Upadacitinib

Upadacitinib is a prescription medication used to treat the symptoms of Rheumatoid Arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.

• Upadacitinib is available under the following different brand names: Rinvoq

Adult and pediatric dosage

Tablet, Extended-Release

• 15mg

Rheumatoid Arthritis

Adult dosage

• 15 mg orally once a day

Psoriatic Arthritis

Adult dosage

• 15 mg orally once a day

Atopic Dermatitis

Adult and geriatric dosage

Adults below 65 years

• 15 mg orally once a day initially; consider increasing to 30 mg once a day if an adequate response is not achieved
• Discontinue if 30-mg dose if an adequate response is not achieved
• Adults above 65 years: 15 mg orally once a day

Pediatric dosage

• Children above 12 years and weighing more than 40 kg
• 15 mg orally once a day initially; consider increasing to 30 mg once a day if an adequate response is not achieved
• Discontinue if 30-mg dose if an adequate response is not achieved

Ulcerative Colitis

Adult dosage

• Induction: 45 mg orally once a day for 8 weeks

Maintenance

• 15 mg orally once a day
• Refractory, severe, or extensive disease: Consider 30 mg once a day
• Use the lowest effective dosage needed to maintain response
• Discontinue if unable to achieve adequate therapeutic response with 30 mg/day

Ankylosing Spondylitis

Adult dosage

• 15 mg orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Upadacitinib include:

• upper respiratory tract infections,
• nausea,
• cough, and
• fever

Serious side effects of Upadacitinib include:

• unusual tiredness,
• pale skin,
• fast heartbeat,
• nausea,
• vomiting,
• loss of appetite,
• stomach pain,
• yellowing eyes or skin (jaundice),
• dark urine,
• severe stomach pain,
• fever,
• severe dizziness,
• fainting,
• severe nausea or vomiting,
• rash,
• itching,
• swelling of the face, tongue, throat,
• severe dizziness, and
• trouble breathing

Rare side effects of Upadacitinib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

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.

• Upadacitinib has severe interactions with no other drugs.
• Upadacitinib has serious interactions with at least 52 other drugs.
• Upadacitinib has moderate interactions with at least 27 other drugs.
• Upadacitinib 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 product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to upadacitinib or any of its excipients

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Malignancies reported; consider risks and benefits of treatment before initiating in patients with known malignancy, other than previously treated nonmelanoma skin cancer; screen for malignancies during treatment according to guidelines; periodic skin examination recommended for patients who are at increased risk for skin cancer
• Thrombosis reported, including DVT, PE, and arterial thrombosis; avoid therapy in patients that may be at increased risk of thrombosis
• Gastrointestinal perforation reported; unknown if JAK inhibition is implicated in these events; many patients were also receiving NSAIDs
• A higher rate of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke) was reported with another JAK inhibitor Vs TNF blockers in RA patients
• In patients with RA aged above 50 years with at least 1 cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed
• May cause neutropenia, lymphopenia, anemia, elevated lipids, or elevated liver enzymes; monitor for abnormal laboratory values and assess the need to interrupt dosing
• Exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen
• Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported; if a clinically significant hypersensitivity reaction occurs, discontinue therapy and institute appropriate therapy
• Based on findings in animal studies, may cause fetal harm when administered to pregnant females
• Serious and fatal infections
  • Serious and fatal infections reported
  • Most frequent infections reported included pneumonia and cellulitis
  • Opportunistic infections reported included TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis
  • Closely monitor for developing signs and symptoms of infection during and after treatment
  • Interrupt therapy if a serious or opportunistic infection develops
  • Initiate prompt and complete diagnostic testing appropriate for an immunocompromised patient if a new infection develops; initiate appropriate antimicrobial therapy, closely monitor, and interrupt therapy if not responding to antimicrobial therapy; resume once infection controlled
  • Evaluate and test patients for latent and active tuberculosis (TB) infection before treating; patients with latent TB should be treated with standard antimycobacterial therapy before initiating treatment
  • Avoid use with an active, serious infection, including localized infections
  • Consider risks and benefits of treatment before initiating in the following patients
    • With chronic or recurrent infection
    • Who have been exposed to Tuberculosis
    • With a history of serious or opportunistic infection
    • Who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
    • With underlying conditions that may predispose them to infection
  • Viral reactivation
    • Viral reactivation, including cases of herpes virus reactivation (.g, herpes zoster) and hepatitis B virus reactivation, was reported
    • If herpes zoster develops, consider temporarily interrupting therapy until the episode resolves
    • Screen for viral hepatitis and monitor for reactivation by clinical guidelines before starting and during therapy
  • Increased risk of serious heart-related problems and cancer
    • On September 1st, 2021, FDA is requiring revisions to warnings for upadacitinib 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 that show a higher occurrence of serious heart-related events and cancer in the tofacitinib-treated group (both doses) compared to the TNF inhibitor-treated group; results also showed an increased risk of blood clots and death with lower doses of tofacitinib
    • Not studied in trials, so risks have not been adequately evaluated; however, owing to similar mechanisms of action, FDA considers upadacitinib may have similar risks
    • A higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers; consider the benefits and risks for the individual patient before initiating or continuing treatment, especially for 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 more than 1 TNF blocker
    • 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 interaction overview
    • The substrate of CYP3A4 (major) and CYP2D6 (minor)
    • Strong CYP3A4 inhibitors
      • Use caution; maintain upadacitinib dose to 15 mg once a day
      • Coadministration of upadacitinib 30 mg once a day with strong CYP3A4 inhibitors is not recommended
      • Upadacitinib systemic exposure is increased when coadministered with strong CYP3A4 inhibitors
    • Strong CYP3A4 inducers
      • Coadministration not recommended
      • Upadacitinib systemic exposure is decreased when coadministered with strong CYP3A4 inducers
  • Vaccines
    • Use of live, attenuated vaccines during or immediately before initiating upadacitinib is not recommended
    • Before initiating, assess vaccination history, including prophylactic zoster vaccinations
    • Ensure vaccinations are current before initiating upadacitinib

Pregnancy & Lactation

• Limited human data on use in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage
• Verify the pregnancy status of females of reproductive potential before starting treatment
• Report pregnancies to the AbbVie Inc.’s Adverse Event reporting line at 1-888-633-9110, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 4 weeks after the final dose
• Clinical considerations
  • Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or ulcerative colitis
  • Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) in infants, and small for gestational age at birth
• Lactation
  • No data is available on the presence of upadacitinib in human milk, the effects on the breastfed infant, or the effects on milk production
  • Available data in animals have shown upadacitinib excreted in milk
  • If a drug is present in animal milk, it is likely the drug will be present in human milk
  • Because of the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with upadacitinib, and for 6 days (approximately 10 half-lives) after the last dose