Pfizer’s Xeljanz and Xeljanz XR treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. The drug works by decreasing the activity of the immune system. In July 2019, the U.S. Food and Drug Administration approved new warnings for the medication after a clinical trial found an increased risk of blood clots in the lungs and death when people took high doses of the drug to treat rheumatoid arthritis.

Xeljanz Facts
  1. MANUFACTURER Pfizer Inc.
  2. ACTIVE INGREDIENT Tofacitinib
  3. USED TO TREAT Rheumatoid arthritis, psoriatic arthritis and ulcerative colitis
  4. RELATED DRUG Olumiant (baricitinib)

Xeljanz is an oral prescription medication approved to treat moderately to severely active rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. It also comes in an extended release formula, Xeljanz XR.

Both formulas contain the active ingredient tofacitinib. The medication belongs to a class of drugs known as Janus kinase inhibitors or JAK inhibitors.

Pfizer first gained U.S. Food and Drug Administration approval to sell Xeljanz in the United States in 2012. Since its release, the drug has become a blockbuster for Pfizer. In 2018, it brought in about $1.8 billion worldwide.

More than 80 countries approved the medication for treatment of rheumatoid arthritis (RA). In addition, over 40 countries approved it for the treatment of active psoriatic arthritis (PsA), and 70 countries approved it for the treatment of ulcerative colitis (UC).

More than 80 countries have approved Xeljanz to treat rheumatoid arthritis.
Source: Pfizer 2018 Financial Report

From January 2013 to July 2018, doctors prescribed the drug to about 132,000 people to treat their rheumatoid arthritis, according to the Xeljanz website.

How Is Xeljanz Different From Xeljanz XR?
Xeljanz tablets dosage
Two times a day with or without food
Xeljanz XR tablets dosage
Once a day with or without food
DOSAGE 5 mg tablet 11 mg extended release tablets
HOW IT'S DELIVERED Immediate-release tablet that releases medication into the bloodstream over the course of several hours Extended-release tablet that releases medication into the bloodstream over the course of a day
The difference between Xeljanz and Xeljanz XR is how many times a day you take the medication. Source: Xeljanz.com

Despite its popularity, the drug may cause a number of side effects. The side effects reported most often during the first three months of rheumatoid arthritis clinical trials were upper respiratory tract infection, cold-like symptoms, diarrhea, headache and hypertension. People who participated in UC clinical trials also reported rashes, gastroenteritis and elevated cholesterol levels.

The drug carries the FDA’s most serious warning, a black box warning, for an increased risk of serious infections and reports of malignancies such as lymphoma.

The FDA released a warning in February 2019 about a safety clinical trial that found people who used higher doses of tofacitinib to treat RA had a higher risk of blood clots and death. After investigating the data, the agency approved a black box warning about an increased risk of blood clots and death in July 2019.

Lawyers are currently investigating these cases and filing lawsuits on behalf of patients.

How Does Tofacitinib Work?

Xeljanz works by inhibiting production of cytokines, which are proteins that help control immune system responses. When our bodies fight infections, cytokine production increases. People with RA overproduce cytokines, and this leads to inflammation and pain. Xeljanz disrupts cell signals in the Janus kinase (JKA) pathways to reduce the production of cytokines, according to a video on the Xeljanz website.

In people with psoriatic arthritis and ulcerative colitis, the drug works the same way to lower inflammatory responses that cause symptoms.

In July 2019, the FDA limited the use of Xeljanz in adults with ulcerative colitis because of safety concerns. The agency had initially approved the drug for the treatment of any adult with moderately to severely active colitis. Now the drug is only approved for adults with UC who have had an inadequate response or are intolerant to TNF blockers.

Recommended Dosages

Depending on the reason doctors prescribe the drug, it may have different dosage instructions. Patients can take the medicine with or without food.

People may take Xeljanz or Xeljanz XR with or without a nonbiologic disease-modifying antirheumatic drug (DMARD) such as methotrexate. But they should not use it with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine.

Patients with severe liver impairment should not use these drugs. Do not take Xeljanz XR for ulcerative colitis.

Rheumatoid Arthritis

Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily; the recommended dosage for people with severe renal impairment or moderate hepatic impairment is Xeljanz 5 mg once daily.

