 1,349 (%) Upper respiratory tract infection 3 4 4 Nasopharyngitis 3 4 3 Diarrhea 2 4 3 Headache 2 4 3 Hypertension 1 2 2 N reflects randomized and treated patients from the seven placebo-controlled clinical trials. * reported in ≥2% of patients treated with either dose of XELJANZ and ≥1% greater than that reported for placebo. **The recommended dose of XELJANZ for the treatment of RA is 5 mg twice daily [see Dosage and Administration ( 2 )].
• Other adverse reactions that occurred in placebo-controlled and open-label extension studies in patients with RA included:
• Blood and lymphatic system disorders:
• Anemia Infections and infestations:
• Diverticulitis Metabolism and nutrition disorders :
• Dehydration Psychiatric disorders:
• Insomnia Nervous system disorders:
• Paresthesia Respiratory, thoracic and mediastinal disorders:
• Dyspnea, cough, sinus congestion, interstitial lung disease (cases were limited to patients with RA and some were fatal) Gastrointestinal disorders:
• Abdominal pain, dyspepsia, vomiting, gastritis, nausea Hepatobiliary disorders:
• Hepatic steatosis Skin and subcutaneous tissue disorders:
• Rash, erythema, pruritus Musculoskeletal, connective tissue and bone disorders:
• Musculoskeletal pain, arthralgia, tendonitis, joint swelling Neoplasms benign, malignant and unspecified (including cysts and polyps):
• Non-melanoma skin cancers General disorders and administration site conditions:
• Pyrexia, fatigue, peripheral edema Clinical Experience in Methotrexate-Naïve Patients Study RA-VI was an active-controlled clinical trial in methotrexate-naïve patients [see Clinical Studies ( 14 )].
• The safety experience in these patients was consistent with Studies RA-I through V.
• Adverse Reactions in
• Adults with Psoriatic Arthritis The safety of XELJANZ was evaluated in 2 double-blind Phase 3 clinical trials in
• adults with active psoriatic arthritis (PsA):
• Study PsA-I (NCT01877668) had a duration of 12 months and enrolled
• adults who had an inadequate response to a nonbiologic DMARD and who were naïve to treatment with a TNF blocker.
• Study PsA-I included a 3-month placebo-controlled period and also included adalimumab 40 mg subcutaneously once every 2 weeks for 12 months.
• Study PsA-II (NCT01882439) had a duration of 6 months and enrolled
• adults who had an inadequate response to at least one approved TNF blocker.
• This clinical trial included a 3-month placebo-controlled period.
• In these combined Phase 3 clinical trials, 238 patients were randomized and treated with XELJANZ 5 mg twice daily and 236 patients were randomized and treated with XELJANZ 10 mg twice daily.
• A dosage of XELJANZ 10 mg twice daily is not recommended for the treatment of PsA.
• For the treatment of
• adults with active PsA [see Indications and Usage (1.2)] , the recommended dosage of XELJANZ is 5 mg twice daily and the recommended dosage for tofacitinib extended-release tablet is 11 mg once daily [see Dosage and Administration (2.3)].
• All patients in the clinical trials in patients with PsA were required to receive treatment with a stable dose of a nonbiologic DMARD [the majority (79%) received methotrexate].
• The study population randomized and treated with XELJANZ (474 patients) included 45 (10%) patients aged 65 years or older and 66 (14%) patients with diabetes at baseline.
• During the 2 PsA controlled clinical trials, there were:
• 3 malignancies (excluding NMSC) in 474 patients who received XELJANZ plus non-biologic DMARD (6 to 12 months exposure) 0 malignancies in 236 patients who received placebo plus non-biologic DMARD group (3 months exposure) and 0 malignancies in 106 patients in patients who received adalimumab plus non-biologic DMARD group (12 months exposure).
• No lymphomas were reported.
• Malignancies have also been observed in the long-term extension study in patients with PsA treated with XELJANZ.
• The safety profile observed in
• adults with active PsA treated with XELJANZ was consistent with the safety profile observed in
• adults with RA.
• Adverse Reactions in
• Adults with Ankylosing Spondylitis The safety of XELJANZ was evaluated in
• adults with active ankylosing spondylitis (AS) in a double-blind placebo-controlled Phase 3 clinical trial (Study AS-I) and in a dose-ranging Phase 2 clinical trial (Study AS-II).
• Study AS-I (NCT03502616) had a duration of 48 weeks and enrolled
• adults who had an inadequate response to at least 2 NSAIDs.
• Study AS-I included a 16-week double-blind period in which patients received XELJANZ 5 mg or placebo twice daily and a 32-week open-label treatment period in which all patients received XELJANZ 5 mg twice daily.
• Study AS-II (NCT01786668) had a duration of 16 weeks and enrolled
• adults who had an inadequate response to at least 2 NSAIDs.
