Upadacitinib is a slow release tablet used to treat certain autoimmune disorders. It was first approved by the FDA in 2019 for rheumatoid arthritis and since then has been approved for types of psoriatic arthritis, eczema and ulcerative colitis.

It is from a class of medicines called Janus kinase inhibitors (JAKi), they block the action of enzymes (Janus kinases) which are involved in inflammation. Blocking the Janus kinases reduces inflammation and helps bring symptoms under control.

What is upadacitinib used for?

Upadacitinib is used to treat:

• adults with moderate to severe rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
• adults with active psoriatic arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
• adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.
• adults with moderate to severe ulcerative colitis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.

Upadacitinib is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.

It is not known if this medicine is safe and effective in children with juvenile idiopathic arthritis or with psoriatic arthritis.

It is not known if this medicine is safe and effective in children under 12 years of age with atopic dermatitis.

It is not known if upadacitinib is safe and effective in children with ulcerative colitis.

Upadacitinib can cause serious side effects, including:

Serious Infections. Upadacitinib is a medicine that affects your immune system. It can lower the ability of your immune system to fight infections. Some people have had serious infections while taking this medicine, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections.

Your healthcare provider should test you for TB before starting treatment with upadacitinib.

Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with upadacitinib.

You should not start taking upadacitinib if you have any kind of infection unless your healthcare provider tells you it is okay. You may be at a higher risk of developing shingles (herpes zoster).

Before starting upadacitinib, tell your healthcare provider if you:

• are being treated for an infection.
• have had an infection that does not go away or that keeps coming back.
• have diabetes, chronic lung disease, HIV, or a weak immune system.
• have TB or have been in close contact with someone with TB.
• have had shingles (herpes zoster).
• have or have had hepatitis B or C.
• live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections. These infections may happen or become more severe if you use upadacitinib. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.
• think you have an infection or have symptoms of an infection such as:
  • fever, sweating, or chills
  • shortness of breath
  • warm, red, or painful skin or sores on your body
  • muscle aches
  • feeling tired
  • blood in your phlegm
  • diarrhea or stomach pain
  • cough
  • weight loss
  • burning when you urinate or urinating more often than usual

After starting upadacitinib, call your healthcare provider right away if you have any symptoms of an infection. upadacitinib can make you more likely to get infections or make worse any infections that you have. If you get a serious infection, your healthcare provider may stop your treatment with upadacitinib until your infection is controlled.

Increased risk of death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking a medicine in the class of medicines called Janus kinase (JAK) inhibitors. upadacitinib is a JAK inhibitor medicine. 

Cancer and immune system problems. 

Upadacitinib may increase your risk of certain cancers by changing the way your immune system works.

Lymphoma and other cancers, including skin cancers can happen in people taking upadacitinib. People taking a medicine in the class of medicines called Janus kinase (JAK) inhibitors have a higher risk of certain cancers including lymphoma and lung cancer, especially if you are a current or past smoker.

Tell your healthcare provider if you have ever had any type of cancer. Follow your healthcare provider’s advice about having your skin checked for skin cancer during treatment with upadacitinib. Limit the amount of time you spend in sunlight. Avoid using tanning beds or sunlamps. Wear protective clothing when you are in the sun and use a sunscreen with a high protection factor (SPF 30 and above). This is especially important if your skin is very fair or if you have a family history of skin cancer. 

Increased risk of major cardiovascular events such as heart attack, stroke or death in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and taking a medicine in the class of medicines called JAK inhibitors, especially if you are a current or past smoker.

Get emergency help right away if you have any symptoms of a heart attack or stroke while taking upadacitinib, including:

• discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
• severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• pain or discomfort in your arms, back, neck, jaw, or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded
• weakness in one part or on one side of your body
• slurred speech

Blood Clots (thrombosis).

Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) and arteries (arterial thrombosis) can happen in some people taking upadacitinib. This may be life-threatening and cause death. Blood clots in the veins of the legs (DVT) and lungs (PE) have happened more often in people who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking a medicine in the class of medicines called Janus kinase (JAK) inhibitors. 

Tell your healthcare provider if you have had blood clots in the veins of your legs or lungs in the past.

Get medical help right away if you have signs and symptoms of blood clots during treatment with upadacitinib, including: 

• swelling
• pain or tenderness in one or both legs
• sudden unexplained chest or upper back pain
• shortness of breath or difficulty breathing

Allergic reactions.

Symptoms such as rash (hives), trouble breathing, feeling faint or dizzy, or swelling of your lips, tongue, or throat, that may mean you are having an allergic reaction have been seen in people taking upadacitinib. Some of these reactions were serious. If any of these symptoms occur during treatment with upadacitinib, stop taking upadacitinib and get emergency medical help right away.

Tears (perforation) in the stomach or intestines. 

Tell your healthcare provider if you have had diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines. Some people taking upadacitinib can get tears in their stomach or intestines. This happens most often in people who take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.

Get medical help right away if you get stomach-area pain, fever, chills, nausea, or vomiting.

Changes in certain laboratory test results.

