Pronunciation:

ue-pad-a-SYE-ti-nib

Brand Names:

• Rinvoq

Dosage Forms:

• Tablet, Extended Release

Warnings:

Serious InfectionsPatients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt upadacitinib until the infection is controlled. Reported infections include:Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before upadacitinib use and during therapy. Treatment for latent infection should be considered prior to upadacitinib use.Invasive fungal infections, including cryptococcosis and pneumocystosis.Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogensThe risks and benefits of treatment with upadacitinib should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with upadacitinib, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.MortalityIn a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.MalignanciesLymphoma and other malignancies have been observed in patients treated with upadacitinib. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.Major Adverse Cardiovascular EventsIn RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue upadacitinib in patients that have experienced a myocardial infarction or stroke.ThrombosisThrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Many of these adverse events were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid upadacitinib in patients at risk. Patients with symptoms of thrombosis should discontinue upadacitinib and be promptly evaluated .

Classifications:

Therapeutic—

Antirheumatic

Pharmacologic—

Tyrosine Kinase Inhibitor

Uses of This Medicine:

Upadacitinib is used to treat moderate to severely active rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis (a type of arthritis in the spine) with objective signs of swelling, moderate to severe ulcerative colitis, and moderate to severe Crohn's disease in patients who have taken other medicines (eg, methotrexate) that did not work well. It is also used to treat moderate to severe atopic dermatitis (eczema) in patients who have taken other medicines that did not work well and whose condition is not well controlled with other treatments or in patients who cannot tolerate these treatments.

Upadacitinib is a Janus kinase (JAK) inhibitor that works on the immune system.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of upadacitinib to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, and Crohn's disease in children and to treat atopic dermatitis in children younger than 12 years of age. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of upadacitinib in the elderly. However, elderly patients are more likely to have serious infections and cancer, which may require caution in patients receiving upadacitinib.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abametapir
• Abatacept
• Adenovirus Vaccine
• Apalutamide
• Bacillus of Calmette and Guerin Vaccine, Live
• Baricitinib
• Boceprevir
• Carbamazepine
• Cholera Vaccine, Live
• Clarithromycin
• Cobicistat
• Conivaptan
• Dengue Tetravalent Vaccine, Live
• Ebola Zaire Vaccine, Live
• Enzalutamide
• Fedratinib
• Fosphenytoin
• Idelalisib
• Indinavir
• Influenza Virus Vaccine, Live
• Itraconazole
• Ketoconazole
• Lopinavir
• Lumacaftor
• Mavacamten
• Measles Virus Vaccine, Live
• Mitotane
• Mumps Virus Vaccine, Live
• Nefazodone
• Nelfinavir
• Omaveloxolone
• Phenobarbital
• Phenytoin
• Poliovirus Vaccine, Live
• Posaconazole
• Primidone
• Rifampin
• Ritonavir
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Ruxolitinib
• Saquinavir
• Smallpox Monkeypox Vaccine, Live Non-Replicating
• Smallpox Vaccine
• St John's Wort
• Telaprevir
• Telithromycin
• Typhoid Vaccine, Live
• Varicella Virus Vaccine, Live
• Voriconazole
• Yellow Fever Vaccine
• Zoster Vaccine, Live

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia (blood condition) or
• Cancer or
• Diabetes or
• Hyperlipidemia (high cholesterol in the blood) or
• Infection, history of or
• Lung disease or
• Neutropenia (blood disease) or
• Stomach or bowel problems (eg, diverticulitis, perforation, ulcers), history of—Use with caution. May make these conditions worse.

• Heart or blood vessel disease or
• Hepatitis B, history of or
• Hepatitis C, history of or
• Herpes zoster infection or
• Tuberculosis, active or history of or
• Weakened immune system—May cause side effects to become worse.

• Infection, active or
• Kidney disease, end stage or
• Liver disease, severe—Use is not recommended in patients with these conditions.

• Kidney disease, severe—Use with caution in patients with atopic dermatitis, Crohn's disease, or ulcerative colitis. The effects may be increased because of slower removal of the medicine from the body.

• Smoker, current or past—May increase risk for serious side effects.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more or less of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

Swallow the extended-release tablet whole with water. Do not cut, crush, break, or chew it.

