What is the interaction between Zepbound and Nexplanon (etonogestrel)

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Interaction Between Zepbound and Nexplanon

There is no documented clinically significant interaction between Zepbound (tirzepatide) and Nexplanon (etonogestrel implant), and patients can safely use both medications concurrently.

Understanding the Medications

Zepbound (tirzepatide)

  • A GLP-1/GIP receptor agonist used for weight management
  • Metabolized through proteolytic breakdown of the peptide backbone
  • Not metabolized through the cytochrome P450 system

Nexplanon (etonogestrel)

  • A single-rod subdermal contraceptive implant
  • Provides continuous release of etonogestrel for up to 3 years
  • Contraceptive efficacy relies on maintaining adequate serum etonogestrel levels (approximately 200 pg/ml at steady state) 1

Potential for Drug Interactions

Metabolism Pathways

  • Nexplanon (etonogestrel) is metabolized through the cytochrome P450 3A4 pathway
  • Medications that induce CYP3A4 enzymes can reduce etonogestrel levels and potentially decrease contraceptive efficacy 2
  • Zepbound (tirzepatide) is not known to affect the CYP450 enzyme system

Known Interactions with Hormonal Contraceptives

  • According to contraceptive guidelines, medications that significantly interact with hormonal contraceptives include:
    • Certain anticonvulsants (carbamazepine, phenytoin, etc.)
    • Rifampicin/rifabutin
    • Some antiretroviral medications 2
  • Zepbound is not listed among medications known to interact with hormonal contraceptives

Clinical Implications

Contraceptive Efficacy

  • Nexplanon is highly effective with a typical failure rate of <1% (0.05%) 3
  • No evidence suggests that Zepbound reduces this efficacy
  • Nexplanon works primarily by inhibiting ovulation through preventing the mid-cycle LH surge 1

Side Effects

  • Common side effects of Nexplanon include:
    • Changes in menstrual bleeding patterns (most common)
    • Emotional lability (6.1%)
    • Weight increase (3.3%)
    • Depression (2.4%)
    • Acne (1.5%) 4
  • These side effects are not expected to be exacerbated by concurrent Zepbound use

Special Considerations

Monitoring Recommendations

  • Monitor for changes in menstrual bleeding patterns, which are common with Nexplanon regardless of Zepbound use
  • The most common bleeding pattern with Nexplanon is infrequent bleeding (less than three episodes in a reference period) 4
  • No additional monitoring is required specifically for the combination of these medications

Weight Management

  • Nexplanon has been associated with weight gain in some users (3.3% discontinued due to weight increase) 4
  • Zepbound is indicated for weight management and may help counteract this potential side effect

Conclusion

Based on available evidence, there is no known interaction between Zepbound and Nexplanon that would affect the safety or efficacy of either medication. Patients can use both medications concurrently without requiring dose adjustments or additional monitoring beyond what is standard for each medication individually.

References

Research

The pharmacokinetics and pharmacodynamics of Implanon, a single-rod etonogestrel contraceptive implant.

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2000

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Menometrorrhagia Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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.

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