Acid-reducing agents like PPIs and absorption interactions summarized, US

I didn’t expect a casual chat at the pharmacy counter to send me down a rabbit hole about stomach acid, but that’s exactly what happened. A friend asked why their antifungal wasn’t working as expected while they were also taking a proton pump inhibitor (PPI). That one question tugged on a long thread about how changing stomach acidity can nudge (or shove) medicine absorption in different directions. I wanted to collect what finally made this topic “click” for me—without hype, with real-world examples, and with the kind of practical notes I wish I’d had earlier.

Why raising stomach pH can change a pill’s fate

Here’s the image that stuck with me: imagine your stomach as the “front door” to the rest of the digestive tract. Many medicines are formulated expecting a certain level of acidity at that door. When we take acid-reducing agents—PPIs (like omeprazole, esomeprazole, lansoprazole), H₂ blockers (famotidine), or antacids (aluminum/magnesium hydroxide, calcium carbonate)—we raise the pH. For some drugs that rely on an acidic environment to dissolve, that shift can mean less dissolved drug and less getting into the bloodstream. For others, it may not matter much—or the timing is what matters.

• PPIs are potent and longer-acting; they suppress the “acid pumps” for much of the day.
• H₂ blockers typically act faster but for a shorter window.
• Antacids neutralize acid on contact and also bring minerals like calcium, magnesium, or aluminum that can bind (chelate) certain meds and block absorption.

Two big mechanisms keep showing up: pH-dependent solubility (the drug needs acid to dissolve) and chelation (the drug binds to minerals and can’t get absorbed). Understanding which mechanism is at play helps me decide whether to avoid a combo entirely, separate the timing, or switch the formulation.

• DHHS HIV guidance on acid-suppressors with rilpivirine
• NIH ODS calcium fact sheet
• NIH ODS iron fact sheet

The culprits I actually see in day-to-day life

These are patterns that come up over and over—in my notes, in pharmacy counseling, and in reader emails. I’m keeping the list short on purpose so it stays usable.

• Rilpivirine (an HIV medicine) and strong acid suppression — PPIs and rilpivirine generally do not mix because the drug needs stomach acid to dissolve well. Guidance recommends not using PPIs with rilpivirine; H₂ blockers can be used only with careful spacing (at least 12 hours before or 4 hours after the rilpivirine dose). This is one of those combinations where the details really matter. See the official summary here.
• Atazanavir (another HIV medicine) and acid reducers — Atazanavir also needs an acidic environment. Depending on the regimen and experience level, guidance may instruct strict avoidance or very specific timing caps for PPIs and H₂ blockers. This is a “don’t wing it” situation; clinicians use detailed tables to decide what’s acceptable. A concise starting point is the federal HIV guidance for protease inhibitors and acid reducers.
• Itraconazole capsules and antacids/PPIs — The capsule formulation (unlike the oral solution) is classic pH-dependent absorption. Antacids should be separated (e.g., taken 1 hour before or 2 hours after the antifungal), and PPIs/H₂ blockers can reduce exposure. See the patient-friendly instructions on MedlinePlus.
• Levothyroxine and minerals — Calcium, iron, aluminum, and magnesium can physically bind levothyroxine and block it from being absorbed. The practical move is separating the dose by about 4 hours. This is laid out clearly on MedlinePlus.
• Calcium supplements when acid is low — If you’re on long-term PPIs or you just don’t make much acid (common as we age), calcium citrate tends to absorb better than calcium carbonate. The NIH Office of Dietary Supplements explains this distinction clearly for clinicians and the public.
• Iron and acid suppression — Nonheme iron absorption is already finicky, and PPIs can make it harder. The NIH ODS iron fact sheet notes that PPIs can potentially reduce iron absorption; in practice, spacing, vitamin C with iron, or using different iron formulations may help, but it’s individualized.

Simple mental checklists that keep me out of trouble

When I’m skimming a medication list or looking at my own pillbox, this is the quick script I run through:

• Step 1 Notice — Is there a strong acid reducer (a PPI) or a mineral-heavy product (antacids, calcium, iron, magnesium, aluminum, multivitamins, sucralfate)? If yes, I flag meds known for pH sensitivity (some HIV meds, itraconazole capsules) and chelation risk (levothyroxine, some antibiotics, iron itself).
• Step 2 Compare — Is the sensitive medicine one that absolutely must not be combined with a PPI (e.g., rilpivirine), or will careful spacing be enough (e.g., levothyroxine with minerals)? I remind myself that capsules vs solutions can matter (itraconazole solution behaves differently), and that individual labels can be very specific.
• Step 3 Confirm — I verify the exact timing on a trusted source and then write it down. For example:
  • Rilpivirine timing with H₂ blockers and PPI avoidance.
  • Itraconazole capsule instructions with antacids.
  • Levothyroxine separation from calcium/iron.

Each time I do this, I’m struck by how a small scheduling tweak can reduce a lot of uncertainty—and how often we forget to write the plan down in a place we’ll actually see it the next morning.

What I changed in my own routine

I used to keep all supplements in one bin. Predictably, that meant I’d swallow calcium, magnesium, and a multivitamin right after breakfast—sometimes near my prescription meds. Now I do three low-tech things:

• Separate trays by “morning-stomach-empty,” “with food,” and “bedtime.” Levothyroxine lives in the first tray by itself. Minerals and antacid-like products moved into the “with food” tray, often at lunch or dinner, far away from thyroid medicine.
• Write the timing into the bottle label. I add: “4 hours away from thyroid med” or “avoid with PPI” so Future Me doesn’t mess it up.
• Choose forms that fit the physiology. If calcium is needed while on a PPI, I consider calcium citrate rather than carbonate and match it with meals I’m likely to remember.

