Does Doxycycline Interact with Glipizide?
No clinically significant drug-drug interaction exists between doxycycline and glipizide that would require dose adjustment or avoidance of concurrent use.
Mechanism and Evidence Base
The available evidence does not demonstrate a direct pharmacokinetic or pharmacodynamic interaction between doxycycline and glipizide:
- Glipizide is metabolized primarily by CYP2C9, not by pathways affected by doxycycline 1, 2
- Doxycycline does not inhibit or induce CYP2C9, the primary enzyme responsible for glipizide metabolism 2
- No guidelines or drug interaction databases identify this as a clinically relevant combination 1
Important Distinction: Fluoroquinolones vs. Tetracyclines
A critical pitfall is confusing doxycycline (a tetracycline) with fluoroquinolones, which DO interact with sulfonylureas:
- Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) significantly increase hypoglycemia risk when combined with sulfonylureas like glipizide 3, 2, 4
- Trimethoprim-sulfamethoxazole also increases glipizide exposure and hypoglycemia risk through CYP2C9 inhibition 3, 2
- Doxycycline is NOT a fluoroquinolone and does not share this interaction profile 1
Safe Concurrent Administration
When prescribing doxycycline and glipizide together:
- No dose adjustment of glipizide is required when starting doxycycline 1
- Standard monitoring of blood glucose is appropriate, as with any patient on sulfonylurea therapy 1
- Counsel patients on proper doxycycline administration: take with a full glass of water and food (non-dairy), remain upright for 1 hour, and avoid dairy products for 2 hours before and after the dose 5
Clinical Monitoring Recommendations
While no interaction exists, maintain standard diabetes management practices:
- Monitor for hypoglycemia symptoms as baseline risk with any sulfonylurea, particularly in elderly patients or those with renal impairment 1, 3
- Glipizide carries lower hypoglycemia risk compared to glyburide and is preferred in older adults and those with kidney disease 1, 3
- If hypoglycemia occurs, evaluate other contributing factors (reduced food intake during illness, other interacting medications, worsening renal function) rather than attributing it to doxycycline 1, 3
Key Takeaway for Practice
Doxycycline and glipizide can be safely prescribed together without dose modification. The confusion likely arises from the well-documented interaction between fluoroquinolone antibiotics and sulfonylureas—an interaction that does NOT apply to tetracyclines like doxycycline 1, 3, 2.