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

Apretude (cabotegravir) has a specific and important drug interaction profile. Unlike many medications, its interactions are driven by a single metabolic pathway — and knowing which drugs interfere with that pathway could determine whether Apretude is safe and effective for you.

How Apretude Is Metabolized (The Key to Understanding Its Interactions)

Cabotegravir is primarily metabolized by the enzyme UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) with some contribution from UGT1A9. These are liver and intestinal enzymes that process and eliminate many drugs.

The interaction risk is one-directional: drugs that strongly induce (speed up) these UGT enzymes will dramatically reduce cabotegravir plasma concentrations — potentially dropping them below the level needed to prevent HIV. This is not just a "monitor closely" situation — several inducers are contraindicated with Apretude.

Contraindicated Drugs: Do Not Use With Apretude

The following drugs are contraindicated with Apretude because they are strong UGT1A1 or UGT1A9 inducers that significantly decrease cabotegravir exposure:

Rifampin (used to treat tuberculosis and some bacterial infections)

Rifapentine (used to treat TB)

Carbamazepine (Tegretol — used for seizures and nerve pain)

Oxcarbazepine (Trileptal — used for seizures)

Phenobarbital (used for seizures)

Phenytoin (Dilantin — used for seizures)

Apalutamide (Erleada — used for prostate cancer)

If you are taking any of these medications, Apretude is not appropriate for you unless the interacting drug can be safely discontinued. Talk to your prescriber about alternative seizure medications or alternative PrEP options (oral PrEP is not affected by the same enzyme pathway).

Rifabutin: Requires Dose Adjustment (Not Contraindicated)

Rifabutin (used for certain infections including TB) is a moderate UGT inducer. Unlike rifampin and rifapentine, it's not contraindicated — but the Apretude injection schedule must be adjusted. Specifically, patients on rifabutin require more frequent Apretude injections (every 4 weeks instead of every 8 weeks). See the full prescribing information for the specific dosing schedule.

Antacids, Calcium, and Other Products: Oral Lead-In Only

Certain antacids and polyvalent cation products can bind to oral cabotegravir in the gut and reduce absorption. This applies only to the oral lead-in (Vocabria tablets) — not to the injectable Apretude, since the injection bypasses the GI tract entirely.

If using Vocabria oral lead-in, take the following at least 2 hours before or 4 hours after the oral tablet:

Antacids containing aluminum or magnesium (Tums, Maalox, Mylanta)

Calcium carbonate supplements

Iron supplements

Buffered aspirin (aspirin/citric acid/sodium bicarbonate)

Medications You CAN Take Safely With Apretude

Drug interaction studies have confirmed that the following can be used with cabotegravir without dose adjustment:

Oral contraceptives containing levonorgestrel and ethinyl estradiol — safe to use concurrently

Midazolam — safe (no clinically significant interaction)

Etravirine — can be co-administered after discontinuation

Rilpivirine — compatible (used together in Cabenuva, the HIV treatment formulation)

What to Tell Your Doctor Before Starting Apretude

Before your first Apretude injection, make sure your provider has a complete list of your current medications, including:

All prescription medications

Over-the-counter medications (including antacids and supplements)

Herbal products and supplements (St. John's Wort may also induce UGT enzymes — discuss with your provider)

Any medications you take for seizures, TB, or prostate cancer — these have the highest likelihood of interaction

For information on Apretude's side effect profile, see our guide on Apretude side effects. To find a provider who administers Apretude near you, visit medfinder.com.