▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.
XELJANZ®▼(tofacitinib) Prescribing Information:
Please refer to the Summary of Product Characteristics (SmPC) before prescribing XELJANZ. Presentations: Film-coated tablets containing tofacitinib citrate, equivalent to 5 mg or 10 mg tofacitinib. Prolonged-release tablets containing tofacitinib citrate, equivalent to 11 mg tofacitinib. Indications: In combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate. In combination with MTX for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease modifying antirheumatic drug (DMARD) therapy. For the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. Dosage: Tofacitinib is given orally with or without food. RA: The recommended dose is 5 mg orally twice daily or 11mg once daily. Patients may be switched between 5 mg film coated tablets and 11 mg prolonged release tablets after the last day of their dosing. PsA: The recommended dose is 5 mg orally twice daily. UC: The recommended dose is 10 mg given orally twice daily for induction for 8 weeks and 5 mg given twice daily for maintenance. For patients who do not achieve adequate therapeutic benefit by week 8, the induction dose of 10 mg twice daily can be extended for an additional 8 weeks (16 weeks total), followed by 5 mg twice daily for maintenance. Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16. Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known venous thromboembolism (VTE) risk factors, unless there is no suitable alternative treatment available. For patients with UC who are not at increased risk for VTE, tofacitinib 10 mg orally twice daily may be considered if the patient experiences a decrease in response on tofacitinib 5 mg twice daily and failed to respond to alternative treatment options for ulcerative colitis such as tumour necrosis factor inhibitor (TNF inhibitor) treatment. Tofacitinib 10 mg twice daily for maintenance treatment should be used for the shortest duration possible. The lowest effective dose needed to maintain response should be used. Dose interruption: Tofacitinib treatment should be interrupted if a patient develops a serious infection until the infection is controlled. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including lymphopenia, neutropenia, and anaemia. It is recommended not to initiate dosing in patients with an absolute lymphocyte count (ALC) less than 0.75 x 109/l, an absolute neutrophil count (ANC) less than 1x109 /l or in patients with haemoglobin less than 9 g/dL. Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment the dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal renal function is 5 mg twice daily or 11mg once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal renal function is 10 mg twice daily. Patients with severe renal impairment should remain on a reduced dose even after haemodialysis. Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment. In patients with moderate hepatic impairment dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal hepatic function is 5 mg twice daily or 11mg once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal hepatic function is 10 mg twice daily. Tofacitinib should not be used in patients with severe hepatic impairment. Elderly: No dose adjustment is required in patients aged 65 years and older, use with caution as increased risk and severity of adverse events. Tofacitinib should only be considered for patients over 65 years of age if no suitable alternative treatment is available. Drug–drug Interactions: Total dose should be reduced by half in patients receiving potent inhibitors of cytochrome (CYP) P450 3A4 (e.g., ketoconazole) and in patients receiving one or more concomitant medicinal products that result in both moderate inhibition of CYP3A4 as well as potent inhibition of CYP2C19 (e.g., fluconazole). Coadministration of tofacitinib with potent CYP inducers (e.g., rifampicin) may result in a loss of or reduced clinical response. Coadministration of potent inducers of CYP3A4 with tofacitinib is not recommended. Contraindications: Hypersensitivity to any of the ingredients, active tuberculosis (TB), serious infections such as sepsis, or opportunistic infections, severe hepatic impairment, pregnancy and lactation. Warnings and Precautions: Tofacitinib should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of the condition for which tofacitinib is indicated. Patients treated with tofacitinib should be given a patient alert card. There was a higher incidence of adverse events for the combination of tofacitinib with MTX versus tofacitinib as monotherapy in RA clinical studies. Tofacitinib should be avoided in combination with biologics and potent immunosuppressants such as azathioprine, 6-mercaptopurine, ciclosporine and tacrolimus. Venous thromboembolism (VTE): Serious VTE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking tofacitinib. A dose dependent increased risk for VTE was observed in a clinical study with tofacitinib compared to TNF inhibitors. Tofacitinib should be used with caution in patients with known risk factors for VTE, regardless of indication and dosage. VTE risk factors include previous VTE, patients undergoing major surgery, immobilisation, myocardial infarction (within previous 3 months), heart failure, use of combined hormonal contraceptives or hormone replacement therapy, inherited coagulation disorder, malignancy. Additional VTE risk factors such as age, obesity (BMI ≥30), diabetes, hypertension, smoking status should also be considered. Patients should be re-evaluated periodically during tofacitinib treatment to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue tofacitinib in patients with suspected VTE, regardless of dose or indication. Infections: Serious and sometimes fatal infections have been reported in patients administered tofacitinib. Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection. Patients should be closely monitored for infections, with prompt diagnosis and treatment. Treatment should be interrupted if a serious infection develops. Use carefully in elderly or patients predisposed to, or with a history of infection (e.g. diabetes). Tofacitinib should only be considered for patients over 65 years of age if no suitable alternative treatment is available. Tuberculosis: Patients should be evaluated for both active and latent TB prior to being treated with tofacitinib, patients who test positive for latent TB should be treated with standard antimycobacterial therapy before administering tofacitinib. Viral Reactivation: In clinical studies viral reactivation and cases of herpes zoster have been observed. The incidence may be increased in patients treated with 10 mg twice daily. Screening for viral hepatitis should be performed in accordance with clinical guidelines prior to starting therapy with tofacitinib the impact on chronic viral hepatitis is not known. Vaccinations: Prior to initiating tofacitinib, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines. Live vaccines should not be given concurrently with tofacitinib. Malignancy: Lymphomas and other malignancies have been observed in patients treated with tofacitinib. Patients with highly active disease may be at higher risk than the general population the effect of tofacitinib on the development and course of malignancies is not known. NMSCs have been reported, the risk of NMSC may be higher in patients treated with tofacitinib 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended in patients at increased risk. Interstitial lung disease: Caution is recommended in patients with a history of chronic lung disease as they may be more prone to infection. Asian patients are known to be at higher risk of ILD caution should be exercised with these patients. Gastrointestinal perforations: Tofacitinib should be used with caution in patients who may be at increased risk e.g. diverticulitis or concomitant use of corticosteroids or NSAIDs. Cardiovascular risk: risk factors should be managed as part of usual standard of care. Hypersensitivity: cases of drug hypersensitivity associated with tofacitinib administration have been reported. Allergic reactions included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, tofacitinib should be discontinued immediately Laboratory Parameters: increased incidence of lymphopenia and neutropenia have been reported and decreases in haemoglobin and should be monitored in accordance with the SmPC. Monitor ANC and haemoglobin at baseline, 4-8 weeks and 3 monthly, ALC at baseline and 3 monthly. Tofacitinib has been associated with increases in lipid parameters maximal effects are observed at 6 weeks monitoring should be performed 8 weeks after initiation and managed according to hyperlipidemia guidelines. Increases in liver enzymes greater than 3x ULN were uncommonly reported, use caution when initiating with potential hepatotoxic medicinal products. Pregnancy & Lactation: Use of tofacitinib during pregnancy and breast-feeding is contraindicated. Side Effects: The most common serious adverse reactions were serious infections; pneumonia, cellulitis, herpes zoster, UTIs, diverticulitis, appendicitis and opportunistic infections. The most commonly reported adverse reactions during the first 3 months in controlled clinical trials were headache, upper respiratory tract infections, nasopharyngitis, diarrhoea, nausea and hypertension. The most commonly reported adverse reactions in patients receiving tofacitinib 10 mg twice daily in the UC induction studies were headache, nasopharyngitis, nausea, and arthralgia. Commonly reported adverse reactions (>1/100 to <1/10) from clinical studies in patients with RA, PsA, and UC, were pneumonia, influenza, herpes zoster, urinary tract infection, sinusitis, bronchitis, nasopharyngitis, pharyngitis, anaemia, headache, hypertension, cough, abdominal pain, vomiting, diarrhoea, nausea, gastritis, dyspepsia, rash, arthralgia, pyrexia, oedema peripheral, fatigue, blood creatine phosphokinase increased. Refer to SmPC for further information on side effects. Legal Category: POM. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. Package quantities, Marketing Authorisation Numbers and Basic NHS Price XELJANZ 5 mg, 56 film-coated tablets, EU/1/17/1178/003 £690.03; XELJANZ 10 mg, 56 film-coated tablets, EU/1/17/1178/007 £1380.06 ; XELJANZ 11 mg, 28 prolonged release tablets, EU/1/17/1178/012 £690.03. Further information is available on request from: Medical Information at Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK. Tel: +44 (0) 1304 616161
Last revised: 01/2020
Ref: XJ 8_0
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Pfizer Medical Information on 01304 616161.
XELJANZ Risk Minimisation Programme (RMP) materials, including a Patient Alert Card, Prescriber Checklists and a Prescriber Brochure are available from www.medicines.org.uk/emc/. Patients treated with XELJANZ should be given the Patient Alert Card.
PP-XEL-GBR-2204 March 2020