Instructions for Tofacitinib

1. Generic name: tofacitinib

Product name: XELJANZ

All names: Tofacitinib, Tofacitinib, Tofacitinib, Xeljanz, Shangjie

2. Indications:

1. Rheumatoid arthritis: Tofacitinib (Tofacitinib) is suitable for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have insufficient response or intolerance to one or moreTNF blockers.

2. Psoriatic arthritis: Tofacitinib is indicated for the treatment of adult patients with active psoriatic arthritis (PsA) who have an inadequate response to or are intolerant to one or more TNF blockers.

3. Ankylosing spondylitis: Tofacitinib is suitable for the treatment of adult patients with active ankylosing spondylitis (AS) who have insufficient response or intolerance to one or more TNF blockers.

4. Ulcerative colitis: Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have an inadequate response to or are intolerant to one or more TNF blockers.

5. Polyarticular juvenile idiopathic arthritis: Tofacitinib oral solution is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pcJIA) patients 2 years and older who have an inadequate response to or are intolerant to one or more TNF blockers.

6. Limitations of use: It is not recommended to use tofacitinib in combination with biological disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants (such as azathioprine and cyclosporine).

3. Usage and dosage:

1. Recommended dosage:

(1) For use in adults with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis Tofacitinib tablets are usually taken at 5 mg twice daily; and tofacitinib extended-release tablets are usually taken once daily at 11 mg.

(2)Tofacitinib tablets for adult patients with ulcerative colitis are usually administered at 10 mg twice daily for at least 8 weeks, with the patient evaluated based on treatment response and transition to maintenance therapy at 5 mg twice daily for up to 16 weeks. Tofacitinib extended-release tablets are typically taken once daily at 22 mg for at least 8 weeks, transitioning to maintenance therapy at 11 mg once daily for up to 16 weeks.

(3) For pediatric patients with polyarticular course of juvenile idiopathic arthritis, the recommended dose of tofacitinib oral solution is related to body weight. For patients weighing 10-20kg, 3.2 times a day is recommended. mg (3.2 ml oral solution), 4 mg (4 ml oral solution) twice daily for patients weighing 20-40 kg, and 5 mg (one 5 mg tablet or 5 ml oral solution) twice daily for patients weighing 40 kg and above.

2. Dose conversion: Tofacitinib extended-release tablets are not interchangeable or substituted with tofacitinib oral solution. Patients taking tofacitinib tablets (5 mg, twice daily) can take tofacitinib extended-release tablets (11 mg, once daily) the day after taking the last dose of tofacitinib 5 mg. Patients receiving tofacitinib 10 mg tablets (twice daily) may switch to tofacitinib extended-release tablets (22 mg once daily) the day after their last dose of tofacitinib 10 mg.

4. Adverse reactions:

The most common side effects of tofacitinib (which may affect up to 1 in 10 people) are headache, nose and throat infection and inflammation, diarrhea, nausea, and high blood pressure. The most common serious side effects are serious infections such as pneumonia (lung infection), shingles, urinary tract infection, cellulitis, diverticulitis, and appendicitis, as well as opportunistic infections that may occur in patients with weakened immune systems. Adverse reactions due to drug allergy have occurred after tofacitinib was put on the market (events such as angioedema and urticaria have been observed).

5. Storage:

Tofacitinib tablets are available in two strengths: 5mg and 10mg. Tofacitinib extended-release tablets are available in 11mg and 22mg. They are usually stored at 20°C to 25°C (68°F to 77°F); tofacitinib Oral solution is a clear, colorless solution containing 1 mg of tofacitinib. Store at 20°C to 25°C (68°F to 77°F), with an excursion allowed between 15°C to 30°C (59°F to 86°F). Store in the dark and discard remaining oral solution after 60 days after opening.

6. Special groups:

1. Breastfeeding: There are no data on the presence of tofacitinib in breast milk, the effects on breastfed infants, or the effects on milk production in patients during treatment and for at least 18 hours after the last dose of tofacitinib/tofacitiniboral solution or for at least 18 hours after the last dose of tofacitinibBreastfeeding is not recommended within 36 hours.

2. Hepatic impairment: Tofacitinib oral solution is not recommended for patients with severe liver impairment.

7. Mechanism of action:

Tofacitinib is an inhibitor ofJanus kinase (JAK). JAK is an intracellular enzyme that transmits signals generated by cytokine or growth factor-receptor interactions on the cell membrane to affect cellular processes of hematopoietic and immune cell function. In the signaling pathway, JAK phosphorylates and activates signal transducers and activators of transcription (STATs), regulating intracellular activities, including gene expression. Tofacitinib regulates signaling pathways at JAKs points and prevents the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signals through the pairing of JAKs (such as JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, JAK2/JAK2). Tofacitinib inhibits the in vitro activity of the JAK combination with IC50s of 406, 56 and 1377nM respectively.

Tofacitinibhas been launched in China and has entered the scope of Class B medical insurance. The common specification is tofacitinib citrate tablets. The price paid by medical insurance is relatively cheap, but the reimbursement ratio is different in different regions, and the price after reimbursement will be different. Overseas, there are also tofacitinib generic drugs produced in other countries. The price of each box produced by a Bangladeshi pharmaceutical factory is around RMB 300 (the price may fluctuate due to the exchange rate). The ingredients of domestic original drugs and foreign generic drugs are basically the same, and the prices of different specifications will be different.