Guide
Drug interactions: how checkers work and where the evidence comes from
A drug interaction happens when another substance, such as a medicine, food, drink, herb or supplement, changes how a medicine works or adds to its side effects. Online checkers such as Drugs.com and Medscape look up known pairs in a curated database and give each a severity grade. They are a screening aid. Your pharmacist interprets the result for you.
This is information about reading evidence, not medical advice. Talk to your doctor or pharmacist before changing anything.
The main kinds of interaction
Drugs.com describes three types:
- Drug-drug: one medicine affects another. Two medicines that both cause drowsiness, for example, can add up.
- Drug-food and drug-drink: grapefruit juice and alcohol are the familiar examples.
- Drug-disease: a condition changes how a medicine acts, or a medicine worsens a condition.
Mechanisms fall into two broad groups. Some interactions change how much of a drug reaches the blood (absorption, breakdown or removal). Others change what the drug does once it is there, such as two medicines with the same effect adding together.
How interaction checkers work
A checker does not run an experiment on your medicines. It looks up each pair in a database that editors and pharmacists build from product information, published studies and case reports, then shows a grade and a short explanation.
Severity grades differ between checkers. Two public examples:
| Drugs.com | Medscape |
|---|---|
| Major: "These combinations are best avoided because the risks usually outweigh any potential benefit." | Contraindicated: "Risk of concomitant use of these drugs outweigh the benefits" |
| Moderate: "sometimes used under close medical supervision but are generally avoided unless necessary" | Serious - Use Alternative: avoid concomitant use or consider an alternative |
| Minor: "may not cause problems for most people" | Monitor Closely: monitor for increased effects, adverse effects, or reduced efficacy |
| Unknown: "Interaction data are limited or unavailable" | Minor: no clinically meaningful difference, or unknown |
Drugs.com itself says the categories "are only general guidelines" and that actual risk "can vary from person to person."
Checkers do not always agree. A 2016 study by Kheshti and colleagues compared five interaction programs (Lexi-Interact, Micromedex, iFacts, Medscape and Epocrates) against a clinical pharmacist's assessment and reference sources. Accuracy scores ranged from 191 to 250 out of 400, and the authors concluded that sensitivity improves when more than one program is combined with "expert pharmacist intervention." The results reflect those versions in 2016; databases have changed since. The lesson holds: a clean result from one checker is not proof of no interaction, and a flag is not proof of harm.
Where the evidence comes from
Interaction evidence is uneven, and it helps to know what sits under a grade:
- Product information and labels, which may list interactions found in formal studies during development.
- Pharmacokinetic studies, often small, measuring drug levels when two substances are combined.
- Case reports, which can raise a signal but cannot show how often something happens.
- Observational studies in large populations.
Pharmacists have formal tools for weighing case reports. The Drug Interaction Probability Scale (Horn, Hansten and Chan, Annals of Pharmacotherapy, 2007) was proposed to assess how likely it is that an interaction caused the event described in a case. One case report, however vivid, is the weakest rung.
Grapefruit: a well-documented example
The grapefruit effect was first reported in 1991, when Bailey and colleagues found that grapefruit juice raised the bioavailability of the blood pressure medicine felodipine in six men (The Lancet). It has since been studied widely.
The US FDA explains the mechanism: many drugs are broken down with the help of an enzyme called CYP3A4 in the small intestine, and grapefruit juice "can block the action of intestinal CYP3A4," so more drug enters the blood. The FDA lists examples of affected drug types, including some statins, some blood pressure medicines and some transplant medicines, and notes that grapefruit "does not affect all the drugs in the categories above." The amount of CYP3A4 varies from person to person, so the effect varies too.
The FDA's advice is to ask your doctor or pharmacist whether grapefruit affects your medicine, and to read the information supplied with it.
Herbs and supplements: what the evidence says
"Natural" does not mean free of interactions. The evidence quality differs a lot by product.
- St John's wort: strong evidence of interactions. The US National Center for Complementary and Integrative Health (NCCIH) says "it has been clearly shown that St. John's wort can interact in dangerous, sometimes life-threatening ways with a variety of medicines." It can weaken the effect of many medicines, including some antidepressants, birth control pills and cyclosporine.
- Ashwagandha: some evidence, mostly cautionary. NCCIH says there is evidence it "might interact with some medications," including those for diabetes and high blood pressure, immunosuppressants, sedatives, anticonvulsants and thyroid hormone medicines. It also notes rare reported cases of liver injury.
- Turmeric and curcumin: limited evidence. NCCIH says "we don't know enough to definitively conclude if turmeric or curcumin is beneficial for any health purposes," and that highly bioavailable curcumin formulations "may harm your liver." Its general advice applies: talk with your health care provider before using any herbal product alongside medicines.
Because supplements are less tightly studied than prescription medicines, some interactions may simply not be known yet. A checker that shows nothing for a herb may be showing a gap in the data, not a clean bill of health.
What to do
- Keep one up-to-date list of everything you take, including supplements and over-the-counter products.
- Show it to your pharmacist whenever you start or stop something.
- If a checker flags something, do not stop a prescribed medicine on your own. Call your doctor or pharmacist.
- Treat a checker as a prompt for a conversation, not as the answer.
Where MIA fits
MIA is not an interaction checker and does not give dosing or medication advice. Its role is narrower and comes later. When a pharmacist, clinician, researcher or medico-legal expert has the underlying case report or study in hand, MIA reads that paper and separates what it shows, what may be drawn from it, and what it does not establish. A single case stays a single case. An abstract without the full paper stays a gap.
Read the study behind a flag with MIA: 150 free credits, no card.
FAQ
What is the best drug interaction checker? Public checkers such as Drugs.com and Medscape are widely used, and professional databases such as Lexicomp and Micromedex are used in clinical settings. Studies show checkers can disagree, so the best check is your pharmacist reviewing your full list.
What do major, moderate and minor mean? They are severity grades. On Drugs.com, major means the combination is best avoided, moderate means it is generally avoided unless necessary and used with supervision, and minor means it may not cause problems for most people. Other checkers use different labels.
Can herbal supplements interact with medicines? Yes. St John's wort has well-documented interactions with many medicines. Evidence for others, such as ashwagandha and turmeric, is more limited. Tell your doctor and pharmacist about every supplement you take.
Is MIA a drug interaction checker? No. MIA reads the papers a professional brings, such as a case report or study, and separates what they show from what they do not establish. It gives no dosing or medication advice.
This is information about reading evidence, not medical advice. Talk to your doctor or pharmacist before changing anything.
Sources
- Drugs.com. Drug Interaction Checker, FAQs (last updated 5 Nov 2025). https://www.drugs.com/drug_interactions.html - Medscape. Drug Interactions Checker, "About". https://reference.medscape.com/drug-interactionchecker - Kheshti R, Aalipour M, Namazi S. A comparison of five common drug-drug interaction software programs regarding accuracy and comprehensiveness. J Res Pharm Pract. 2016;5(4):257-263. doi:10.4103/2279-042X.192461 - Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41(4):674-680. - Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet. 1991;337(8736):268-269. doi:10.1016/0140-6736(91)90872-m - US Food and Drug Administration. Grapefruit Juice and Some Drugs Don't Mix (consumer update). https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix - NCCIH. St. John's Wort. https://www.nccih.nih.gov/health/st-johns-wort - NCCIH. Ashwagandha. https://www.nccih.nih.gov/health/ashwagandha - NCCIH. Turmeric. https://www.nccih.nih.gov/health/turmeric