Psoriatic Arthritis (in combination with nonbiologic DMARDs)

Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily; the recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily.

Ulcerative Colitis

Xeljanz 10 mg twice daily for at least eight weeks; then 5 mg or 10 mg twice daily. Patients should talk to their doctor about stopping the drug if they’ve taken 10 mg twice daily for 16 weeks and they’re not getting the benefits they thought they would. Patients should use the lowest effective dose to maintain the benefits. People with moderate and severe renal impairment or moderate hepatic impairment should use half the dose recommended for people with normal liver and kidney function.

Drug Effectiveness and Interactions

Pfizer studied the effectiveness of Xeljanz in patients who took the drug alone or with another DMARD such as methotrexate. The company conducted six studies of more than 4,200 patients with moderate to severe RA.

In clinical studies, medication reduced RA joint pain in as little as two weeks. Though for some patients, the drug may take three to six months to work, according to the Xeljanz website.

In clinical studies, Xeljanz reduced rheumatoid arthritis joint pain in as little as two weeks.

In the ORAL Solo Study of patients who took Xeljanz without methotrexate, 30 percent of tofacitinib patients (71 out of 240) experienced a 20 percent reduction in tender and swollen joints after two weeks. In comparison, 12 percent (14 out of 119) patients in the placebo group experienced the same result.

For UC, the drug can improve the appearance of the intestinal lining and reduce rectal bleeding and stool frequency in as little as two weeks, according to Pfizer.

Drug Interactions

Combining tofacitinib with other medicines that treat rheumatoid arthritis, psoriatic arthritis or ulcerative colitis may increase the risk of infection. The drug’s label recommends against taking the medicine in combination with biologic DMARDs or potent immunosuppresants.

Drugs that may increase the risk of infection if taken with tofacitinib include:
  • Actemra (tocilizumab)
  • Enbrel (etanercept)
  • Humira (adalimumab)
  • Remicade (infliximab)
  • Rituxan (rituximab)
  • Orencia (abatacept)
  • Kineret (anakinra)
  • Cimzia (certolizumab)
  • Simponi (golimimab)
  • Stelara (ustekinumab)
  • Cosentryx (secukinumab)
  • Entyvio (vemdolizumab)
  • Azathioprine
  • Cylcosporine
  • Medications that affect liver enzymes

People who plan to take Xeljanz should tell their doctors about all the supplements, vitamins and drugs they take.

Checklist to ask your doctor about Xeljanz
Source: Xeljanz.com

FDA Safety Alerts

On Feb. 25, 2019, the FDA released a Safety Communication about an increased risk for blood clots in the lungs, known as pulmonary embolisms, and death in patients who took Xeljanz during a safety trial.

When the FDA approved the drug, it required Pfizer to conduct a clinical trial to evaluate the risk of heart-related events, cancer and opportunistic infections in rheumatoid arthritis patients who take the drug in combination with methotrexate.

The trial was designed to evaluate the treatment at two doses and compare the risks to another drug called a tumor necrosis factor, or TNF, inhibitor. Drugs in the TNF inhibitor class include Humira, Remicade and Enbrel.

A safety monitoring committee found the increased risk after it reviewed the results from the ongoing study. The increased risk occurred specifically in people with rheumatoid arthritis who took 10 mg of the drug twice daily. The FDA has not approved this dose for people with RA but has approved it in patients with UC.

Risk of Blood Clots and Death
On July 26, 2019, the FDA approved a black box warning about an increased risk of blood clots and death.

In a long-term UC extension study, four people had pulmonary embolisms and one patient with advanced cancer died, according to a Dear Healthcare Provider letter.

“Patient safety is of the utmost importance to Pfizer and the company continually monitors the safety of its medicines,” Pfizer’s Chief Medical Officer, Inflammation and Immunology, Dr. Tamas Koncz said in the letter. “As such we continue to work with FDA on this safety signal.”

The FDA continued its investigation, and on July 26, 2019, the agency approved adding a black box warning about an increased risk of blood clots and death.

According to the warning, patients 50 years old and older with RA and at least one cardiovascular risk factor who took 10 mg of Xeljanz twice a day had a higher rate of death, including sudden cardiovascular death, compared to people who took a lower dose or a TNF blocker.

