Can the use of Bactrim (Trimethoprim/Sulfamethoxazole) with methotrexate cause vaginitis?

Bactrim DS and Methotrexate: Risk of Vaginitis

The combination of Bactrim DS (trimethoprim-sulfamethoxazole) with methotrexate does not directly cause vaginitis, but this drug combination creates a serious and potentially life-threatening interaction that can lead to severe mucocutaneous toxicity, bone marrow suppression, and immunosuppression—which may secondarily increase susceptibility to vaginal infections. 1, 2

The Critical Drug Interaction

Co-trimoxazole and methotrexate should be avoided together due to severe toxicity risk. 3

Mechanism of Toxicity

• Both drugs are folic acid antagonists, creating additive antifolate effects that can result in severe bone marrow suppression, mucocutaneous ulceration, and renal insufficiency 1, 2
• Trimethoprim reduces renal elimination of methotrexate within hours of administration, leading to elevated and toxic methotrexate levels 1
• This interaction can cause pancytopenia even after a single dose and can occur at any time during treatment 1

Clinical Manifestations of the Interaction

The toxic effects of this combination include:

• Mucocutaneous toxicity: ulcerative stomatitis, mouth ulcers, and skin lesions 1, 2
• Bone marrow suppression: leukopenia, thrombocytopenia, anemia 3, 1, 2
• Gastrointestinal effects: nausea, vomiting, diarrhea, GI ulceration 1
• Renal insufficiency 2
• Immunosuppression increasing susceptibility to infections 1

Indirect Link to Vaginitis

While vaginitis is not a direct side effect of this drug combination, the severe immunosuppression caused by methotrexate toxicity can increase susceptibility to vaginal infections:

• Methotrexate-induced immunosuppression increases risk of infections generally 1
• Immunocompromised states can predispose to candidal vulvovaginitis and bacterial vaginosis 3
• Approximately 75% of women experience at least one episode of vulvovaginal candidiasis in their lifetime, with immunosuppression being a risk factor 3

Clinical Management Recommendations

Absolute Avoidance

Co-trimoxazole, trimethoprim, and other antifolate drugs must be avoided in patients taking methotrexate. 3

If Antibiotics Are Needed

• For urinary tract infections or other bacterial infections requiring treatment, select antibiotics that do not interfere with methotrexate metabolism or renal elimination 1
• If antibiotics are given for severe infection, methotrexate should be stopped until the patient recovers and the antibiotic course is complete 3

If Toxicity Occurs

• Obtain urgent complete blood count with differential to assess for neutropenia and pancytopenia 1
• Consider leucovorin (folinic acid) rescue for severe toxicity 1
• Maintain hydration and consider urine alkalinization 1
• Filgrastim may be used for toxic bone marrow suppression 1

Risk Factors for Severe Toxicity

Patients at highest risk for severe toxicity from this combination include those with:

• Renal insufficiency (major modifiable risk factor) 1
• Advanced age 1
• Hypoalbuminemia 1
• Folic acid deficiency 1
• Concurrent use of NSAIDs 3, 1