Nexplanon is one of the most effective forms of birth control available, with a failure rate well under 1%. But certain medications, supplements, and insertion issues can reduce its effectiveness or, in rare cases, cause it to fail entirely. Here’s what actually interferes with the implant and what doesn’t.
Medications That Lower Hormone Levels
The most well-documented threat to Nexplanon’s effectiveness is a category of drugs called enzyme inducers. These medications speed up the liver’s ability to break down hormones, which can lower the concentration of etonogestrel (the active hormone in Nexplanon) in your bloodstream. When hormone levels drop far enough, the implant may no longer reliably prevent ovulation.
The FDA’s prescribing information lists the following as drugs that may reduce Nexplanon’s effectiveness:
- Seizure medications: phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate, rufinamide, and barbiturates
- Antibiotics: rifampicin (used for tuberculosis) and rifabutin
- HIV medications: efavirenz, nevirapine, nelfinavir, ritonavir, and several ritonavir-boosted protease inhibitors including darunavir, lopinavir, and tipranavir
- Hepatitis C medications: boceprevir and telaprevir
- Other: bosentan (a pulmonary hypertension drug), griseofulvin (an antifungal), and aprepitant (an anti-nausea drug)
Rifampicin is considered one of the strongest enzyme inducers and is frequently highlighted as a particular concern. If you take any of these medications long-term, your provider will typically recommend a different contraceptive method that isn’t affected by liver enzyme activity, such as a copper IUD.
One common misconception: standard antibiotics like amoxicillin or azithromycin do not interfere with Nexplanon. The concern is specific to rifampicin and rifabutin, which are rarely prescribed outside of tuberculosis treatment.
St. John’s Wort
St. John’s Wort, a popular herbal supplement used for mild depression, is classified by the FDA as a strong inducer of the same liver enzyme (CYP3A4) that breaks down contraceptive hormones. A “strong inducer” can reduce the amount of active drug in your system by 80% or more. Since contraceptive hormones are metabolized through this exact pathway, the interaction is real and clinically meaningful.
A systematic review found four reported cases of unintended pregnancies in women using etonogestrel implants alongside St. John’s Wort, along with additional cases in oral contraceptive users. Those numbers are small, but they’re enough for the FDA to include St. John’s Wort on its list of products that may decrease Nexplanon’s effectiveness. If you use St. John’s Wort regularly, it’s worth discussing alternatives with your provider, either a different supplement or a different contraceptive method.
Incorrect Insertion or Timing
Nexplanon works from the moment it’s placed, but only if two things go right: the rod is actually inserted into your arm, and it’s placed at the right time in your cycle.
Insertion failures are rare but documented. In one large prospective study (the NORA study), a pregnancy occurred in a case classified as a “noninsertion,” meaning the implant wasn’t properly placed despite the clinical visit. After insertion, you should always be able to feel the small rod under your skin. If you can’t feel it, contact your provider, because an implant that isn’t there can’t protect you.
Timing also matters. If Nexplanon is placed during the first five days of your period, it’s effective immediately. If it’s placed at any other point in your cycle, you need to use condoms or abstain from sex for seven days afterward. Skipping that backup window is a preventable cause of early failure.
Does Body Weight Affect Effectiveness?
This is one of the most common concerns, and the answer is more reassuring than you might expect. The original approval trial for Nexplanon excluded women above 130% of their ideal body weight, which led to a label warning about potentially decreased effectiveness in heavier women. However, a later FDA-reviewed study that specifically enrolled overweight and obese women (38% of participants) found consistent efficacy across all BMI groups over a two-year period.
The FDA has noted that the two-year study duration may not be long enough to fully rule out reduced effectiveness in the final year of use for higher-weight individuals. But the available evidence does not show a meaningful increase in pregnancy risk based on weight. Nexplanon delivers hormone directly into the bloodstream at a steady rate, which makes it less susceptible to weight-related absorption issues than methods like the pill or patch.
What About GLP-1 Weight Loss Drugs?
With the rise of semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), many people have wondered whether these drugs affect hormonal birth control. GLP-1 medications slow stomach emptying, which can theoretically interfere with how oral medications are absorbed. For Nexplanon, this is not a concern. The implant delivers hormone directly through the tissue in your arm, completely bypassing the digestive system. No extra precautions are needed when using Nexplanon alongside any GLP-1 medication.
Using Nexplanon Beyond Three Years
Nexplanon is FDA-approved for three years of use. Some providers may discuss extended use based on emerging clinical data, but the approved duration remains three years. If your implant is past its labeled lifespan and hasn’t been replaced, its hormone output has dropped, and effectiveness may be reduced. The simplest way to stay protected is to schedule a replacement before the three-year mark.
If your implant is placed within the recommended window, you’re not taking enzyme-inducing medications or St. John’s Wort, and you can feel the rod under your skin, Nexplanon remains one of the most reliable contraceptive options available. The vast majority of the rare pregnancies that occur with the implant trace back to one of the specific factors above rather than a flaw in the method itself.