Top 100 Drug Interactions You Need to Know

top 100 drug interactions

Introduction

Drug interactions are an important part of the pharmacy exam. As a healthcare professional of medicine, you are expected to have an intimate knowledge of many of the key drug interactions and the consequences those interactions have.
Learning drug interactions isn’t always easy. After all, there are many thousands of drug interactions. Candidates are not expected, of course, to commit all known medicine interactions to memory. That would be absurd.

Instead, candidates should know the most important interactions. Often, these are the drug interactions that are either the most serious or the most common. By learning these interactions, you cast as wide a net as possible in your learning.

As part of our online courses, we’ve put together a range of NAPLEX practice questions that cover drug interactions – preparing you for the needs and demands of your next pharmacy exam.

How to Memorize Drug Interactions

If you’re finding it difficult to recall drug interactions, first think about the underlying mechanism of each medicine to determine any potential interaction.

In many cases, the interaction is intuitive.

Take allopurinol. This medicine works by inhibiting the enzyme xanthine oxidase; the same enzyme that metabolises the immunosuppressant drugs, azathioprine and mercaptopurine. By knowing these mechanistic facts, you can conclude that taking both allopurinol and one of those two drugs together will increase the risk of azathioprine / mercaptopurine toxicity.

Many more drug interactions require you to know about CYP enzymes. Learn which drugs are strong CYP inhibitors and strong CYP inducers. By knowing how a medicine is metabolised at the hepatic level (if metabolised by this route at all), it should trigger those inhibitors and inducers and give you a strong indication of how the drug interaction plays out.

When learning about drug interactions, you will come across many themes. Learn these themes as best possible. For example, there are many drugs whose adverse effect is to prolong the QT interval. Once you know these medicines – which include macrolides and quinine and amiodarone – you can put together that list. When any two of those drugs are taken together, then, it increases the risk of QT prolongation and/or arrhythmias. Another list you may want to keep in mind is drugs that have anticholinergic effects and drugs that increase the risk of serotonin syndrome. Drugs that have central, sedative effects tend to have additive effects when taken with other centrally acting sedative medicines. There are many, many more examples we could sketch out.

Again, it often comes down to knowing drug mechanisms.

Of course, there will always be outlier drugs that don’t neatly fit under any one summary. Put these interactions to one side and learn them collectively. Once your study of drug interactions is framed in a defined and structured manner, you have a methodology that allows you to build on your knowledge in a logical and constructive manner. Learning drug interactions in a random, almost haphazard way is simply never going to work – don’t even consider it.

Below, try to make a note of any drug interaction you haven’t yet heard of and, in the days and weeks ahead, commit those interactions to memory. Of course, this is not intended to be an exhaustive list. What is does do, though, is act as a convenient study aid onto which you can further layer your knowledge of drug interactions.

Let’s get started.

Top 100 Drug Interactions

Drug Drug Interactions
N-acetylcysteine No clinically significant drug interactions.
Acetaminophen CYP inducers – such as phenytoin and carbamazepine – increase rate of NAPQI production / liver toxicity, after acetaminophen overdose.
Activated charcoal Prevents absorption of many drugs. For this reason, it is used in cases of toxicity / overdose.
Acyclovir Probenecid increases acyclovir concentration.

Interferon increases acyclovir concentration.

Adenosine Dipyridamole blocks cellular uptake of adenosine.

Theophylline is a competitive antagonist at adenosine receptors.

Epinephrine Beta-blockers can induce widespread vasoconstriction.
Aldosterone antagonists ACE inhibitors; ARBs and other K-elevating drugs / supplements increase hyperkalemia risk.
Antacids / alginates Divalent ions reduce serum conc. Of drugs such as bisphosphonates, levothyroxine, tetracyclines, digoxin and PPIs.

Antacids increase alkalinity of urine and so increase lithium and aspirin excretion.

Albendazole Plasma concentration lowered by phenytoin and carbamazepine.

Cimetidine increases albendazole concentration.

Allopurinol Toxicity risk of mercaptopurine / azathioprine increases because allopurinol inhibits xanthine oxidase.

Amoxicillin increases skin rash risk.

ACE inhibitors and thiazide diuretics increase risk of hypersensitivity reactions.

