Ortho Tri-Cyclen 28 Day Drug Interactions

Ortho Tri-Cyclen 28 Day (Norgestimate/Ethinyl Estradiol) is a combination birth control pill that can interact with a number of other medications, supplements, and even some foods. Some interactions reduce the pill's effectiveness — meaning you could get pregnant. Others increase your risk of dangerous side effects like blood clots. This guide covers the interactions you need to know about.

How Drug Interactions Work with Birth Control

Most interactions with Ortho Tri-Cyclen fall into two categories:

1. Medications that speed up how your liver processes the pill's hormones (called enzyme inducers). These cause your body to break down Ethinyl Estradiol and Norgestimate faster, reducing their levels in your blood and making the pill less effective at preventing pregnancy.
2. Medications whose levels are affected by the pill's hormones. Ethinyl Estradiol can interfere with how your body processes certain other drugs, making them either stronger or weaker.

Medications That Interact with Ortho Tri-Cyclen

Major Interactions (Avoid or Use Extra Precautions)

• Hepatitis C Medications (Ombitasvir/Paritaprevir/Ritonavir) — Contraindicated. Do not take these with any estrogen-containing birth control. This combination can cause dangerous liver enzyme elevations. Brand names include Viekira Pak and Technivie.
• Rifampin (Rifadin) — This tuberculosis antibiotic is one of the strongest enzyme inducers and can dramatically reduce the effectiveness of oral contraceptives. If you need Rifampin, use a non-hormonal backup method (like condoms) or switch to a non-oral contraceptive.
• Anticonvulsants / Anti-Seizure Medications:
  • Phenobarbital
  • Phenytoin (Dilantin)
  • Carbamazepine (Tegretol)
  • Topiramate (Topamax) — at doses above 200 mg/day
  • Felbamate (Felbatol)
  • Oxcarbazepine (Trileptal)

  These medications speed up the breakdown of contraceptive hormones and can significantly reduce effectiveness. Talk to your doctor about alternative seizure medications or backup contraception.

• Bosentan (Tracleer) — Used for pulmonary arterial hypertension. Reduces contraceptive efficacy.
• HIV Medications:
  • Certain protease inhibitors (Ritonavir/Norvir, Nelfinavir/Viracept, Lopinavir) can decrease contraceptive hormone levels
  • Some NNRTIs (Nevirapine/Viramune, Efavirenz/Sustiva) may also reduce effectiveness

  Women taking HIV medications should work with their provider to find a contraceptive method that won't be affected.

• Tranexamic Acid (Lysteda) — Used for heavy menstrual bleeding. Combining it with estrogen-containing birth control increases the risk of blood clots. This combination should generally be avoided.

Moderate Interactions (Monitor Closely)

• Lamotrigine (Lamictal) — This is a two-way interaction. Oral contraceptives can decrease Lamotrigine levels by up to 50%, potentially triggering seizures. When you stop the pill, Lamotrigine levels can spike. Your neurologist may need to adjust your Lamotrigine dose when you start or stop birth control.
• Tizanidine (Zanaflex) — Oral contraceptives can increase Tizanidine levels, potentially causing excessive drowsiness and low blood pressure.
• Dantrolene (Dantrium) — Combined use may increase the risk of liver toxicity.
• Thyroid Hormone Replacement (Levothyroxine/Synthroid) — Estrogen can increase the protein that binds thyroid hormone, potentially requiring a dose adjustment of your thyroid medication. Your doctor should monitor your thyroid levels.
• Certain Antibiotics (Ampicillin, Tetracycline) — There's a theoretical concern that broad-spectrum antibiotics may reduce contraceptive effectiveness by disrupting gut bacteria that help absorb the pill. The evidence is weak for most antibiotics, but Rifampin is the exception — it definitively reduces effectiveness. For other antibiotics, using backup contraception during the course is a reasonable precaution.

Supplements and OTC Medications to Watch

• St. John's Wort — This is a major one. St. John's Wort is a popular herbal supplement for depression and mood, but it's a potent enzyme inducer that can significantly reduce the effectiveness of Ortho Tri-Cyclen. Do not take St. John's Wort while on combination birth control. If you need treatment for depression, talk to your doctor about prescription options.
• Activated Charcoal — Sometimes used for detox or digestive issues. It can absorb medications in your stomach, including birth control pills, reducing their effectiveness. Avoid taking it within 2 hours of your pill.
• High-Dose Vitamin C — Very high doses (1,000+ mg) may theoretically increase estrogen levels by competing for the same metabolic pathway. This is unlikely to be clinically significant at normal supplement doses.

Food and Drink Interactions

• Grapefruit Juice — Grapefruit can slightly increase Ethinyl Estradiol levels by inhibiting the enzyme that breaks it down (CYP3A4). This is unlikely to cause problems at normal consumption levels, but drinking large quantities daily could slightly increase estrogen-related side effects.
• Alcohol — Alcohol doesn't directly reduce the pill's effectiveness, but heavy drinking can lead to vomiting (which could mean you don't absorb the pill) and may impair your ability to take the pill on time consistently.
• St. John's Wort Tea — Same concern as the supplement. Herbal teas containing St. John's Wort should be avoided.

What to Tell Your Doctor

Before starting Ortho Tri-Cyclen 28 Day, make sure your doctor knows about:

• All prescription medications you take, especially anticonvulsants, HIV medications, antibiotics, and blood thinners
• All supplements and herbal products, especially St. John's Wort
• Any OTC medications you use regularly
• Any planned surgeries — your doctor may ask you to stop the pill 4–6 weeks before major surgery to reduce blood clot risk
• Changes to your medication list — anytime a new medication is added or removed, check with your pharmacist about interactions

Your pharmacist is also an excellent resource. Every time you fill a prescription, they automatically check for interactions in their system. Don't hesitate to ask them questions.

Final Thoughts

The most important interactions to remember with Ortho Tri-Cyclen 28 Day are:

1. St. John's Wort — avoid completely
2. Rifampin — use backup contraception or a different birth control method
3. Anticonvulsants — many reduce the pill's effectiveness
4. Hepatitis C drugs with Ritonavir — contraindicated
5. Lamotrigine — the pill reduces Lamotrigine levels, which can be dangerous

When in doubt, ask your doctor or pharmacist before combining any medication with your birth control. For more about this medication, see our guides on side effects and how Ortho Tri-Cyclen works. If you need help finding your prescription, Medfinder can check pharmacy availability near you.