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

Rinvoq XR (upadacitinib) is a powerful immunomodulator that can interact with many other medications. Some of these interactions are contraindicated — meaning they should never be combined — while others require close monitoring. Here's what you need to know before starting Rinvoq XR.

Contraindicated Combinations: Never Take These With Rinvoq XR

Other JAK Inhibitors

Combining Rinvoq XR with another JAK inhibitor is contraindicated due to the risk of additive immunosuppression and serious infections. Never combine Rinvoq XR with:

Tofacitinib (Xeljanz, Xeljanz XR)

Baricitinib (Olumiant)

Abrocitinib (Cibinqo)

Ruxolitinib (Jakafi, Opzelura)

Biologic DMARDs (Disease-Modifying Antirheumatic Drugs)

Rinvoq XR should not be combined with biologic DMARDs due to the risk of additive immunosuppression. This includes:

TNF inhibitors: adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade), certolizumab (Cimzia), golimumab (Simponi)

IL-6 inhibitors: tocilizumab (Actemra), sarilumab (Kevzara)

B-cell depleting agents: rituximab (Rituxan)

T-cell costimulation modulators: abatacept (Orencia)

IL-4/13 inhibitors: dupilumab (Dupixent)

Medications Not Recommended With Rinvoq XR

Potent Immunosuppressants

Combining Rinvoq XR with potent immunosuppressants is not recommended due to excessive immune suppression risk:

Azathioprine (Imuran) — commonly used in IBD and autoimmune diseases

Cyclosporine — used in transplant patients and some autoimmune conditions

Strong CYP3A4 Inducers

Rinvoq XR is metabolized primarily by CYP3A4 enzymes in the liver. Strong CYP3A4 inducers speed up the breakdown of upadacitinib, significantly reducing its blood levels and potentially making it ineffective:

Rifampin (Rifadin) — antibiotic for TB — coadministration is NOT recommended

Carbamazepine (Tegretol) — seizure and mood disorder medication

Phenytoin (Dilantin) — anti-seizure medication

Medications That Require Caution (Monitor Closely)

Strong CYP3A4 Inhibitors

Strong CYP3A4 inhibitors slow the breakdown of upadacitinib, increasing its blood levels and potentially intensifying side effects. Use caution if combining with:

Ketoconazole, voriconazole, itraconazole — antifungal medications

Clarithromycin — antibiotic

HIV protease inhibitors — ritonavir, tipranavir, lopinavir/ritonavir

Live Vaccines

Because Rinvoq XR suppresses the immune system, live vaccines should not be given while you are taking it. This includes the live shingles vaccine (Zostavax — now largely replaced by the non-live Shingrix) and the live flu nasal spray (FluMist). Non-live (inactivated) vaccines are acceptable and encouraged. Get all recommended vaccines, especially the recombinant Shingrix (shingles) vaccine, before starting Rinvoq XR.

Medications That Are Generally Safe With Rinvoq XR

Rinvoq XR can be combined with:

Methotrexate (MTX) — conventional DMARD; widely used in combination with Rinvoq XR for RA

Hydroxychloroquine (Plaquenil) — conventional DMARD

Sulfasalazine — conventional DMARD for RA and IBD

NSAIDs (ibuprofen, naproxen, etc.) — with awareness that NSAIDs may increase GI perforation risk when combined with immunosuppressants

Corticosteroids (prednisone) — often used as bridge therapy; use lowest effective dose

What to Tell Every Healthcare Provider

Always inform any healthcare provider — including dentists, urgent care providers, and pharmacists — that you are taking Rinvoq XR. In particular, let them know before:

Any surgery or procedure (increased infection risk)

Starting any new prescription or over-the-counter medication

Receiving any vaccine

Starting an antibiotic (especially rifampin or antifungals)

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