Tofacitinib

Tofacitinib is a prescription medication used to treat Rheumatoid Arthritis, Psoriatic Arthritis, Ulcerative Colitis, and Ankylosing Spondylitis. 

• Tofacitinib is available under the following different brand names: Xeljanz, Xeljanz XR.

Adult and pediatric dosage

Tablet (Xeljanz)

• 5mg
• 10mg

Oral solution (Xeljanz)

Pediatric dosage

• 1mg/mL

Tablet, extended-release (Xeljanz XR)

Adult dosage

• 11mg
• 22mg

Rheumatoid Arthritis 

Adult dosage

• Xeljanz: 5 mg orally twice daily
• Xeljanz XR: 11 mg orally once daily

Polyarticular Course Juvenile Idiopathic Arthritis

Pediatric dosage

• Children 2 years of age or older: 
  • Oral solution
    • 10 to less than 20 kg: 3.2 mg orally twice daily
    • 20 to 40 kg: 4 mg orally twice daily
  • Oral solution or tablet
    • 40 kg or over: 5 mg orally twice daily

Psoriatic Arthritis

Adult dosage

• Xeljanz: 5 mg orally twice daily
• Xeljanz XR: 11 mg orally once daily

Ulcerative Colitis

Adult dosage

• Xeljanz:
  • Induction
    • 10 mg orally twice daily for at least 8 weeks
    • If needed, continue 10 mg twice daily for a maximum of 16 weeks; discontinue after 16 weeks if the adequate therapeutic benefit is not achieved
  • Maintenance
    • 5 mg orally twice daily; may consider 10 mg twice daily (limited to shorter duration) in patients with loss of response during maintenance treatment
    • Use the lowest effective dose needed to maintain response
• Xeljanz XR:
  • Induction
    • 22 mg orally once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response
    • If needed, continue 22 mg once daily for a maximum of 16 weeks; discontinue after 16 weeks if the adequate therapeutic benefit is not achieved
  • Maintenance
    • 11 mg orally once daily; may consider 22 mg once daily (limited to shorter duration) in patients with loss of response during maintenance treatment
    • Use the lowest effective dose needed to maintain response

Ankylosing Spondylitis

Adult dosage

• Xeljanz: 5 mg orally twice daily
• Xeljanz XR: 11 mg orally once daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Tofacitinib include:

• skin rash, 
• shingles, 
• increased blood pressure, 
• abnormal blood tests, 
• fever, 
• headache, 
• nausea, 
• vomiting, 
• diarrhea, 
• stuffy nose, 
• sneezing, and
• sore throat 

Serious side effects of Tofacitinib include:

• hives, 
• difficult breathing, 
• swelling of the face, lips, tongue, or throat, 
• sudden shortness of breath, 
• chest pain or pressure that may spread to the jaw, shoulder, arms, or back, 
• nausea, 
• vomiting, 
• cold sweat, 
• lightheadedness, 
• weakness on one side of the body, 
• slurred speech,
• drooping on one side of the mouth, 
• pain, swelling, or redness in an arm or a leg, 
• fever, 
• chills, 
• night sweats, 
• constant tiredness, 
• wheezing, 
• severe or worsening cough, 
• increased urination, 
• pain or burning while urinating, 
• unexplained weight loss, 
• lumps in your neck, armpits, or groin, 
• flu-like symptoms, 
• tingly or painful blistering rash on one side of the body, 
• severe stomach pain, 
• diarrhea, 
• changes in the bowel habits, 
• loss of appetite, 
• vomiting, 
• stomach pain (upper right side), 
• dark urine, 
• clay-colored stools, and
• yellowing of the skin or eyes (jaundice)

Rare side effects of Tofacitinib include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Tofacitinib has severe interactions with no other drugs.
• Tofacitinib has serious interactions with at least 110 other drugs. 
• Tofacitinib has moderate interactions with at least 74 other drugs.
• Tofacitinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Tofacitinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tofacitinib?”

