Thioridazine and Levonorgestrel: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Thioridazine
No brand names on recordLevonorgestrel
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
Reduced levonorgestrel exposure and increased risk of breakthrough bleeding and/or contraceptive failure
Interaction Deep Dive
Concomitant use of a hormonal contraceptive (HC), such as levonorgestrel, and a CYP3A4 inducer may decrease contraceptive exposure and lead to breakthrough bleeding and/or contraceptive failure. If unavoidable, use a non-HC or a back-up method during and for at least 28 days after use of a CYP3A4 inducer3. In patients receiving a CYP3A4 inducer in need of emergency contraception, consider use of a copper intrauterine system (IUS), or alternatively, a double dose of oral levonorgestrel (3 mg) 2. Use of intrauterine or intravaginal HC may be preferable during CYP3A inducer coadministration 4; effect occurs via direct release into the uterine cavity and is unlikely to be affected by enzyme-mediated drug interactions 1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of levonorgestrel
Literature reports
3 reports — tap to read
a) Participants with HIV who received double-dose levonorgestrel (3 mg; n=35) in combination with efavirenz-based antiretroviral therapy (ART) had a similar levonorgestrel AUC and Cmax 8 hours after dosing compared with control (levonorgestrel 1.5 mg plus dolutegravir-based ART; n=32) in an open-label partially randomized 48-hour pharmacokinetic study. Similar results were seen with rifampicin plus levonorgestrel 3 mg in those without HIV receiving tuberculosis therapy (n=34), except levonorgestrel Cmax was 27% higher than control. Participants receiving the standard dose of levonorgestrel (1.5 mg; n=17) plus efavirenz experienced a 50% lower AUC compared with control. Compared with efavirenz plus levonorgestrel 1.5 mg, those receiving efavirenz plus levonorgestrel 3 mg had an AUC that remained 88% to 90% higher 24- and 48-hours after dosing and Cmax was 61% higher. Adverse events were similar between groups, and were reported in 4% for levonorgestrel 1.5 mg (Grade 2 nausea and heavy menstrual bleeding) and 3% for levonorgestrel 3 mg (Grade 2 nausea and intermenstrual bleeding, and Grade 3 headache). Participants were without an indication for emergency contraception and were not on hormonal contraception; median age was 34 years and BMI was 23.2 kg/m(2). Levonorgestrel is a CYP3A4 substrate, and administration of double-dose levonorgestrel has been suggested in patients receiving CYP3A4 inducers (such as efavirenz and rifampicin). It is not known if the AUC correction over the first 8 hours of dosing with levonorgestrel 3 mg in combination with efavirenz-based ART is adequate to maintain emergency contraceptive efficacy 5.
b) In an integrated physiologically-based pharmacokinetic (PBPK) modeling and model-based metaanalysis (10 studies; N=26,887 patients over 1 year/13 cycles), simulated coadministration of oral levonorgestrel and strong CYP3A4 inducers predicted significantly decreased levonorgestrel exposure of 50% to 65% in patients with BMI less than 25 kg/m(2) and 70% to 75% in patients with obesity (BMI 30 kg/m(2) or greater). Studies included use of combination oral contraceptives containing levonorgestrel and ethinyl estradiol 150 mcg/30 mcg (LNG150) or 100 mcg/20 mcg (LNG100), except for 1 study using levonorgestrel 30 mcg (progestin only pill). With coadministration of a CYP3A4 inducer and LNG150 or LNG100, mean Pearl Index increased 1.2 to 1.3 or 1.8 to 2.1 pregnancies/100 women years with BMI less than 25 kg/m(2) (incidence rate ratios [IRRs], 1.7 to 2.2) and 1.6 to 1.8 or 2.4 to 2.85 in patients with obesity (IRRs, 2.2 to 3), respectively. CYP3A4 inducer simulations included daily doses of rifAMPin 100 mg, carBAMazepine 400 mg, and efavirenz 600 mg 6.
c) Concomitant use of a CYP3A4 inducer with oral or implantable contraceptive products containing levonorgestrel (684 events) or etonogestrel/desogestrel (864 events) was associated with a disproportionately higher rate of unintended pregnancy compared to all other event types reported to the FDA Adverse Event Reporting System (FAERS) between 1971 and 2020 [levonorgestrel (14,504 total events); etonogestrel/desogestrel (9348 total events)]. When compared between CYP3A4 inducer exposure vs no exposure, cases of unintended pregnancy made up a significantly higher proportion of total events when levonorgestrel was administered orally (32.8% vs 10.5%) or as an implant (51.9% vs 11.9%), and a similar association was identified with implanted etonogestrel products (42.5% vs 13.1%). However, when contraceptives were administered as an intrauterine device (levonorgestrel, 10.3% vs 11.5%) or intravaginal ring (etonogestrel, 10.9% vs 8.7%), no significant associations were identified. Oral desogestrel (pro-drug of etonogestrel) in combination with ethynyl estradiol also was not significantly affected (11.8% vs 17.4%). Intrauterine and vaginal ring products may be preferred in lieu of oral and implantable contraceptive products in women concomitantly receiving CYP3A4 inducers 4.
Common questions
Can I take Thioridazine and Levonorgestrel together?
Reduced levonorgestrel exposure and increased risk of breakthrough bleeding and/or contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Thioridazine and Levonorgestrel interaction?
It is rated major. Potentially serious — often needs a change or close 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.
Questions for your pharmacist
- Does my dose of Thioridazine 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 a safer alternative to one of these medications for me?
References (6)
- Product Information: MIRENA(R) intrauterine system, levonorgestrel intrauterine system. Bayer HealthCare Pharmaceuticals Inc (per FDA), Whippany, NJ, 2022.
- International Consortium for Emergency Contraception (ICEC): Emergency contraceptive pills: medical and service delivery guidance, 4th ed. Reproductive Health Supplies Coalition. Washington, DC. 2018.
- Product Information: LOESTRIN(R) 24 Fe oral tablets, norethindrone acetate ethinyl estradiol oral tablets, ferrous fumarate oral tablets. Teva Pharmaceuticals USA Inc (per FDA), Parsippany, NJ, 2023. DailyMed
- Sunaga T, Cicali B, Schmidt S, et al: Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system. Contraception 2021; 103(4):222-224. PubMed
- Scarsi KK, Smeaton LM, Podany AT, et al: Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens. Contraception 2023; 121:109951. DOI
- Lingineni K, Chaturvedula A, Cicali B, et al: Determining the exposure threshold for levonorgestrel efficacy using an integrated model based meta-analysis approach. Clin Pharmacol Ther 2022; 111(2):509-518. PubMed
Keep reading about Thioridazine
Keep reading about Levonorgestrel
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