Dosing in UC

An alternative way to treat patients with UC

Dosing and administration of XELJANZ1

Please note tablets depicted in table above are not true to size.

*If there has been a loss of response, reinduction with tofacitinib 10 mg BID may be considered. The treatment interruption period in clinical studies extended up to 1 year. Efficacy may be regained by 8 weeks of 10 mg BID therapy.1

  • Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16. In patients who have responded to treatment with XELJANZ, corticosteroids may be reduced and/or discontinued in accordance with standard of care.1
  • 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.
  • Xeljanz 5 mg and 10 mg tablets an be given with or without food
  • For patients who have difficulties swallowing, tofacitinib 5 mg and 10 mg tablets may be crushed and taken with water.
  • Terminal half-life is approximately 3 hours.
  • This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Packs shown not true to size.

Contraindications and special populations1

Contraindications for use:

  • Hypersensitivity to the active substance of XELJANZ or to any of its excipients*
  • Active TB, serious infections such as sepsis, or opportunistic infections
  • Severe hepatic impairment
  • Pregnancy and lactation

Special Populations:

Renal impairment

  • No dose adjustment is required in mild-to-moderate renal impairment
  • In patients with severe renal impairment (creatinine clearance <30 mL/min), where the dose in the presence of normal function is; 5 mg BID, reduce to 5 mg once daily; 10 mg BID, reduce to 5 mg BID.
  • Patients with severe renal impairment should remain on a reduced dose even after haemodialysis.

Hepatic impairment

  • In patients with moderate hepatic impairment (Child Pugh B), where the dose in the presence of normal function is; 5 mg BID , reduce to 5 mg once daily; 10 mg BID, reduce to 5 mg BID.
  • XELJANZ should not be used in patients with severe hepatic impairment (Child Pugh C).

Elderly

  • No dose adjustment is required in patients aged ≥65 years based on age alone (see other special populations). There are limited data in patients aged 75 years and older.
  • The elderly population in general has an increased risk of infections; caution should be used when treating in elderly. In patients over 65 years of age XELJANZ should only be considered if no suitable alternative treatment is available.

Dose adjustment for drug-drug interactions1

Please note tablets depicted in table above are not true to size.

  • Co-administration of XELJANZ with potent CYP inducers (e.g., rifampicin) may result in a loss of or reduced clinical response
  • Co-administered of potent inducers of CYP3A4 with XELJANZ is not recommended
  • Co-administration of XELJANZ did not have an effect on the pharmacokinetics of oral contraceptives, levonorgestrel and ethinyl estradiol, in healthy female volunteers

Select the second tab at the top of the page to view 'practical considerations for use'.

XELJANZ Risk Minimisation Programme (RMP) materials, including a Patient Alert Card, Prescriber Checklists and a Prescriber Brochure are available from https://www.medicines.org.uk/emc/. Patients treated with XELJANZ should be given the Patient Alert Card.

* XELJANZ contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

PLEASE SEE XELJANZ SUMMARY OF PRODUCT CHARACTERISTICS FOR FULL INFORMATION

TB - tuberculosis; UC - ulcerative colitis; BID - twice daily.
1. XELJANZ Summary of Product Characteristics

XELJANZ Prescribing Information

PP-XEL-GBR-2227 March 2020

Practical considerations for use

Laboratory Monitoring

 

Vaccination

  • Prior to initiating XELJANZ it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines
  • It is recommended that live vaccines not be given concurrently with XELJANZ. The decision to use live vaccines prior to XELJANZ treatment should take into account the pre-existing immunosuppression in a given patient
  • Prophylactic zoster vaccination should be considered in accordance with vaccination guidelines. Particular consideration should be given to patients with longstanding rheumatoid arthritis who have received two or more prior biological DMARDs. If live zoster vaccine is administered; it should only be administered to patients with a known history of chickenpox or those that are seropositive for varicella zoster virus (VZV). If the history of chickenpox is considered doubtful or unreliable it is recommended to test for antibodies against VZV
  • Vaccination with live vaccines should occur at least 2 weeks, but preferably 4 weeks prior to initiation of XELJANZ or in accordance with current vaccination guidelines regarding immunomodulatory medicinal products

Combination with other therapies

  • XELJANZ has not been studied and its use should be avoided in patients in combination with biologics such as TNF antagonists, IL-1R antagonists, IL-6R antagonists, anti-CD20 monoclonal antibodies, IL‑17 antagonists, IL‑12/IL‑23 antagonists, anti-integrins, and selective co-stimulation modulators and potent immunosuppressants such as azathioprine, 6-mercaptopurine, cyclosporine and tacrolimus because of the possibility of increased immunosuppression and increased risk of infection
  • There is a higher incidence of adverse events for the combination of XELJANZ plus MTX versus XELJANZ as monotherapy in RA clinical trials

Serious infections

  • Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving tofacitinib. The risk of opportunistic infections is higher in Asian geographic regions (see section 4.8 of the XELJANZ Summary of Product Characteristics). Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection.
  • Tofacitinib should not be initiated in patients with active infections, including localised infections. The risks and benefits of treatment should be considered prior to initiating tofacitinib in patients:
    • with recurrent infections,
    • with a history of a serious or an opportunistic infection,
    • who have resided or travelled in areas of endemic mycoses,
    • who have underlying conditions that may predispose them to infection.,
    • who are over 65 years of age
  • Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ. Treatment must be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with XELJANZ should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient, appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored
  • As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. In patients over 65 years of age tofacitinib should only be considered if no suitable alternative treatment is available.
  • Risk of infection may be higher with increasing degrees of lymphopenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. Discontinuation and monitoring criteria for lymphopenia are discussed in section 4.2 of the XELJANZ Summary of Product Characteristics.

Tuberculosis

  • The risks and benefits of treatment should be considered prior to initiating XELJANZ in patients:

    • who have been exposed to TB
    • who have resided or travelled in areas of endemic TB or endemic mycoses
  • Patients should be evaluated and tested for latent or active infection prior to and per applicable guidelines during administration of XELJANZ

Viral reactivation

  • Viral reactivation and cases of herpes virus reactivation (e.g, herpes zoster) were observed in clinical studies with XELJANZ. In patients treated with XELJANZ, the risk of herpes zoster appears to be increased in:

    • Japanese and Korean patients
    • Patients with an absolute lymphocyte count (ALC) less than 1.0 cells x 109/L
    • Patients with long standing RA who have previously received two or more biologic DMARDs
    • Patients treated with 10 mg twice daily*

Malignancies and lymphoproliferative disorder [excluding non-melanoma skin cancer (NMSC)]

  • The risks and benefits of XELJANZ treatment should be considered prior to initiating therapy in patients with current or a history of malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing XELJANZ in patients who develop a malignancy. The possibility exists for XELJANZ to affect host defences against malignancies
  • Lymphomas have been observed in patients treated with XELJANZ. Patients with RA, particularly those with highly active disease may be at a higher risk (up to several-fold) than the general population for the development of lymphoma. The role of XELJANZ in the development of lymphoma is uncertain
  • Other malignancies were observed in clinical studies and the post-marketing setting, including, but not limited to, lung cancer, breast cancer melanoma, prostate cancer and pancreatic cancer
  • The effect of XELJANZ on the development and course of malignancies is not known

Non-melanoma skin cancer

  • Non-melanoma skin cancers (NMSCs) have been reported in patients treated with XELJANZ. The risk of NMSC may be higher in patients treated with XELJANZ 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended for patients who are at increased risk for skin cancer

Interstitial lung disease

  • Events of interstitial lung disease (some of which had a fatal outcome) have been reported in patients treated with XELJANZ in RA clinical trials and in the post-marketing setting although the role of Janus kinase (JAK) inhibition in these events is not known. Asian RA patients are known to be at higher risk of interstitial lung disease, thus caution should be exercised in treating these patients

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 (see sections 4.8 and 5.1 of XELJANZ Summary of Product Characteristics).
  • Tofacitnib should be used with caution in patients with known risk factors for VTE, regardless of indication and dosage.
  • Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known VTE risk factors, unless there is no suitable alternative treatment available (see section 4.2 of XELJANZ Summary of Product Characteristics).
  • 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.

Gastrointestinal perforations

  • Events of gastrointestinal perforation have been reported in clinical trials although the role of Janus-kinase inhibition in these events is not known
  • XELJANZ should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g. patients with a history of diverticulitis and patients with concomitant use of corticosteroids and/or nonsteroidal anti-inflammatory medicinal products). Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of gastrointestinal perforation

Liver enzyme elevations

  • Treatment with XELJANZ was associated with an increased incidence of liver enzyme elevation in some patients 
  • Caution should be exercised when considering initiation of XELJANZ treatment in patients with elevated ALT or AST

Lymphocytes, Neutrophils & Haemoglobin

  • Interruption of dosing may be needed for management of dose related laboratory abnormalities including lymphopenia, neutropenia and anaemia
  • Recommendations for temporary dose interruption or permanent discontinuation of treatment are made according to the severity of laboratory abnormailites

Lipids

  • Treatment with XELJANZ was associated with increases in lipid parameters such as total cholesterol, LDL and HDL, maximum effects were generally observed within 6 weeks. 
  • Patients should be managed according to clinical guidelines for the management of hyperlipidaemia.

XELJANZ Risk Minimisation Programme (RMP) materials, including a Patient Alert Card, Prescriber Checklists and a Prescriber Brochure are available from https://www.medicines.org.uk/emc/. Patients treated with XELJANZ should be given the Patient Alert Card.

PLEASE SEE XELJANZ SUMMARY OF PRODUCT CHARACTERISTICS FOR FULL INFORMATION

* For further information on the use of 10 mg BID in UC patients, please refer to the first tab titled "Dosing" and the XELJANZ Summary of Product Characteristics for further information.

1. XELJANZ (tafacitinib citrate) Summary of Product Characteristics

XELJANZ Prescribing Information

PP-XEL-GBR-2228 March 2020