Tofacitinib
Indications
Tofacitinib is used for:
Rheumatoid Arthritis
Adult Dose
Rheumatoid Arthritis
Indicated as second-line treatment for moderate-to-severe active rheumatoid arthritis in patients with an inadequate response or intolerance to methotrexate; may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs
Adult: Recommended Dose: 5 mg twice daily.
Hepatic impairment
Mild: No dosage adjustment required
Moderate: Not to exceed 5 mg qDay
Severe: Not recommended
Child Dose
Safety and efficacy not established
Renal Dose
Renal impairment
Mild: No dosage adjustment required
Moderate-to-severe: Not to exceed 5 mg qDay
Administration
May be taken with or without food.
Contra Indications
Hypersensitivity to the active substance or to any of the excipients.
Precautions
Do not initiate therapy in patients w/ an active infection including localized infections, chronic or recurrent infections, or those who have been exposed to TB, history of a serious or an opportunistic infection, resided or travelled in areas of endemic TB or endemic mycoses; underlying conditions that may predispose to infection.
Evaluate & test patients for latent or active infection prior to administration. Monitor for signs & symptoms of TB. Perform screening for viral hepatitis before starting therapy. Malignancy & lymphoproliferative disorder excluding nonmelanoma skin cancer. Periodic skin exam for patients who are at increased risk of skin cancer. Patients who may be at increased risk for GI perforation (eg, history of diverticulitis).
Monitor lymphocyte at baseline & every 3 mth thereafter; neutrophils & Hb at baseline & after 4-8 wk of treatment & every 3 mth thereafter. Discontinue if Hb levels <8>2 g/dL while on treatment. Assess lipid parameters approx 4-8 wk following initiation of therapy. Not recommended to be given w/ concurrent live vaccines. Moderate or severe renal impairment. Severe hepatic impairment. Avoid use in RA patients in combination w/ biological DMARDs.
Pregnancy & lactation. Childn <18 yr. Elderly ≥65 yr.
Pregnancy-Lactation
Interactions
Increased exposure w/ potent CYP3A4 inhibitors (eg, ketoconazole), moderate CYP3A4 inhibitors & potent CYP2C19 inhibitors (eg, fluconazole). Decreased exposure w/ potent CYP inducers (eg, rifampin). Increased AUC & decreased Cmax w/ tacrolimus & cyclosporine. Decreased AUC & Cmax of MTX.
Adverse Effects
Side effects of Tofacitinib :
>10%
Overall infections (20-22%)
1-10%
URTI (4.5%),Headache (4.3%),Diarrhea (4%),Nasopharyngitis (3.8%),UTI (2%),Hypertension (1.6%)
<1%
ANC <500/mm³ (0.07%),Lymphocytes <500/mm³ (0.04%)
Frequency Not Defined
Serious infections: 1.7 events per 100 patient-years
Malignancies: 0.3 events per 100 patient-years
Mechanism of Action
Janus kinases (JAKs) pathways inhibitor; JAK consists of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoieses 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.
These signals are essential in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAKs reduces production of and modulates proinflammatory cytokines central to RA.