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Tofacitinib: Uses,Dosage,Side Effects

Generic Name
Tofacitinib
Therapeutic Class:
Disease-modifying Antirheumatic

Indications:
Tofacitinib / Tofacitinib XR is a Janus kinase (JAK) inhibitor.
  •  Rheumatoid Arthritis: Tofacitinib / Tofacitinib XR is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).
  • Psoriatic Arthritis: Tofacitinib / Tofacitinib XR is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
  •  Ulcerative Colitis: Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).
  • Limitations of Use: Use of Tofacitinib / Tofacitinib XR in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine are not recommended.
Presentation
Tofacitinib 5: Each tablet contains Tofacitinib Citrate INN equivalent to Tofacitinib 5 mg
Tofacitinib XR 11: Each Extended-Release tablet contains Tofacitinib Citrate INN equivalent to Tofacitinib 11 mg

Description
Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. JAK enzymes transmit cytokine signaling through the pairing of JAKs (e.g., JAK1/JAK3, JAK1/JAK2, JAK1/TyK2, and JAK2/JAK2). Tofacitinib inhibited the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC50 of 406, 56, and 1377 nM, respectively. However, the relevance of specific JAK combinations to therapeutic effectiveness is not known.

Dosage & Administration:
Administration Instructions
Do not initiate Tofacitinib / Tofacitinib XR if absolute lymphocyte count <500 cells/mm3
, an absolute neutrophil count (ANC) <1000 cells/mm3 or hemoglobin <9 g/dL.
Recommended Dosage:
  • Rheumatoid Arthritis: Tofacitinib 5 mg twice daily or Tofacitinib XR 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 XR 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: Induction: Tofacitinib 10 mg twice daily or Tofacitinib XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue Tofacitinib 10 mg twice daily or Tofacitinib XR 22 mg once daily for a maximum of 16 weeks. Discontinue Tofacitinib 10 mg twice daily or Tofacitinib XR 22 mg once daily after 16 weeks if the adequate therapeutic response is not achieved. 
  • Maintenance: Tofacitinib 5 mg twice daily or Tofacitinib XR 11 mg once daily. For patients with loss of response during maintenance treatment, Tofacitinib 10 mg twice daily or Tofacitinib XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response. 
  • Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment.

Side Effects:
The most common adverse reactions are:
  • Rheumatoid and Psoriatic Arthritis: Reported during the first 3 months in rheumatoid arthritis controlled clinical trials and occurring in ≥2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs: upper respiratory tract infection, nasopharyngitis, diarrhea, and headache.
  • Ulcerative Colitis: Reported in ≥5% of patients treated with either 5 mg or 10 mg twice daily of Tofacitinib and ≥1% greater than reported in patients receiving placebo in either the induction or maintenance clinical trials: nasopharyngitis elevated cholesterol levels, headache, upper respiratory tract infection, increased blood creatine phosphokinase, rash, diarrhea, and herpes zoster.
Precautions:
  • Serious Infections: Use of Tofacitinib / Tofacitinib XR should be avoided during an active serious infection, including localized infections.
  • Gastrointestinal Perforations: Caution should be used in patients that may be at increased risk.
  • Laboratory Monitoring: Laboratory Monitoring should be recommended due to potential changes in lymphocytes, neutrophils,
  • hemoglobin, liver enzymes, and lipids.
  • Immunizations: Live vaccines: Use with Tofacitinib / Tofacitinib XR should be avoided.
Use in Pregnancy & Lactation:
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Tofacitinib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Tofacitinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Tofacitinib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother. Pediatric Use: The safety and effectiveness of Tofacitinib in pediatric patients have not been established. Geriatric Use: The frequency of serious infection among Tofacitinib-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Interaction:
Strong CP3A4 Inhibitors (e.g., ketoconazole): Dosage adjustment of Tofacitinib / Tofacitinib XR is recommended.
Moderate CYP3A4 Inhibitors Coadministered with Strong CYP2C19 Inhibitors (e.g., fluconazole): Dosage adjustment of Tofacitinib /
Tofacitinib XR is recommended.
Strong CYP3A4 Inducers (e.g., rifampin): Coadministration with Tofacitinib / Tofacitinib XR is not recommended.
Immunosuppressive drugs (e.g., azathioprine, tacrolimus, and cyclosporine): Coadministration with Tofacitinib / Tofacitinib XR is not
recommended.

Storage:
Do not store above 30 0C. Keep away from light and out of the reach of children.

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