Can vancomycin or cefepime cause testicular pain?

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Last updated: September 30, 2026 • View editorial policy

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Can Vancomycin or Cefepime Cause Testicular Pain?

Neither vancomycin nor cefepime lists testicular pain as a recognized adverse effect in their FDA-approved labeling, though vancomycin has demonstrated testicular toxicity in animal studies.

Evidence from FDA Drug Labels

Cefepime

The FDA label for cefepime 11 does not include testicular pain, scrotal pain, or any genitourinary pain syndromes in its comprehensive adverse reaction profile. The documented adverse reactions include:

  • Local reactions (phlebitis, pain at infusion site)
  • Rash, pruritus, urticaria
  • Gastrointestinal effects (diarrhea, nausea, colitis)
  • Neurological effects (encephalopathy, seizures, confusion)
  • Hematologic changes

No testicular or scrotal symptoms are reported in clinical trials or postmarketing surveillance.

Vancomycin

Similarly, the FDA label for vancomycin 2 does not list testicular pain among its adverse reactions. Documented effects include:

  • Nephrotoxicity
  • Ototoxicity
  • Infusion-related reactions (hypotension, flushing, erythema, pruritus)
  • Neutropenia
  • Thrombophlebitis
  • Chemical peritonitis (with intraperitoneal administration)

Again, no testicular or scrotal pain is documented in human clinical use.

Animal Research Evidence

However, preclinical research reveals a different picture for vancomycin. A 2023 rat study 3 demonstrated that vancomycin (200 mg/kg for 7 days) caused:

  • Significant reduction in testosterone levels
  • Decreased sperm counts and motility
  • Histological damage to testicular tissue
  • Reduced thickness of the basal lamina

This testicular toxicity was reversible with resveratrol administration, suggesting oxidative stress mechanisms may be involved.

Clinical Context

The guidelines on chronic scrotal content pain 4 and acute scrotal pain 5 focus on infectious causes (epididymitis, orchitis) and mechanical causes (torsion), but do not identify antibiotics as causative agents for testicular pain. When antibiotics are mentioned, they are the treatment for infectious causes, not the etiology.

If a patient develops testicular pain while on vancomycin or cefepime, consider:

  • Epididymitis/orchitis - The most common cause of acute scrotal pain in adults, which may develop despite antibiotic therapy if the organism is resistant or the antibiotic spectrum is inadequate
  • Inadequate treatment of an underlying infection
  • Coincidental timing rather than drug causation
  • Other concurrent conditions (testicular torsion, trauma, referred pain from other sources)

Clinical Recommendation

Do not attribute testicular pain to vancomycin or cefepime as a direct drug effect based on current human evidence. Instead, evaluate for:

  1. Infectious causes requiring ultrasound with Doppler to assess blood flow and rule out epididymitis/orchitis 5
  2. Testicular torsion (surgical emergency) - particularly if pain is acute onset
  3. Treatment failure if antibiotics were given for a genitourinary infection
  4. Alternative diagnoses unrelated to antibiotic therapy

The animal data on vancomycin 3 suggests theoretical concern but has not translated to documented human toxicity in decades of clinical use. The absence of testicular pain in FDA labeling and clinical trials involving thousands of patients 112 strongly argues against a causal relationship in humans.

References

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.