Levonorgestrel Drug Interactions: What You Need to Know

Levonorgestrel is one of the most common hormones used in birth control pills, IUDs, and emergency contraception. But what most people don’t realize is that levonorgestrel doesn’t work in isolation. It can be affected by other medications you’re taking - sometimes in ways that could reduce its effectiveness or increase side effects. If you’re using levonorgestrel for birth control or emergency contraception, skipping this info could mean an unplanned pregnancy.

How Levonorgestrel Works (Simply)

Levonorgestrel is a synthetic progestin. It stops ovulation, thickens cervical mucus to block sperm, and thins the uterine lining. Its job is to prevent pregnancy. But for it to do that, your body needs to absorb and process it correctly. That’s where other drugs can interfere.

Some medications speed up how fast your liver breaks down levonorgestrel. Others might block its absorption. Either way, if levonorgestrel leaves your system too fast, it won’t work as well. And that’s not theoretical - real cases of unintended pregnancy have happened because of these interactions.

Medications That Can Reduce Levonorgestrel’s Effectiveness

Here are the big ones you need to watch out for:

• Anticonvulsants - Drugs like carbamazepine, phenytoin, and phenobarbital (used for epilepsy) are strong enzyme inducers. They boost liver enzymes that break down levonorgestrel. Studies show these can cut levonorgestrel levels by more than 50%. If you’re on one of these, your birth control might as well be a placebo.
• Some antibiotics - Rifampin (used for tuberculosis) is the worst offender. It’s proven to reduce levonorgestrel effectiveness. But common antibiotics like amoxicillin or azithromycin? They don’t. A lot of people panic over these, but the science says they’re safe. Don’t assume all antibiotics interfere.
• HIV medications - Protease inhibitors like ritonavir and non-nucleoside reverse transcriptase inhibitors like efavirenz can interfere. Some boost levels of levonorgestrel (increasing side effects), while others lower them. If you’re on HIV treatment, talk to your doctor before starting any hormonal contraception.
• St. John’s Wort - This herbal supplement, often used for mild depression, is a hidden danger. It activates the same liver enzymes as anticonvulsants. One study found it reduced levonorgestrel levels by up to 60%. Many people take it thinking it’s “natural” and harmless - but it’s not safe with hormonal birth control.
• Some antifungals - Griseofulvin, used for fungal skin infections, can also reduce levonorgestrel levels. It’s less common now, but still used in some cases.

What About Painkillers, Antacids, or Allergy Meds?

Good news: most everyday meds won’t touch levonorgestrel.

Paracetamol (acetaminophen), ibuprofen, aspirin, omeprazole, loratadine, and most cold and flu remedies? They’re safe. No interaction. No need to double up on condoms.

Even some antidepressants like sertraline or escitalopram don’t interfere. But there’s one exception: the antidepressant fluvoxamine. It can slow down how quickly your body clears levonorgestrel, which might lead to higher levels and more side effects like nausea or spotting. Not dangerous, but worth noting if you’re having unusual symptoms.

Emergency Contraception: A Higher Risk

Emergency contraception (like Plan B or Postinor) uses a high dose of levonorgestrel all at once. But if you’re on one of those enzyme-inducing drugs, it might not work at all.

A 2020 review in the British Journal of Clinical Pharmacology found that women taking rifampin or carbamazepine had up to a 40% higher chance of pregnancy after using emergency contraception compared to those not on those drugs.

If you’re on any of the high-risk medications listed above and need emergency contraception, don’t rely on levonorgestrel alone. Ask your doctor about ulipristal acetate (Ella) or a copper IUD - both are much less affected by liver enzyme changes.

What to Do If You’re on a Risky Medication

Don’t panic. But do act.

1. Check your meds - Go through your prescription list. Look for the drugs mentioned above. If you’re unsure, bring your pill bottle to your pharmacist. They can check for interactions in seconds.
2. Use backup contraception - If you’re on a drug that interferes, use condoms every time you have sex. Even if you’re on a pill, patch, or ring. Don’t trust the hormone alone.
3. Ask about alternatives - If you need long-term birth control, consider a non-hormonal IUD (copper), a progestin-only implant (etonogestrel), or a hormonal IUD (like Mirena). These are less affected by liver enzymes.
4. Never stop your other meds - If you’re taking antiseizure or HIV meds, don’t quit them. Work with your doctor to find a birth control option that works with your treatment plan.

Signs Levonorgestrel Might Not Be Working

If you’re on a drug that interferes, here’s what to watch for:

• Breakthrough bleeding - spotting between periods
• Missing a period when you usually don’t
• Increased nausea or breast tenderness - could mean hormone levels are spiking erratically
• Getting pregnant despite using birth control

If any of this happens, take a pregnancy test. And tell your doctor what you’re taking. It’s not your fault - it’s a known interaction.

What About Alcohol or Food?

Alcohol doesn’t affect levonorgestrel. You can drink normally. Grapefruit juice? It doesn’t interfere with levonorgestrel like it does with some other hormones (like estrogen). So no need to avoid it.

Food doesn’t change absorption either. You can take levonorgestrel with or without meals. Just take it at the same time every day if you’re on a daily pill.

When to See a Doctor

Don’t wait until you miss a period. If you’re starting a new medication - even an over-the-counter one - and you’re using levonorgestrel, ask your doctor or pharmacist: “Will this affect my birth control?”

It’s especially important if:

• You’re starting or stopping epilepsy, HIV, or TB treatment
• You’ve been taking St. John’s Wort for months
• You’re planning to use emergency contraception and take any of the high-risk drugs
• You’ve had a recent unplanned pregnancy while on birth control

Your doctor might switch your birth control to something more reliable, like a copper IUD or implant. Or they might adjust your other meds if possible.

Bottom Line: Know Your Meds, Protect Yourself

Levonorgestrel is effective - but only if nothing else is speeding up how fast your body gets rid of it. The biggest risks come from epilepsy drugs, HIV meds, tuberculosis treatment, and St. John’s Wort. Most antibiotics, painkillers, and cold meds? Fine.

If you’re unsure, assume it’s risky until proven otherwise. Use condoms. Talk to your pharmacist. Don’t rely on memory or Google. Birth control failure isn’t always user error - sometimes, it’s a hidden drug interaction.

Knowing this could be the difference between planning your future - and being forced to make unplanned choices.