- Manufacturer: Pfizer, Inc.
- FDA Approval: November 2012
- Generic Name: tofacitinib
- Dosage Form: tablet, film coated
- Treatment For: rheumatoid arthritis, ulcerative arthritis, psoriatic arthritis
- Dose 5 mg/ 10 mg/ 11 mg
Xeljanz (tofacitinib) is an oral drug that belongs to a class of medication referred to as immunomodulators. It’s used to treat moderate to severe forms of rheumatoid arthritis or active psoriatic arthritis. It’s usually administered in patients who have tried methotrexate or other arthritis medication without successful treatment of symptoms. Xeljanz can also be administered in combination with methotrexate or other arthritis medication, in order to decrease the inflammation, tenderness, or pain in the joints. Rheumatoid arthritis (RA) occurs when the body’s immune system attacks the tissue found in internal organs and joints. Tofacitinib works by reducing the actions of chemicals in the body that induce the reaction. Consequently, this reduces the inflammation and immune response that occurs with RA.
Xeljanz was first approved by the U.S. Food and Drug Administration (FDA)in November 2012 and was meant to help patients who have allergic or insufficient response to methotrexate. Later in 2016, a once-daily, extended-release form of medication was approved. In addition, The FDA required that Pfizer conducts a post-marketing study to determine Xeljanz’s long-term outcomes on heart disease, cancer, and other serious infections. The FDA also asked the company to determine what the differences there are between a group of patients on Xeljanz and another on a different approved medication.
How Xeljanz Works
The active ingredient in Xeljanz (tofacitinib) works by blocking the action of enzymes called Janus kinases (JAK). These enzymes or proteins that play a major role in the process of inflammation that tends to result in psoriatic and rheumatoid arthritis as well as ulcerative colitis. JAKs also regulate chemical signaling pathways that control biologic processes such as immune response that causes tenderness, pain, and swelling as well as blood formation. These enzymes are found in many cells, particularly stem cells in joints and bones. By blocking the action of these enzymes, tofacitinib helps reduce inflammation, tissue destruction and symptoms associated with the inflammation of rheumatoid arthritis. As such, Xeljanz is known to be a Janus kinase inhibitor.
Dosage Forms and Strengths
Xeljanz tablets are available in 5 mg tofacitinib and 10 mg tofacitinib. The 5 mg tablet is a white, round, film-coated, immediate-release tablets debossed with “JKI 5” on one side and “Pfizer” on the other side. The 10 mg tablet, on the other hand, is a blue, round, film-coated tablet debossed with “JKI 10” on one side and “Pfizer” on the other. There’s also the 11 mg tofacitinib (Xeljanz XR), which is a pink, oval, film-coated tablet with “JKI 11” printed on one side of the tablet and a drilled hole on the other side of the tablet. Xeljanz is an immediate-release tablet that released the medication into the bloodstream over several hours. Conversely, Xeljanz XR is an extended-release tablet that releases medication over the course of a day.
The 5 mg and 10 mg Xeljanz tablets are taken twice daily while the Xeljanz XR is taken once daily. The tablets can be taken with or without methotrexate. XELJANZ XR should not be taken for ulcerative colitis. The dosage recommended depends on a patient’s medical condition, lab tests, response to treatment, and other medications one may be taking.
Xeljanz or Xeljanz XR should not be initiated in patients with hemoglobin levels less than 9 g/dl, neutrophil count (ANC) less than 1000 cells/mm3 or absolute lymphocyte count less than 500 cells/mm3. Dose interruption is recommended for management of anemia, neutropenia, and lymphopenia. The use of Xeljanz should be interrupted if a patient develops severe infections. This should be done until the infection is controlled. Xeljanz tablets should be swallowed whole and intact without chewing, splitting, or crushing. Doing so can increase the risk of serious side effects because it releases all of the drug at once.
Xeljanz dosage should be reduced to 5 mcg once daily in patients:
- with moderate hepatic impairment
- with moderate or severe renal insufficiency
- receiving concomitant medications that result in both potent inhibition of CYP2C19 such as fluconazole and moderate inhibition of CYP3A4
- receiving potential inhibitors of cytochrome p450 3a4 such as ketoconazole
CHMP Had Initially Advised Turning Down the Application of Xeljanz
Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency had initially rejected the use of Xeljanzas the organization stated that there was no proven significant benefit for Xeljanz over other RA drugs. This means that there were not sufficient studies to show a consistent reduction in structural damage and disease activity, especially with the use of the lower 5-mg dose. There were also serious concerns about the drug’s overall safety because it carries serious side effects. The committee said that were significant and unresolved concerns regarding the type of serious infections and risk factors associated with tofacitinib, which are not related to Xeljanz’s immunosuppressant action.
