Detailed info on Tofacitinib

Tofacitinib, a Janus kinase (JAK) inhibitor class drug, is a medication tablet sold under the brand name Xeljanz (except in Russia, where it is marketed as Jakvinus or Jaquinus) and is used for the treatment of psoriatic arthritis, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, which was discovered by National Institutes of Health and Pfizer. It interferes with the JAK-STAT signaling pathway which influences DNA transcription [source Wikipedia]. There have been disapproval of the uses of this drug in the past by European regulatory agencies but eventually was approved, although the box must be printed with the warning of possible injury and death due to the severe side effects as per U.S. Food and Drug Administration (FDA).

It’s Appearance

XELJANZ Tablets:

• 5 mg: Round tablet white in color debossed with “Pfizer” and “JKI 5” on either side.
• 10 mg: Round tablet blue in color debossed with “Pfizer” and “JKI 5” on either side.

XELJANZ XR Tablets:

• 11 mg: Oval tablet pink in color and a drilled hole at one side and debossed “JKI 11” on the other side.

Warnings and Precautions

WARNING: SERIOUS INFECTIONS AND MALIGNANCY Serious infections may lead to hospitalization or death, If a seriousness develops, discontinue Tofacitinib until the infection is controlled.

• Always advise patients to read the FDA-approved labeling.
• Inform patients that intake of the drug may lower the immune system and not initiate the intake if already have an active infection and advise them to contact the healthcare provider immediately if encounter any symptoms suggesting infection.
• Do not initiate Tofacitinib if, an absolute lymphocyte count is less than 500 cells/mm^3, ANC less than 1000 cells/mm^3 or hemoglobin is less than 9g/dL.
• It should also not be initiated if the patients have a history of chronic or recurrent infections, or any live localized active infection due to reports of sometimes serious infections, commonly pneumonia, herpes zoster, and urinary tract infection.

Dosage and intake procedure

• Patients with a high risk of Pulmonary embolism are not advised to follow the dosage of 10-mg twice a day.
• Laboratory monitoring of the patient is required due to severe side effects irrespective of risk factors.
• It can be used to treat Rheumatoid Arthritis patients as a monotherapy or in combination with methotrexate or other DMARDs (but immunosuppressants such as azathioprine and cyclosporine is not recommended).
• The recommended dosage:

1. For Rheumatoid Arthritis is XELJANZ 5 mg twice a day or XELJANZ  XR 11 mg once a day.
2. For patients with renal impairment or hepatic impairment is XELJANZ 5 mg once a day.

Interaction with other drugs

Although there is no contraindication according to the report by the FDA, always ask the specialist about the interaction and possible effects of drugs being taken as medication.

• Dosage of tofacitinib is advised to reduced if the patient is under medication of potent inhibitors of Cytochrome P450 3A4 and CYP2C19.
• Interaction with:

( R ) - warfarin and ( S ) - warfarin: Risk of bleeding may increase.

2-Methoxyethanol, Abetimus: May increases immunosuppressive activities. 

It can take with or without food but Grapefruit, St. John’s Wort should be avoided.

Pharmacodynamics

• Patients receiving Tofacitinib 5mg or 10mg of tofacitinib twice a day for placebo-controlled trials of rheumatoid shows increase in ACR20 responses within 2weeks in some patients.
• Tofacitinib intake shows an increased risk of lymphomas, and other malignancies (including lung, breast, gastric, and colorectal cancer).
• Patients under the medication should be under proper monitoring of lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids.

Possible side effects

Common side effects: Diarrhea, headache, high blood pressure, nasopharyngitis.Severe side effects: Infections, Cancer, Pulmonary embolism, risk of blood clot, Tuberculosis.

Usages in some special conditions

• Renal transplant patients show an adverse effect while on immunosuppressive medications.
• If the patient is suffering from a serious localized infection, they should avoid the use of Tofacitinib citrate.
• There is a potential of risk to a fetus, thus pregnant women and females are advised to enroll in XELJANZ/XELJANZ XR pregnancy register.
• It is not advised to breastfeed during the treatment with Tofacitinib.
• It may impair fertility in females, based on studies found in rats.
• In pediatric patients, there is no safety and effectiveness of XELJANZ/XELJANZ XR.
• In Diabetics patients, there is a higher risk of infection.

OVERDOSE: No specific antidote is available for now. In the case of overdose, patients must be monitored for signs and symptoms of adverse reactions.