PlainMeds guide · FDA labeling
Understanding Drug Interactions
Labeled pair volume and major-grade count are separate maps. The drug with the most pairs is not the drug with the most major grades.
Data updated 2026-05-15
Warfarin is labeled-pair volume #1 of 559 (163) at major-count #61 (2) ≠ Theophylline major-count #1 (27) at pair-volume #11 (86).
Pair counts and major counts are FDA label grades on documented pairs, not per-patient risk and not advice about combining medicines. See /methodology.
Pair volume versus major count
Warfarin is labeled-pair volume #1 of 559 (163) at major-count #61 (2) ≠ Theophylline major-count #1 (27) at pair-volume #11 (86).
- 163
- Warfarin pairs
- #61
- that drug on major-count
- 27
- Theophylline majors
- 559
- drugs with a pair
According to FDA Structured Product Labeling compiled on /methodology. A missing pair is not proof that none exists. This page is not medical advice.
Labeled pair severity mix
Exclusive cut of 3,919 FDA-labeled drug-drug pairs. Orthogonal to the pair-volume vs major-count dual above - registry grades, not per-patient risk.
Source: FDA Structured Product Labeling. Try the interaction checker for a specific pair lookup.
What Is a Drug Interaction?
A drug interaction occurs when one substance affects how another substance works in your body. This can mean a drug becomes less effective, more potent than intended, or produces unexpected side effects. Interactions can happen between:
- Drug + Drug - two medications interfering with each other
- Drug + Food/Drink - certain foods or beverages affecting medication
- Drug + Supplement - vitamins, herbs, or supplements altering drug effects
- Drug + Health Condition - a medical condition changing how a drug works
How Interactions Work
Most drug interactions fall into one of three categories:
1. Pharmacokinetic Interactions (How Your Body Processes the Drug)
These affect how much of a drug gets into your bloodstream and how quickly it's cleared. The most common mechanism involves liver enzymes called cytochrome P450 (CYP) enzymes, which metabolize the majority of medications.
- Enzyme inhibitors slow the breakdown of other drugs, causing them to build up to dangerously high levels. Example: grapefruit juice inhibits CYP3A4, increasing blood levels of statins like atorvastatin.
- Enzyme inducers speed up drug metabolism, causing other drugs to be cleared too quickly and lose effectiveness. Example: St. John's Wort induces CYP3A4, reducing the effectiveness of birth control pills.
2. Pharmacodynamic Interactions (What the Drug Does)
These occur when two drugs act on the same system, either amplifying or canceling each other's effects.
- Additive effects - two sedatives together produce excessive drowsiness
- Synergistic effects - alcohol plus benzodiazepines multiply sedation beyond what either would cause alone
- Antagonistic effects - a beta-blocker can reduce the effectiveness of an asthma inhaler
3. Combined Toxicity
Two drugs that individually are safe may together overwhelm the same organ. Example: NSAIDs and ACE inhibitors can both affect kidney function, together, they significantly increase the risk of kidney damage.
Most Common Dangerous Interactions
| Drug A | Drug B | Risk | Severity |
|---|---|---|---|
| Warfarin (Coumadin) | Aspirin / NSAIDs | Increased bleeding risk | Major |
| SSRIs (Zoloft, Prozac) | MAOIs | Serotonin syndrome (potentially fatal) | Major |
| Opioids (codeine, oxycodone) | Benzodiazepines (Xanax, Valium) | Respiratory depression | Major |
| Statins (atorvastatin) | Grapefruit juice | Muscle damage (rhabdomyolysis) | Moderate |
| ACE inhibitors (lisinopril) | Potassium supplements | Dangerous potassium levels (hyperkalemia) | Moderate |
| Metformin | Alcohol (excessive) | Lactic acidosis | Moderate |
| Birth control pills | St. John's Wort | Reduced contraceptive effectiveness | Moderate |
| Levothyroxine (Synthroid) | Calcium / Iron supplements | Reduced thyroid med absorption | Moderate |
Food & Drink Interactions
Grapefruit
Grapefruit (and to a lesser extent, Seville oranges and pomelos) inhibits the CYP3A4 enzyme in the intestine. This can increase blood levels of more than 85 medications, including statins, calcium channel blockers, some antihistamines, and certain immunosuppressants. The effect lasts up to 72 hours after eating grapefruit.
Dairy Products
Calcium in milk, cheese, and yogurt binds to certain antibiotics (tetracycline, ciprofloxacin) and thyroid medications (levothyroxine), reducing absorption. Individual FDA labels describe product-specific administration instructions; this registry does not determine a timing plan for a person or a medicine.
Alcohol
Alcohol interacts with hundreds of medications. The most dangerous combinations include alcohol with sedatives, opioids, anti-anxiety medications, and acetaminophen. Even moderate drinking can amplify side effects or reduce effectiveness of many common drugs.
Vitamin K-Rich Foods
FDA labeling records vitamin K as a factor relevant to warfarin management. Leafy greens such as spinach, kale, and broccoli are vitamin K sources. The label record does not turn that fact into a diet or dosing instruction for an individual.
Supplement Interactions
Many people don't realize that "natural" supplements can interact with prescription medications just as powerfully as other drugs.
- St. John's Wort - one of the most prolific interactors. Reduces effectiveness of birth control, HIV medications, warfarin, statins, antidepressants, and many more.
- Ginkgo biloba - increases bleeding risk when taken with blood thinners or aspirin
- Garlic supplements - can increase bleeding risk with warfarin and reduce effectiveness of some HIV drugs
- Fish oil (high doses) - may increase bleeding risk with blood thinners
- Melatonin - can increase sedation with benzodiazepines and may affect blood pressure medications
What this catalogue does not see
Pair volume and major-count are label grades on documented pairs. This extract does not see a patient list, a dose, or a timing. A missing row is not proof that no interaction exists. The interaction checker looks up labeled pairs only.
Registry pages: pair checker · mechanism guide. Educational information from FDA labels, not medical advice.