PrEP Drug Interactions: Meds and Supplements to Mention

Why the pills and shots interact differently

The PrEP medicines are handled by the body in different ways, so they interact with different drugs:

• Tenofovir and emtricitabine (Truvada, generics, Descovy) are cleared mainly by the kidneys. Drugs that strain the kidneys, or compete for the same kidney clearance, matter most. Descovy's tenofovir alafenamide is also sensitive to drugs that speed up its breakdown.
• Cabotegravir (Apretude) can be broken down faster by certain enzyme-inducing drugs, which lowers its levels.
• Lenacapavir (Yeztugo) is affected by drugs that change the CYP3A enzyme and some drug transporters. It can also change other drugs' levels for months.

Daily pills: Truvada and generic F/TDF

Kidney-stressing drugs

Truvada's label says tenofovir disoproxil fumarate should be avoided with current or recent use of a kidney-toxic drug. It specifically notes reports of acute kidney failure with high-dose or multiple NSAIDs, such as ibuprofen, naproxen and diclofenac. Occasional over-the-counter use is common, but regular or high-dose use is worth raising.

Drugs cleared by the kidneys

The label notes that drugs eliminated through active tubular secretion can raise emtricitabine or tenofovir levels. Examples include acyclovir and valganciclovir (used for herpes and CMV) and aminoglycoside antibiotics. CDC's guidance lists the same examples and advises caution, not avoidance. Many people take acyclovir or valacyclovir with PrEP under their prescriber's supervision.

Other label interactions

The label also lists some HIV and hepatitis C medicines that change tenofovir levels. These matter mostly for people being treated for those conditions. If you're starting hepatitis C treatment, tell that prescriber you're on PrEP.

Daily pills: Descovy (F/TAF)

Descovy shares the kidney-related cautions, including NSAIDs and drugs like acyclovir, valacyclovir and aminoglycosides. It also has interactions with drugs that lower tenofovir alafenamide levels:

• Seizure medicines: carbamazepine, oxcarbazepine, phenobarbital and phenytoin. The label says to consider an alternative.
• Rifamycin antibiotics: rifampin, rifabutin and rifapentine, used for tuberculosis and some other infections. Using them together is not recommended.
• St. John's wort: using them together is not recommended.
• Tipranavir/ritonavir (an HIV treatment): not recommended together.

If you need one of these, generic F/TDF or an injectable may fit better. See Descovy vs. Truvada.

Apretude (cabotegravir)

Apretude's label lists these as contraindicated, meaning they shouldn't be used together, because they can drop cabotegravir to unprotective levels:

• Seizure medicines: carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• Antimycobacterials: rifampin, rifapentine

Rifabutin also lowers cabotegravir levels. The label allows it with a modified injection schedule. Because Apretude stays in the body for months, tell any new prescriber you've had it, even after you've stopped.

Yeztugo (lenacapavir)

Yeztugo's label and CDC's 2025 recommendation flag two directions of interaction:

• Drugs that lower lenacapavir: strong or moderate CYP3A inducers can significantly decrease lenacapavir levels. The label calls for supplemental doses in those cases rather than an outright ban. Drugs in this group include some tuberculosis antibiotics, some seizure medicines and St. John's wort. Your prescriber will check the label's list and tables for your specific medicine.
• Drugs that are not recommended together: the label says Yeztugo isn't recommended with drugs that strongly inhibit P-gp, UGT1A1 and CYP3A together.
• Lenacapavir raising other drugs' levels: lenacapavir can increase concentrations of some medicines processed by CYP3A for up to 9 months after the last injection, so those doses may need adjusting.

More on the two shots in Yeztugo vs. Apretude and our injectable PrEP guide.

Quick reference

"Not a label issue" means the interaction isn't flagged in that drug's prescribing information as summarized here. It doesn't replace a pharmacist's check.

Gender-affirming hormones, supplements and everyday products

• Hormonal birth control: CDC reports no known interactions with PrEP.
• Gender-affirming hormones: research hasn't shown estrogen meaningfully lowering PrEP drug levels. Our trans women's PrEP guide covers this. List your hormones for your prescriber either way.
• Creatine and high-protein supplements don't interact with PrEP, but they can raise creatinine on kidney tests, which can look like a kidney problem. Mention them before your labs.
• Herbal products: St. John's wort is the one named on the labels. With any herbal product, ask before you combine.
• Alcohol and recreational drugs: not listed as interacting on the PrEP labels. The practical risk is missed doses (see PrEP and alcohol).

Situations where interactions come up

Getting treated for an STI

The first-line antibiotics for gonorrhea, chlamydia and syphilis, such as ceftriaxone, doxycycline and penicillin, aren't on the PrEP labels' interaction lists. Aminoglycosides like gentamicin, sometimes used as alternatives, are on the oral PrEP caution list, so mention PrEP if one is offered. Treatment for an STI generally doesn't mean pausing PrEP. Keep taking it unless your prescriber says otherwise. DoxyPEP (doxycycline after sex) is also commonly combined with PrEP. Our sister site explains the STI testing schedule that comes with PrEP.

Starting tuberculosis treatment

Rifamycin antibiotics are the most important interaction across the PrEP options. If you're diagnosed with TB or latent TB, make sure both prescribers know about each other, because your PrEP option or dose may need to change.

Managing epilepsy or mood conditions

Several older seizure medicines, some of which are also used for mood or nerve pain, interact with Descovy, Apretude or Yeztugo. Generic F/TDF isn't flagged for these in its label, which is one reason prescribers sometimes choose it for people on these drugs.

Living with chronic pain

Regular NSAID use and tenofovir disoproxil fumarate is a combination the Truvada label specifically warns about. Options include closer kidney monitoring, a different pain plan, or a PrEP option that's easier on the kidneys.

Seeing a new doctor after an injectable

Because Yeztugo can affect other drugs for up to 9 months after the last shot, and both injectables linger for months, mention past injections even after you've stopped PrEP.

How to stay safe

• Use one pharmacy when you can, so interaction checks see everything.
• Tell every new prescriber, dentist and urgent care clinic you take PrEP. If you've had an injectable in the past year or so, mention that too.
• If you start a new medicine and notice changes in urination, unusual swelling or new side effects, call your prescriber. Our side effects guide explains what's typical.

This guide is general health information, not medical advice, and it doesn't replace a conversation with a clinician who knows your history. Guidance and program rules change; we last reviewed this page on October 12, 2026. Spot something out of date? Tell us.