What are the potential interactions between Rinvoq (upadacitinib) and antibiotics like ciprofloxacin or Septra (sulfamethoxazole/trimethoprim)?

Rinvoq and Antibiotic Interactions: Ciprofloxacin and Septra

Rinvoq (upadacitinib) can be safely used with both ciprofloxacin and Septra (trimethoprim-sulfamethoxazole), but ciprofloxacin requires dose adjustment of Rinvoq due to a significant drug-drug interaction through CYP3A4 inhibition, while Septra has no major pharmacokinetic interaction and can be used without dose modification.

Ciprofloxacin Interaction with Rinvoq

Mechanism and Clinical Impact

• Ciprofloxacin is a moderate CYP3A4 inhibitor that significantly increases plasma concentrations of upadacitinib (Rinvoq), requiring mandatory dose adjustment 1
• The interaction occurs because upadacitinib is metabolized primarily through the CYP3A4 pathway, and ciprofloxacin blocks this enzyme, leading to drug accumulation 1

Required Dose Modifications

• When ciprofloxacin must be used with Rinvoq, reduce the Rinvoq dose according to product labeling recommendations for moderate CYP3A4 inhibitors 1
• This dose adjustment is not optional—failure to reduce the dose increases risk of adverse effects including serious infections, cardiovascular events, and malignancies that are already part of Rinvoq's boxed warnings 2

Clinical Decision-Making

• Consider alternative antibiotics that do not inhibit CYP3A4 when treating infections in patients on Rinvoq 1
• If ciprofloxacin is the only appropriate antibiotic based on culture sensitivities or clinical scenario, proceed with dose-adjusted Rinvoq rather than switching the JAK inhibitor 1

Septra (Trimethoprim-Sulfamethoxazole) Interaction with Rinvoq

Safety Profile

• Septra does not have a clinically significant pharmacokinetic interaction with Rinvoq and can be used at standard doses without modification of either medication 1
• Unlike ciprofloxacin, trimethoprim-sulfamethoxazole is not a CYP3A4 inhibitor and does not affect upadacitinib metabolism 3

Monitoring Considerations

• Monitor complete blood counts when using Septra with Rinvoq, as both medications can independently cause bone marrow suppression 4
• Check baseline and periodic liver function tests, as both agents have potential hepatotoxicity 4
• In elderly patients or those with renal impairment, increase monitoring frequency for hematologic effects 4

Special Populations Requiring Caution

• Patients over 65 years require more frequent monitoring when combining these medications due to increased risk of adverse effects 4
• Dose adjustment of Septra (not Rinvoq) is necessary in patients with creatinine clearance <30 mL/min 4
• Patients taking ACE inhibitors or ARBs concurrently need electrolyte monitoring for hyperkalemia risk from Septra 4, 5

Practical Clinical Algorithm

When Antibiotic Therapy is Needed in Rinvoq Patients:

1. First choice: Use Septra at standard doses if clinically appropriate for the infection 1

   • No Rinvoq dose adjustment needed
   • Implement CBC monitoring every 1-2 weeks during antibiotic course 4

2. If ciprofloxacin is required:

   • Reduce Rinvoq dose per manufacturer guidelines for moderate CYP3A4 inhibitors 1
   • Resume full Rinvoq dose 3-5 days after completing ciprofloxacin course 1
   • Monitor for signs of infection control and JAK inhibitor toxicity 1

3. Consider alternative fluoroquinolones:

   • Levofloxacin and moxifloxacin have weaker CYP3A4 inhibition than ciprofloxacin 1
   • May be preferable when fluoroquinolone coverage is needed 1

Common Pitfalls to Avoid

• Do not continue full-dose Rinvoq when prescribing ciprofloxacin—this significantly increases risk of serious adverse events 1
• Do not assume all fluoroquinolones have the same interaction profile; ciprofloxacin has the strongest CYP3A4 inhibition 1
• Do not forget to resume full Rinvoq dosing after completing the ciprofloxacin course 1
• Avoid using Septra solely for prophylaxis in immunocompromised patients on Rinvoq unless there is documented history of recurrent infections, as routine antibiotic prophylaxis is not recommended and promotes resistance 1

Monitoring Protocol During Concurrent Use

For Septra + Rinvoq:

• Baseline CBC, comprehensive metabolic panel, and liver function tests 4
• Repeat CBC at 1-2 week intervals during antibiotic therapy 4
• Monitor for rash, unusual bleeding/bruising, or jaundice 4

For Ciprofloxacin + Rinvoq:

• Confirm Rinvoq dose reduction before starting ciprofloxacin 1
• Monitor for signs of JAK inhibitor toxicity (infections, cytopenias) 2
• Assess infection response at 48-72 hours 1
• Document plan to resume full Rinvoq dose after antibiotic completion 1