Plan B One-Step Drug Interactions: What to Avoid and What to Tell Your Doctor

Plan B One-Step is a single-dose emergency contraceptive that most people can take without drug interaction concerns. However, if you are on certain prescription medications or supplements, the effectiveness of Plan B One-Step can be significantly reduced — potentially to the point where it may not protect you from pregnancy.

Here's everything you need to know about Plan B One-Step drug interactions in 2026 — what to avoid, why it matters, and what to do if you're on one of these medications.

Why Do Some Medications Reduce Plan B One-Step Efficacy?

Levonorgestrel (the active ingredient in Plan B One-Step) is metabolized in the liver by an enzyme system called CYP3A4. Certain drugs and herbal supplements are CYP3A4 inducers — meaning they accelerate the activity of this enzyme system, causing levonorgestrel to be broken down faster than normal. The result: lower levonorgestrel blood levels and reduced ability to prevent ovulation.

Medications That Reduce Plan B One-Step Effectiveness (Avoid or Use Alternative)

The following drugs and supplements are known to reduce levonorgestrel efficacy. If you're taking any of these, Plan B One-Step may not adequately protect you from pregnancy:

Rifampin (rifampicin) — used for tuberculosis (TB) treatment. The strongest CYP3A4 inducer of all the drugs listed; significantly reduces levonorgestrel plasma concentrations.

Efavirenz — HIV antiretroviral medication. Reduces levonorgestrel AUC (blood exposure) by approximately 50%; may substantially reduce efficacy.

Anti-seizure medications (anticonvulsants): Several are significant CYP3A4 inducers — Carbamazepine (Tegretol), Phenytoin (Dilantin), Phenobarbital, Oxcarbazepine (Trileptal), Topiramate (Topamax — at higher doses), Felbamate (Felbatol)

St. John's Wort (Hypericum perforatum) — a widely used herbal supplement. A clinically significant CYP3A4 inducer; can meaningfully reduce progestin blood levels and EC efficacy.

Griseofulvin — an antifungal medication (used for fungal nail or skin infections). Note: other antifungals like fluconazole do not have this interaction.

Certain HIV medications (HIV protease inhibitors and NNRTIs) — besides efavirenz, some other antiretrovirals can alter levonorgestrel levels. If you're on any HIV medication, consult your provider or pharmacist.

Perampanel (Fycompa) — an anti-seizure medication; high doses reduce levonorgestrel levels by approximately 40%.

Omaveloxolone — a newer CYP3A4 inducer; may reduce levonorgestrel efficacy.

What to Do If You're on One of These Medications

If you are currently on rifampin, an anticonvulsant, efavirenz, St. John's Wort, or another CYP3A4 inducer, Plan B One-Step is likely to be significantly less effective. Your best alternatives are:

Copper IUD (ParaGard) — inserted within 5 days of unprotected sex; over 99% effective; not affected by liver enzyme-inducing drugs; the best EC option for patients on CYP3A4 inducers

ella (ulipristal acetate) — NOTE: ella is also metabolized via CYP3A4, so similar interactions apply. It is generally not recommended as an alternative when the patient is on strong CYP3A4 inducers. The copper IUD remains the best option.

Medications That Do NOT Interact with Plan B One-Step

Many medications that patients worry about do not interact with Plan B One-Step:

Most antibiotics (amoxicillin, azithromycin, doxycycline, etc.) — contrary to a common myth, most antibiotics do NOT reduce hormonal contraceptive efficacy; only rifampin does

Most antifungals — only griseofulvin has the interaction, not fluconazole (Diflucan) or other azole antifungals

Alcohol — no known interaction between levonorgestrel and alcohol; effects on levonorgestrel efficacy are unknown but no significant clinical interaction has been documented

Food — there are no known food interactions with levonorgestrel; it can be taken with or without food

What to Tell Your Doctor or Pharmacist

Before taking Plan B One-Step, it's important to inform your healthcare provider or pharmacist about:

All prescription medications — especially anticonvulsants, HIV medications, and antibiotics for TB

All OTC supplements and herbal products — especially St. John's Wort

Any medications you've taken in the past month that might still be active in your system

If you're on medications that reduce Plan B One-Step's effectiveness, see our guide on alternatives to Plan B One-Step — including the copper IUD, which is not affected by drug interactions.

If you need to find Plan B One-Step or a generic in stock near you quickly, medfinder can help by calling pharmacies in your area and texting you which ones have it available.