Ogsiveo Drug Interactions: What to Avoid and What to Tell Your Doctor

Ogsiveo (nirogacestat) is a complex drug that interacts with a significant number of other medications. Understanding these interactions is important — not just for your safety, but because some common over-the-counter medications and foods can reduce Ogsiveo's effectiveness. This guide covers the key interactions you need to know before starting Ogsiveo.

Always tell your doctor and pharmacist about every medication you take — including prescription drugs, over-the-counter medications, vitamins, and herbal supplements — before starting Ogsiveo.

Why Does Ogsiveo Have So Many Drug Interactions?

Ogsiveo is primarily metabolized by the liver enzyme CYP3A4 (with minor involvement of CYP2C19, CYP2C9, and CYP2D6). This means that any drug that affects CYP3A4 activity can change how much nirogacestat circulates in your blood:

Drugs that inhibit CYP3A4 slow down Ogsiveo's breakdown → Ogsiveo levels increase → greater toxicity risk

Drugs that induce (speed up) CYP3A4 accelerate Ogsiveo's breakdown → Ogsiveo levels decrease → reduced effectiveness

Additionally, Ogsiveo itself inhibits CYP3A4 and induces CYP2B6, CYP2C8, CYP2C9, and CYP2C19 — which means Ogsiveo can change how other drugs are metabolized in your body.

Drugs That Increase Ogsiveo Levels (CYP3A4 Inhibitors) — AVOID

These medications inhibit CYP3A4 and cause Ogsiveo blood levels to rise significantly, increasing the risk of toxicity. Avoid them if at all possible:

Strong CYP3A4 inhibitors (AVOID — can increase Ogsiveo levels 3–6x): Itraconazole, ketoconazole (antifungals); clarithromycin (antibiotic); some HIV medications (ritonavir, cobicistat)

Moderate CYP3A4 inhibitors (AVOID if possible — can increase Ogsiveo levels 2–3x): Erythromycin, fluconazole, diltiazem, verapamil, amiodarone

Drugs That Decrease Ogsiveo Levels (CYP3A4 Inducers) — AVOID

These medications speed up the breakdown of Ogsiveo, reducing its effectiveness. Strong CYP3A4 inducers can reduce Ogsiveo levels by up to 85%:

Strong CYP3A4 inducers (AVOID — can reduce Ogsiveo levels by ~85%): Rifampin (rifampicin), an antibiotic commonly used for tuberculosis

Moderate CYP3A4 inducers (AVOID if possible — can reduce Ogsiveo levels by ~67%): Carbamazepine (Tegretol), phenytoin, oxcarbazepine — anticonvulsants/seizure medications; cenobamate; butalbital; apalutamide; bosentan

If you are taking a seizure medication, do not stop it without talking to your neurologist — but make sure your oncologist knows you are on it, as they may need to use an alternative or adjust monitoring.

Acid-Reducing Medications — IMPORTANT INTERACTION

This is one of the most practically important Ogsiveo drug interactions because so many patients take antacids, PPIs, or H2 blockers for heartburn or GERD.

Ogsiveo is poorly soluble at pH ≥6. Acid-reducing medications raise stomach pH, which significantly decreases Ogsiveo absorption:

Proton pump inhibitors (PPIs) — AVOID: Omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), pantoprazole (Protonix). These raise stomach pH for extended periods and cannot be effectively timed around Ogsiveo dosing.

H2 blockers — AVOID if possible: Famotidine (Pepcid AC), cimetidine, nizatidine. These also raise pH for several hours.

Antacids — CAN be used with timing: Tums (calcium carbonate), Rolaids, Mylanta. If you need an antacid, take Ogsiveo at least 2 hours before or 2 hours after the antacid to minimize the interaction.

If you need treatment for acid reflux or GERD while on Ogsiveo, discuss alternatives with your doctor — antacids taken with proper timing are the preferred option.

Drugs That Ogsiveo Affects (Ogsiveo as the Perpetrator)

Ogsiveo itself inhibits CYP3A4, which means it can increase blood levels of other drugs metabolized by CYP3A4. This includes:

Lomitapide (Juxtapid) — CONTRAINDICATED: Nirogacestat dramatically increases lomitapide exposure; concomitant use is contraindicated.

Brigatinib (Alunbrig) — avoid: Ogsiveo increases brigatinib exposure; concomitant use should be avoided.

CYP2C19 substrates: Ogsiveo induces CYP2C19, which can decrease levels of drugs metabolized by this enzyme (e.g., some antidepressants, proton pump inhibitors, certain anticoagulants).

Foods to Avoid During Ogsiveo Treatment

Three foods/drinks can increase Ogsiveo blood levels by inhibiting intestinal CYP3A4:

Grapefruit and grapefruit juice — avoid entirely during treatment

Seville oranges (also called bitter oranges or sour oranges, often found in marmalades) — avoid during treatment

Starfruit — avoid during treatment

Contraception and Hormonal Medications

Women of reproductive potential must use effective contraception during Ogsiveo treatment and for one week after the last dose. Because Ogsiveo may affect hormone metabolism, women using hormonal contraceptives are advised to add a barrier method (such as a condom) for additional protection. Discuss your contraceptive needs with your oncologist before starting therapy.

For a full overview of what to watch for on treatment, see Ogsiveo side effects and when to call your doctor. For general information about Ogsiveo, visit our guide on what is Ogsiveo and how it's used.