Can I take medroxyprogesterone acetate while on Zepbound (tirzepatide)?

Can You Take Medroxyprogesterone While on Zepbound?

Yes, you can safely take medroxyprogesterone acetate (MPA) while on Zepbound (tirzepatide), but you must use additional non-oral contraception or add a backup method for 4 weeks after each dose escalation if using oral MPA for contraceptive purposes. 1

Key Interaction Mechanism

• Tirzepatide delays gastric emptying, particularly after the first dose and during dose escalations, which can reduce absorption of oral medications 2
• This effect undergoes tachyphylaxis (tolerance) after subsequent doses at the same strength, but reappears with each dose increase 2
• Injectable depot medroxyprogesterone acetate (DMPA) has no interaction with tirzepatide since it bypasses the gastrointestinal tract entirely 3

Specific Recommendations by Formulation

Injectable DMPA (Depot Medroxyprogesterone Acetate)

• No precautions needed - DMPA 150 mg intramuscularly every 12-13 weeks or 104 mg subcutaneously every 13 weeks can be used without restriction while on tirzepatide 3, 4
• The CDC classifies DMPA as safe for use without restriction (Category 1) in women using medications that affect gastric emptying 3
• DMPA maintains its high contraceptive efficacy (≈0.2% failure with perfect use, ≈6% with typical use) regardless of concurrent tirzepatide therapy 5

Oral Medroxyprogesterone Acetate

• If used for contraception: Add a non-oral backup contraceptive method (condoms, copper IUD, etc.) for 4 weeks after initiating tirzepatide and after each dose escalation 1
• If used for endometrial protection or bleeding control (typical doses 2.5-10 mg daily): The clinical significance is less clear, but absorption may be reduced during dose escalation periods 4, 2
• Clinical trial data show tirzepatide causes statistically significant reductions in area under the curve, maximum concentration, and time to maximum concentration of oral hormonal contraceptives 2

Practical Management Algorithm

Step 1: Identify your MPA formulation

• Injectable DMPA → No interaction, proceed without changes 3
• Oral MPA for contraception → Add backup method during titration 1
• Oral MPA for other indications → Monitor clinical response 4

Step 2: If using oral MPA for contraception

• Start non-oral backup method before initiating tirzepatide 1
• Continue backup method for 4 weeks after each dose increase (2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg) 1
• Once stable on maintenance dose for 4+ weeks, oral MPA absorption normalizes due to tachyphylaxis 2

Step 3: Consider switching to DMPA

• DMPA eliminates the interaction concern entirely 3
• Provides superior contraceptive efficacy and eliminates daily pill burden 4
• Particularly advantageous during the 16-20 week tirzepatide titration period 1

Important Caveats

• Do not assume prior tolerance to other GLP-1 agonists predicts tirzepatide's effect - tirzepatide has a greater impact on gastric emptying than semaglutide or liraglutide, creating a unique interaction profile 2
• The interaction is most pronounced during dose escalation, not at steady state 2
• Absolute contraindications to MPA remain unchanged by tirzepatide use: known/suspected pregnancy, undiagnosed vaginal bleeding, breast malignancy, active thrombophlebitis, and liver dysfunction 4
• Monthly injectables containing MPA are inappropriate for patients with heart failure due to fluid retention risk, but this is unrelated to tirzepatide 3

Alternative Contraceptive Options

If the interaction concerns you or backup methods are unacceptable:

• Levonorgestrel IUD - no interaction, reduces menstrual blood loss by 40-50% 3
• Copper IUD - no hormonal interaction whatsoever 3
• Etonogestrel implant - no interaction with medications affecting gastric emptying 3
• Barrier methods - condoms have no drug interactions 3

Monitoring Recommendations

• If using oral MPA for endometrial protection, assess bleeding patterns monthly during tirzepatide titration 4
• If breakthrough bleeding occurs despite oral MPA, consider switching to DMPA or increasing oral MPA dose after consulting with your provider 4
• For diabetic patients, reduce insulin or sulfonylurea doses by 20-30% when starting tirzepatide to minimize hypoglycemia risk 1