Does doxycycline interact with Dilantin (phenytoin)?

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Last updated: June 7, 2025View editorial policy

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From the FDA Drug Label

Drugs whose efficacy is impaired by phenytoin include: ... doxycycline, ... Doxycycline is listed as a drug whose efficacy is impaired by phenytoin.

  • Key Interaction: Phenytoin (Dilantin) may impair the efficacy of doxycycline. This indicates a potential interaction between doxycycline and Dilantin (phenytoin) 1.

From the Research

Doxycycline can interact with Dilantin (phenytoin), and this interaction may decrease the effectiveness of doxycycline by increasing its metabolism and clearance from the body. When taken together, phenytoin, a strong inducer of liver enzymes, can speed up the breakdown of doxycycline, potentially resulting in lower blood levels of the antibiotic 2. This interaction may reduce doxycycline's ability to treat infections effectively.

Some key points to consider:

  • Phenytoin is a strong inducer of liver enzymes, specifically cytochrome P450 enzymes, which can increase the metabolism of doxycycline 2.
  • The mean half-life of doxycycline was significantly shorter in patients taking diphenylhydantoin (phenytoin) compared to control patients, indicating increased clearance of doxycycline 2.
  • If you need to take both medications, your healthcare provider might recommend increasing the doxycycline dose or choosing an alternative antibiotic.
  • Monitoring for decreased effectiveness of doxycycline therapy is important when these medications are used concurrently.
  • Always inform your healthcare provider about all medications you're taking to manage potential interactions appropriately.

It's worth noting that while doxycycline has anti-inflammatory properties and can be used to treat various conditions, its interaction with phenytoin is a significant concern in terms of reducing its effectiveness as an antibiotic 3, 4. Additionally, phenytoin's hepatotoxic potential should be considered when choosing antiepileptic drugs, especially in patients with liver disease 5. However, the primary concern in this context is the potential interaction between doxycycline and phenytoin, and monitoring and adjusting the doxycycline dose or choosing an alternative antibiotic may be necessary to ensure effective treatment.

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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