Xeljanz Side Effects

The most common side effects of Xeljanz include upper respiratory tract infection, cold-like symptoms, diarrhea and headache. The arthritis and colitis medication can also cause more severe problems such as serious infections and cancer. In July 2019, the U.S. Food and Drug Administration approved a black box warning about an increased risk of blood clots and death with the 10 mg twice daily dose.

Xeljanz
Xeljanz Side Effects Facts
  1. COMMON SIDE EFFECTS Diarrhea, headache, upper respiratory tract infection, elevated cholesterol, herpes zoster
  2. SERIOUS SIDE EFFECTS Tuberculosis, bacterial and fungal infections, lymphoma, blood clots
  3. BLACK BOX WARNING Serious infections and malignancies, increased risk of blood clots and death

Xeljanz and Xeljanz XR are Janus kinase (JAK) inhibitors that treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis by regulating the activity of the immune system. Tofacitinib is the active ingredient in the drug.

Most of the drug’s common side effects are minor and range from headaches to cold-like symptoms. But the drug also carries a black box warning for serious infections and malignancies such as lymphoma.

Between 2013 and 2018, the FDA Adverse Events Reporting System (FAERS) received 42,528 reports of adverse reactions for the two drugs. Of these, 14,679 were serious and 983 involved deaths.

The data from FAERS are self-reported, and the U.S. Food and Drug Administration cannot verify if they are accurate. But the agency will sometimes use them to determine if it should get more data on certain adverse effects.

REPORTED ADVERSE EVENTS
From 2013 to Dec, 31, 2018, the FDA Adverse Events Reporting System (FAERS) received 42,528 reports of adverse reactions for Xeljanz and Xeljanz XR.

On Feb. 25, 2019, the FDA released a safety communication to alert the public that a safety trial found an increased risk of blood clots in the lungs and death among people with rheumatoid arthritis who took a higher dose of the drug. After this communication went public, lawyers began investigating lawsuits against Pfizer.

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

Common Side Effects

In Pfizer’s clinical trials, researchers considered side effects common if they occurred in 2 percent or more of patients who took 5 mg of Xeljanz twice daily or 10 mg twice daily. About 4 percent of trial participants who took Xeljanz quit clinical trials because of adverse events compared to 3 percent of people who took a placebo.

The most common side effect in patients with rheumatoid arthritis was upper respiratory tract infection. This occurred in 4 percent of 1,336 patients who had taken 5 mg of the drug twice daily and 4 percent of 1,349 patients who had taken 10 mg twice daily. People with psoriatic arthritis had the same safety profile as those with rheumatoid arthritis.

In patients with ulcerative colitis, the most common side effect was cold-like symptoms. This occurred in 10 percent of 198 patients who had taken 5 mg twice daily and 14 percent of 196 patients who had taken 10 mg twice daily. In general, people with ulcerative colitis who took the drug suffered more side effects than people with rheumatoid arthritis who took the drug.

Common side effects:
  • Headache
  • Elevated cholesterol levels
  • Upper respiratory tract infection
  • Rash
  • Diarrhea
  • Herpes zoster (shingles)
  • Gastroenteritis
  • Anemia
  • Nausea
  • Increased blood creatine phosphokinase
  • Hypertension

While the majority of side effects in clinical trials were not severe, the medicine does have a few serious risks, according to the drug’s label. Some patients shouldn’t take the drug and some might be at higher risk of side effects. Doctors may monitor white blood cell counts, hemoglobin levels and liver enzymes.

2019 Black Box Warning About Blood Clots and Death

The tofacitinib Rheumatology Data Safety Monitoring Board reviewed additional safety data from an ongoing study by Pfizer and found an increase in the frequency of blood clots in the lungs and death in patients who took Xeljanz. The at-risk patients had rheumatoid arthritis and took a higher than normal dose of 10 mg twice daily — a dose not approved to treat the condition.

The study, called A3921133, is one of the postmarketing studies the FDA required Pfizer to conduct after the agency approved the drug. The FDA released a safety communication about the findings in February 2019, and Pfizer sent a letter to health care providers about the risk.

Illustration of a blood blot in the lung
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The FDA released a safety communication on Feb. 25, 2019, to alert the public that a safety clinical trial found an increased risk of blood clots in the lungs and death in patients with rheumatoid arthritis who took 10 mg of tofacitinib twice daily.

Then in July 2019, the FDA approved the addition of a black box warning about an increased risk of blood clots and death with Xeljanz and Xeljanz XR. In addition to the warning, the agency limited the drugs’ use for ulcerative colitis to patients who have an inadequate response or who are intolerant to another family of medications called TNF blockers.

The increased risks were seen in patients 50 or older with RA and at least one cardiovascular risk factor who took a 10 mg twice daily dose, according to data found in the ongoing postmarket safety study.

“While the increased risks of blood clots and of death were seen in patients taking [the 10 mg twice daily] dose for RA, these risks may also apply to those taking tofacitinib for ulcerative colitis.”

U.S. Food and Drug Administration

While the FDA did not approve the 10 mg twice daily dose for people with rheumatoid arthritis, it did approve the dose for people with ulcerative colitis.

