Tri-Lo-Sprintec Drug Interactions: What to Avoid and What to Tell Your Doctor

Tri-Lo-Sprintec 28 Day is metabolized in the liver, which means many other medications and supplements can affect how well it works. Some interactions reduce its contraceptive effectiveness. Others can increase the risk of side effects. Here's what you need to know.

Drugs That Reduce How Well Tri-Lo-Sprintec Works (Enzyme Inducers)

The most important category of interactions involves drugs that activate liver enzymes — specifically cytochrome P450 3A4 (CYP3A4). These drugs speed up the breakdown of ethinyl estradiol and norgestimate in your body, reducing their blood levels and potentially making Tri-Lo-Sprintec less effective at preventing pregnancy.

If you take any of these medications, use a backup contraceptive method (condoms) while taking them and for 28 days after stopping:

• Rifampin (rifampicin): Antibiotic for tuberculosis and certain other infections. Considered the most significant interaction — strongly reduces COC effectiveness.
• Rifabutin, rifapentine: Related antibiotics with similar enzyme-inducing effects.
• Phenytoin (Dilantin): Anti-seizure medication. Significantly reduces COC effectiveness.
• Carbamazepine (Tegretol): Anti-seizure and mood-stabilizing medication.
• Phenobarbital (and other barbiturates): Anti-seizure medications; also used for anxiety.
• Topiramate (Topamax): Anti-seizure and migraine medication; also used for weight loss.
• Oxcarbazepine (Trileptal): Anti-seizure medication.
• Bosentan (Tracleer): Used for pulmonary arterial hypertension.
• Aprepitant (Emend): Anti-nausea medication used with chemotherapy.
• Griseofulvin: Antifungal medication.

Contraindicated: Hepatitis C Drug Combinations

Tri-Lo-Sprintec must NOT be used with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir (brand name Technivie or Viekira Pak), with or without dasabuvir. These combinations have been shown to cause significantly elevated liver enzymes (ALT elevations greater than 5 times the upper limit of normal) when used with estrogen-containing medications.

Supplements and Natural Products to Watch Out For

Not all interactions come from prescription drugs. These over-the-counter supplements and natural products can also affect Tri-Lo-Sprintec:

• St. John's Wort (Hypericum perforatum): A commonly used herbal supplement for depression. Strongly induces CYP3A4 and can significantly reduce COC effectiveness. Avoid while taking Tri-Lo-Sprintec.
• Modafinil (Provigil): Wakefulness agent (also sold as Nuvigil/armodafinil); mild CYP3A4 inducer.
• Soy isoflavone supplements: May interact with estrogenic activity.

Food Interactions

Grapefruit juice can affect how ethinyl estradiol is metabolized. Unlike some other medications where grapefruit increases drug levels (increasing risk of side effects), with COCs the interaction is complex. As a precaution, avoid large amounts of grapefruit juice while taking Tri-Lo-Sprintec.

Drugs That Tri-Lo-Sprintec Can Affect

Tri-Lo-Sprintec can also increase or decrease the levels of other medications in your blood:

• Cyclosporine: COCs can increase cyclosporine blood levels — monitor closely.
• Theophylline: COCs may increase theophylline levels.
• Lamotrigine (Lamictal): Estrogen-containing COCs can significantly decrease lamotrigine blood levels, potentially reducing seizure control. This requires close monitoring.

What Should You Tell Your Doctor?

Before starting Tri-Lo-Sprintec, tell your prescriber about all medications you take, including:

• All prescription medications (especially anti-seizure drugs, HIV medications, antibiotics, and antifungals)
• All over-the-counter medications and supplements
• Any herbal products, including St. John's Wort

Related: Tri-Lo-Sprintec Side Effects: What to Expect and When to Call Your Doctor.

For general drug information: What Is Tri-Lo-Sprintec? Uses, Dosage, and What You Need to Know in 2026.