What are the interactions between Depo Provera (medroxyprogesterone) and naproxen?

Depo-Provera and Naproxen Interactions

No Clinically Significant Drug Interaction

There is no clinically significant drug interaction between Depo-Provera (depot medroxyprogesterone acetate/DMPA) and naproxen, and they can be safely used together. 1

Evidence Supporting Safe Concurrent Use

Pharmacokinetic Data

• Studies examining rivaroxaban (an anticoagulant) with naproxen showed only a 10% increase in drug plasma concentrations when naproxen was co-administered, which is not clinically significant 1
• The U.S. Medical Eligibility Criteria for Contraceptive Use does not list NSAIDs, including naproxen, as having any contraindications or interactions with DMPA 1

Mechanism Considerations

• DMPA is administered as a depot injection (150 mg IM or 104 mg SC every 13 weeks) and does not undergo significant hepatic metabolism that would be affected by naproxen 2, 3
• Unlike methotrexate, which has documented serious interactions with naproxen due to reduced renal elimination, DMPA does not share this pharmacokinetic pathway 1
• Naproxen acts locally on endometrial tissue to reduce prostaglandin synthesis and does not interfere with progestin-mediated contraceptive mechanisms 4

Clinical Benefits of Combination

Therapeutic Advantages

• Naproxen can effectively treat menstrual irregularities and dysmenorrhea that commonly occur with DMPA use 1, 4
• The combination may be particularly useful since menstrual disturbances are the main disadvantage of DMPA, occurring in most users 5
• Naproxen reduces endometrial prostaglandin E2 secretion and COX-2 expression, which can help manage breakthrough bleeding associated with DMPA 4

No Impact on Contraceptive Efficacy

• DMPA maintains its highly effective contraceptive profile (0.2% perfect use failure rate, 6% typical use failure rate) regardless of naproxen co-administration 2, 5
• No antiretroviral or other drug interactions significantly affect DMPA levels or contraceptive effectiveness 1, 3

Important Clinical Considerations

Common Pitfalls to Avoid

• Do not withhold naproxen from DMPA users who need NSAID therapy for pain management, as there is no contraindication 1
• Do not confuse DMPA interactions with those of combined hormonal contraceptives (which have different metabolic pathways) 1
• Do not assume that interactions documented with methotrexate and naproxen apply to DMPA, as these are entirely different drug classes with different elimination pathways 1

When NSAIDs Are Particularly Useful

• Heavy or prolonged bleeding patterns in DMPA users can be managed with naproxen without concern for drug interaction 1
• Dysmenorrhea occurring during irregular bleeding episodes on DMPA responds well to naproxen therapy 1, 4