“This dose is only approved for ulcerative colitis for initial treatment and for long-term use in limited situations,” the agency said in its July safety communication. “While the increased risks of blood clots and of death were seen in patients taking this dose for RA, these risks may also apply to those taking tofacitinib for ulcerative colitis.”

According to Pfizer’s prescribing information for patients in the United States, four people with ulcerative colitis who took the 10 mg twice-a-day dose during a long-term extension study suffered blood clots in the lungs, known as pulmonary embolisms. One of those patients with advanced cancer died.

Prior to the black box warning added in July 2019, Pfizer did not include a warning about a blood clot risk in its Xeljanz drug label. While the FDA worked with Pfizer to investigate the blood clots, the drugmaker reduced the dosage in the ongoing A3921133 study to 5 mg twice daily.

The FDA shared preliminary study results as of January 2019:
  • 19 cases of blood clots in the lung in patients who received tofacitinib 10 mg twice daily compared to three cases in patients who received TNF blockers
  • 45 cases of death in patients who received tofacitinib 10 mg twice daily compared to 25 cases in patients who received TNF blockers

Infections

Infections are some of the more serious risks of Xeljanz, and the risk of infection could increase in patients who take the drug in combination with other immunosuppressants such as methotrexate or corticosteroids.

In clinical trials, researchers reported more serious infections in patients who took the drug versus a placebo. Clinical trial participants suffered from infections including pneumonia, cellulitis and urinary tract infections. In general, people who took higher doses had a higher risk of developing an infection.

Some infections may require hospitalization or may be fatal. In Pfizer’s seven controlled clinical trials, researchers found that more people who took Xeljanz had serious infections than those who took a placebo. Scientists classified a serious infection as one that required hospitalization or intravenous antibiotic treatment, according to Pfizer’s website for health professionals.

SERIOUS INFECTIONS
Pfizer gathered safety data from studies with 2,300 patients. Of those patients, 9.4 percent suffered serious infection.

The drug’s black box warning says that reported infections include tuberculosis, bacterial infections, viral infections such as herpes zoster, and fungal infections, including cryptococcosis and pneumocystosis.

Cancer

Because tofacitinib affects the immune system, it may increase the risk of certain cancers. Pfizer lists these as malignancies in its safety data and includes this information in the black box warning.

Taking higher doses of the drug increases the risk. People who have had cancer in the past should consider the risks and benefits of taking the medication.

About 3 percent of 2,300 patients who took the drug during studies suffered malignancies. None of the people who took a placebo reported cancers or lymphomas.

REPORTED CANCERS
Lymphoma and non-melanoma skin cancers were the most commonly reported malignancies with Xeljanz.

The most commonly reported cancers were lymphoma and non-melanoma skin cancer. Other types of cancer reported include lung cancer, breast cancer, melanoma, prostate cancer and pancreatic cancer.

Kidney transplant patients who took Xeljanz with immunosuppressive medications suffered Epstein Barr Virus-associated post-transplant lymphoproliferative disorder, which is a rare disorder than can lead to enlargement of organ tissue or lymphoma. Specifically, the patients took Xeljanz with basiliximab, high-dose corticosteroids, and mycophenolic acid products.

Shingles, GI Perforations and Abnormal Lab Tests

In addition to infections and malignancies, Xeljanz’s drug label and safety data warns about herpes zoster, gastrointestinal perforations and lab abnormalities.

Herpes Zoster

Tofacitinib may increase the risk of herpes zoster, also known as shingles. According to safety data from Pfizer, the virus occurred more in patients who took Xeljanz than those who took a placebo.

In Phase 1, 2, 3, and long-term extension studies with 2,300 patients, 11 percent of patients got herpes zoster. In Phase 3 studies, there were 143 cases. Eleven were serious and required hospitalization or intravenous antibiotic therapy.

The risk appears to be higher in patients treated in Japan and Korea. Pfizer recommends patients avoid live vaccines while they are taking tofacitinib.

Gastrointestinal Perforations

While rare, some patients in clinical trials who took Xeljanz suffered gastrointestinal perforations. In long-term studies of 1,525 patients, three people suffered gastrointestinal perforations.

The problems occurred more in people who took Xeljanz with methotrexate, non-steroidal anti-inflammatory drugs or corticosteroids. Researchers aren’t sure if JAK inhibitors played a role in the perforations.

Lab Abnormalities

Clinical trial participants also had lab abnormalities. Researchers reported decreases in white blood cell counts, anemia, and elevations in cholesterol and liver enzymes.

Patients on tofacitinib should have their blood monitored for abnormalities.

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

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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

11 Cited Research Articles

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  3. National Organization for Rare Disorders. (n.d.). Post-Transplant Lymphoproliferative Disease. Retrieved from https://rarediseases.org/rare-diseases/posttransplant-lymphoproliferative-disorders/
  4. 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
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  7. Pfizer. (n.d.). Xeljanz: The first oral JAK inhibitor approved for RA. Retrieved from https://www.pfizerpro.com/product/xeljanz/ra/ra-safety-data
  8. 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
  9. 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
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