What are the contraindications for starting a patient on Rinvoq (upadacitinib)?

Contraindications for Starting Rinvoq (Upadacitinib)

Rinvoq is contraindicated only in patients with known hypersensitivity to upadacitinib or any excipients, but several absolute warnings require careful evaluation before initiation. 1

Absolute Contraindication

• Known hypersensitivity to upadacitinib or any excipients is the only FDA-labeled absolute contraindication 1

Critical Warnings That Function as Practical Contraindications

Active or Severe Infections

• Do not initiate Rinvoq in patients with active, serious infections, including localized infections 1
• Active tuberculosis must be excluded and latent TB treated before starting therapy 2
• Active sepsis or opportunistic infections (including Clostridium difficile) are contraindications 2
• Hepatitis B surface antigen-positive patients (active chronic HBV) should avoid JAK inhibitors if possible; if unavoidable, require concomitant antiviral prophylaxis with entecavir, tenofovir, or tenofovir alafenamide alongside hepatologist consultation 2

Pregnancy and Lactation

• Pregnancy is an absolute contraindication due to animal teratogenicity data and potential fetal harm 2, 1
• Women of childbearing potential must use effective contraception during treatment 1
• Breastfeeding is contraindicated—advise patients not to breastfeed while taking Rinvoq 1

Severe Organ Dysfunction

• Decompensated advanced chronic liver disease (Child-Pugh score ≥9 or history of hepatic decompensation including ascites, hepatic encephalopathy grade ≥2, or variceal bleeding) is a contraindication 2
• Severe renal impairment with creatinine clearance <15 mL/min is a contraindication 2
• For creatinine clearance 15-30 mL/min, dose reduction to 15 mg once daily is required 1

Current or Recent Malignancy

• Current malignancy (except adequately treated non-melanoma skin cancer or cervical carcinoma in situ) should be considered a contraindication 2
• History of malignancy within the past 5 years requires careful risk-benefit assessment, particularly given ORAL Surveillance data showing increased malignancy risk with JAK inhibitors 2

Hematologic Thresholds

• Avoid initiation if absolute lymphocyte count <500 cells/mm³, absolute neutrophil count <1000 cells/mm³, or hemoglobin <8 g/dL 1
• These parameters must be checked at baseline before starting therapy 2

History of Thromboembolic Events

• History of arterial or venous thromboembolic events requires careful risk-benefit evaluation and may function as a practical contraindication 2
• Unprovoked or recurrent VTE events are particularly concerning given dose-dependent increased thromboembolism risk with JAK inhibitors 2

High Cardiovascular Risk Populations

• Patients aged ≥65 years should only receive Rinvoq when no suitable alternatives are available due to increased risk of major cardiovascular events, serious infections, and malignancy 2
• Patients aged ≥50 years with cardiovascular risk factors should not receive JAK inhibitors as first-line therapy when TNF inhibitors remain an option 3
• Current or long-term past smokers are at increased risk and should be considered for alternative treatments 2

Vaccination Status

• Live vaccines are contraindicated during Rinvoq therapy 2, 1
• Patients should be up-to-date with vaccinations, including recombinant zoster vaccine (Shingrix), before initiating treatment 2

Combination Therapy Restrictions

• Rinvoq is not recommended in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants (azathioprine, cyclosporine, tacrolimus) due to increased immunosuppression risk and potential for infection or lymphoma 2, 1

Required Pre-Treatment Screening

Before initiating Rinvoq, the following must be completed:

• Infection screening: TB testing (interferon-gamma release assay or tuberculin skin test), hepatitis B (anti-HBs, anti-HBc, HBsAg), hepatitis C, and chest X-ray unless recently performed 2
• Laboratory testing: Complete blood count with differential, comprehensive metabolic panel (liver enzymes, renal function), lipid panel 2
• Pregnancy testing in women of reproductive potential 2
• Cardiovascular risk assessment: History of VTE, MACE, smoking status, and cardiovascular risk factors 2, 3
• Skin examination for non-melanoma skin cancer in at-risk patients 2

Common Pitfalls to Avoid

• Do not assume that absence of symptoms excludes latent TB—formal testing is mandatory 2
• Do not overlook occult HBV infection in anti-HBc positive patients; obtain baseline HBV DNA to rule out active infection 2
• Do not initiate therapy in patients over 65 years without exhausting alternative treatment options first 2
• Do not combine Rinvoq with biologic DMARDs or other JAK inhibitors, even if the underlying disease is refractory 1