Nuances that helped me avoid oversimplifying

It’s tempting to reduce everything to “PPIs block absorption.” The reality is more nuanced:

• Formulation matters. Itraconazole capsules are pH dependent; the solution behaves differently. Always check the exact product.
• Some combinations are absolute no-gos. Rilpivirine + PPIs is the poster child. Others allow precise timing workarounds (e.g., H₂ spacing with rilpivirine).
• Antacids bring minerals. Even when pH isn’t the main issue, calcium/magnesium/aluminum can bind certain drugs. That’s chelation, a different mechanism than “needs-acid-to-dissolve.”
• Nutrients are medications too (functionally). Iron and calcium aren’t just “food”—they have real interactions. NIH ODS sheets are gold for this.
• We’re all different. Age, gastric physiology, other illnesses, and even surgery history (like bariatric surgery) can change how we absorb things. Personalized plans matter.

Timing “rules of thumb” I keep on a sticky note

I don’t rely on memory for the big ones; I write them down and verify against a reliable source:

• Rilpivirine — Avoid PPIs; if using an H₂ blocker, give it at least 12 hours before or 4 hours after the rilpivirine dose (federal HIV guidance).
• Itraconazole capsules — Separate antacids (e.g., 1 hour before or 2 hours after the antifungal). PPIs/H₂ blockers may reduce exposure; confirm specifics on the label or MedlinePlus.
• Levothyroxine — Take on an empty stomach consistently; keep calcium/iron/antacids at least 4 hours away (MedlinePlus).
• Calcium supplements with low acid — Consider calcium citrate if you’re on a PPI; it’s less dependent on acid than carbonate (NIH ODS).
• Iron — PPIs can potentially reduce nonheme iron absorption; timing with vitamin C or choosing different iron strategies can help (individualized; see NIH ODS).

Bottom line: if you see a PPI/H₂/antacid and one of these “sensitive” meds on the same list, pause and double-check the timing or consider alternatives with your clinician.

Signals that tell me to slow down and call for backup

These are the moments when I stop tinkering and get professional input:

• Antiviral regimens where maintaining levels is critical (e.g., HIV therapy with rilpivirine or atazanavir).
• Persistent symptoms despite “perfect” dosing—like ongoing fungal symptoms while on itraconazole capsules plus an acid reducer.
• Thyroid numbers drifting after starting a new supplement or antacid; I ask about levothyroxine timing and consider a recheck with my clinician.
• Fatigue or new anemia in someone on long-term PPIs; I review iron intake and lab plans with a clinician.
• Post-surgery anatomy (e.g., bariatric surgery) where absorption is inherently different.

What I’m keeping and what I’m letting go

I’m keeping a few principles taped inside the kitchen cabinet:

• Write timing where I’ll see it (on the bottle, not in a forgotten note app).
• Match the form to the physiology (calcium citrate when acid is low; be picky about capsule vs solution with pH-dependent meds).
• Respect the “no-go” pairs (rilpivirine + PPI) and don’t improvise; check authoritative guidance.

And I’m letting go of the myth that “all acid reducers are the same.” They aren’t—how they reduce acid and how long they act often determine whether a timing workaround is safe or if we need a different plan entirely.

FAQ

1) Do PPIs reduce the absorption of every medication?
Answer: No. The effect is selective. Some medicines require stomach acid to dissolve (e.g., certain HIV meds, itraconazole capsules), while others are unaffected. The key is knowing which meds are acid-dependent or prone to mineral binding and then adjusting timing or therapy accordingly.

2) If I need a calcium supplement and take a PPI, which form is better?
Answer: Many clinicians prefer calcium citrate when stomach acid is reduced; it’s less acid-dependent than calcium carbonate. See the NIH Office of Dietary Supplements’ clinician sheet for context.

3) How should I take levothyroxine if I also use antacids or iron?
Answer: Take levothyroxine on an empty stomach consistently, and keep calcium/iron/antacids about 4 hours away from it. MedlinePlus outlines this clearly.

4) I’m on rilpivirine for HIV and have heartburn. Can I use an H₂ blocker or PPI?
Answer: PPIs are generally not used with rilpivirine. Some H₂ blockers may be used only with specific spacing (e.g., 12 hours before or 4 hours after). This is a “check official guidance and talk to your HIV clinician” moment.

5) Are antacids safer than PPIs for interactions?
Answer: “Safer” is too simple. Antacids can chelate medicines like levothyroxine or certain antibiotics; PPIs can reduce acid and affect pH-dependent drugs. The best option depends on which medicine you’re pairing them with and whether timing fixes the issue.

Sources & References

• DHHS HIV Guidelines — NNRTIs and acid-reducing agents (2024)
• MedlinePlus — Itraconazole capsules (2025)
• MedlinePlus — Levothyroxine drug information
• NIH ODS — Calcium fact sheet for health professionals (2025)
• NIH ODS — Iron fact sheet for health professionals (2025)

This blog is a personal journal and for general information only. It is not a substitute for professional medical advice, diagnosis, or treatment, and it does not create a doctor–patient relationship. Always seek the advice of a licensed clinician for questions about your health. If you may be experiencing an emergency, call your local emergency number immediately (e.g., 911 [US], 119).