What it's for (Indications)
- Tofacitinib, a Janus kinase (JAK) inhibitor, is indicated for the treatment of various autoimmune and inflammatory conditions.
- It is approved for adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more TNF blockers.
- Additionally, it is indicated for adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more TNF blockers.
- Tofacitinib is also used in adults with moderately to severely active ulcerative colitis (UC) who have experienced an inadequate response or intolerance to one or more TNF blockers.
- Furthermore, it is approved for adults and pediatric patients 2 years of age and older with active polyarticular course juvenile idiopathic arthritis (pcJIA) who have had an inadequate response or intolerance to one or more TNF blockers.
- Lastly, it is indicated for adults with active ankylosing spondylitis (AS) who have had an inadequate response to conventional therapy.
- The decision to initiate tofacitinib should be based on a thorough assessment of the patient's individual risk-benefit profile, considering its potent immunomodulatory effects and associated warnings.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The dosage of tofacitinib varies depending on the specific indication and patient factors, including renal and hepatic function. For moderately to severely active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), the recommended dose is 5 mg orally twice daily. For patients with RA who have had an inadequate response to 5 mg twice daily, 10 mg twice daily may be considered, but this higher dose is associated with increased risks. In moderately to severely active ulcerative colitis (UC), an initial induction dose of 10 mg orally twice daily is typically given for at least 8 weeks, which may be extended to 16 weeks if needed. The maintenance dose for UC is 5 mg orally twice daily, with consideration for 10 mg twice daily if loss of response occurs. For polyarticular course juvenile idiopathic arthritis (pcJIA), dosing is weight-based. Dose adjustments are required for patients with moderate to severe renal impairment or moderate hepatic impairment. Co-administration with strong CYP3A4 inhibitors or dual CYP3A4 and CYP2C19 inhibitors necessitates dose reduction. It is imperative to use the lowest effective dose for all indications to minimize potential risks, and careful monitoring for adverse effects is essential throughout treatment. |
Safety & Warnings
Common Side Effects
- Tofacitinib can cause a range of side effects, some of which are common and others potentially serious.
- Common side effects include upper respiratory tract infections (e.
- g.
- , nasopharyngitis, sinusitis), headache, diarrhea, nausea, and hypertension.
- Laboratory abnormalities such as increased cholesterol levels (total and LDL), elevated liver enzymes (ALT, AST), and anemia have also been observed.
- More serious side effects include a heightened risk of serious infections, encompassing bacterial, mycobacterial (e.
- g.
- , tuberculosis), invasive fungal, viral (e.
- g.
- , herpes zoster), and opportunistic infections, which can lead to hospitalization or death.
- Malignancies, including lymphomas, lung cancer, and non-melanoma skin cancer, have been reported.
- A significant concern is the increased risk of thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, some of which have been fatal.
- Gastrointestinal perforations, particularly in patients with pre-existing diverticulitis, are another serious risk.
- Hematologic abnormalities like lymphopenia and neutropenia, and severe hypersensitivity reactions (e.
- g.
- , anaphylaxis, angioedema), also warrant careful monitoring.
- Patients should be counseled on these potential side effects and instructed to report any unusual symptoms promptly.
Serious Warnings
- Black Box Warning: Tofacitinib carries multiple prominent Black Box Warnings due to significant risks identified in clinical trials and post-marketing surveillance: **1. SERIOUS INFECTIONS:** Patients treated with tofacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. These include active tuberculosis (TB), invasive fungal, bacterial, and other opportunistic infections. Screening for latent and active TB is required before and during therapy. Tofacitinib should be avoided in patients with an active serious infection. **2. MORTALITY:** An increased rate of all-cause mortality, including sudden cardiovascular death, was observed in a large, randomized post-marketing safety study in rheumatoid arthritis (RA) patients 50 years or older with at least one cardiovascular risk factor treated with tofacitinib 10 mg twice daily compared to TNF blockers or tofacitinib 5 mg twice daily. **3. MALIGNANCY:** Malignancies, including lymphomas and lung cancers, have occurred in patients treated with tofacitinib. In the RA study noted above, a higher rate of malignancies (excluding non-melanoma skin cancer) was observed in tofacitinib-treated patients compared to TNF blockers. Non-melanoma skin cancer has also been reported. The risks of malignancy with tofacitinib may be higher in patients with a history of malignancy or those who are current or past smokers. **4. MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE):** In the aforementioned RA study, a higher rate of MACE (defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) was observed in tofacitinib-treated patients, particularly those 50 years or older with at least one cardiovascular risk factor, compared to TNF blockers. Tofacitinib should be used with caution in patients with cardiovascular risk factors. **5. THROMBOSIS:** Thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, has occurred in patients treated with tofacitinib. Some of these events have been fatal. Tofacitinib should be avoided in patients with known risk factors for thrombosis (e.g., prior DVT/PE, malignancy, oral contraceptives, hormone replacement therapy, inherited coagulopathy), except for the treatment of ulcerative colitis where the known benefits outweigh these risks in appropriately selected patients. If signs or symptoms of thrombosis occur, tofacitinib should be discontinued and patients should be evaluated promptly.
- Several critical warnings are associated with tofacitinib therapy, necessitating vigilant patient monitoring and risk assessment.
- Patients are at an increased risk of developing serious infections, including active tuberculosis (TB) and other opportunistic pathogens, which may require hospitalization or be fatal.
- Screening for active and latent TB is mandatory before initiating and during therapy.
- Tofacitinib should be avoided in patients with active serious infections.
- There is an increased risk of malignancies, including lymphomas and lung cancers, particularly in patients who are current or past smokers.
- Non-melanoma skin cancer (NMSC) incidence is also elevated, requiring routine skin examinations.
- Tofacitinib carries a heightened risk of thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, some of which have resulted in fatalities.
- It should be used with caution, or avoided, in patients with known risk factors for thrombosis.
- Gastrointestinal perforations have occurred, especially in patients with diverticulitis, warranting prompt evaluation of new abdominal symptoms.
- Laboratory abnormalities, such as elevated lipid parameters, liver enzymes, and changes in hematologic counts (lymphocytes, neutrophils, hemoglobin), necessitate regular monitoring.
- Live vaccines should not be administered concurrently with tofacitinib.
- An increased risk of major adverse cardiovascular events (MACE) has been observed in a large safety study, particularly in rheumatoid arthritis patients 50 years or older with at least one cardiovascular risk factor.
How it Works (Mechanism of Action)
Tofacitinib functions as a selective inhibitor of Janus kinase (JAK) enzymes, primarily targeting JAK1 and JAK3, and to a lesser extent JAK2. JAKs are critical intracellular non-receptor tyrosine kinases that play a pivotal role in mediating cytokine and growth factor signaling. Upon ligand binding to their respective receptors, JAKs become activated and subsequently phosphorylate Signal Transducers and Activators of Transcription (STATs). The activated STATs then translocate to the nucleus, where they regulate gene expression, thereby controlling various cellular processes, including hematopoiesis, immune cell development, and inflammatory responses. By inhibiting JAK1 and JAK3, tofacitinib disrupts the signaling pathways of numerous pro-inflammatory and immunomodulatory cytokines, such as interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-9, IL-15, and IL-21. This blockade prevents the activation of STATs and consequent gene transcription, leading to a reduction in inflammation and immune system overactivity. This immunomodulatory effect is the basis for its therapeutic efficacy in autoimmune conditions like rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, polyarticular course juvenile idiopathic arthritis, and ankylosing spondylitis.
Commercial Brands (Alternatives)
No other brands found for this formula.