There was also a concern about the increased risk of problems with increased lipid levels in the blood, certain cancers, liver damage, and gastrointestinal perforations (holes in the wall of the gut). However, the main issue that contributed to the committee’s view that the treatment’s benefits did not outweigh unresolved and significant safety concerns was the lack of robust evidence on prevention of structural damage. The CHMP ended up refusing marketing authorizations. However, this decision was later changed on 22 March 2017. After conducting several studies on Xeljanz, the European Medicines Agency concluded that the medication was effective for the treatment of psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. Also, the agency stated that the fact that Xeljanz is taken orally may be an advantage when compared to those taken as an injection under the skin. In general, the risks of this medication were similar to others of its class and the agency concluded that the benefits are greater than its risks.
Xeljanz Drug Interactions
Xeljanz may interact with other medication and for this reason, it’s important to let your doctor know about all medications you’re taking, including prescription, over-the-counter, herbal medicines, nutritional, recreational, dietary, or illegal drugs. It’s also important to tell your prescriber about any supplements you take since alcohol, caffeine, street drugs, and the nicotine from cigarettes can affect the action of many medications.
There may be an interaction between Xeljanz and the following drugs:
- remicade (infliximab)
- cimzia (certolizumab)
- orencia (abatacept)
- gengraf, neoral, or sandimmune (cyclosporine)
- decadron or dexpak (dexamethasone)
- simponi (golimumab)
- prograf (tacrolimus)
- kineret (anakinra)
- rheumatrex or trexall (methotrexate)
- imuran (azathioprine)
- sterapred (prednisone)
- actemra (tocilizumab)
- medrol (methylprednisolone)
- enbrel (etanercept)
- humira (adalimumab)
- rituxan (rituximab)
- Equetro (carbamazepine) or Carbatrol, Tegretol
- Rifadin, Rifamate, or Rifater, (rifampin)
- St. John’s Wort
- anti-tumor necrosis factor agents (e.g., etanercept, adalimumab, thalidomide, infliximab)
- beta-blockers (e.g., labetalol, carvedilol, propranolol, metoprolol,)
- "azole" antifungals (e.g., ketoconazole, itraconazole, voriconazole)
- corticosteroids (e.g., hydrocortisone, dexamethasone, fluticasone, budesonide, prednisone)
- HIV protease inhibitors (e.g., indinavir, atazanavir, saquinavir, ritonavir)
- Certain antifungal medications, such as Sporanox (itraconazole), Diflucan (fluconazole), and Nizoral (ketoconazole)
- medications to treat cancer (e.g., vincristine, carboplatin, doxorubicin, cyclophosphamide, ifosfamide)
- macrolide antibiotics (e.g., erythromycin, clarithromycin)
- Aspirin and other non-steroidal anti-inflammatory medications (NSAIDs), such as Aleve or Naprosyn (naproxen) and Motrin or Advil (ibuprofen)
- hepatitis C medications boceprevir or telaprevir
- medications to treat excess stomach acid
- heart or blood pressure medicines
- other arthritis medications
- seizure medications
Xeljanz may also interact with grapefruit and interfere with how the medication works in the body. Consult with your doctors before consuming grapefruit of grapefruit juice.
This is not a complete list of all possible interactions with this medication. Contact your doctor and inform them about other medications you’re taking. It’s also worth noting that an interaction between two medications does not always mean that you stop taking one or all the medications. You should consult with your doctor about how an interaction can be managed. Based on the specifics of your condition, your doctor may recommend that you:
- Change how you’re taking one or both medications,
- Change one of the medications to another,
- Stop taking the medications, or
- leave everything as is
Common Side Effects of Xeljanz
- runny or stuffy nose
- loss of appetite
While most of these side effects don’t occur very often, it’s important to check with your doctor to avoid progression to serious problems. You should also seek medical attention if the following side effects occur:
- increased blood pressure
- development or change in the appearance of lesions
- shortness of breath (new or worsening)
- swelling of arms, hand, ankles, or legs
- signs of anemia or low red blood cells (e.g., pale skin, weakness, unusual tiredness, dizziness, or shortness of breath)
- flu-like symptoms (sore throat, fever, sudden lack of energy)
- symptoms of herpes zoster infection/ shingles such as painful skin rash with blisters
- signs of heart problems (e.g., chest pain, difficulty breathing, fast or irregular heartbeat or pulse, leg swelling, sudden weight gain)
- symptoms of a urinary tract (e.g., low back or flank pain, urinating more often, pain when urinating)
- signs of bleeding in the stomach (e.g., tarry, bloody, or black stools; vomiting blood or black material; spitting up of blood)
Patients taking Xeljanz may also see the empty shell of the tablet in their stool but this is not a concern because the medication has been absorbed by the body.
Black Box Warning
- Serious Infections
Xeljanz tends to reduce the body’s response to infection. Serious and even fatal infections due to viral, invasive fungal, bacterial, mycobacterial, or other opportunistic pathogens have been reported in patients using Xeljanz. Patients taking this medication face a higher risk of developing severe infections that are not only difficult to treat but may also cause prolonged hospitalization or death. The most common infections reported with the use of Xeljanz include urinary tract infections, appendicitis, herpes zoster, cellulitis, diverticulitis, and pneumonia. Among opportunistic infections, cytomegalovirus infections, esophageal candidiasis, multidermatomal herpes zoster, cryptococcosis, tuberculosis and other mycobacterial infections, listeriosis, histoplasmosis, BK virus infection, and pneumocystosis were reported with Xeljanz.
These infections are more likely to occur if the patient is taking another medication that also suppresses the activity of the immune system. Some patients have presented with disseminated disease and were usually taking corticosteroids or methotrexate, which are immunomodulating agents. In addition, there was a greater risk of infections for patients receiving the 10 mg twice daily Xeljanz treatment compared to those taking 5 mg twice daily. Opportunistic herpes zoster infections, including ophthalmologic, disseminated cutaneous, and meningoencephalitis) were higher in patients treated with Xeljanz 10 mg twice daily. Side effects such as coccidioidomycosis may also occur.
Doctors should avoid recommending the use of Xeljanz or Xeljanz XR in patients with serious, active infections. The risks and benefits of tofacitinib should be considered prior to initiating Xeljanz in patients:
- with a history of an opportunistic or serious infection
- with chronic or recurrent infection
- with medical conditions that may increase the likelihood of infections
- with underlying conditions that may expose them to infection
- who have been exposed to tuberculosis
- who have traveled or resided in areas of endemic mycoses or endemic tuberculosis
During and after treatment with Xeljanz or Xeljanz XR, patients should be closely monitored for any signs and symptoms associated with common infections. This medication should be interrupted if the patient develops sepsis, an opportunistic infection, or a serious infection. A patient who develops a new infection during treatment should undergo a complete and prompt diagnostic testing necessary for an immunocompromised patient. In addition, the physician should initiate proper antimicrobial therapy and monitor the patient closely.
Physicians should be cautious when dealing with patients who develop interstitial lung disease or in those with a history of chronic lung disease since they may be more prone to serious infections. Increasing degrees of lymphopenia may result in a higher risk of infection, and as such, the lymphocyte counts should be considered when assessing individual patient risk of infection. If possible, patients taking Xeljanz should avoid being around people who are sick or have contagious infections.
In one study, 107 out of 5671 patients who received wither Xeljanz 5 mg or 10 mg twice daily developed malignancies (excluding non-melanoma skin cancer). In the seven controlled trial, malignancies were reported in 5 patients who received 5 mg twice daily of Xeljanz during the 0 to 12 months exposure while 7 patients who received 10 mg twice daily of Xeljanz developed malignancy. The most common malignancies observed during the long-term extension were lung cancer, followed by breast cancer, gastric cancer, colorectal cancer, renal cell cancer, prostate cancer, lymphoma, and malignant melanoma.
Xeljanz may also be responsible for non-melanoma skin cancers and this was more common with 10 mg twice daily treatment. Epstein Barr Virus-associated with post-transplant lymphoproliferative disorder was reported at an increased rate and usually affected patients who received renal transplants and also treated with concomitant immunosuppressive medications and Xeljanz.
Before and during the administration of Xeljanz or Xeljanz XR, patients should be evaluated and tested for active or latent tuberculosis. Patients with a past history of active or latent tuberculosis should be subjected to anti-tuberculosis therapy before the administration of Xeljanz. This also applies to patients with a negative test for latent tuberculosis but then have risk factors for infection. A patient should check with a doctor with expertise in the treatment of tuberculosis in order to help determine whether it would be appropriate to initiate anti-tuberculosis therapy.
