Drug Action
Tofacitinib selectively inhibits the Janus- associated tyrosine kinases JAK1 and JAK3.
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Individual generic drug information
Extracted information for Tofacitinib only.
Tofacitinib selectively inhibits the Janus- associated tyrosine kinases JAK1 and JAK3.
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Moderate to severe active rheumatoid arthritis in patients who have had an inadequate response to, or are intolerant to one or more disease-modifying anti- rheumatic drugs (as monotherapy or in combination with methotrexate) (specialist use only) | Active psoriatic arthritis in patients who have had an inadequate response to, or are intolerant to one or more disease- modifying anti-rheumatic drugs (in combination with methotrexate) (specialist use only) ▶BY MOUTH ▶Adult: 5 mg twice daily, for dose adjustments due to side-effects—consult product literature Moderate to severe active ulcerative colitis in patients who have had an inadequate or lost response to, or are intolerant to either conventional therapy or a biologic agent (specialist use only) ▶BY MOUTH ▶Adult: Initially 10 mg twice daily for 8 weeks, then maintenance 5 mg twice daily, if an adequate therapeutic response is not achieved after 8 weeks, the initial dose can be extended for an additional 8 weeks, discontinue treatment if no response 16 weeks after initial dose, for dose adjustments due to side-effects, decreased response during maintenance treatment or following treatment interruption—consult product literature
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DUE TO INTERACTIONS ▶Manufacturer advises reduce dose with concurrent use of potent CYP3A4 inhibitors, or concurrent use of a moderate CYP3A4 inhibitor and a potent CYP2C19 inhibitor, or concurrent use of drugs which are both moderate CYP3A4 and potent CYP2C19 inhibitors. Dose should be reduced to 5 mg once daily in patients receiving 5 mg twice daily. Dose should be reduced to 5 mg twice daily in patients receiving 10 mg twice daily.
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Absolute lymphocyte count less than 750 cells/mm3 (do not initiate). absolute neutrophil count less than 1000 cells/mm3 (do not initiate). active infection including localised infection. active tuberculosis . haemoglobin less than 9 g/dL (do not initiate). risk Musculoskeletal system factors for pulmonary embolism (high doses)
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Active, chronic or recurrent infection. elderly. predisposition to infection. previous or current malignancy. raised serum transaminases (particularly in combination with potentially hepatotoxic drugs). risk of gastrointestinal perforation (new onset abdominal signs and symptoms should be evaluated promptly). risk of viral reactivation (consult product literature) CAUTIONS, FURTHER INFORMATION Manufacturer advises patients should receive all recommended vaccinations before starting treatment (consider prophylactic varicella zoster vaccination); live vaccines should be given at least 2 weeks, but preferably 4 weeks before treatment initiation—consult product literature. ▶Tuberculosis Manufacturer advises consider anti- tuberculosis therapy prior to initiation of tofacitinib in patients with previously untreated latent tuberculosis.
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Manufacturer advises patients should be evaluated for tuberculosis and viral hepatitis before treatment.
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NICE decisions Musculoskeletal system ▶Tofacitinib for moderate-to-severe rheumatoid arthritis (October 2017) NICE TA480 Tofacitinib (Xeljanz ®), with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to intensive therapy with a combination of conventional DMARDs, only if: . disease is severe (a disease activity score [DAS28] of more than 5.1), and . the manufacturer provides tofacitinib with the discount agreed in the patient access scheme. Tofacitinib (Xeljanz ®), with methotrexate, is recommended as an option for treating active rheumatoid arthritis in adults whose disease has responded inadequately to, or who cannot have, other DMARDs, including at least 1 biological DMARD, only if: . disease is severe (a DAS28 of more than 5.1), and . they cannot have rituximab, and . the manufacturer provides tofacitinib with the discount agreed in the patient access scheme. Tofacitinib can be used as monotherapy for adults who cannot take methotrexate because it is contra-indicated or because of intolerance, when the above criteria are met. Continue treatment only if there is a moderate response measured using European League Against Rheumatism (EULAR) criteria at 6 months after starting therapy. After an initial response within 6 months, withdraw treatment if at least a moderate EULAR response is not maintained. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta480 ▶Tofacitinib for treating active psoriatic arthritis after inadequate response to DMARDs (October 2018) NICE TA543 Tofacitinib (Xeljanz ®), with methotrexate, is recommended as an option for treating active psoriatic arthritis in adults, only if: . it is used as described in NICE’s technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis (TA199 recommendations 1.1 and 1.2), or . the person has had a tumour necrosis factor (TNF)-alpha inhibitor but their disease has not responded within the first 12 weeks or has stopped responding after 12 weeks, or . TNF-alpha inhibitors are contra-indicated but would otherwise be considered (as described in NICE’s technology appraisal guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis). Tofacitinib is only recommended if the manufacturer provides it according to the commercial arrangement. Assess the response to treatment after 12 weeks. Treatment should only be continued if there is clear evidence of response, defined as an improvement in at least 2 of the 4 Psoriatic Arthritis Response Criteria (PsARC), 1 of which must be joint tenderness or swelling score, with no worsening in any of the 4 criteria. People whose disease has a Psoriasis Area and Severity Index (PASI) 75 response but whose PsARC response does not justify continuing treatment should be assessed by a dermatologist. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta543 ▶Tofacitinib for moderately to severely active ulcerative colitis (November 2018) NICE TA547 Tofacitinib (Xeljanz ®) is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment. It is recommended only if the manufacturer provides tofacitinib with the discount agreed in the commercial arrangement. www.nice.org.uk/guidance/ta547 Scottish Medicines Consortium (SMC) decisions SMC No. 1298/18 The Scottish Medicines Consortium has advised (February 2018) that tofacitinib citrate (Xeljanz ®) is accepted for restricted use within NHS Scotland in combination with methotrexate in adults with severe active rheumatoid arthritis (a disease activity score [DAS28] greater than 5.1) that has not responded to intensive therapy with a combination of conventional DMARDs. In patients with severe disease inadequately controlled by a tumour necrosis factor (TNF) antagonist it may be used in patients ineligible to receive rituximab. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. SMC2116 The Scottish Medicines Consortium has advised (January 2019) that tofacitinib (Xeljanz ®) is accepted for restricted use within NHS Scotland in combination with methotrexate for the treatment of adults with psoriatic arthritis whose disease has not responded adequately to at least two conventional DMARDs, given either alone or in combination. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. SMC2122 The Scottish Medicines Consortium has advised (February 2019) that tofacitinib (Xeljanz ®) is accepted for use within NHS Scotland for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower.
