Diazepam and Levonorgestrel: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diazepam
Levonorgestrel
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.
What happens
Diazepam toxicity (CNS depression, hypotension)
Interaction Deep Dive
Combination contraceptives may decrease the metabolism of diazepam, alprazolam, triazolam and chlordiazepoxide. Combination contraceptives may increase the effect of diazepam on psychomotor performance123. 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 1.
Why it happens (mechanism)
Inhibition of oxidative diazepam metabolism by the contraceptive
Literature reports
2 reports — tap to read
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) 1. 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 1.
Common questions
Can I take Diazepam and Levonorgestrel together?
Diazepam toxicity (CNS depression, hypotension) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam and Levonorgestrel interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diazepam or Levonorgestrel 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 anything you'd monitor while I'm on both?
References (3)
- Abernethy DR, Greenblatt DJ, Divoli M, et al: Impairment of diazepam metabolism by low dose estrogen containing oral contraceptive steroids. N Engl J Med 1982; 306:791-792. PubMed
- Shenfield GM & Griffin JM: Clinical pharmacokinetics of contraceptive steroids: an update. Clin Pharmacokinet 1991; 20:15-37. PubMed
- Kroboth PD, Smith RB, Stoehr GP, et al: Pharmacodynamic evaluation of the benzodiazepine-oral contraceptive interaction. Clin Pharmacol Ther 1985; 38:525-532. DOI
Keep reading about Diazepam
Keep reading about Levonorgestrel
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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