Alpha blockers Other blood pressure lowering drugs increase risk of first-dose hypotension and hypotension risk generally thereafter.
Aminoglycosides Loop diuretics / vancomycin increase ototoxicity risk.

Cyclosporine, platinum chemotherapy, cephalosporins and vancomycin increase nephrotoxicity risk.

Aminosalicylates PPIs increase gastric pH and so may affect gastric coating of aminosalicylates.

Lactulose reduces stool pH and so can prevent 5-ASA release into the intestine.

Amiodarone Amiodarone increases plasma concentration of digoxin, diltiazem and verapamil – increasing risk of AV block, bradycardia and heart failure.
ACE inhibitors Hyperkalemia risk increases when taken with other potassium-elevating drugs / supplements.

Renal failure risk increases when taken with NSAIDs.

Amphotericin B Increased risk of flucytosine toxicity.

Increased renal toxicity with cisplatin / diuretics.

Increased risk of hypokalemia with corticosteroids.

Renal damage with aminoglycosides / other nephrotoxic drugs.

Angiotensin-receptor

blockers

Same as ACE inhibitors above.
Antidepressants

SSRIs

Serotonin syndrome when taken with other serotonergic drugs, such as MAO inhibitors.

Anticoagulants increase bleeding risk of SSRIs.

Avoid with QT prolonging drugs such as macrolides,

quinine and antipsychotics.

Antidepressants

Tricyclic / related drugs

Serotonin syndrome when taken with other serotonergic drugs, such as MAO inhibitors.

TCAs augment antimuscarinic and sedative effects of other drugs.

Antiemetics

H1 antagonists

Sedation risk increases when taken with other sedative drugs – benzodiazepines, Z-drugs etc.

Anticholinergic effects more pronounced when taken with ipratropium / tiotropium etc.

Antiemetics

Prochlorperazine

Chlorpromazine

QT prolongation risk increases when taken with antipsychotics, quinine, SSRIs, macrolides, fluoroquinolones and ciprofloxacin.
Antiemetics

5-HT3 antagonists

Same QT prolongation interactions above.
Antifungal Drugs

Fluconazole

Fluconazole inhibits CYP enzymes – increasing plasma concentration of phenytoin, carbamazepine, warfarin, simvastatin and sulfonylureas.

Reduces the antiplatelet effect of clopidogrel.

Risk of arrhythmias increases when taken with QT prolonging drugs (see above).

Antihistamines

H1 antagonists

No major drug interactions.

[Cetirizine / Loratadine / Fexofenadine etc.]

Antimotility Drugs

Loperamide

P-glycoprotein inhibitors – such as quinidine, ritonavir and ketoconazole – increase loperamide levels.
Antimuscarinics

Bronchodilators

Ipratropium / tiotropium

Low systemic absorption reduces risk of any major drug interactions.
Antimuscarinics

Cardiovascular

Atropine

Hyoscine butylbromide

Antimuscarinic effects more pronounced when taken with other drugs with the same effects, such as tricyclic antidepressants.
Antimuscarinics

Genito-urinary

Oxybutynin

Tolterodine

Solifenacin

Same as above.
Antipsychotics

Typical drugs

Atypical drugs

Avoid with QT-prolonging drugs (see above).

Avoid with dopamine-blocking antiemetics.

Aspirin Antiplatelets and anticoagulant drugs increase risk of bleeding.
Benzodiazepines Sedative risk increases with other sedation-causing drugs and substances, including alcohol and opioids.

CYP inhibitors – such as macrolides, fluconazole, amiodarone and protease inhibitors – increase their effects.

Beta-2 agonists Beta-blockers reduce their effectiveness.

Corticosteroids increase risk of hypokalemia.

Beta blockers Avoid with non-dihydropyridine calcium channel blockers – such as verapamil and diltiazem – as the combination can lead to bradycardia, heart failure and asystole.
Bisphosphonates Divalent ions reduce drug absorption.

For example: antacids, iron

Calcium Oral calcium reduces absorption of bisphosphonates, tetracyclines and levothyroxine.

Avoid with sodium bicarbonate when taken IV to eliminate risk of precipitation.

Calcium channel blockers Avoid with beta-blockers (see above).
Carbamazepine Induces CYP 450 enzymes to reduce concentration of drugs such as warfarin, progestogens and estrogens.

Drugs that lower the seizure threshold – such as TCAs, SSRIs and tramadol – reduce efficacy of anticonvulsant medicines.

Cephalosporins

Carbapenems

Enhance the anticoagulant effect of warfarin.

Increase nephrotoxicity of aminoglycosides.

Carbapenems reduce efficacy of valproate.

Clopidogrel CYP 450 inhibitors block its activation – omeprazole, erythromycin, antifungals, SSRIs etc.

Lansoprazole / pantoprazole preferred if gastroprotection is needed.

Risk of bleeding increases with antiplatelet, anticoagulant drugs and NSAIDs.

Corticosteroids

Systemic

Prednisolone

Hydrocortisone

Dexamethasone

NSAIDs increase risk of peptic ulceration / bleeding.

Risk of hypokalemia when taken with B2-agonists, loop or thiazide diuretics.

Efficacy reduced by CYP inducers such as phenytoin and rifampin.

Corticosteroids reduce immune response to vaccines.

Corticosteroids

Inhaled

Beclometasone

Budesonide

Fluticasone

As these drugs are inhaled, there are no clinically significant drug interactions.
Corticosteroids

Topical

Hydrocortisone

Betamethasone

No significant drug interactions.
Cyclophosphamide Rifampin and phenytoin accelerate metabolism of cyclophosphamide into active metabolites.

Corticosteroids / TCAs / allopurinol slow conversion of cyclophosphamide to its metabolites, reducing therapeutic and toxic effects.

Prolongs neuromuscular blockade with succinylcholine.

Tricyclic antidepressants lead to delayed bladder emptying, increasing acrolein accumulation and risk of bladder bleeding.

Digoxin Digoxin toxicity increases when taken with loop or thiazide diuretics, amiodarone, calcium channel blockers, spironolactone and quinine.
Dipyridamole Inhibits cellular uptake of adenosine.

Bleeding risk increases when taken with antiplatelet or anticoagulant medicines.

Diuretics

Loop

Loop diuretics reduce lithium excretion.

Due to diuretic-linked hypokalemia, digoxin toxicity risk increases.

Increase risk of ototoxicity / nephrotoxicity when taken with aminoglycosides.

Diuretics

Potassium-sparing

Amiloride

Avoid potassium-elevating drugs / supplements.

Renal clearance of lithium / digoxin reduced.

Diuretics

Thiazide (-like)

NSAIDs reduce thiazide effectiveness.
Dopaminergic drugs

Parkinson’s disease

Levodopa

Ropinirole

Pramipexole

Due to opposing effects on dopamine receptors, dopaminergic drugs should not be taken with antipsychotics, particularly typical antipsychotics.
Emollients

Aqueous cream

Liquid paraffin

No clinically significant drug interactions.
Fibrates

Fenofibrate

Bile acid sequestrants (eg. Cholestyramine) bind to fenofibrate, reducing absorption.

Increased risk of renal dysfunction with cyclosporine.

Increased risk of bleeding with warfarin.

Increased risk of myopathies with statins.

Fibrinolytic drugs

Alteplase

Tenecteplase

Antiplatelet drugs / anticoagulants increase risk of bleeding.

ACE inhibitors increase risk of anaphylactoid reactions.

Flucytosine Anticancer drug cytarabine inhibits the antimycotic effects of flucytosine.

Increases toxicity of amphotericin B.

Fluoroquinolones Divalent ions reduce absorption / efficacy.

Ciprofloxacin increases theophylline toxicity risk.

NSAIDs increase risk of seizures.

Prednisolone increases tendon rupture risk.

QT-prolonging drugs increase QT-prolongation risk and arrhythmia risk.

Gabapentin / Pregabalin Sedative effects enhanced when taken with other sedative-inducing drugs, such as opioids and benzodiazepines.
H2 receptor antagonists

Ranitidine

No clinically significant drug interactions.
Heparins Antithrombotic drugs increase risk of bleeding.
Insulin Taking insulin with systemic corticosteroids increases insulin requirements.
Iron Reduces absorption of levothyroxine, bisphosphonates and tetracyclines.
Isoniazid Increases acetaminophen toxicity.

Decreases metabolism of carbamazepine.

Increases valproate levels.

Isotretinoin Vitamin A supplements increase toxicity risk.

Increased risk of pseudotumor cerebri if taken with tetracyclines.

Laxatives

Bulk-forming

Osmotic

Stimulant

No clinically significant drug interactions.

Effective of warfarin slightly increased when taken with osmotic laxatives.

Lidocaine Epinephrine prolongs local anesthetic effect.
Linezolid Increased risk of serotonin syndrome if taken with MAO inhibitors or other serotonergic drugs.
Macrolides Clarithromycin / erythromycin inhibit CYP 450 enzymes (but not azithromycin) – increasing bleeding risk with drugs such as warfarin, and myopathy risk with statins. QT prolongation risk increases when taken with other QT prolonging drugs – quinine, amiodarone, antipsychotics, SSRIs, fluoroquinolones etc.
Metformin IV contrast media increases risk of renal impairment, metformin accumulation and lactic acidosis. Prednisolone and diuretics (loop/thiazide) reduce efficacy of metformin. Drugs that impair renal function increase risk of metformin accumulation (NSAIDs, ACE inhibitors etc.).
Methotrexate Penicillins and NSAIDs inhibit renal excretion.

Trimethoprim and phenytoin increase risk of hematological adverse effects.

Neutropenia risk increases with clozapine.

Probenecid inhibits methotrexate excretion.

Metronidazole Increases risk of bleeding with warfarin.

Increases risk of toxicity of phenytoin.

Increases risk of toxicity of lithium.

Naloxone Antagonizes the effect of opioids.
Nicotine addiction

Bupropion

CYP 450 inhibitors – such as valproate – increase bupropion concentration.

CYP 450 inducers – phenytoin, carbamazepine – reduces bupropion levels.

Nitrates Concurrent use of nitrates with PDE5 inhibitors, such as sildenafil, can cause pronounced hypotension.

Hypotensive effects augmented by other antihypertensive drugs.

Nitrofurantoin No clinically significant drug interactions.
NSAIDs Aspirin, corticosteroids – GI ulceration

Anticoagulants, SSRIs – GI bleeding

Renal impairment – ACE inhibitors, diuretics

NSAIDs increase bleeding risk of warfarin.

Ocular, artificial tears

Hypromellose

Carbomers

White soft paraffin

No clinically significant drug interactions.
Estrogens

Progestogens

CYP 450 inducers – such as rifampin – reduce the efficacy of hormonal contraception (higher risk with progestogen-only formulations).
Opioids Other sedating drugs – benzodiazepines, antipsychotics, Z-drugs and TCAs – increase risk of sedation.

Tramadol should be avoided with drugs that lower the seizure threshold – eg. SSRIs, TCAs.

Oxygen No clinically significant drug interactions.
Penicillins Reduce renal elimination of methotrexate, increasing toxicity risks.

Enhance anticoagulant effect of warfarin by killing gut flora that ordinarily produce vitamin K.

Phenytoin As an enzyme inducer, phenytoin reduces plasma concentration of warfarin, estrogens and progestogens. Adverse effects of phenytoin increased by CYP inhibitors such as fluconazole, amiodarone and diltiazem. Efficacy of phenytoin reduced by drugs that lower the seizure threshold (eg. SSRIs, antipsychotics, tramadol).
PDE5 inhibitors

Sildenafil

Tadalafil

Concurrent use with nitrates produces pronounced vasodilation / hypotension.

Caution required with vasodilators such as alpha-blockers and calcium channel blockers due to these combined hypotensive risks.

CYP inhibitors – such as fluconazole, amiodarone and diltiazem – increase plasma concentration of PDE5 inhibitors.

Potassium – oral Additive effects with other potassium-elevating drugs / supplements – such as ACE inhibitors, ARBs, potassium-sparing diuretics, IV potassium chloride and aldosterone antagonists.
Propofol Respiratory effects are enhanced when taken with other drugs that cause respiratory depression, such as benzodiazepines and opioids.
Prostaglandin eye drops

Bimatoprost

Latanoprost

No clinically significant drug interactions.
Proton-pump inhibitors

Lansoprazole

Pantoprazole

Omeprazole

Omeprazole reduces antiplatelet effect of clopidogrel by reducing its activation by CYP enzymes. Other PPIs are not associated with this drug interaction.
Quinine Increased risk of QT prolongation with other QT-prolonging drugs – macrolides, fluoroquinolones, amiodarone, antipsychotics and SSRIs.
Rifampin Most powerful inducer of CYP 450 enzymes – increasing metabolism of many medicines. Reduces effectiveness of antiretroviral drugs, atorvastatin, clarithromycin, voriconazole, rosiglitazone and lorazepam, among many others.

Reduces efficacy of birth control pills or hormonal contraception.

Ritonavir Inhibits CYP 1A2 and induces CYP 3A4 / 2D6 – meaning it is linked to many drug interactions. It is used as an inhibitor to ‘boost’ the clinical effects of other protease inhibitors.
Statins

Simvastatin

Atorvastatin

Pravastatin

Metabolism reduced by CYP inhibitors such as amiodarone, itraconazole, macrolides and protease inhibitors – increasing the risk of myopathy-like adverse effects.
Sulfonylureas

Gliclazide

Risk of hypoglycemia with metformin, thiazolidinediones (eg. Pioglitazone), and insulin.

Efficacy reduced by drugs that elevate blood glucose such as prednisolone, loop and thiazide diuretics.

Tetracyclines

Minocycline

Tetracycline

Doxycycline

Divalent ions reduce absorption / efficacy.

Reduce anticoagulant effect of warfarin.

Thiamazole

(methimazole)

Increased anticoagulant effect of warfarin.
Thiazolidinediones

Pioglitazone

Hypoglycemia risk when taken with other anti-diabetic drugs.

Efficacy reduced by drugs that elevate blood glucose such as prednisolone, loop and thiazide diuretics.

Thyroid hormones

Levothyroxine

Absorption reduced by antacids, calcium or iron salts.

Phenytoin / carbamazepine increase its metabolism.

Levothyroxine enhances the effects of warfarin.

Trimethoprim Potassium-elevating drugs increase the risk of hyperkalemia.

Folate antagonists (eg. Methotrexate) and drugs that enhance folate metabolism (eg. Phenytoin) increase risk of hematological adverse effects.

Trimethoprim enhances the anticoagulant effect of warfarin.

Vaccines Immunosuppressive drugs, including systemic corticosteroids, dampen the immunological response to vaccines and, in the case of live vaccines, may confer generalised infection.
Valproate Inhibits CYP 450 enzymes – increasing toxicity of warfarin and other antiepileptics.

Risk of seizures increases when valproate is taken with phenytoin / carbamazepine / carbapenems.

Adverse effects of valproate increased by macrolides and protease inhibitors.

Aspirin displaces valproate from protein binding sites.

Efficacy of valproate reduced by drugs that lower the seizure threshold.

Vancomycin Risk of ototoxicity / nephrotoxicity increases when vancomycin is taken with loop diuretics, aminoglycosides or cyclosporine.
Vitamin K Vitamin K and warfarin have opposing effects.
Warfarin CYP 450 inhibitors – such as macrolides and protease inhibitors – increase bleeding risk.

Inducers – such as phenytoin and rifampin – increase warfarin metabolism and therefore increase the risk of clot formation.

Z-drugs

Zaleplon

Zolpidem

Zopiclone

Sedative effects of alcohol, benzodiazepines, opioids and antihistamines is enhanced.

Hypotensive effect of antihypertensive drugs is enhanced.

P450 inhibitors – like macrolides – enhance sedative effects of Z-drugs.

P450 inducers – like rifampin – impair sedation.

5-alpha reductase inhibitors

Finasteride

Dutasteride

No clinically significant drug interactions.
5-HT4 antagonists

Sumatriptan

Zolmitriptan

Serotonergic drugs – including MAO inhibitors – increase the risk of serotonin syndrome.

Conclusion

Learning about drug interactions is essential to pass your pharmacy exam.

If you’d like to test your knowledge of drug interactions, take a few moments to become a registered member of NAPLEX Study Guide. With over 2,500 NAPLEX practice questions, we remain the leading online course that helps you master the science and practice of pharmacy.

Memorizing drug interactions doesn’t need to be difficult. With a structured learning approach, and through consistent study, you can be sure to ace this part of the pharmacy exam when it matters most.

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