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Extracted information for Tofacitinib only.
MHRA/CHM ADVICE: TOFACITINIB (XELJANZ ®): NEW MEASURES TO MINIMISE RISK OF VENOUS THROMBOEMBOLISM AND OF SERIOUS AND FATAL INFECTIONS (MARCH 2020) New recommendations have been issued following a European safety review that found a dose-dependent increased risk of serious venous thromboembolism (VTE) associated with tofacitinib. Healthcare professionals are advised to use tofacitinib with caution in any patients with known risk factors for VTE, in addition to the underlying disease. In patients with risk factors being treated for ulcerative colitis, the use of tofacitinib 10 mg twice daily as maintenance treatment is not recommended, unless no suitable alternative is available. In all patients being treated for rheumatoid or psoriatic arthritis, the recommended daily dose of tofacitinib should not be exceeded— see Indications and Dose. Patients should be informed of the signs and symptoms of VTE before starting treatment and advised to seek urgent medical attention if these develop. Tofacitinib should be permanently discontinued if signs of VTE occur. Tofacitinib was also found to increase the risk of serious and fatal infections, with higher rates of infections in the elderly. Use of tofacitinib in patients older than 65 years is not recommended, unless no suitable alternative is available.
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→Appendix 1: tofacitinib
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▶Common or very common Anaemia. cough. diarrhoea. fatigue. fever. gastrointestinal discomfort. gastrointestinal disorders. headache. hypertension. increased risk of infection. joint disorders. nausea. peripheral oedema. skin reactions. vomiting ▶Uncommon Decreased leucocytes. dehydration. dyslipidaemia. dyspnoea. hepatic steatosis. insomnia. ligament sprain. muscle strain. musculoskeletal pain. neoplasms. neutropenia. paraesthesia. sinus congestion. tendinitis. venous thromboembolism (discontinue permanently). weight increased ▶Rare or very rare Meningitis cryptococcal. sepsis ▶Frequency not known Angioedema. BK virus infection. deep vein thrombosis (discontinue permanently). interstitial lung disease (including fatal cases). malignancy. pulmonary embolism (discontinue permanently). reactivation of infections
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Manufacturer advises effective contraception during and for at least 4 weeks after treatment in women of child-bearing potential.
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises caution in moderate impairment; avoid in severe impairment. Dose adjustments Manufacturer advises dose reduction in moderate impairment—consult product literature.
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Dose adjustments Manufacturer advises reduce dose in severe impairment —consult product literature.
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▶Manufacturer advises monitor for signs and symptoms of infection during and after treatment. ▶Manufacturer advises periodic skin examination in patients at increased risk for skin cancer. ▶Manufacturer advises monitor liver function routinely; monitor lipid profile 8 weeks after treatment initiation. ▶Manufacturer advises monitor lymphocytes at baseline and every 3 months thereafter; neutrophils and haemoglobin should be monitored at baseline, after 4 to 8 weeks of treatment and every 3 months thereafter.
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Extracted information for Tofacitinib only.
Manufacturer advises tablets may be crushed and taken with water.
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There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Xeljanz (Pfizer Ltd) A Tofacitinib (as Tofacitinib citrate) 5 mg Xeljanz 5mg tablets | 56 tablet P £690.03 (Hospital only) Tofacitinib (as Tofacitinib citrate) 10 mg Xeljanz 10mg tablets | 56 tablet P £1,380.06 (Hospital only)
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Filter the extracted dose blocks for this individual drug.
First line only; read the complete Indications and dose section above.
5 mg twice daily, for dose adjustments due to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 1189
First line only; read the complete Indications and dose section above.
Initially 10 mg twice daily for 8 weeks, then
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 1189