Norgestimate 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
Norgestimate
No brand names on recordIsotretinoin
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.
Isotretinoin (like Accutane) is a very strong acne medicine that can cause serious birth defects if a pregnancy happens while taking it. Your birth control pill contains norgestimate, a progestin hormone. The concern here is that birth control may not work as reliably during isotretinoin treatment, and pregnancies have happened even in women using hormonal birth control.
Because of this, women who can become pregnant are asked to use two forms of birth control at the same time while on isotretinoin. This isn't something to panic about, it's a well-known safety step. Your care team will walk you through the plan and monitor you closely.
Effect: Potential decreased contraceptive effectiveness when norgestimate-containing hormonal contraception is used during isotretinoin therapy.
- Mechanism: Unknown; PK/PD changes to estrogens and progestins are described as small but highly variable and unpredictable.
- Direction: Reduced contraceptive reliability; contraceptive failure and pregnancies have been reported.
- Evidence: Theoretical, but clinically important given the teratogenicity of isotretinoin.
- Management: Per iPLEDGE/REMS, require two simultaneous forms of contraception. Micro-dosed progestin-only (estrogen-free) minipills may be inadequate. Counsel on pregnancy-risk behaviors and confirm negative pregnancy testing per protocol.
What happens
Decreased effectiveness of hormonal contraceptives
Interaction Deep Dive
The pharmacokinetic and pharmacodynamic effects on estrogens and progestins that occur when they are given together with isotretinoin are minor, yet they are highly variable and cannot be reliably predicted. Cases of pregnancy have been documented in women relying on combined oral contraceptives, and also in those using topical, injectable, implantable, or insertable hormonal contraceptive products. These reports have been more common among individuals depending on a single contraceptive method. The likelihood of contraceptive failure is increased with micro-dosed progestin-only pills when they are taken alongside isotretinoin. Throughout isotretinoin treatment, female patients capable of becoming pregnant are required to use 2 contraceptive methods at once, and one of them should be among the following: 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
The key here is preventing pregnancy, because isotretinoin can cause severe birth defects. Keep taking your medications as prescribed and follow your prescriber's contraception plan.
- Use two forms of contraception at the same time during isotretinoin therapy (unless you have agreed to complete abstinence or have had a hysterectomy).
- One form should be a highly reliable method such as birth control pills, an IUD, an implant/injectable, tubal ligation, or a partner's vasectomy.
- Be aware that progestin-only "minipills" may not be enough on their own.
- Ask your pharmacist or prescriber to review your exact contraception before and during treatment.
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 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. As measured by radioimmunoassay, plasma levels 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 ethinyl estradiol/norethindrone product, the pharmacokinetic and pharmacodynamic changes were inconsistent and relatively small. In a single-center, open-label drug interaction study, 26 healthy women completed a study in which they received ethinyl estradiol/norethindrone oral contraceptive (OC) triphasic tablets (35 micrograms and 0.5/0.75/1 milligrams, respectively) daily. At the beginning of the third month, once pregnancy had been excluded, participants additionally received isotretinoin 1 milligrams/kilogram/day in two divided doses to complete 16 to 20 weeks of isotretinoin treatment 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 compared with the OC alone phase; however, patient variability was high. Follicle stimulating hormone concentration fell 44% (p=0.03) when isotretinoin was added to the regimen, again with a high degree of variability; serum progesterone and luteinizing hormone levels remained unchanged. No pregnancies were reported 5.
Common questions
Can I take Norgestimate and Isotretinoin together?
Isotretinoin can make hormonal birth control less reliable, and pregnancy during treatment risks serious birth defects, so use two forms of contraception at the same time and confirm your plan with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Norgestimate 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 Norgestimate and Isotretinoin interaction managed?
The key here is preventing pregnancy, because isotretinoin can cause severe birth defects. Keep taking your medications as prescribed and follow your prescriber's contraception plan. Use two forms of contraception at the same time during isotretinoin therapy (unless you have agreed to complete abstinence or have had a hysterectomy). One form should be a highly reliable method such as birth control… 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 Norgestimate 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 Norgestimate
Keep reading about Isotretinoin
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