During treatment with Xeljanz, patients should check with their physicians right away if they experience any symptoms of TB, including:
- chest pain
- loss of muscle tone
- loss of appetite
- night sweats
- weight loss
- coughing up blood or mucus
Other adverse reactions that may occur during treatment with Xeljanz include:
- Respiratory, mediastinal, and thoracic disorders: Cough, interstitial lung disease, sinus congestion, dyspnea
- Musculoskeletal, bone, and connective tissue disorders: arthralgia, joint swelling, tendonitis, musculoskeletal pain
- Hepatobiliary disorders: Hepatic steatosis
- Gastrointestinal disorders: dyspepsia, vomiting, nausea, gastritis, abdominal pain,
- Nervous system disorders: Paresthesia
- Metabolism and nutrition disorders: Dehydration
- Skin and subcutaneous tissue disorders: pruritus, erythema, rash
- Psychiatric disorders: Insomnia
- General disorders and administration site conditions: peripheral edema, fatigue, pyrexia
Warnings and Precautions
- Xeljanz and Pregnancy
Before you begin using Xeljanz, be sure to inform your doctors of any allergies or other medical conditions that you may have, whether there are other medications that you’re currently taking or any other significant facts that concern your health. These are factors that may affect how the medication is used. You should also inform your prescriber if you’re pregnant or plan to become pregnant. It’s not known how Xeljanz may affect a fetus. Therefore, if you’re pregnant and the doctor suggests that the benefits of this medication outweigh the risks, you may be listed on a pregnancy registry just to track the outcome as well as evaluate possible effects of Xeljanz on the baby. In addition, it’s not known if Xeljanz could harm a lactating baby and for this reason, nursing mothers are advised not to use this medication.
However, increased disease activity and other side effects of the drug can be associated with ulcerative colitis and rheumatoid arthritis. Adverse pregnancy outcomes include low birth weight infants, low birth weight, and small gestational age at birth.
Gastrointestinal Perforation: There have been cases of gastrointestinal perforation reported in clinical studies with Xeljanz, although it’s unknown the role of JAK inhibition in these cases. However, many patients involved in these studies were receiving background therapy with anti-inflammatory drugs. As such patients with new onset of abdominal symptoms should undergo prompt evaluation in order to identify gastrointestinal perforation as early as possible. Xeljanz should be used with caution in patients who may be at increased risk.
Vaccinations: Patients taking Xeljanz should not receive certain vaccines. Also, the interval between the initiation of tofacitinib and live vaccinations should be based on the guideline of immunosuppressive agents. In clinical trials, a patient experienced varicella zoster virus, 2 days after treatment start with Xeljanz 5mg twice daily and 26 days after vaccination with live Zostavax
Lab Abnormalities: Before and while a patient takes Xeljanz, the doctors should do blood tests to check for various side effects and changes in lab test results. Treatment with Xeljanz was associated with lymphocytosis at one-month exposure. This was followed by a gradual decrease and change in mean absolute lymphocyte counts. Lymphocytes are the white cells that help fight off infections. An increased incidence of treated and serious infection can result in lymphocyte count less than 500 cells/mm3. Treatment with Xeljanz should not be initiated in patients with a low neutrophil, low lymphocyte, low red blood cell count, or liver tests that are too high.
A physician should routinely check certain blood and liver tests. Treatment may be stopped for a period of time if needed since the blood test results may change with time. Laboratory tests such as cholesterol levels may also change and this calls for the health care provider to do regular tests.
Generally, before starting Xeljanz, tell your doctor if you:
- Are being treated for an infection
- Have symptoms of an infection or think you have an infection
- Have TB, or have been in close contact with someone with TB
- Have a weak immune system, diabetes, HIV, or chronic lung disease
- Get a lot of infections that keep coming back
- Have or have had hepatitis B or C.
- Live or have lived or traveled to areas where there’s an increased chance for getting certain forms of fungal infections (including blastomycosis, coccidioidomycosis, histoplasmosis). These infections may develop or become more severe if Xeljanz is used. Ask your healthcare provider if you’re not sure whether you’ve lived in an area where these infections are common.
Infertility: Based on findings in rats, reduced fertility in females with reproductive potential may occur as a result of treatment with Xeljanz. It’s unknown if the effects on fertility are reversible.
Finding Help for a Xeljanz Lawsuit Near Me
If you’re suffering from serious side effects after taking Xeljanz or Xeljanz XR, you could be eligible for compensation. Consumer Alert Now helps connect patients from all over the United States with an experienced attorney. An attorney will provide a free case review and consultation and identify the legal options that you have. They will let you know whether you have a claim and whether they’re able to handle your case. Filing a lawsuit can help you recover lost wages, damages, medical treatment and ease your stress, pain, and suffering. Consumer Alert Now helps you start this process. If you’re ready to get started, contact our legal partners at (800) 511-0747 or fill out our online contact form.