Your healthcare provider should do blood tests before you start taking upadacitinib and while you take upadacitinib to check for the following:

• low neutrophil and lymphocyte counts. Neutrophils and lymphocytes are types of white blood cells that help the body fight off infections.
• low red blood cell counts. Red blood cells carry oxygen. Low red blood cells means you may have anemia, which may make you feel weak and tired.
• increased cholesterol levels. Your healthcare provider should do blood tests to check your cholesterol levels approximately 12 weeks after you start taking upadacitinib, and as needed.
• elevated liver enzymes. Liver enzymes help to tell if your liver is functioning normally. Elevated liver enzymes may indicate that your healthcare provider needs to do additional tests on your liver.

You should not take upadacitinib if your neutrophil count, lymphocyte count, or red blood cell count is too low or your liver tests are too high. Your healthcare provider may stop your upadacitinib treatment for a period of time if needed because of changes in these blood test results.

See “What are the side effects of upadacitinib?” on the page below for more information about side effects.

Take upadacitinib tablets exactly as your healthcare provider tells you to use it.
Take your upadacitinib tablet one time a day, it can be taken with or without food.
You should swallow your tablet whole, do not split, crush, or chew the tablets.
If you take too much upadacitinib, call your healthcare provider or poison control center at 1-800-222-1222, or go to the nearest hospital emergency room right away.

Your dose of upadacitinib will depend on which condition you are treating, your age, whether you have liver or kidney impairment, and other medications you are currently taking. 
Some conditions have an induction period when you start taking upadacitinib and then you go onto a maintenance dose. Your dose may change or be stopped if you start having side effects, infections or changes in your blood tests.

• See “Important information” above on this page.

 Tell your healthcare provider about all of your medical conditions, including if you

• have an infection.
• are a current or past smoker.
• have had a heart attack, other heart problems, or stroke.
• have liver problems.
• have kidney problems.
• have unexplained stomach (abdominal) pain, have a history of diverticulitis or ulcers in your stomach or intestines, or are taking NSAIDs.
• have low red or white blood cell counts.
• have recently received or are scheduled to receive an immunization (vaccine). People who take upadacitinib should not receive live vaccines.
• are pregnant or plan to become pregnant. Based on animal studies, upadacitinib may harm your unborn baby. You should  avoid becoming pregnant during treatment with upadacitinib  and for 4 weeks after your last dose of upadacitinib. See pregnancy section below for more information on upadacitinib and pregnancy.
• are breastfeeding or plan to breastfeed. Upadacitinib may pass into your breast milk. Do not breastfeed during treatment with upadacitinib and for 6 days after your last dose. See breastfeeding section below for more information on upadacitinib and breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Upadacitinib and other medicines may affect each other causing side effects.

Who should not use upadacitinib?

Do not take this medicine if you are allergic to upadacitinib or any of the inactive tablet  ingredients.. See the end of this page for a complete list of ingredients in upadacitinib.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it either in the refrigerator or at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

Avoid drinking grapefruit juice or eating grapefruit while taking upadacitinib.

Avoid receiving a "live" vaccine during or immediately before treatment with upadacitinib. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles). Before starting upadacitinib treatment it is recommended that you should be up to date with all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.

Upadacitinib may cause serious side effects, including:

• See “Important information” above on this page for serious side effect information.

The most common side effects for rheumatoid arthritis patients being treated with upadacitinib include:

• upper respiratory tract infections (common cold, sinus infections)
• shingles (herpes zoster)
• herpes simplex virus infections, including cold sores
• Bronchitis
• nausea
• cough
• fever
• acne

The most common side effects for atopic dermatitis patients include:

• upper respiratory tract infections (common cold, sinus infections)
• acne
• herpes simplex virus infections, including cold sores
• headache
• increased blood levels of creatine phosphokinase
• cough
• allergic reactions
• inflammation of hair follicles
• nausea
• stomach-area (abdominal) pain
• fever
• increased weight
• shingles (herpes zoster)
• flu
• tiredness
• low white blood cell count (neutropenia)
• muscle pain
• flu-like illness

The most common side effects for ulcerative colitis patients include:

• upper respiratory tract infections (common cold, sinus infections)
• Acne
• herpes simplex virus infections, including cold sores
• inflammation of the hair follicles
• rash
• flu
• shingles (herpes zoster)
• increased blood cholesterol levels
• increased blood levels of creatine phosphokinase
• increased liver enzyme levels
• low number of certain types of white blood cells (neutropenia, lymphopenia)

Separation or tear to the lining of the back part of the eye (retinal detachment) has happened in people with atopic dermatitis treated with upadacitinib. Call your healthcare provider right away if you have any sudden changes in your vision during treatment with upadacitinib.

These are not all the possible side effects of upadacitinib.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Upadacitinib and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

• medicines for fungal infections (such as ketoconazole, itraconazole, posaconazole or voriconazole) or clarithromycin (for bacterial infections) as these medicines may increase the amount of upadacitinib in your blood.
• rifampicin (for bacterial infections) or phenytoin (for neurological disorders) as these medicines may decrease the effect of upadacitinib.
• medicines that affect your immune system (such as azathioprine and cyclosporine) as these medicines may increase your risk of infection.

Ask your healthcare provider or pharmacist, if you are not sure if you are taking any of these medicines.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.