Ethinyl Estradiol; Norethindrone with Atazanavir Interaction Details
Brand Names Associated with Atazanavir
- Atazanavir
- ATZ
- Reyataz®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
An increase in exposure to the combination contraceptive
Interaction Summary
Concomitant use of atazanavir (with/without ritonavir) and a combination ethinyl estradiol/norgestimate or norethindrone oral contraceptive has resulted in a substantial increase in progesterone exposure and both increases and decreases in ethinyl estradiol exposure In a study in healthy HIV-negative women (n=20), coadministration of atazanavir/ritonavir and an oral contraceptive containing ethinyl estradiol and norgestimate resulted in increased exposure of norgestimate and decreased exposure of ethinyl estradiol; however, the reduction in ethinyl estradiol levels was not expected to decrease contraceptive efficacy. Results of this study indicate that an oral contraceptive containing at least 30 mcg of ethinyl estradiol would be sufficient to maintain adequate exposure of ethinyl estradiol . Use caution when prescribing oral contraceptives in patients receiving atazanavir. A combination oral contraceptive with the appropriate dose of ethinyl estradiol (at least 35 mcg with concomitant atazanavir plus ritonavir and no more than 30 mcg with concomitant atazanavir) is recommended. An alternate method of contraception is recommended when the patient is using other hormonal contraceptives (eg, patch, vaginal ring, injection), oral contraceptives that contain progestins other than norethindrone or norgestimate, or oral contraceptives that contain less than 25 mcg of ethinyl estradiol, as studies have not been conducted .
Severity
Moderate
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Use caution when coadministering atazanavir (with or without ritonavir) and a combination ethinyl estradiol/norgestimate or norethindrone oral contraceptive as concomitant use has resulted in substantial increases in progesterone exposure and both reductions and elevations in ethinyl estradiol exposure. If an oral contraceptive is administered with atazanavir plus ritonavir, the oral contraceptive should contain at least 35 mcg of ethinyl estradiol. If administered with atazanavir alone, the oral contraceptive should contain no more than 30 mcg of ethinyl estradiol. An alternative method of contraception is recommended if atazanavir (with or without ritonavir) is being considered for a patient who is using other hormonal contraceptives (eg, patch, vaginal ring, or injection), oral contraceptives that contain progestins other than norethindrone or norgestimate, or oral contraceptives that contain less than 25 mcg of ethinyl estradiol, as studies have not been conducted in these cases .
Mechanism Of Interaction
Unknown
Literature Reports
A) Concomitant use of atazanavir (with or without ritonavir) and a combination ethinyl estradiol/norgestimate or norethindrone oral contraceptive has resulted in substantial increases in progesterone exposure. Long-term effects of increases in progestational agent bioavailability are not known and could result in an increased risk of insulin resistance, dyslipidemia, and acne. Concomitant use of atazanavir 300 mg plus ritonavir 100 mg once daily with an ethinyl estradiol/norgestimate oral contraceptive resulted in decreased ethinyl estradiol and increased norgestimate exposure. Coadministration of atazanavir 400 mg once daily with an ethinyl estradiol/norethindrone contraceptive resulted in increased exposure to both ethinyl estradiol and norethindrone. No studies have been conducted on the concomitant use of atazanavir (with or without ritonavir) with other hormonal contraceptives (eg, patch, vaginal ring, or injection), with oral contraceptives that contain progestins other than norethindrone or norgestimate, or with oral contraceptives that contain less than a 25-mcg dose of ethinyl estradiol .
B) In a pharmacokinetic study in healthy HIV-negative women (n=20; mean age 28 years), coadministration of atazanavir/ritonavir and an oral contraceptive containing ethinyl estradiol (EE) and norgestimate (NGM) resulted in increased exposure of norgestimate and decreased exposure of ethinyl estradiol; however the reduction in ethinyl estradiol levels was not expected to decrease contraceptive efficacy. In this open-label, three-period study, participants received in the lead-in period a full 28-day cycle of Ortho Tri-CyClen(R) (EE 0.035 mg plus NGM 0.18/0.215/0.25 mg). This was followed by period 1 in which participants received a second cycle of daily Ortho Tri-CyClen(R) (treatment A). Participants with satisfactory safety assessments began a third cycle on day 29 of Ortho Tri-Cyclen LO(R) (EE 0.025 mg plus NGM 0.18/0.215/0.25 mg) coadministered with atazanavir 300 mg/ritonavir 100 mg once daily for 14 days (treatment B). A dose normalization was performed to account for the different EE doses in the 2 treatments and to estimate the magnitude of reduction in EE exposures. Coadministration of atazanavir/ritonavir plus dose-normalized EE/NGM resulted in geometric mean reductions in EE of 16%, 19%, and 37% for Cmax, AUC, and Cmin, respectively. For NGM exposure, Cmax, AUC, and Cmin were increased by 68%, 85%, and 102%, respectively. Results of this study indicate that an oral contraceptive containing at least 30 mcg of EE would be sufficient to maintain adequate exposure of EE. Since the contraceptive efficacy of Ortho Tri-Cyclen(R) is primarily dependent on progestin, the contraceptive efficacy was not expected to be compromised .
Atazanavir Overview
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Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
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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.
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