Potential Side Effects of Rinvoq (Upadacitinib)
Rinvoq (upadacitinib) carries significant side effects including serious infections, increased risk of major adverse cardiovascular events, malignancies, and blood clots, particularly in patients over 50 years with cardiovascular risk factors.
Major Side Effects
Serious Infections
- Increased risk of bacterial, fungal, and viral infections that can spread throughout the body 1
- Some infections may become severe and lead to hospitalization or death
- Higher risk of herpes zoster (shingles) 2
- Tuberculosis reactivation risk requires screening before initiation 2
Cardiovascular Risks
- Black box warning for increased risk of major adverse cardiovascular events (MACE) 2
- Particularly concerning for patients 50 years and older with at least one cardiovascular risk factor 1
- FDA warning based on safety data from JAK inhibitor class 2
Cancer Risk
- Increased risk of malignancies, including lymphoma and skin cancers 1
- Higher risk in current or past smokers 1
- Requires regular skin examinations 2
Blood Clots
Laboratory Abnormalities
- Leukopenia (low white blood cell count) 2
- Elevated liver enzymes 2
- Elevated creatine phosphokinase (CPK) levels 3, 4
- Lipid elevations (cholesterol, triglycerides) 2
Common Side Effects
Gastrointestinal
- Nausea 2
- Abdominal pain
- Diarrhea
Skin-Related
Infections
Other Common Side Effects
Monitoring Requirements
Before Starting Treatment
- Tuberculosis screening 2
- Hepatitis B and C screening 2
- Complete blood count (CBC) with differential 2
- Comprehensive metabolic panel (CMP) 2
- Lipid profile 2
During Treatment
- CBC with differential: 4-8 weeks after starting and every 3 months thereafter 2
- Liver function tests: 4-8 weeks after starting and periodically thereafter 2
- Lipid levels: 4-8 weeks after starting, then annually 2
- Monitor for signs of infection, particularly herpes zoster 2
- Regular skin examinations for skin cancer 2, 1
Special Precautions
Vaccination
- Live vaccines should be avoided during treatment 2
- Consider shingles vaccination before starting treatment, especially in older patients 2
Pregnancy and Breastfeeding
- Contraindicated in pregnancy due to potential risks 1
- Avoid breastfeeding during treatment
Drug Interactions
- Avoid grapefruit or grapefruit juice during treatment 1
- May interact with other immunosuppressive medications
Long-term Safety Considerations
Recent long-term studies show consistent safety profiles with continued use, with the most common adverse events being upper respiratory infections, herpes zoster, and laboratory abnormalities 5. The safety profile appears similar between the 15mg and 30mg doses, though some dose-dependent effects have been observed 5.
Comparison to Other JAK Inhibitors
Despite being a selective JAK1 inhibitor, upadacitinib appears to have a similar safety profile to less-selective JAK inhibitors 6. The higher doses (30 mg daily) demonstrate greater efficacy but may also have increased risk of adverse events 2.
When considering Rinvoq treatment, the benefits must be carefully weighed against these potential risks, particularly in patients with pre-existing risk factors for cardiovascular disease, infections, or malignancies.