Drug interactions and contraindications: the five types and the big ones
PTCB topic: Drug interactions and contraindications
- Five types: drug–drug, drug–supplement, drug–nutrient, drug–lab and drug–disease.
- Contraindicated means do not use: sildenafil with nitrates.
- Benzodiazepine plus opioid: boxed warning for slowed breathing, coma and death.
- Take levothyroxine at least 4 hours apart from calcium or iron.
- Technicians flag interactions for the pharmacist and never override alerts.
Key facts
- Sildenafil (Viagra) is contraindicated with organic nitrates such as nitroglycerin because the combination can drop blood pressure dangerously.
- Simvastatin (Zocor) is contraindicated with strong CYP3A4 inhibitors such as clarithromycin, and its label says to avoid grapefruit juice.
- Benzodiazepines plus opioids carry a boxed warning: profound sedation, respiratory depression, coma and death.
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- Take levothyroxine (Synthroid) at least 4 hours apart from calcium carbonate or iron.
- Warfarin patients should keep vitamin K intake consistent; a sudden rise in leafy greens can lower the INR response.
- Metronidazole (Flagyl): no alcohol during therapy and for at least 3 days after, because of a disulfiram-like reaction.
- Biotin can distort some lab tests; the Synthroid label says stop it at least 2 days before TSH or T4 testing.
Quick check1 question · 2 more at the end
Viagra (sildenafil) labeling lists a contraindication with which group of drugs?
Correct answer: A.
Sildenafil strengthens the blood-pressure-lowering effect of nitrates, so the Viagra label contraindicates its use with organic nitrates or nitrites in any form. Alpha-blockers are a caution, not a contraindication: the patient should be stable on the alpha-blocker and start at a low sildenafil dose. A contraindication means the two should not be used together.
A Correct: the Viagra label contraindicates use with organic nitrates because of the risk of severe low blood pressure.
B Alpha-blockers need caution and a low starting dose, but the label does not contraindicate them.
C Statins are not listed as a contraindication in the Viagra label.
D Proton pump inhibitors are not listed as a contraindication in the Viagra label.
Full lesson
Each part starts with its main idea. Open a part when you want the details.
The short answer: An interaction is when another drug, supplement, food, lab test or disease changes how a drug works or how safe it is. A contraindication means the combination should not be used, such as sildenafil with nitrates. The PTCE outline lists five types: drug–drug, drug–supplement, drug–lab, drug–nutrient and drug–disease. Technicians flag them for the pharmacist.
1 What are the five interaction types?An interaction happens when something else changes how a drug works or how safe it is. 1 min
An interaction happens when something else changes how a drug works or how safe it is. The 2026 PTCE outline lists five types, each with label-backed examples:
| Type | What changes the drug | Example |
|---|---|---|
| Drug–drug | Another medicine | Sildenafil (Viagra) + nitroglycerin: contraindicated |
| Drug–supplement | A vitamin, mineral or herb | Levothyroxine + calcium carbonate: separate by at least 4 hours |
| Drug–nutrient | A food or drink, including alcohol | Metronidazole (Flagyl) + alcohol: disulfiram-like reaction |
| Drug–lab | A lab test result | Biotin can distort TSH and T4 test results |
| Drug–disease | A condition the patient has | Metformin is contraindicated when eGFR is below 30 |
2 What is the difference between a contraindication and a caution?A contraindication means the drug should not be used in that situation, while a caution means it can be used with care. 1 min
A contraindication means the drug should not be used in that situation, while a caution means it can be used with care. The Viagra label shows both: it contraindicates organic nitrates in any form, but alpha-blockers only need a stable patient and a 25 mg starting dose.
Learn these label contraindications:
- Simvastatin (Zocor): strong CYP3A4 inhibitors, such as clarithromycin and itraconazole; also cyclosporine, danazol and gemfibrozil.
- Sertraline (Zoloft): MAOIs, including linezolid and IV methylene blue, or within 14 days of stopping one, because of serotonin syndrome.
- Metformin: severe kidney impairment (eGFR below 30 mL/min/1.73 m2).
3 Which drug–drug interactions are life-threatening?The most dangerous interactions cause deep sedation, very low blood pressure, bleeding or serotonin syndrome. 1 min
The most dangerous interactions cause deep sedation, very low blood pressure, bleeding or serotonin syndrome. Know these four:
- Benzodiazepine + opioid (for example, Xanax + oxycodone): the Xanax label carries a boxed warning for profound sedation, respiratory depression, coma and death.
- Sildenafil + nitrates: sildenafil strengthens the blood-pressure-lowering effect of nitrates.
- Warfarin + drugs that raise bleeding risk: antiplatelets such as aspirin and clopidogrel, NSAIDs and SSRIs.
- Clopidogrel (Plavix) + omeprazole or esomeprazole: these PPIs block the enzyme that activates clopidogrel, weakening its effect.
4 How do foods, supplements and lab tests interact?Foods and supplements can raise, lower or block a drug, and some supplements change lab results. 1 min
Foods and supplements can raise, lower or block a drug, and some supplements change lab results. Common examples:
- Grapefruit juice raises simvastatin levels, so the Zocor label says to avoid it.
- Vitamin K in leafy greens works against warfarin. The label says to keep intake consistent and avoid drastic diet changes.
- Alcohol with metronidazole (Flagyl) can cause a disulfiram-like reaction; the label says to avoid it during therapy and for at least 3 days after.
- St. John's wort can weaken birth control pills, warfarin and some antidepressants (NCCIH).
- Biotin supplements can interfere with TSH, T4 and T3 lab tests; the Synthroid label says to stop biotin at least 2 days before those tests.
5 What the technician doesThe technician notices the interaction and brings in the pharmacist; the pharmacist counsels and decides. 1 min
The technician notices the interaction and brings in the pharmacist; the pharmacist counsels and decides. The PTCE outline lists drug interactions among issues that require pharmacist intervention.
- Enter every medicine, supplement and allergy the patient reports, so the software can screen them.
- Route interaction alerts to the pharmacist without overriding them.
- Refer questions about alcohol, food or OTC products to the pharmacist.
Common mistakes
The traps students fall into most. Read these before you practice.
Watch out: A contraindication means do not combine, not just monitor more closely.
Watch out: Alpha-blockers with sildenafil need caution and a low starting dose, not a contraindication; nitrates are the contraindication.
Watch out: Pantoprazole had less effect on Plavix than omeprazole; omeprazole and esomeprazole are the PPIs the label says to avoid.
Watch out: Linezolid is an antibiotic, but the Zoloft label treats it as an MAOI, not a harmless add-on.
Watch out: Drug–lab interactions change the test result, not the disease; biotin can make a TSH or T4 result wrong without any change in the thyroid.
How to remember it
Use the phrase "Drugs Simply Never Like Disease" to recall drug, supplement, nutrient, lab and disease. For each new drug you learn, ask: what drug, food or condition makes it unsafe?
Self-check:
- Name the drug group that is contraindicated with sildenafil.
- Say how far apart levothyroxine and calcium carbonate should be taken.
- Explain what a sudden increase in leafy greens does to warfarin.