Tofanib (Tofacitinib 5mg)

Tofacitinib

Indications

Rheumatoid arthritis: Tofacitinib is indicated for the treatment of moderate to severely active rheumatoid arthritis adult patients with insufficient response or intolerance to methotrexate. It can be used as a monotherapy or in combination with methotrexate or other non-biologically ameliorating anti-rheumatic drugs (DMARDs).

Psoriatic Arthritis: Tofacitinib is indicated for the treatment of adult patients with active psoriatic arthritis who have insufficient response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARD).

Ulcerative colitis: Tofacitinib is indicated for the treatment of adult patients with moderate to severe active ulcerative colitis (UC).

Pharmacology

Rheumatoid arthritis is an autoimmune disease characterized by the dysregulation of pro-inflammatory cytokines, including IL7, IL15, IL21, IL6, IFNα, and IFNβ. (3) Cytokine signaling stimulates the recruitment and activation of immune cells through the janus kinase signaling pathway, leading to tissue inflammation and joint damage.

Tofacitinib is a partially reversible janus kinase (JAK) inhibitor that prevents the body from responding to cytokine signals. By inhibiting JAK, tofacitinib prevents the phosphorylation and activation of STAT. The JAKSTAT signaling pathway is involved in the transcription of cells involved in hematopoietic and immune cell functions. Tofacitinib plays a therapeutic role by inhibiting the JAKSTAT pathway to reduce inflammation. However, there is evidence that it can achieve healing effects in other ways as well.

Dosage & Administration

Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily. Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs): Tofacitinib 5 mg twice daily or Tofacitinib 11 mg once daily.  Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is Tofacitinib 5 mg once daily.

Ulcerative Colitis: Tofacitinib 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response.

Interaction

• Potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., Ketoconazole)
• Recommended dose is Tofacitinib 5 mg once daily: One or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)
• Recommended dose is Tofacitinib 5 mg once daily Potent CYP inducers (e.g.Rifampin): May result in loss of or reduced clinical response.

Side Effects

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

Pregnancy & Lactation

Pregnancy category C. There are no adequate and well-controlled studies of pregnant women. Tofacitinib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown whether tofacitinib is excreted in human milk. Since many drugs are excreted in human milk, and because tofacitinib may have serious adverse reactions to nursing babies, it is necessary to decide whether to stop breastfeeding or the drug, taking into account the importance of the drug for breastfeeding. .

Precautions & Warnings

• Severe infections: Avoid using tofacitinib during active severe infections, including local infections.
• Gastrointestinal perforation: Use with caution in patients with increased risk.
• Laboratory monitoring: recommended because lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids may change.
• Vaccine: Live vaccine: Avoid use with tofacitinib.
•  If the absolute lymphocyte count is less than 500 cells/mm3, the absolute neutrophil count (ANC) <1000 cells/mm3 or hemoglobin <9 g/dL.

Therapeutic Class

Immunosuppressant

Storage Conditions

Do not store at temperatures above 30°C. Keep out of children’s reach.

Pharmaceutical Name

Globe Pharmaceuticals Ltd.