Xeljanz Tofacitinib Citrate Tablets

1. Indications and Usage
Rheumatoid Arthritis (RA): Treatment of adult patients with moderately to severely active RA, often in combination with methotrexate or other non-biologic DMARDs, or as monotherapy.
Psoriatic Arthritis (PsA): Treatment of adult patients with active PsA, as monotherapy or in combination with methotrexate or other non-biologic DMARDs.
Ulcerative Colitis (UC): Treatment of adult patients with moderately to severely active UC.
Juvenile Idiopathic Arthritis (JIA): Treatment of polyarticular JIA in patients 2 years of age and older.
2. Dosage and Administration
Route of Administration: For Oral Use ONLY. Swallow tablets whole.
Recommended Dosage (Immediate Release):
Standard Dose: 5 mg twice daily.
Dose Adjustment: May be increased to 10 mg twice daily in RA and PsA if clinical response is inadequate, though lower doses are preferred to minimize risk.
Dose Adjustments (Comorbidities/Interactions):
Renal Impairment: Reduce dose to 5 mg once daily in severe renal impairment.
Hepatic Impairment: Reduce dose to 5 mg once daily in moderate hepatic impairment. Not recommended in severe hepatic impairment.
Drug Interactions: Reduce dose to 5 mg once daily when co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole) or combinations of moderate CYP3A4 inhibitors and strong CYP2C19 inhibitors.
3. Mechanism of Action
JAK Inhibition:
Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transmit signals from the cell surface to the DNA, regulating the production of cytokines and chemokines involved in inflammation.
Blocking Signaling:
Tofacitinib inhibits the activity of JAK1 and JAK3, and to a lesser extent JAK2. By blocking this JAK-STAT signaling pathway, it reduces the inflammatory response.
4. Safety and Warnings
Serious Infections:
Patients are at increased risk for serious infections (e.g., herpes zoster, pneumonia, tuberculosis) that may lead to hospitalization or death. Screen for TB prior to initiation.
Malignancy and Lymphoproliferative Disorders:
Increased risk of malignancies, including lymphoma and lung cancer, particularly in patients >50 years with cardiovascular risk factors.
Major Adverse Cardiovascular Events (MACE):
Increased risk of myocardial infarction, stroke, or cardiovascular death in patients with cardiovascular risk factors.
Thrombosis:
Boxed Warning: Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported. Risk is higher at the 10 mg dose.
Gastrointestinal Perforations:
Cases of GI perforation have been reported, primarily in patients with UC. Monitor for signs of perforation.
5. Adverse Reactions
Most Common (Incidence ≥2% and greater than placebo):
Upper respiratory tract infections (nasopharyngitis), headache, diarrhea, nasopharyngitis, and increased cholesterol levels (LDL, HDL).
Laboratory Abnormalities:
Elevated liver enzymes (ALT/AST), neutropenia, lymphopenia, and anemia.
6. Drug Interactions
Strong CYP3A4 Inhibitors:
Significantly increase tofacitinib exposure. Dose reduction to 5 mg once daily is required.
Immunosuppressants:
Concomitant use with biologic DMARDs or potent immunosuppressants (e.g., azathioprine, cyclosporine) is not recommended due to increased risk of immunosuppression.
Live Vaccines:
Avoid administration of live vaccines concurrently.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Tofacitinib Citrate.
Available Strength: 5 mg (white, oval) and 10 mg (pink, oval) tablets.
Storage: Store at 20°C–25°C (68°F–77°F).