Rinvoq XR Side Effects: What to Expect and When to Call Your Doctor

Before starting any medication, it's important to understand the full picture of what you might experience. Rinvoq XR (upadacitinib) is an effective JAK inhibitor, but it carries real risks — including an FDA Boxed Warning, the agency's most serious level of caution. Here's a clear breakdown of what to expect, what's manageable at home, and what requires an urgent call to your doctor.

The FDA Boxed Warning: What It Means for You

Rinvoq XR carries a Boxed Warning — the FDA's strongest safety signal — covering five serious risks. This doesn't mean you'll definitely experience these, but they're serious enough that your doctor needs to evaluate your individual risk before prescribing:

Serious infections: Rinvoq XR lowers your immune defenses. Serious infections — including tuberculosis (TB), bacterial infections, and fungal infections — have occurred. Some have been fatal. You'll be tested for TB before starting.

Increased mortality: Patients 50 years and older with at least one cardiovascular risk factor have shown increased risk of death in studies of similar drugs. Your doctor will evaluate whether the benefit outweighs this risk for you.

Malignancies: Including lymphoma and other cancers. Risk is higher in current or past smokers and in patients over 50 with cardiovascular risk factors.

Major adverse cardiovascular events (MACE): Heart attack, stroke, and cardiovascular death. Risk is elevated in patients with existing heart disease risk factors.

Thrombosis: Deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial clots. Stop taking Rinvoq XR and call your doctor immediately if you develop sudden shortness of breath, chest pain, leg swelling, or leg pain.

Common Side Effects (Reported in ≥1% of Patients)

These are the side effects most frequently reported across clinical trials. Most are manageable and often improve over time:

Upper respiratory infections (most common) — colds, sinus infections, sore throat. These are usually mild and self-resolving.

Herpes zoster (shingles) — more common than in the general population. Getting vaccinated against shingles before starting Rinvoq XR is strongly recommended.

Acne — a common and typically mild side effect, especially in the first few months. Your dermatologist can help manage this if it's bothersome.

Nausea — often mild and improves over time. Taking the medication with food may help.

Cough — commonly reported but typically mild.

Headache — particularly in atopic dermatitis patients.

Elevated CPK (creatine phosphokinase) — detected on blood tests; usually not clinically significant.

Elevated liver enzymes — monitored with periodic blood tests; your doctor will watch for this.

Neutropenia — low white blood cell count detected on labs; may require dose adjustment or temporary stopping.

Lab Abnormalities to Monitor

Your doctor will order regular blood tests while you're on Rinvoq XR. Key things they're monitoring include:

CBC with differential — monitoring for neutropenia, lymphopenia, or anemia

Liver function tests (LFTs) — monitoring for elevated liver enzymes

Lipid panel — JAK inhibitors can increase LDL and total cholesterol

CPK — monitoring for muscle enzyme elevation

When to Call Your Doctor Immediately

Stop taking Rinvoq XR and call your doctor or go to the ER immediately if you experience:

Sudden shortness of breath or chest pain (possible PE or heart attack)

Leg swelling, pain, or warmth (possible DVT)

High fever, chills, or feeling very sick (possible serious infection)

Severe or worsening abdominal pain (possible GI perforation)

Signs of a stroke: sudden facial drooping, arm weakness, or speech difficulty

Severe skin reaction or anaphylaxis: hives, swelling of face/throat, difficulty breathing

Painful, blistering rash — possible shingles (herpes zoster)

Medication Residue in Stool

Some patients — particularly those with faster GI transit times, ostomies, or inflammatory bowel disease — may notice the tablet shell in their stool. This does NOT mean the medication hasn't worked. The active drug is absorbed before the shell passes through. However, if you have shortened GI transit times and your condition isn't improving, inform your doctor so they can evaluate whether absorption is adequate.

Also read: Rinvoq XR Drug Interactions: What to Avoid and What to Tell Your Doctor