Tofacitinib Drug By Dr. Hardik N. Jayswal

Tofacitinib drug explained in detail by Dr. Hardik N. Jayswal

1. Tofacitinib
Dr. Hardik N. Jayswal

2. Introduction
Tofacitinib ( xeljanz )is an medication used to treat
rheumatoid arthritis, psoriatic arthritis, and ulcerative
colitis. It works by blocking the activity of JAK ( janus
kinase ) enzymes involved in the inflammatory response,
helping to reduce joint pain, swelling, and other symptoms.

3. Mechanism of Action
Tofacitinib is a Janus kinase (JAK) inhibitor that selectively targets the JAK1
and JAK3 enzymes. This disrupts the signaling pathways involved in the
inflammatory response, reducing the production of pro-inflammatory
cytokines and mediators.

By inhibiting JAK1 and JAK3, tofacitinib blocks the signaling of key cytokines
such as interleukin-6, interferon-gamma, and various interleukins, leading to
decreased activation of downstream transcription factors that drive
inflammation.

5. Pharmacokinetics
Tofacitinib is rapidly absorbed after oral administration, with a time to maximum concentration
(Tmax) of 0.5-1 hour. The absolute bioavailability of tofacitinib is approximately 74%. The drug is
metabolized primarily by the liver, with the cytochrome P450 (CYP) 3A4 and 2C19 enzymes
playing a major role.

Tofacitinib has a half-life of 3-4 hours. The drug is excreted primarily in the urine, with about
30% of the dose eliminated unchanged. Tofacitinib exposure is increased in patients with renal
or hepatic impairment, and dose adjustments may be necessary in these populations.

6. Dosage and administration
Recommend dose of tofacitinib is 5mg twice Daily or 10mg once a day orally.
After starting of the treatment, results seen in 12 weeks.

7. Indications
Approved uses
●Psoriatic arthritis
●Rheumatoid arthritis
●Ulcerative colitis
Off-label uses
Autoimmune Dermatoses
●Psoriasis
●Alopecia areata
●Vitiligo
●Dermatomyositits

Dermatitis
●Atopic dermatitis
Photodermatoses
●Chronic actinic dermatits
Other
●Erythema multiforme
●Hypereosinophillic syndrome

8. Contraindications
1.No any specific contraindications listed
use with caution in patients of :-
●TB
●Hepes virus infections
●HBV
●HCV
●HIV

9. Adverse effects
●Reactivation of herpes virus
infections( within 12 months )
●Malignancy risks like
lymphoma,lung,breast,
colorectal,renal cell, prostate etc.
●Gastrointestinal like perforation
●Pulmonary like ILD
●Cardiovascular like decrease HR and
prolonged PR interval
●Hematological like lymphocytopenia,
neutropenia,anemia etc
●Hepatic like hepatitis

10. Clinical evaluation
●Discuss the risks, benefits and adverse effects with each patient
●Discuss alternative treatments
●Discuss the requirement of multiple blood tests
●Elicit history of malignancy and lymphoproliferative disorders
●Elicit history of herpes infections, interstitial lung disease, diverticulitis, renal
dysfunction
●Perform thorough physical examination

11. Laboratory investigations

●Complete blood count with leukocyte differential
●Liver enzyme panel
●Lipid panel
●Basic chemistry panel focusing on glomerular filtration rate
●Pregnancy test (for women of childbearing potential)
●Hepatitis B virus panel
●Hepatitis C virus panel
●Pretreatment evaluation for the presence of latent tuberculosis
After 4-8 weeks evaluate by investigations like
●CBC
●LFT
●Lipid profile
●RFT

14. Drug interactions
Increased levels due to CYP3A4 inhibitors. Eg-Ketoconazole, Fluconazole
Reduced levels due to CYP inducers. Eg- Rifampicin
Do not give with other immunosuppressants. Eg-Azathioprine, Cyclosporine,
DMARD and Biologicals

15. Thank you