Learning Drug Interactions Flashcards
Amiodarone + Warfarin
Ami = CYP2C9 inhibitor, Warfarin = CYP2C9 substrate –> increase warfarin concentration = increase in INR
- If adding ami after warfarin already being used, decrease warfarin dose by 30-50%
- If adding warfarin after ami already bring used, start warfarin at a lower dose
- If patient already using both, monitor INR and adjust as needed
Amiodarone + Digoxin
Ami inhibits P-gp, digoxin is substrate. = digoxin ADRs and toxicity.
Both also reduce HR, so risk of bradycardia.
- If adding ami after existing digoxin, reduce PO digoxin dose by 50%
- If adding dig after existing ami, start dig at lower dose
- If taking both: tell pt to monitor for dig tox, brady (HR), check for other drugs that lower BP like beta blockers, clonidine, diltiazem, verapamil.
Digoxin + Loop Diuretics
Loops DECREASE K Mg Ca and Na; Dig tox risk is increased with low K and Mg levels and increased Ca levels; monitor electrolytes
Drugs that DECREASE HR
Ami
Beta blockers
Dig
Clonidine
Statins + Strong CYP3A4 Inhibitors
= increased levels of CYP3A4 substrates ALS atorva, lova, simva
= increased myopathy and/or rhabdo risk
Simva and lova are CI-ed –> rec a non-CYP3A4 substrate statin like pita, prava, rosuva
Warfarin + CYP2C9 inhibitors and inducers
inhibitors increase warfarin conc; increased INR and bleeding risk
inducers decrease warfarin conc; decrease INR and increased risk of clotting
Valproate + Lamotrigine
Valproate is an inhibitor of lamotrigine metabolism; using together can cause increase lamotrigine concentration; main concern is increased risk for skin reactions, can combat with use of lamotrigine starter kit
MAOI’s
isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue
MAO-I +
Drugs that INCREASE Epi, NE, DA +
Drugs that INCREASE Serotonin
MAO enzyme metabolizes E, NE, DA.
MAO inhibitor + drugs that increase E, NE, DA = increase in E, NE, or DA = hypertensive crisis
MAO inhibitors + drugs that increase serotonin = serotonin syndrome; do not combine these drugs. use a 2 week washout between serotonergic drugs and other antidepressant; if using fluoxetine and switching to MAO-inhibitor, a five week washout period is needed.
Drugs that INCREASE Epi, NE, DA
Epi, NE, PSE, phenylephrine, dobutamine, SNRIs, bupropion, stimulants like amphetamines for ADHD [ex; methylphenidate, lisdexamphetamine, dextroamphetamine]
Drugs that INCREASE Serotonin
Antidepressants, opioids, others
Antidepressants: SSRIs, SNRIs, TCAs, MAO inhibitors, mirtazapine, trazodone
Opioids: fentanyl, methadone, tramadol
Others: buspirone, dextromethorphan, lithium, St. John’s Wort
MAO-I + tyramine-rich foods/drinks
Tyramine increases NE.
MAO metabolizes tyramine.
Eating tyramine rich foods while on a MAO inhibitor can increase tyramine concentration, leading to increase NE, which can cause hypertensive crisis.
Tyramine-rich foods/drinks
Aged, pickled, fermented or smoked; including aged cheese, air-dried meats, sauerkraut, some wines and beers.
CYP2D6 INHIBITORS
Amiodarone, fluoxetine, paroxetine, fluvoxamine
CYP2D6 substrates
many; avoid using together or decrease dose of the substrate
CYP3A4, P-GP inhibitors +
calcineurin inhibitors (CNIs) OR
mTOR Kinase inhibitors
decrease in drug metabolism, increase in ADRs/toxicity; avoid using together and monitor drug levels, lower CNI or mTOR kinase drug dose
Calcineurin inhibitors (CNIs)
tacrolimus, cyclosporine
mTOR Kinase inhibitors
sirolimus, everolimus
Phenytoin, Phenobarbital, Primidone, Carbamazepine, Oxcarbazepine
+
Other drugs metabolized by CYP enzymes
reduced effect of drug, monitor drug levels, if substrate is lamotrigine and pt on CYP inducer, use the starter kit that has the higher dose.
