Ulipristal 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
Ulipristal
Isotretinoin
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.
Here's the important thing to know, and it works in two directions. First, isotretinoin (Accutane and similar) can make hormonal birth control less reliable, so pregnancy is possible even when you use it correctly. This matters a lot because isotretinoin can cause very serious birth defects.
Second, ulipristal (Ella) is an emergency contraceptive that works on the same hormone pathway as regular birth control, and taking it can actually make your ongoing hormonal birth control work less well for a while. So neither of these should be leaned on as your only protection.
The good news: your care team can absolutely manage this. The key is using two forms of birth control at the same time during isotretinoin. Please talk with your prescriber or pharmacist before combining these.
Effect: Potential decreased contraceptive effectiveness, raising unintended pregnancy risk during isotretinoin therapy (a known teratogen).
- Mechanism: Unknown/theoretical. Isotretinoin produces small but highly variable, unpredictable PK/PD changes in estrogens and progestins. Ulipristal is a selective progesterone receptor modulator that can independently reduce efficacy of concurrent hormonal contraceptives via PD interference.
- Direction: Reduced contraceptive effect (neither is a prodrug relevant here).
- Evidence: Theoretical; pregnancies reported, more often with a single contraceptive method. Micro-dosed progestin-only pills are inadequate.
- Management: Per iPLEDGE, require two simultaneous forms of contraception (unless abstinence/hysterectomy). Counsel on pregnancy-risk behaviors. Do not rely on ulipristal alone.
What happens
Decreased effectiveness of hormonal contraceptives
Interaction Deep Dive
The pharmacokinetic and pharmacodynamic effects on estrogens and progestins when given together 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, as well as those using topical, injectable, implantable, or insertable hormonal contraceptive products. These reports have arisen more often in women depending on a single contraceptive method. Micro-dosed progestin-only pills raise the likelihood of contraceptive failure when used alongside isotretinoin. Throughout isotretinoin treatment, female patients who could become pregnant are required to use 2 contraceptive methods at the same time, with one of them being: tubal ligation, a partner's vasectomy, intrauterine devices, birth control pills, or topical/injectable/implantable/insertable hormonal contraceptive products123.
Why it happens (mechanism)
Unknown
How to manage this interaction
The core rule during isotretinoin: use two effective forms of contraception at the same time, unless you have agreed to complete abstinence or have had a hysterectomy. One form should be a primary method such as an IUD, birth control pills, an implant/injection/patch/ring, tubal ligation, or a partner's vasectomy.
- Keep using your prescribed contraception exactly as directed, and do not rely on any single method.
- Note that minipills (progestin-only, no estrogen) may not be reliable enough here.
- Do not use ulipristal (Ella) as your ongoing method, and tell your prescriber if you have taken it.
Ask your prescriber or pharmacist to confirm your contraception plan meets isotretinoin program requirements before starting or continuing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In one study, isotretinoin showed no interaction with oral contraceptives. Nine women who were taking isotretinoin 0.5 mg/kg for severe pustular acne had been receiving oral contraceptives (brand unknown) for at least three months before beginning isotretinoin. As measured by radioimmunoassay, the plasma concentrations of ethinyl estradiol and levonorgestrel during the control cycle and during two cycles after isotretinoin was started were comparable 4.
b) When isotretinoin was administered together with a combination product of ethinyl estradiol and norethindrone, 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. Beginning at the start of the third month, and after pregnancy had been excluded, the participants additionally received isotretinoin 1 milligrams/kilogram/day in two divided doses in order to complete 16 to 20 weeks of isotretinoin therapy for severe, recalcitrant nodular acne. The plasma concentrations of ethinyl estradiol and norethindrone were slightly lowered (9% and 11%, respectively) during the OC plus isotretinoin phase relative to the OC alone phase; however, variability among patients was high. Follicle stimulating hormone concentration fell 44% (p=0.03) when isotretinoin was added to the regimen, once more with a high degree of variability; serum progesterone and luteinizing hormone levels remained unchanged. No pregnancies were reported 5.
Common questions
Can I take Ulipristal and Isotretinoin together?
Isotretinoin can make hormonal birth control less reliable, and ulipristal (Ella) is not a dependable ongoing method, so use two effective forms of contraception at once and confirm your plan with your prescriber or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ulipristal 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 Ulipristal and Isotretinoin interaction managed?
The core rule during isotretinoin: use two effective forms of contraception at the same time, unless you have agreed to complete abstinence or have had a hysterectomy. One form should be a primary method such as an IUD, birth control pills, an implant/injection/patch/ring, tubal ligation, or a partner's vasectomy. Keep using your prescribed contraception exactly as directed, and do not rely on any… 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 Ulipristal 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 Ulipristal
Keep reading about Isotretinoin
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