Is it okay to stop Plaquenil (hydroxychloroquine) and Methotrexate to take Bactrim (trimethoprim/sulfamethoxazole) for uncomplicated pyelonephritis?

Management of Plaquenil and Methotrexate During Bactrim Treatment for Uncomplicated Pyelonephritis

Direct Recommendation

You must stop methotrexate during Bactrim treatment for pyelonephritis, but you can continue Plaquenil (hydroxychloroquine) without interruption. 1

Methotrexate: Mandatory Discontinuation

The British Association of Dermatologists explicitly states that methotrexate should be stopped until the patient recovers and the antibiotic course is complete when antibiotics are given for a severe infection. 1

Why Methotrexate Must Be Stopped:

• Co-trimoxazole (Bactrim) with methotrexate causes bone marrow suppression and immunosuppression through multiple mechanisms: 1

  • Sulfonamides displace methotrexate from protein binding sites, increasing free methotrexate concentrations 2
  • Both trimethoprim and methotrexate are antifolate drugs, creating additive folic acid deficiency 1
  • Sulfonamides compete with renal transport of methotrexate, further increasing toxicity 2

• The FDA drug label for Bactrim explicitly states to avoid concurrent use with methotrexate, listing it as a contraindication. 2

• Even low-dose prophylactic Bactrim (used for PJP prevention) requires monitoring when combined with methotrexate, and treatment-dose Bactrim for pyelonephritis poses substantially higher risk. 1, 3

Clinical Algorithm for Methotrexate:

1. Stop methotrexate immediately when starting Bactrim 1
2. Complete the full Bactrim course (7-14 days for pyelonephritis) 4, 5, 6
3. Wait until clinical recovery from pyelonephritis is confirmed 1
4. Resume methotrexate only after antibiotic course completion and symptom resolution 1

Plaquenil (Hydroxychloroquine): Safe to Continue

Hydroxychloroquine has no significant drug interaction with trimethoprim-sulfamethoxazole and does not require discontinuation. There is no evidence in the guidelines or drug labels indicating any interaction between these medications. 1, 2

Treatment Duration for Pyelonephritis

For uncomplicated pyelonephritis in women, a 7-day course of Bactrim may be as effective as longer regimens: 6

• A 2017 study demonstrated that 7 days of TMP-SMX resulted in similar clinical outcomes compared with 7 days of ciprofloxacin (adjusted OR 2.30; 95% CI 0.72-7.42 for recurrent UTI) 6
• Historical data supported 2-week regimens, but more recent evidence suggests shorter courses are sufficient 4, 5
• The 14-day recommendation in older guidelines may be unnecessarily long based on contemporary evidence 5, 6

Critical Monitoring During Treatment

If you must use Bactrim in a patient recently on methotrexate (stopped appropriately), monitor for: 7, 2

• Complete blood counts every 3-5 days during the first week to detect bone marrow suppression 7
• Serum electrolytes every 3-5 days for hyperkalemia and hyponatremia, especially in elderly patients 7, 2
• Renal function if baseline renal impairment exists 1, 7
• Any rash development requires immediate discontinuation due to risk of Stevens-Johnson syndrome 7

Common Pitfalls to Avoid

• Never assume prophylactic-dose Bactrim safety data applies to treatment doses - the risk of methotrexate interaction is dose-dependent and substantially higher with treatment dosing 1, 3
• Do not restart methotrexate immediately after completing Bactrim - wait for clinical recovery confirmation 1
• Elderly patients with any degree of renal impairment face compounded risk from both the drug interaction and Bactrim's inherent nephrotoxicity 1, 7
• Patients on ACE inhibitors or ARBs have dramatically increased hyperkalemia risk (adjusted OR 6.7) when taking Bactrim, requiring even more vigilant electrolyte monitoring 7