• This clinical trial included a 12-week treatment period in which patients received either XELJANZ 2 mg (40% of the recommended dose), 5 mg, 10 mg, or placebo twice daily.
• A dosage of XELJANZ 10 mg twice daily is not recommended for the treatment of AS.
• For the treatment of
• adults with active AS [see Indications and Usage (1.3)], the recommended dosage of XELJANZ is 5 mg twice daily and the recommended dosage for tofacitinib extended-release tablets is 11 mg once daily [see Dosage and Administration ( 2.3 )].
• In the combined Phase 2 and Phase 3 clinical trials, a total of 420 patients were treated with either XELJANZ 2 mg, 5 mg, or 10 mg twice daily.
• Of these, 316 patients were treated with XELJANZ 5 mg twice daily for up to 48 weeks.
• In the combined double-blind period, 185 patients were randomized to and treated with XELJANZ 5 mg twice daily and 187 to placebo for up to 16 weeks.
• Concomitant treatment with stable doses of nonbiologic DMARDs, NSAIDs, or corticosteroids (≤10 mg/day) was permitted.
• The study population randomized and treated with XELJANZ included 13 (3%) patients aged 65 years or older and 18 (4%) patients with diabetes at baseline.
• The safety profile observed in
• adults with AS treated with XELJANZ was consistent with the safety profile observed in
• adults with RA and PsA.
• Adverse Reactions in
• Adults with Ulcerative Colitis The safety of XELJANZ has been evaluated in
• adults with moderately to severely active UC in 4 randomized, double-blind, placebo-controlled trials (UC-I, UC-II, UC-III, and dose-ranging UC-V) and an open-label long-term extension study (UC-IV) [see Clinical Studies ( 14.5 )].
• Adverse reactions reported in ≥5% of patients treated with either XELJANZ 5 mg or 10 mg twice daily and ≥1% greater than reported in patients receiving placebo in either the induction or maintenance clinical trials of patients with UC were:
• nasopharyngitis, elevated cholesterol levels, headache, upper respiratory tract infection, increased blood creatine phosphokinase, rash, diarrhea, and herpes zoster.
• Induction Trials in
• Adults with UC Common adverse reactions reported in ≥2% of patients treated with XELJANZ 10 mg twice daily and ≥1% greater in XELJANZ-treated patients than placebo-treated patients in the 3 induction trials of patients with UC (Studies UC-I, UC-II, and UC-V) were:
• headache, nasopharyngitis, elevated cholesterol levels, acne, increased blood creatine phosphokinase, and pyrexia.
• Maintenance Trial in
• Adults with UC Common adverse reactions reported in ≥4% of patients treated with either dosage of XELJANZ and ≥1% greater than reported in patients treated with placebo in the maintenance trial of patients with UC (Study UC-III) are shown in Table 6.
• Table 6:
• Common Adverse Reactions* in
• Adults with UC During the 52-Week Maintenance Trial (Study UC-III) Preferred Term Placebo XELJANZ 5 mg Twice Daily XELJANZ 10 mg Twice Daily N = 198 (%) N = 198 (%) N = 196 (%) Nasopharyngitis 6 10 14 Elevated cholesterol levels** 1 5 9 Headache 6 9 3 Upper respiratory tract infection 4 7 6 Increased blood creatine phosphokinase 2 3 7 Rash 4 3 6 Diarrhea 3 2 5 Herpes zoster 1 1 5 Gastroenteritis 3 3 4 Anemia 2 4 2 Nausea 3 1 4 * Reported in ≥4% of patients treated with either XELJANZ dosage and ≥1% greater in XELJANZ-treated patients than placebo-treated patients. ** Includes hypercholesterolemia, hyperlipidemia, blood cholesterol increased, dyslipidemia, blood triglycerides increased, low-density lipoprotein increased, low-density lipoprotein abnormal, or lipids increased.
• Dose-dependent adverse reactions seen in patients treated with XELJANZ 10 mg twice daily, in comparison to 5 mg twice daily, include the following:
• herpes zoster infections, serious infections, and NMSC [see Warnings and Precautions ( 5.1 , 5.3 )].
• During the UC controlled clinical studies (8-week induction and 52-week maintenance studies), which included 1,220 patients, 0 cases of solid cancer or lymphoma were observed in XELJANZ-treated patients.
• In the long-term extension study, malignancies (including solid cancers, lymphomas and NMSC) were observed in patients treated with XELJANZ 5 mg and 10 mg twice daily [see Warnings and Precautions ( 5.3 )] .
• Five cases of pulmonary embolism were reported in patients taking XELJANZ 10 mg twice daily, including one fatality in a patient with advanced cancer [see Warnings and Precautions ( 5.5 )].
• 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tofacitinib extended-release tablets.
• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Immune system disorders:
• Drug hypersensitivity (events such as angioedema and urticaria have been observed) Metabolism and nutrition disorders:
• Hypoglycemia Skin and subcutaneous tissue disorders:
• Acne

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

• Advise patients to read the FDA-approved patient labeling (Medication Guide).
• Serious Infections Inform patients that tofacitinib extended-release tablets may lower the ability of their immune system to fight infections.
• Advise patients not to start taking tofacitinib extended-release tablets if they have an active infection.
• Instruct patients to contact their healthcare provider immediately during treatment
• if symptoms suggesting infection appear to ensure rapid evaluation and appropriate treatment [see Warnings and Precautions ( 5.1 )].
• Advise patients that the risk of herpes zoster, some cases of which can be serious, is increased in patients treated with tofacitinib extended-release tablets [see Warnings and Precautions ( 5.1 )].
• Malignancies and Lymphoproliferative Disorders Inform patients that tofacitinib extended-release tablets may increase their risk of certain cancers, and that lymphoma and other cancers have been observed in patients taking XELJANZ.
• Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions ( 5.3 )].
• Major Adverse Cardiovascular Events Inform patients that tofacitinib extended-release tablets may increase their risk of major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, and cardiovascular death.
• Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions ( 5.4 )].
• Thrombosis Advise patients to stop taking tofacitinib extended-release tablets and to call their healthcare provider right away if they experience any symptoms of thrombosis (sudden shortness of breath, chest pain worsened with breathing, swelling of leg or arm, leg pain or tenderness, red or discolored skin in the affected leg or arm) [see Warnings and Precautions ( 5.5 )].
• Hypersensitivity Advise patients to stop taking tofacitinib extended-release tablets and to call their healthcare provider right away if they experience any symptoms of allergic reactions while taking tofacitinib extended-release tablets [see Warnings and Precautions ( 5.7 )].
• Hypoglycemia in Patients with Diabetes Consider advising patients with diabetes to increase monitoring of blood glucose since hypoglycemia, including severe hypoglycemia, has been reported after starting tofacitinib extended-release tablets.
• Advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia [see Warnings and Precautions ( 5.8 )].
• Important Information on Laboratory Abnormalities Inform patients that tofacitinib extended-release tablets may affect certain lab test results, and that blood tests are required before and during tofacitinib extended-release tablets treatment [see Warnings and Precautions ( 5.9 )].
• Pregnancy Advise pregnant females and females of reproductive potential of the potential risk to a fetus.
• Advise females to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )].
• Lactation Advise women not to breastfeed during treatment with tofacitinib extended-release tablets and for at least 36 hours after the last dose of tofacitinib extended-release tablets [see Use in Specific Populations ( 8.2 )].
• Infertility Advise females of reproductive potential that tofacitinib extended-release tablets may impair fertility [see Use in Specific Populations ( 8.3 ), Nonclinical Toxicology ( 13.1 )].
• It is not known if this effect is reversible.
• Manufactured by: Manufactured for: Apotex Inc.
• Apotex Corp.
• Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 This product’s labeling may have been updated.
• For the most recent prescribing information, please visit www.apotex.com XELJANZ is a registered trademark of Pfizer, Inc.
• XELJANZ Oral Solution is a registered trademark of Pfizer, Inc.
• All trademarks are the property of their respective owners.
• Rev. 08

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

• FORMS AND STRENGTHS
• Tofacitinib Extended-Release Tablets:
• 11 mg ( 3 ) Tofacitinib extended-release tablets:
• o 11 mg of tofacitinib:
• White to off-white, oval shape, biconvex film-coated tablet. Engraved “T1” on one side, plain on the other side.

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

• How supplied information for tofacitinib extended-release tablets are shown in Table 23.
• Table 23:
• How Supplied Information for Tofacitinib Extended-Release Tablets Dosage Form, Strength, and Description Bottle Size (number of tablets) NDC Number Tofacitinib Extended-Release Tablets 11 mg White to off-white, oval shape, biconvex film-coated tablet.
• Engraved “T1” on one side, plain on the other side. 30 NDC 60505-4858-3 Store tofacitinib extended-release tablets at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature].
• Do not repackage.

Quoted from the official label, section “How Supplied”.

How to store it

Store tofacitinib extended-release tablets at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature]. Do not repackage.

Quoted from the official label, section “Storage and Handling”.

What is in it

• Tofacitinib extended-release tablets are formulated with the citrate salt of tofacitinib, a JAK inhibitor. Tofacitinib citrate is a white to off-white powder with the following chemical name:
• (3R,4R)-4-Methyl-3-(methyl-7H-pyrrolo [2,3- d ]pyrimidin-4-ylamino)-β-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1). The solubility of tofacitinib citrate in water is 2.9 mg/mL. Tofacitinib citrate has a molecular weight of 504.49 g/mol (or 312.37 g/mol as the tofacitinib free base) and a molecular formula of C 16 H 20 N 6 O
• C 6 H 8 O 7 . The chemical structure of tofacitinib citrate is:
• Tofacitinib extended-release tablets are supplied for oral administration as a:
• 11 mg white to off-white, oval shape, biconvex film-coated tablet. Engraved “T1” on one side, plain on the other side. Each 11 mg tablet of tofacitinib extended-release tablet contains 11 mg tofacitinib (equivalent to 17.77 mg tofacitinib citrate) and the following inactive ingredients:
• colloidal silicon dioxide, dibutyl sebacate, ethylcellulose, hydroxypropyl methylcellulose 2208, hydroxypropyl methylcellulose 2910, MAA (methacrylic acid) and ETAC (ethyl acrylate) copolymer, magnesium stearate, mannitol, and talc. structure.jpg

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

Same active substance, strength and form in other countries

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Details

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

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