bDMARDs Quick Reference Guide

Tofacitinib

Tofacitinib

Active ingredient

Tofacitinib

Mechanism of action

Janus Kinase [JAK] 1, 2 & 3 inhibitor

Molecule type

Small molecule

PBS listed indications

Severe active psoriatic arthritis

Severe active rheumatoid arthritis

Moderate to severe ulcerative colitis

Reference product (brand)

Xeljanz

Administration information

Mode of administration

Oral

Administration devices and strengths

5mg film coated tablet

10mg film coated tablet

Frequency of administration

Twice a day

Storage

Store in the original packaging at temperatures below 30oC

Standard dosing

Rheumatoid and psoriatic arthritis: 5mg twice a day

Ulcerative colitis: 

Induction: 10mg twice a day for 8 weeks

If inadequate response is achieved in 8 weeks, induction may be extended for another 8 weeks (16 weeks total).

Maintenance: 5mg twice a day

Treatment with csDMARDs (e.g., methotrexate) may be continued during treatment with tofacitinib.

Dose variations

Patients with rheumatoid arthritis who are in remission or have low disease activity may have their dose of tofacitinib down-titrated by their rheumatologist.

 

 Dose variation
 Rheumatoid and psoriatic arthritisUlcerative colitis
Interactions with other medicines
Patients receiving:

Potent CYP3A4 inhibitors (e.g. ketoconazole) OR

A moderate CYP3A4 inhibitor(s) with a potent CYP2C19 inhibitor(s) (e.g. fluconazole)

5mg once dailyIf taking 10mg twice a day – reduce to 5mg twice a day

If taking 5mg twice a day – reduce to 5mg once daily

Renal impairment
eGFR ≤50mL/min/1.73m2 (including but not limited to those with severe renal impairment who are undergoing haemodialysis)5mg once dailyIf taking 10mg twice a day – reduce to 5mg twice a day

If taking 5mg twice a day – reduce to 5mg once daily

Hepatic impairment
Moderate hepatic impairment5mg once dailyIf taking 10mg twice a day – reduce to 5mg twice a day

If taking 5mg twice a day – reduce to 5mg once daily

Special notes

Tofacitinib is metabolised by CYP3A4; drugs that induce CYP3A4 (e.g. rifampicin, phenytoin) may decrease its concentration, which may affect its efficacy; avoid combinations or consider increasing tofacitinib dose and carefully monitoring the response. Combinations with strong inducers of CYP3A4 are not recommended.

 

Tofacitinib is eliminated primarily via hepatic metabolism and is contraindicated in severe impairment.

 

Tofacitinib can reduce the heart rate and prolong the PR interval. Use cautiously when the heart rate is <60 beats/minute if the patient has a condition that may be worsened by these effects or is taking drugs with similar effects.

 

Tofacitinib should be avoided in patients at increased risk of thrombosis.

 

Tofacitinib should not be used with other cytokine modulators (e.g. TNF-alpha inhibitors, rituximab, tocilizumab) or with potent immunosuppressants (e.g. ciclosporin, azathioprine). Such combinations increase the risk of infection.

Check for active or latent TB, or hepatitis B or C before starting and during treatment. Tofacitinib may reactivate inactive herpes virus and latent TB (begin TB treatment before starting tofacitinib).
Patients with suspected latent or active TB should be treated in consultation with an Infectious Diseases physician.

 

Check full blood count prior to starting therapy with tofacitinib. Do no start treatment if absolute neutrophil count (ANC) <1x109 cells/L or absolute lymphocyte count (ALC) <0.75x109 cells/L.

Check neutrophils after 4–8 weeks, then every 3 months; if ANC:

  • persistently 0.5–1x109 cells/L, halve dose if taking 10 mg twice daily or, if taking 5 mg twice daily, interrupt treatment until >1x109 cells/L
  • <0.5x109 cells/L, stop treatment.

Check lymphocytes every 3 months; if ALC:

  • persistently 0.5–0.75x109 cells/L, halve dose if taking 10 mg twice daily or, if taking 5 mg twice daily, interrupt treatment until >0.75x109 cells/L
  • <0.5x109 cells/L, stop treatment.

References

Pharmaceutical benefits Scheme (PBS) listing. Available from   https://www.pbs.gov.au/medicine/item/10511F-10517M-11675L-11690G [accessed 8/10/21]

Product information. Available from   https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2015-PI-01192-1 [accessed 8/10/21]

Australian Medicines Handbook 2020 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2020 July. Available from: https://amhonline.amh.net.au/    [accessed 8/10/21]

NPS Medicinewise. Down-titration strategies. Available from https://www.nps.org.au/bdmards/rheumatology-conditions/titration-strategies [accessed 12/5/21]