A part of the extended-release tablet may pass into your stools. This is normal and is nothing to worry about.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For atopic dermatitis:
    • Adults and children 12 years of age and older weighing at least 40 kilograms (kg)—At first, 15 milligrams (mg) once a day. Your doctor may adjust your dose as needed.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
  • For Crohn's disease:
    • Adults—At first, 45 milligrams (mg) once a day for 12 weeks, then 15 mg once a day. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • For rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis:
    • Adults—15 milligrams (mg) once a day.
    • Children—Use and dose must be determined by your doctor.
  • For ulcerative colitis:
    • Adults—At first, 45 milligrams (mg) once a day for 8 weeks, then 15 mg once a day. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if this medicine is working properly and to decide whether you should continue to use it. Blood tests are needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using this medicine to make sure you are not pregnant. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 4 weeks after the last dose. If you think you have become pregnant while using this medicine, tell your doctor right away.

Using this medicine together with azathioprine or cyclosporine is not recommended.

You will need to have a skin test for tuberculosis before you start using this medicine. Tell your doctor if you or anyone in your home has ever had a positive reaction to a tuberculosis skin test.

Your body's ability to fight infections may be reduced while you are using upadacitinib. It is very important that you call your doctor at the first sign of an infection. Check with your doctor right away if you have a fever, chills, cough, flu-like symptoms, or unusual tiredness or weakness.

This medicine may increase your risk of serious heart or blood vessel problems (eg, heart attack, stroke), especially in patients with rheumatoid arthritis who are 50 years of age and older and with a heart or blood vessel disease. Call your doctor right away if you have chest pain or discomfort, confusion, difficulty in speaking, double vision, headache, inability to move arms, legs, or facial muscles, nausea, pain or discomfort in the arms, jaw, back, or neck, sweating, trouble breathing, or vomiting.

This medicine may increase your risk of cancer (eg, lymphoma, lung cancer, non-melanoma skin cancer). Tell your doctor right away if you have black, tarry stools, general feeling of illness, swollen glands, weight loss, yellow skin and eyes, persistent non-healing sore, reddish patch or irritated area, shiny bump, pink growth, or white, yellow or waxy scar-like area on the skin.

This medicine may increase your risk of developing blood clots (eg, arterial thrombosis, deep vein thrombosis, pulmonary embolism), especially in patients with rheumatoid arthritis who are 50 years of age and older and with a heart or blood vessel disease. Check with your doctor right away if you have anxiety, chest pain, cough, dizziness, lightheadedness, or fainting, fast heartbeat, pain, redness, or swelling in the arm or leg, pains in the chest, groin, or legs, especially calves of the legs, severe headaches, sudden loss of coordination, sudden onset of slurred speech, sudden vision changes, or trouble breathing.

This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and require immediate medical attention. Check with your doctor right away if you have chest tightness, cough, difficulty swallowing, dizziness, fast heartbeat, hives, itching, skin rash, large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, trouble breathing, or unusual tiredness or weakness.

Upadacitinib can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection:

• If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor right away if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects, such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds.

Before treatment with upadacitinib, while you are being treated with it, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Upadacitinib may lower your body's resistance and there is a chance you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

This medicine may increase the level of cholesterol and fat in your blood. Talk to your doctor if you have concerns.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Body aches or pain

chills

cough

ear congestion

fever

headache

itching, pain, redness, swelling, tenderness, warmth on the skin

loss of voice

runny or stuffy nose

sneezing

sore throat

unusual tiredness or weakness

Less common

Black, tarry stools

burning or stinging of the skin

chest tightness

difficulty swallowing

dizziness

fast heartbeat

hives, itching, skin rash

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

lower back or side pain

painful blisters on the trunk of the body

painful cold sores or blisters on the lips, nose, eyes, or genitals

painful or difficult urination

pale skin

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

ulcers, sores, or white spots in the mouth or tongue

unusual bleeding or bruising

Rare

Coughing or spitting up blood

difficulty with breathing

heartburn

indigestion

muscle aches

nausea

night sweats

pale skin

persistent non-healing sore

pink growth

reddish patch or irritated area

severe stomach pain, cramping, or burning

shiny bump

sudden high fever or low-grade fever for months

trouble breathing

vomiting of material that looks like coffee grounds, severe and continuing

white, yellow or waxy scar-like area

Incidence not known

Chest pain or discomfort

confusion

difficulty in speaking

double vision

inability to move the arms, legs, or facial muscles

inability to speak

no blood pressure or pulse

pain or discomfort in the arms, jaw, back, or neck

slow speech

stopping of heart

sweating

unconsciousness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Blemishes on the skin

pimples

Less common

Burning, itching, and pain in hairy areas, pus at the root of hair

difficulty in moving

muscle cramps, pains, or stiffness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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