Mestranol and Isotretinoin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Isotretinoin
Mestranol
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
This one is really important if you take isotretinoin for acne. Mestranol is the estrogen part of some birth control pills. When you take isotretinoin at the same time, your hormonal birth control may not work as reliably as it should. Pregnancy has happened in women using pills, patches, shots, implants, and IUDs while on isotretinoin, most often when only one method was being used.
Isotretinoin can cause very serious harm to a developing baby, so this is not a risk to take lightly. The good news is your care team has a clear plan: using two forms of birth control at the same time. Please talk with your doctor or pharmacist about your options.
Effect: Potential decreased contraceptive effectiveness when hormonal contraceptives (mestranol/estrogen-progestin) are used during isotretinoin therapy.
- Mechanism: Unknown. Reported PK/PD changes to estrogens and progestins are small but highly variable and unpredictable.
- Direction: Reduced/unreliable contraceptive effect; neither agent is a prodrug requiring activation.
- Evidence: Theoretical, supported by post-marketing pregnancy reports.
- Severity: Major, given isotretinoin's teratogenicity.
Management: Per iPLEDGE/REMS, patients of childbearing potential must use two simultaneous effective forms of contraception (unless abstinent or post-hysterectomy). Micro-dosed progestin-only pills may be inadequate. Confirm negative pregnancy testing and counsel on adherence.
What happens
Decreased effectiveness of hormonal contraceptives
Interaction Deep Dive
The pharmacokinetic and pharmacodynamic effects on estrogens and progestins from concurrent use with isotretinoin are minor, yet they show wide variability and cannot be reliably predicted. Cases of pregnancy have been documented among women relying on combined oral contraceptives, along with those using topical, injectable, implantable, or insertable hormonal contraceptive products. These reports have been more common among individuals depending on only one contraceptive method. When micro-dosed progestin-only pills are used alongside isotretinoin, the likelihood of contraceptive failure increases. Throughout isotretinoin treatment, female patients capable of becoming pregnant are required to employ 2 contraceptive methods at once, with one of them being: tubal ligation, a partner's vasectomy, intrauterine devices, birth control pills, or topical/injectable/implantable/insertable hormonal birth control products123.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep using birth control exactly as directed and do not stop your prescribed treatment on your own. Because isotretinoin can seriously harm a pregnancy, and hormonal birth control may be less reliable during treatment, your care team will typically:
- Have you use two forms of contraception at the same time, unless you have chosen complete abstinence or have had a hysterectomy.
- Include at least one highly reliable method (IUD, birth control pills, implant, injection, patch, tubal ligation, or partner's vasectomy).
- Note that micro-dosed progestin-only minipills may not be enough on their own.
Ask your pharmacist or prescriber to confirm your exact contraception plan and pregnancy testing schedule.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A study found no interaction between isotretinoin and oral contraceptives. Nine women receiving isotretinoin 0.5 mg/kg for severe pustular acne had been taking oral contraceptives (brand unknown) for at least three months before beginning isotretinoin therapy. Using radioimmunoassay, plasma concentrations of ethinyl estradiol and levonorgestrel were comparable in the control cycle and in two cycles following the initiation of isotretinoin 4.
b) When isotretinoin was administered alongside a combination ethinyl estradiol/norethindrone product, the pharmacokinetic and pharmacodynamic alterations were inconsistent and relatively minor. In a single-center, open-label drug interaction study, 26 healthy women completed a protocol in which they received ethinyl estradiol/norethindrone oral contraceptive (OC) triphasic tablets (35 micrograms and 0.5/0.75/1 milligrams, respectively) each day. At the beginning of the third month, once pregnancy had been excluded, participants also received isotretinoin 1 milligrams/kilogram/day in two divided doses to complete 16 to 20 weeks of isotretinoin therapy for severe, recalcitrant nodular acne. Plasma concentrations of ethinyl estradiol and norethindrone were slightly lower (9% and 11%, respectively) during the OC plus isotretinoin phase than during the OC alone phase, though patient variability was high. Follicle stimulating hormone concentration decreased 44% (p=0.03) when isotretinoin was added to the regimen, once again with substantial variability; serum progesterone and luteinizing hormone levels remained unchanged. No pregnancies were reported 5.
Common questions
Can I take Mestranol and Isotretinoin together?
Isotretinoin can make hormonal birth control less reliable, so use two forms of contraception at the same time throughout treatment and confirm your plan with your prescriber or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mestranol and Isotretinoin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Mestranol and Isotretinoin interaction managed?
Keep using birth control exactly as directed and do not stop your prescribed treatment on your own. Because isotretinoin can seriously harm a pregnancy, and hormonal birth control may be less reliable during treatment, your care team will typically: Have you use two forms of contraception at the same time, unless you have chosen complete abstinence or have had a hysterectomy. Include at least one… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Mestranol or Isotretinoin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: Amnesteem(R) oral capsules, isotretinoin oral capsules. Mylan Pharmaceuticals Inc, Morgantown, WV, 2010. DailyMed
- Product Information: Claravis(TM) oral capsules, isotretinoin oral capsules. Barr Laboratories, Inc, Pomona, NY, 2010. DailyMed
- Product Information: Sotret(R) oral capsules, isotretinoin oral capsules. Ranbaxy Laboratories Inc. Jacksonville, FL, 2010. DailyMed
- Orme M, Back DJ, & Shaw MA: Isotretinoin and contraception. Lancet 1984; 2:752-753. PubMed
- Hendrix CW, Jackson KA, Whitmore E, et al: The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther 2004; 75:464-75. PubMed
Keep reading about Isotretinoin
Keep reading about Mestranol
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