The same group of people also had a higher risk of blood clots, including clots in the lungs known as pulmonary embolisms, clots in deep veins known as deep venous thrombosis and clots in the arteries known as arterial thrombosis.

While the risk was found in people with RA, the FDA is concerned it may also affect people with UC.

Please seek the advice of a medical professional before making health care decisions.

Related Pages
Michelle Llamas, Senior Content Writer
Written By Michelle Llamas Senior Writer

Michelle Llamas has been writing articles and producing podcasts about drugs, medical devices and the FDA for seven years. She specializes in fluoroquinolone antibiotics and products that affect women’s health such as Essure birth control, transvaginal mesh and talcum powder. Michelle collaborates with experts, including board-certified doctors, patients and advocates, to provide trusted health information to the public. Some of her qualifications include:

  • American Medical Writers Association (AMWA) Engage Committee and Membership Committee member
  • Centers for Disease Control and Prevention (CDC) Health Literacy certificates
  • Original works published or cited in The Lancet, British Journal of Clinical Pharmacology and the Journal for Palliative Medicine
Edited By

15 Cited Research Articles

  1. Chaplin, S. (2017). Janus kinase inhibitors for autoimmune disorders. Retrieved from https://onlinelibrary.wiley.com/doi/pdf/10.1002/psb.1635
  2. DailyMed. (2018, June 11). Xeljanz/Xeljanz XR. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68e3d6b2-7838-4d2d-a417-09d919b43e13&audience=consumer#section-6
  3. Pfizer. (2018). Annual Review. Retrieved from https://www.pfizer.com/files/investors/financial_reports/annual_reports/2018/assets/pdf/pfizer-2018-annual-review.pdf
  4. Pfizer. (2018). Proxy Statement for 2019 Annual Meeting of Shareholders: 2018 Financial Report. Retrieved from https://s21.q4cdn.com/317678438/files/doc_financials/interactive_proxy/2019/images/Pfizer-Proxy2019.pdf
  5. Pfizer. (2019, February 28). Communication of new safety information for Xeljanz (tofacitinib). Retrieved from https://www.pfizermedicalinformation.com/sites/default/files/attachments/dear-hcp-letter-communication-of-new-safety-information-for-xeljanz-tofacitinib-feb-2019.pdf
  6. Pfizer. (2019, July). Xeljanz/Xeljanz XR Prescribing Information. Retrieved from http://labeling.pfizer.com/ShowLabeling.aspx?format=PDF&id=959
  7. Pfizer. (n.d.). How Xeljanz Works. Retrieved from https://ra.xeljanz.com/about-xeljanz/how-xeljanz-works
  8. Pfizer. (n.d.). What is Xeljanz/Xeljanz XR? Retrieved from https://psa.xeljanz.com/about-xeljanz/what-is-xeljanz
  9. Pfizer. (n.d.). Xeljanz By the Numbers. Retrieved from https://ra.xeljanz.com/about-xeljanz/by-the-numbers
  10. Pfizer. (n.d.). Xeljanz Clinical Trials. Retrieved from https://ra.xeljanz.com/about-xeljanz/clinical-trial-results
  11. Pfizer. (n.d.). Xeljanz. Retrieved from https://www.xeljanz.com/
  12. Pfizer. (n.d.). You Could Take Your Ulcerative Colitis Treatment in a Different Direction. Retrieved from https://uc.xeljanz.com/
  13. U.S. Food and Drug Administration. (2019, February 25). Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/safety-trial-finds-risk-blood-clots-lungs-and-death-higher-dose-tofacitinib-xeljanz-xeljanz-xr
  14. U.S. Food and Drug Administration. (2019, February 25). Xeljanz, Xeljanz XR (tofacitinib): Safety Communication - Safety Trial Finds Increased Risk of Blood Clots in the Lungs and Death with Higher Dose in Rheumatoid Arthritis Patients. Retrieved from https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm632016.htm
  15. U.S. Food and Drug Administration. (2019, July 26). FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and
View All Sources
Who Am I Calling?

Calling this number connects you with a Drugwatch representative. We will direct you to one of our trusted legal partners for a free case review.

Drugwatch's sponsors support the organization's mission to keep people safe from dangerous drugs and medical devices. For more information, visit our sponsors page.

(877) 518-2629