CYP3A4 inducers + opioids that are CYP3A4 substrates
analgesia reduced effect, avoid just increasing opioid dose, maybe another non-opioid for breakthrough pain control
Opioids that are CYP3A4 substrates
fentanyl, hydrocodone, oxycodone, methadone
CYP2D6 UMs + Prodrugs (ex: codeine, tramadol)
Rapid and more conversion of a prodrug to its active form; increase tox risk
CYP3A4, P-GP inducers +
Calcineurin inhibitors (CNIs) OR
mTOR Kinase inhibitors
Decreased transplant drug level, increased risk of transplant rejection; avoid concurrent use but if needed, monitor transplant drug levels [trough] for efficacy
Smoking + some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, R-isomer warfarin
current smoker; substrate levels will be sub-therapeutic, a higher dose may be required.
on a substrate and smoking but not quitting; substrate levels may increase and cause toxicity
P-GP substrates
anticoagulants, CV drugs, immunosuppressants, HCV drugs, other
anticoags: apixaban, rivaroxaban
CV drugs: dig, diltiazem, verapamil
immunosuppressants: cyclosporine, tacrolimus
HCV drugs: ombitasvir, paritaprevir, dasabuvir
other: colchicine
P-GP inducers
similar to CYP3A4 inducers; carbamazepine, rifampin, st johns wort, phenytoin, phenobarbital
P-GP inhibitors
similar to CYP3A4 inhibitors
CYP3A4 inhibitors
ami, azoles, dilt, verap, cyclosporine
CYP3A4 inducers
PSPORCS
phenytoin, smoking, phenobarbital, oxcarbazepine, carbamazepine, rifampin, St. John’s Wort
Warfarin is a substrate of which enzymes?
CYP2C9 (major), 1A2, 2C19, 3A4
***Serotonergic toxicity - Drug combos causing additive side effects
antidepressants, MAO-I, buspirone [works on 5HT-1A], dextromethorphan, dihydroergotamine (migraine meds), lithium, lorcaSERin, opioids, metoclopramide, triptans, St. John’s Wort, I-tryptophan, tegaSERod
***Bleeding risk - Drug combos causing additive side effects
anticoagulants, anti-platelets, NSAIDs, SSRIs and SNRIs***, natural products [5 G’s; ginger gingko garlic ginseng glucosamine, vitamin E, willow bark, high dose fish oils]
***Hyperkalemia risk - Drug combos causing additive side effects
- highest risk - spironolactone, eplerenone,
- RAAS drugs - ACE, ARBs, aliskiren [Tekturna], sacubatril/valsartan [Entresto]
- amiloride, triamterene, salt substitutes (KCl), CNIs (tacrolimus, cyclosporine), canagliflozin, bactrim, drosperinone containing OCs
***QT Prolongation - Drug combos causing additive side effects
anti-arrhythmatics, antibiotics/anti-fungals, antidepressants, most antipsychotics, antiemetics, others
anti-arrhythmatics-
antibiotics/anti-fungals- quinolones, macrolides, azoles [except isovocunazonium (Cresemba)]
antidepressants-
most antipsychotics-
antiemetics-
others- donepazil, fingolimod, methadone
***CNS depression - Drug combos causing additive side effects
opioids, muscle relaxants, antiepileptics, BZDs, barbiturates, hypnotics, mirtazapine, trazodone, dronabinol [antiemetic, appetite stimulant], nabilone [Cesamet, man made form of cannabis], propanolol [Inderal], clonidine, sedating antihistamines, cough syrups with antihistamines or opioids, some NSAIDs, alcohol
ER form of opioids have an added risk with alcohol- ER forms when taken with alcohol can make the drug shorter acting, thus increasing the risk of fatality
***Ototoxicity - Drug combos causing additive side effects
AGs, cisplatin, loop diuretics [especially IV], salicylates [ASA, salsalate, magnesium salicylate], vancomycin
***Nephrotoxicity - Drug combos causing additive side effects
AGs, amphotericin B, polymyxins
***Anticholinergic toxicity - Drug combos causing additive side effects
paroxetine, TCAs, 1st gen antipsychotics, sedating antihistamines [diphenhydramine, bropheniramine, chlorpheniramine, doxylamine, hydroxyzine, cyproheptadine], atropine, belldonna, dicyclomine, meclizine, benztropine, trihexyphenidyl, muscle relaxants [baclofen, carisprodol, cyclobenzaprine], overactive bladder antimuscarinics [oxybutynin, darifenacin, tolterodine]
Hypotension/orthostasis - Drug combos causing additive side effects
PDE-5 inhibitors + CYP3A4 inhibitors OR Nitrates OR Alpha-1 blockers
CYP1A2 substrates, inducers, inhibitors
- substrates: theophylline, R-warfarin
- inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
- inhibitors: ciprofloxacin, fluvoxamine
CYP2C9 substrates, inducers, inhibitors
- substrates: S-warfarin
- inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
- inhibitors: ami, azoles, bactrim
CYP2C19 substrates, inducers, inhibitors
- substrates: clopidogrel
- inducers: carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s Wort
- inhibitors: esomeprazole, omeprazole
CYP2D6 substrates, inducers, inhibitors
- substrates: codeine, meperidine, tramadol, antipsychotics/antidepressants, tamoxifen
- inducers: none [have UMs and PMs]
- inhibitors:
