2: Notable Interactions

ASA / Aspirin

Increased bleeding with anticoagulants/SSRIs; NSAID interactions with ACE inhibitors, diuretics, beta blockers, digoxin, lithium, methotrexate, other NSAIDs; alcohol increases GI bleeding risk

Ibuprofen (Advil, Motrin)

May blunt ACE inhibitor/diuretic/beta-blocker effects; increased risk with anticoagulants, SSRIs, lithium, methotrexate, other NSAIDs

Naproxen (Aleve, Anaprox, Naprosyn)

Same NSAID interaction pattern; caution with anticoagulants, SSRIs, lithium, ACE inhibitors/diuretics

Diclofenac (Voltaren)

Avoid combining with other NSAIDs; caution with anticoagulants, antihypertensives, lithium, methotrexate

Diclofenac + Misoprostol (Arthrotec)

Absolute contraindication in pregnancy; avoid in women of childbearing potential unless appropriate safeguards

Flurbiprofen

Same NSAID interactions

Ketoprofen

Same NSAID interactions

Ketorolac

Avoid with other NSAIDs and anticoagulants; caution renal disease

Etodolac

Same NSAID interactions

Celecoxib (Celebrex)

Do not use with MI/CVA/angina/CHF or high CV risk; use lowest dose shortest duration

Rofecoxib (Vioxx)

Withdrawn due to cardiovascular safety concerns

Acetaminophen / Paracetamol (Tylenol)

Alcohol increases hepatotoxicity risk; watch duplicate acetaminophen-containing products; dose limits important

N-acetylcysteine (Mucomyst)

Give early in acetaminophen overdose; may be oral or IV

Misoprostol (Cytotec)

Absolute contraindication during pregnancy when used for NSAID GI protection; beneficial interaction with NSAIDs for gastric protection

Mifepristone

Used with misoprostol in reproductive indications

Ergonovine

Caution with other vasoconstrictors/HTN

Alprostadil

Additive hypotension with vasodilators

Morphine

CNS depression increased by alcohol, benzodiazepines, sedatives, general anesthetics; histamine release may occur

Codeine

CYP2D6 inhibitors reduce analgesia; ultra-rapid metabolizers risk morphine toxicity; CNS depressant interactions

Acetaminophen + Codeine (Tylenol #1-#4)

Avoid duplicate acetaminophen products; CNS depressants increase opioid toxicity

Methadone

Metabolized by CYP1A2, CYP2D6, CYP3A4 -> many interactions; caution with other QT-prolonging/CNS depressant drugs

Heroin (Diacetylmorphine)

Additive CNS/respiratory depression

Fentanyl (Sublimaze)

High overdose risk; additive with sedatives/alcohol; CYP3A4 inhibitors can increase levels

Oxycodone (OxyNEO, OxyContin)

CNS depressants increase toxicity; abuse/diversion concern

Oxycodone + Acetaminophen (Percocet)

Avoid duplicate acetaminophen; additive CNS depression

Oxycodone + Aspirin (Percodan)

Avoid with anticoagulants/bleeding risk and CNS depressants

Tramadol

Avoid/caution with SSRIs/SNRIs/MAOIs and seizure risk; CNS depressants

Tramadol + Acetaminophen (Tramacet)

Avoid duplicate acetaminophen; caution serotonergic drugs and CNS depressants

Naloxone (Narcan)

Short half-life; repeat dosing/monitoring may be needed for long-acting opioids

Naltrexone (Trexan)

Not for acute overdose; blocks opioid analgesia; avoid in acute hepatitis/liver failure

Buprenorphine (BuTrans, Buprenex)

Can reduce efficacy of full opioid agonists; CNS depressant interactions

Epinephrine

Caution with significant cardiac disease and drugs that sensitize myocardium; do not delay in anaphylaxis

Diphenhydramine (Benadryl)

Potentiates CNS depressants (barbiturates, opioids, anesthetics, alcohol); additive anticholinergic effects

Tripelennamine

Additive CNS depressant and anticholinergic effects

Chlorpheniramine (Chlor-Trimeton)

CNS depressants and anticholinergics increase adverse effects

Promethazine (Phenergan)

CNS depressants increase sedation/respiratory depression

Hydroxyzine (Vistaril)

Additive CNS depression

Cyclizine (Antivert)

CNS depressants and anticholinergics

Meclizine

CNS depressants/anticholinergics

Doxylamine + Pyridoxine (Bendectin/Diclectin-like)

CNS depressants may increase sedation

Cetirizine (Zyrtec)

Fewer CNS interactions; caution severe renal/hepatic dysfunction

Fexofenadine (Allegra)

Fruit juices can reduce absorption (general); fewer CNS effects

Loratadine (Claritin)

Caution severe liver disease; fewer CNS effects

Desloratadine (Clarinex)

Caution severe liver/renal disease

Azelastine

Alcohol/CNS depressants may increase drowsiness

Terfenadine (Seldane)

Withdrawn; ketoconazole, erythromycin, grapefruit juice increased levels

Cimetidine (Tagamet)

CYP450 inhibitor -> increases warfarin, phenytoin, propranolol, metoprolol, quinidine, caffeine, lidocaine, theophylline, benzodiazepines, ethanol, TCAs, CCBs

Ranitidine (Zantac)

May increase ethanol bioavailability; fewer CYP interactions than cimetidine

Famotidine (Pepcid)

Few CYP interactions; lecture notes exception re ethanol bioavailability vs other H2 blockers

Nizatidine (Axid)

May increase ethanol bioavailability

Penicillin G

Very few drug interactions; beta-lactam allergy important

Penicillin V

Very few DIs; allergy/cross-sensitivity considerations

Amoxicillin

Few DIs; combined with clavulanic acid when beta-lactamase coverage needed

Ampicillin

Few DIs; renal elimination

Cloxacillin

Few DIs

Piperacillin + Tazobactam

Few DIs; renal dosing; beta-lactam allergy

Clavulanic acid

Used only in combination; increases GI intolerance

Tazobactam

Used in fixed beta-lactam combinations

Cefazolin

Low penicillin cross-reactivity (~1% in lecture); few DIs

Cephalothin

Few DIs

Cephalexin

Few DIs; moderate oral absorption

Cefoxitin

Few DIs

Cefaclor

Few DIs

Cefuroxime

Few DIs

Cefotaxime

Few DIs

Ceftriaxone

Few DIs; avoid calcium-containing IV solutions in neonates (general)

Ceftazidime

Few DIs

Ceftolozane + Tazobactam

Renal dosing; few CYP interactions

Cefixime

Few DIs

Cefepime

Renal dosing important

Ceftobiprole

Few DIs; renal dosing

Imipenem + Cilastatin

Penicillin cross-sensitivity low (~0.5% in lecture); renal dosing; probenecid/valproate concerns (general)

Meropenem

Renal dosing; can reduce valproate levels (general)

Ertapenem

Renal dosing; fewer antipseudomonal uses

Vancomycin

Nephrotoxicity increased with other nephrotoxins (aminoglycosides, amphotericin B, cyclosporine); infusion rate matters

Daptomycin

Avoid for pneumonia; monitor CPK, caution statins

Streptomycin

Nephrotoxic agents (vancomycin, amphotericin B, cyclosporine) increase toxicity; interacts with neuromuscular blockers

Neomycin

Avoid systemic use; nephrotoxic/neuromuscular blocker interactions

Kanamycin

Nephrotoxic and neuromuscular blocker interactions

Tobramycin

Monitor levels; toxicity increased with vancomycin/amphotericin/cyclosporine and neuromuscular blockers

Gentamicin

Monitor troughs; avoid/add caution nephrotoxins and neuromuscular blockers

Amikacin

Monitor levels; nephrotoxic interactions

Netilmicin

Monitor levels; nephrotoxic interactions

Ciprofloxacin

Aluminum/magnesium/calcium decrease absorption; resistance risk; QT-prolonging drugs

Levofloxacin

Chelation with polyvalent cations; QT interactions

Moxifloxacin

Avoid/caution QT-prolonging drugs; cation chelation reduces absorption

Metronidazole

Alcohol reaction: nausea/vomiting/sweating with alcohol; inhibits alcohol dehydrogenase in lecture

Erythromycin

CYP450 inhibitor; many DIs; QT interactions

Clarithromycin

CYP450 inhibitor; many DIs; cisapride/terfenadine/QT risk examples

Azithromycin

Fewer CYP interactions than erythro/clarithro but QT caution

Clindamycin

Few DIs; highest community-associated C. difficile risk in lecture meta-analysis

Sulfamethoxazole + Trimethoprim (TMP/SMX)

Hydration important; interactions with warfarin and ACEI/ARB/K-sparing drugs (general); renal dosing

Sulfonamides

Hydration; warfarin interaction risk

Trimethoprim

ACEI/ARB and potassium-sparing drugs increase hyperkalemia risk; warfarin interaction

Tetracycline

Chelated by calcium/iron/magnesium; avoid pregnancy/children

Tigecycline

Avoid pregnancy; limited bacteremia utility

Amphotericin B

Give slowly with premeds (acetaminophen, diphenhydramine); pre-hydrate; nephrotoxicity with other nephrotoxins

Liposomal Amphotericin B (Ambisome)

Different dosing than deoxycholate

Amphotericin B deoxycholate (Fungizone)

Monitor renal function/electrolytes; slow infusion

Nystatin

Swish and swallow; contact time >=30 sec; avoid eating/drinking 30 min after