Diazepam with Ethinyl Estradiol; Norethindrone Interaction Details
Brand Names Associated with Diazepam
- Diazepam
- Diazepam Intensol®
- Valium®
- Valrelease®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Diazepam toxicity (CNS depression, hypotension)
Interaction Summary
Combination contraceptives may decrease the metabolism of diazepam, alprazolam, triazolam and chlordiazepoxide. Combination contraceptives may increase the effect of diazepam on psychomotor performance. Therefore, diazepam dosage reduction may be necessary in patients receiving both diazepam and oral contraceptive steroids. Patients should be monitored for the possibility of increased clinical effects although a direct relation between diazepam's plasma concentration and its clinical effectiveness has not clearly been established .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitor patients receiving concurrent hormonal contraceptives and diazepam for an increased response to the benzodiazepine.
Mechanism Of Interaction
Inhibition of oxidative diazepam metabolism by the contraceptive
Literature Reports
A) The long term use of low-dose (less than 50 mcg) estrogen-containing oral contraceptives has been found to impair diazepam clearance and significantly increase the elimination half-life of diazepam. Eight healthy women receiving low-dose estrogen-containing contraceptives for more than 3 months and a control group of 8 patients not taking oral contraceptives received a single dose of diazepam 10 mg given by intravenous infusion over 15 to 30 seconds. Venous blood samples were drawn periodically for up to 7 days following infusion. No difference was observed in diazepam clearance or protein binding between the two groups. However, apparent elimination half-life of diazepam was significantly increased in the contraceptive patients compared with the control patients (69 +/- 9 hours vs 47 +/- 4 hours; p less than 0.05). Total metabolic clearance was also significantly reduced with diazepam plus contraceptives compared with diazepam alone (0.27 +/- 0.02 mL/minute/kg vs 0.45 +/- 0.04 mL/minute/kg; p less than 0.001) . Although these results refer only to intravenous administration of diazepam, it is likely that experience with oral administration of diazepam would be similar since diazepam is rapidly absorbed and 100% bioavailable.
B) Although the mechanism of the diazepam/estrogen-containing oral contraceptive interaction is not clear, it may be related to inhibition of the cytochrome P450 system-mediated diazepam metabolism by the estrogen. This would subsequently reduce the oxidation of diazepam in the liver .
Diazepam Overview
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Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.
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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.
Where Does Our Information Come From?
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.