Ethinyl Estradiol; Norethindrone with Isotretinoin Interaction Details
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Decreased effectiveness of hormonal contraceptives
Interaction Summary
When coadministered with isotretinoin, pharmacokinetic and pharmacodynamic changes to estrogens and progestins are small but highly variable and unpredictable. Pregnancy has been reported in women who have used combined oral contraceptives, as well as topical/injectable/implantable/insertable hormonal birth control products. Such reports have occurred more frequently in those using a single form of contraception. Micro-dosed progestin-only pills elevate the risk of contraceptive failure during concomitant treatment with isotretinoin. During isotretinoin therapy, female patients of child bearing potential must use 2 forms of contraception simultaneously, one form should include: tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, or topical/injectable/implantable/insertable hormonal birth control products.
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Advise patients to use 2 forms of contraception simultaneously during isotretinoin therapy, unless patient has agreed to absolute abstinence or has had a hysterectomy. One form should include one of the following: tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, or topical/injectable/implantable/insertable hormonal birth control products. Micro-dosed progesterone preparations (minipills than do not contain an estrogen) may be inadequate. Counsel patients about contraception and behaviors that increase the risk of pregnancy.
Mechanism Of Interaction
Unknown
Literature Reports
A) Isotretinoin did not interact with oral contraceptives in a study. Nine women taking isotretinoin 0.5 mg/kg for severe pustular acne received oral contraceptives (brand unknown) for at least three months prior to starting isotretinoin therapy. Plasma concentrations of ethinyl estradiol and levonorgestrel in the control cycle and in two cycles after starting isotretinoin were similar as determined by radioimmunoassay .
B) Pharmacokinetic and pharmacodynamic changes were inconsistent and relatively small when isotretinoin was given with a combination ethinyl estradiol/norethindrone product. In a single-center, open-label drug interaction study, 26 healthy women completed a study in which they were given ethinyl estradiol/norethindrone oral contraceptive (OC) triphasic tablets (35 micrograms and 0.5/0.75/1 milligrams, respectively) daily. At the start of the third month and after the possibility of pregnancy was ruled out, participants were also given isotretinoin 1 milligrams/kilogram/day in two divided doses to complete 16 to 20 weeks of isotretinoin treatment for severe, recalcitrant nodular acne. Ethinyl estradiol and norethindrone plasma concentrations were slightly reduced (9% and 11%, respectively) during the OC plus isotretinoin phase compared with the OC alone phase; patient variability was high, however. Follicle stimulating hormone concentration declined 44% (p=0.03) when isotretinoin was added to the regimen, again with a high degree of variability; serum progesterone and luteinizing hormone levels were unchanged. No pregnancies were reported .
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.