Cautions

• Malignancy and lymphoproliferative disorders were reported (see Black Box Warnings); malignancies were observed in clinical studies and the postmarketing setting, including, but not limited to, lung cancer, breast cancer, melanoma, prostate cancer, and pancreatic cancer
• GI perforation reported although the role of JAK inhibition in these events is unknown; caution in patients at increased risk for gastrointestinal perforation (eg, diverticulitis)
• Associated with a gradual decrease in lymphocyte and neutrophils counts, and hemoglobin levels that may require treatment interruption
• Associated with increased LFTs
• Associated with increased lipid parameters including total cholesterol, LDL, and HDL
• Viral reactivation, including cases of herpes virus reactivation (eg, herpes zoster), reported; hepatitis B reactivation reported; impact on chronic viral hepatitis reactivation unknown; perform screening for viral hepatitis by clinical guidelines before starting therapy
• Non-melanoma skin cancers (NMSCs) reported; periodic skin examination recommended for patients at increased risk for skin cancer
• Use caution when treating patients with diabetes; higher incidence of infection in diabetic population in general reported
• Diverticulitis reported
• The twice-daily dosing of tofacitinib 10 mg or 11 mg tofacitinib XR is not recommended in patients with rheumatoid arthritis or psoriatic arthritis
• Rheumatoid arthritis patients 50 years of age or older with at least 1 cardiovascular (CV) risk factor treated with tofacitinib 10 mg BID had a higher rate of all-cause mortality
• Thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis, has occurred
• Higher rate of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke) reported with another JAK inhibitor Vs TNF blockers in RA patients

Structural joint damage progression

• Radiographic response data from the ORAL Scan and ORAL Start studies evaluated the efficacy of tofacitinib on structural joint damage progression as measured by the mean change from baseline in van der Heijde modified Total Sharp Score (mTSS) and its components, erosion score, and joint space narrowing (JSN) score

Serious infections

• Serious and sometimes fatal infections reported due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens; the most common serious infections reported have included pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis
• In the UC population, treatment with 10 mg twice daily was associated with a greater risk of serious infections compared with 5 mg twice daily; additionally, opportunistic herpes zoster infections (including meningoencephalitis, ophthalmologic, and disseminated cutaneous) were seen in patients who were treated with 10 mg twice daily
• Use caution in patients with a history of chronic lung disease, or in those who develop interstitial lung disease, as they may be more prone to infections
• The risk of infection may be higher with increasing degrees of lymphopenia; consideration should be given to lymphocyte counts when assessing the individual patient risk of infection
• Avoid use in patients with an active, serious infection, including localized infections
• Consider the risks and benefits of tofacitinib before initiating treatment
  • Patients with chronic or recurrent infection
  • Patients who have been exposed to tuberculosis
  • Patients with a history of a serious or an opportunistic infection
  • Patients who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
  • Patients with underlying conditions that may predispose them to infection

Extended-release tablet

• Patients may notice an inert tablet shell passing in the stool or via colostomy
• Caution when administering the extended-release tablet to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic); rare reports of obstructive symptoms with strictures in association with the ingestion of other drugs utilizing a non-deformable extended-release formulation

Increased risk of serious heart-related problems and cancer

• On September 1st, 2021, FDA is requiring revisions to the Boxed Warning for tofacitinib to include information about the risks of serious heart-related events, cancer, blood clots, and death
• Revisions are based on results from the completed trial show a higher occurrence of serious heart-related events and cancer in a tofacitinib-treated group (both doses) compared to TNF inhibitor-treated group; results also showed an increased risk of blood clots and death with lower doses of tofacitinib
• Consider the benefits and risks for the individual patient before initiating or continuing treatment, especially the following patients:
  • Who are current or past smokers
  • Who have other cardiovascular risk factors
  • Who has developed a malignancy
  • Who has a known malignancy other than a successfully treated non-melanoma skin cancer?
• Reserve JAK inhibitors (e.g., tofacitinib) if patients have an inadequate response or intolerance to greater than 1 TNF blockers
• Counsel patients about the benefits and risks of these medicines and advise them to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot

Drug interactions overview

• Tofacitinib is a CYP3A4 substrate and a minor CYP2C19 substrate
• Strong CYP3A4 inducers may decrease clinical response
• The decreased dose required if coadministered with strong CYP3A4 inhibitors, or moderate CYP3A4 inhibitors plus CYP2C19 inhibitors (see Dosage Modifications)
• Avoid coadministration with live virus vaccines
• Risk of added immunosuppression when tofacitinib is concomitantly used with potent immunosuppressive drugs (eg, azathioprine, tacrolimus, cyclosporine); combined use of multiple-dose tofacitinib with potent immunosuppressants has not been studied in rheumatoid arthritis and psoriatic arthritis

Pregnancy and Lactation

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women during pregnancy; patients can call the toll free number 1-877-311-8972
• There are no adequate and well-controlled studies therapy in pregnant women
• In the tofacitinib, clinical development programs, birth defects, and miscarriages were reported. 
• It is not known whether the drug is excreted in human milk
• There are no data to assess the effects of the drug on the breastfed child; the drug is excreted in rat milk at concentrations higher than in maternal serum
• Women should not breastfeed while treated; a decision should be made whether to discontinue breastfeeding or to discontinue therapy

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for more than 4 weeks after the last dose. 
• Advise females to inform their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment