3. Drug Interactions Flashcards
Concomitant use of benzodiazepines and opioids may result in ___, ___, ___, and death d/t additive effects
profound sedation, respiratory depression, coma, and death
Which drugs have concern for chelation and should be separated from polyvalent cations or other drugs with binding properties (e.g. antacids, multivitamins, sucralfate, bile acid resins, Al, Ca, Fe, Mg, Zinc, phosphate binders)
Quinolones, tetracyclines, levothyroxine, and oral bisphosphonates
CYP___ metabolizes ~34% of all CYP450 drug substrates
3A4
What is the active metabolite of capecitabine?
Fluorouracil
What is the active metabolite of clopidogrel?
Active metabolite
What is the active metabolite of Codeine?
Morphine
What is the active metabolite of colistimethate?
Colistin
What is the active metabolite of coristone?
Cortisol
What is the active metabolite of Famciclovir?
Penciclovir
What is the active metabolite of fosphenytoin?
Phenytoin
What is the active metabolite of isavuconazonium sulfate?
Isavuconazole
What is the active metabolite of levodopa?
Dopamine
What is the active metabolite of Lisdexamfetamine?
Dextroamphetamine
What is the active metabolite of Prednisone?
Prednisolone
What is the active metabolite of Primidone?
Phenobarbital
What is the active metabolite of Tramadol?
active metabolite
What is the active metabolite of Valacyclovir?
Acyclovir
What is the active metabolite of valganciclovir?
ganciclovir
Codeine is metabolized by ____. What is the risk of use in pts who are ultrametabolizers (UM)?
2D6
Risk of toxicity (rapid conversion to morphine) - do not use
Codeine is metabolized by ____. What is the risk of use in pts who are poor metabolizers (PMs)?
2D6
Risk of poor analgesia effect - use alternative
Clopidogrel is metabolized by ____. What is the risk of use with inhibitors? Give 2 examples
2C19
Inhibitors will block conversion to active form - do NOT use with CYP2C19 inhibitors, including omeprazole and esomeprazole (can decrease antiplatelet effects)
Clopidogrel is metabolized by ____. What is the risk of use in pts who are poor metabolizers (PMs)?
2C19
Lower conversion to active form, reduced antiplatelet activity - use alternative P2Y12 inhibitor in pts who are PM
Are CYP450 enzymes involved in phase I or phase II reactions?
Phase IW
What are some examples of phase II enzymes?
Uridine diphosphate glucuronosyltransferase (UGT)
N-acetyltransferase (NAT)
___ (a phase II enzyme) are highly polymorphic; differences in the degree of isoniazid toxicity were found to be d/t differences in the rate of acetylation by this enzyme
N-acetyltransferase (NAT)
What are some moderate or strong CYP3A4i examples? (Hint: mneumonic)
G <3 PACMAN
Grapefruit
<3
Protease inhibitors (esp ritonavir)
Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, and isavuconazonium)
Cyclosporine, cobicistat
Macrolides (clarithromycin and erythromycin but NOT azithromycin)
Amiodarone, dronedarone
Non-DHP CCBs (diltiazem and verapamil)
Note: Amiodarone has ability to inhibit multiple CYP enzymes (e.g. 3A4, 2C9, 1A2)
What are some moderate or strong CYP3A4 inducers examples? (Hint: mneumonic)
PS PORCS
Phenytoin
Smoking
Phenobarbital
Oxcarbazepine
Rifampin, rifabutin, rifapentine
Carbamazepine (also an auto-inducer)
St. John’s wort
Note: Rifampin has ability to inhibit multiple CYP enzymes
T/F: enzyme inhibition effects take 2-4 weeks
False - enzyme INDUCTION often requires additional enzyme production, which take times, may take up to 4 weeks
When inducer is stopped, it could take ___ for the induction effects to disappear completely
2-4 weeks
Do P-gp efflux pumps in the cell membranes of the GI tract pump drugs and their metabolites into or out of the gut?
They pump INTO the gut to be excreted in the stool
Efflux = to flow out (but in this case out of the body, so pump INTO gut to get OUT of body)
When a drug inhibits P-gp, a P-gp substrate will have (increased/decreased) absorption and the substrate drug level will (increased/decrease)
increased absorption
increased drug level
Common P-gp substrates
Anticoagulants (apixaban, rivaroxaban // edoxaban, dabigatran)
CV drugs (digoxin, diltiazem, verapamil // carvedilol, ranolazine)
Immunosuppressants (cyclosporin, tacrolimus // sirolimus)
HCV drugs (sofosbuvir)
Others (colchicine // atazanavir, dolutegravir, posaconazole, raltegravir, saxagliptin)
Common P-gp inducers
Carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s wort
Others: dexamethasone, tipranavir
Common P-gp inhibitors
Anti-infectives (clarithromycin, itraconazole, posaconazole)
CV drugs (amiodarone, diltiazem, verapamil // carvedilol, conivaptan, dronedarone, quinidine)
HIV drugs (cobicistat, ritonavir)
HCV drugs (ledipasvir)
Others (cyclosporine // flibanserin, ticagrelor)
Which 3A4 inducers are also p-gp inducers (from mneumonic PS PORCS)
Phenytoin
Phenobarbital
Rifampin
Carbamazepine
St. John’s Wort
Which 3A4 inhibitors are also p-gp inhibitors (from mnuemonic G<3PACMAN)
Protease inhibitor = ritonavir
Azole inhibitors (itraconazole, posaconazole)
Cyclosporin, cobicistat
Macrolide (clarithromycin)
Amiodarone
Non-DHP CCBs (diltiazem, verapamil)
What is the DDI between amiodarone and warfarin?
Amiodarone inhibits multiple enzymes include CYP2C9, which metabolizes more potent warfarin isomer (decrease warfarin metabolism = increase INR and bleeding risk)
If amiodarone (1st) + warfarin - start warfarin at lower dose
If warfarin (1st) + amiodarone - decrease warfarin dose 30-50% depending on INR
Which drug needs to be decreased by 30-50% if starting amiodarone?
Warfarin
What is the DDI between amiodarone and digoxin?
Amiodarone inhibits P-gp
Digoxin is P-gp substrate
Decreased digoxin excretion, increased ADRs/toxicity
Amiodarone and digoxin both decrease HR, increase bradycardia, arrhythmia, fatality
If amiodarone (1st) + digoxin - start digoxin at lower dose
If using digoxin (1st) + amiodarone - lower PO digoxin dose 50%
Which drug needs to be decreased by 50% if starting amiodarone?
Digoxin
If taking both amiodarone and digoxin, what are some other drugs to be careful of?
Drugs that decrease HR
beta-blockers, clonidine, diltiazem, verapamil
What is the DDI between digoxin and loop diuretics?
Loop diuretics decrease K, Mg, Ca, and Na (low K, Mg, or Ca will worsen arrhythmias)
Digoxin toxicity risk is increased with decrease K and Mg levels and increased Ca levels
Caution: HF and renal failure often occur together. Digoxin is cleared by P-gp and excreted by kidneys = renal impairment increase digoxin levels and toxicity risk
What is the concern of concomitant use of drugs that decrease HR?
Additive effects
Caution: amiodarone, digoxin, beta-blockers, clonidine, diltiazem, verapamil and dexmedetomidine (Precedex)
Monitor HR
What is the DDI between statins and strong CYP3A4 inhibitors (G PACMAN)?
Increased levels of CYP3A4 substrates: lovastatin, simvastatin, atorvastatin
Higher risk of myopathy, rhabdo risk
Which statins are contraindicated with strong CYP3A4 inhibitors (G PACMAN)?
Simvastatin and lovastatin
Recommend a statin not metabolized by CYP450 enzymes like pitavastatin, pravastatin, and rosuvastatin
Which statins are NOT metabolized by CYP450 enzymes?
pitavastatin, pravastatin, and rosuvastatin
What is the DDI between warfarin and CYP2C9 inhibitors? (azole antifungals, SMX/TMP, amiodarone, metronidazole)
Increase levels of warfarin (increase INR = increase bleeding risk)
What is the DDI between warfarin and CYP2C9 inducers? (rifampin, St. John’s wort)
Decrease levels of warfarin (decrease INR = increase clotting risk)
Which opioids are CYP3A4 substrates?
fentanyl, hydrocodone, oxycodone, and methadone
Do NOT use CYP3A4 inhibitor with opioid metabolized by CYP3A4 - icnreased ADRs, including sedation, may be fatal
Which drugs should not be taken with grapefruit/ grapefruit juice?
Do NOT take with CYP3A4 substrates: amiodarone, simvastatin, lovastatin, nifedipine, and tacrolimus (others have similar risk)
What is the DDI between valproate and lamotrigine?
Valproate decreases lamotrigine metabolism
Increased lamotrigine = increase risk of serious skin reactions (SJS/TEN), can be fatal
Use starter kit (lower lamotrigine doses) and titrate carefully every 2 weeks
If using valproate and lamotrigine together, what should pharmacists recommend?
Initiate lamotrigine using the starter kit that begins with lower lamotrigine doses, titrate carefully every 2 weeks
What is the DDI between MAOi and drugs that increase Epi, Ne, DA, or 5-HT?
MAO enzyme metabolizes Epi, NE, DA, tyramine, and 5-HT
MAOi = increase Epi, NE, DA, and 5-HT
High Epi-NE, and DA = hypertensive crisis
High 5-HT= serotonin syndrome
Do NOT use together
Use 2 week washout period when switching between drugs with MAOi or serotonergic properties (Except with fluoxetine, wait 5 weeks)
What are some examples of MAOi?
Isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid, methylene blue
What are some examples of drugs/foods that increase Epi, NE, or Dopamine?
SNRs, TCAs, bupropion, levodopa, stimulants, including amphetamines used for ADHD (e.g. methylphenidate, lisdexamfetamine, dextramphetamine), tyramine (From foods)
What are some examples of drugs/foods that increase 5-HT?
Antidepressants: SSRIs, SNRIs, TCAs, mirtazapine, trazodone
Opioids and analgesics: fentanyl, methadone, tramadol
Others: buspirone, dextromethorphan (when high doses taken as drug of abuse), lithium, St. John’s wort
When is it recommended to use a 2-week washout period (exception: ____ with 5 week washout period)?
When switching between drugs with MAOi or serotonergic properties
Fluoxetine = 5-week washout
What are some tyramine-rich foods?
Aged, pickled, fermented, or smoked foods like aged cheeses, air-dried meats, sauerkraut, some wines/beers
What is the DDI between CYP2D6 inhibitors and CYP2D6 substrates?
Decrease drug substrate metabolism, increase ADRs/toxicity (or decreased efficacy if prodrug)
Avoid using together if possible
What are some 2D6 inhibitors?
Amiodarone, fluoxetine, paroxetine, fluvoxamine
What are some 2D6 substrates?
Many, including codeine, meperidine, tramadol, tamoxifen
What is the DDI between CYP3A4, P-gp inhibitors and Calcineurin inhibitors (CNIs) or mTOR kinase inhibitors?
Decrease drug substrate metabolism, increase ADR/toxicity including increased BP, nephrotoxicty, metabolic syndrome and other adverse effects
CNIs = tacro, cyclosporine
mTOR kinase inhibitors = sirolimus, everolimus
AVOID using together or decrease dose of CNI or mTOR kinase inhibitor based on drug levels
What is the DDI between antiepileptic drug (AED) CYP inducers (phenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) and other drugs metabolized by CYP enzymes (oral contraceptives, other AEDs, carbamazepine (auto-inducer), others)
Increase substrate metabolism = decrease drug levels
Decrease drug effects; with AEDs, loss of seizure control
Monitor drug level; induction takes up to 4 weeks for full effect, may need to increase substrate drug dose
If substrate is lamotrigine, use the starter kit that begins with higher lamotrigine doses
What is the DDI between rifampin and CYP and p-gp substrates?
Substrate drug conc will greatly decrease
Example: warfarin!
What is the DDI between CYP3A4 inducers and opioids that are 3A4 substrates (fentanyl, hydrocodone, oxycodone, methadone)
Increased metabolism = decreased opioid conc = less analgesia (pain relief)
Patient is a ultrametabolizer of CYP2D6. Which drugs are we concerned about?
Codeine, tramadol
2D6 UM, prodrug will convert more rapidly into active drug = increased active drug conc = toxicity/risk and possible fatality
Do NOT use codeine or tramadol in children <12 or <18yo following tonsillectomy and/or adenoidectomy (contraindication)
Do NOT use opioid prodrug that is metabolized by CYP2D6 (tramadol, codeine) in a breast-feeding mother unless it is known she is NOT an UM.
Which opioids prodrugs are metabolized by 2D6?
Codeine, tramadol
What is the DDI between CYP3A4, P-gp inducers and Calcineurin inhibitors (CNIs) or mTOR kinase inhibitors?
Increased drug metabolism, decrease transplant drug level, increased risk of transplant rejection
Avoid using together or monitor carefully
What is the DDI between smoking and some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, and warfarin (R-isomer)
Smoking induces CYP1A2 (both tobacco and marijuana)
Smokers who quit: When the inducer (cigarettes) is stopped, drug conc of substrates will increase, causing toxicity
Current smoker: CYP1A2 substrate levels decreased
Your patient who is on warfarin tells you they recently stopped smoking. What is your concern?
Monitor INR. The R-isomer of warfarin (less potent isomer) is metabolized by CYP1A2, but the therapeutic range is narrow and could be affected
T/F: Nicotine replacement products (NRT, such as patch/gum) induce CYP enzymes similar to smoking
False - they do NOT induce CYP enzymes
You are going to initiate warfarin in a pt with social hx (+) smoking. Do you consider starting with higher or lower dose?
Higher dose
What are some s/sx of serotonin syndrome?
Autonomic dysfunction (diaphoresis, N/V, hyperthermia)
Altered mental status (akathisia, anxiety, agitation, delirium)
Neuromuscular excitation (hyperreflexia, tremor, rigidity, tonic-clonic seizures)
Which drugs increase risk of serotonergic toxicity?
Anti-depressants: SSRIs, SNRIs, TCA, mirtazapine, trazodone
MAOi antidepressants: isocarboxazid, phenelzine, tranylcypromine
Selective MAO-Bi: selegiline, rasagiline
Other MAOi: linezolid, methylene blue
Opioids: fentanyl, meperidine, methadone, tramadol, tapentadol (risk with any opioid used in combo with serotonergic drug)
Triptans: PRN may be safe, more frequent use can increase risk
Natural products: St. John’s wort, L-tryptophan
Others: buspirone, lithium, dextromethorphan (when taken in excess as drug of abuse)
Doctor is switching med from fluoxetine to duloxetine. What is the washout period?
5 weeks
Doctor is switching med from citalopram to escitalopram. What is the washout period?
2 weeks
Avoid using drugs that increase risk of bleeding in combo with a few exceptions. What are the exceptions?
Aspirin (for cardioprotection) and occasional NSAID use for pain, fever, or inflammation
SSRI/SNRI use and occasional NSAID use for pain, fever or inflammation
Dual antiplatelet therapy for select patients (e.g. to prevent cardiac stent thrombosis)
Bridging/overlap treatment (ex. enoxaparin + warfarin)
Which drugs increase risk for bleeding?
Anticoagulants: warfarin ,dabigatran, apixaban, edoxaban, rivaroxaban, heparin, enoxaparin, dalteparin, fondaparinux, argatroban, bivalirudin
Antiplatelets: salicylates (including aspirin), dipyridamole, clopidogrel, prasugrel, ticagrelor
NSAIDs: ibuprofen, naproxen, diclofenac, indomethacin, others
SSRIs, SNRIs: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, others
Natural products: 5Gs: garlic, ginger, ginko biloba, ginseng, glucosamine, vitamin E, willow bark, fish oils (high doses)
What are the 5G natural products that increase risk of bleeding?
Garlic, ginger, ginko biloba, ginseng, glucosamine
What drugs increase risk for hyperkalemia?
RAAS drugs: ACEi/ARBs, aliskiren, sacubitril/valsartan, spironolactone, eplerenone (highest risk with aldosterone receptor antagonists)
K-sparing diuretics: amiloride, triamterene
Others: Salt substitutes (KCl), CNIs (tacro, cyclosporine), SMX/TMP, canagliflozin, drospirenone-containing oral contraceptives
Do NOT use ACEi with ARBs
Do NOT use sacubitril/valsartan with ACEi or ARBs
Avoid salt substitutes
If risk for hyperkalemia, suggest alternatives to canagliflozin (DM), SMX/TMP (infection) or drospirenone-containing oral contraceptives
The risk of QTc prolongation and TdP increases with:
higher doses
higher drug levels d/t concurrent enzyme inhibitors
higher drug levels d/t reduced drug clearance, such as renal/liver disease
Multiple QT-prolonging drugs used together
Elderly (>60yo) and patients with CVD, including arrhythmias, HF, MI
Generally, limit use of QT-prolonging drugs or select drugs with lower QT risk, especially with arrhythmias, CVD, or CVD risk (exception: ____ is the drug of choice to treat an arrhythmia in pts with HF)
Amiodarone
Do not exceed citalopram dose ____ or ____ in elderly (>60yo), liver disease, or with enzyme inhibitors that decrease clearance
40mg daily
20mg daily with elderly, liver disease, or with enzyme inhibitors
Do not exceed escitalopram ____ or ____ in elderly (>60yo)
20mg daily
10mg daily with elderly
Among SSRIs, ____ is considered safest in pts with CVD
Sertraline
Do not use ___ for inpatient N/V (it is injection only and has restricted use d/t QT prolongation risk)
Droperidol
Which anti-infectives increase risk of QT prolongation?
Antimalarials (e.g. hydroxychloroquine)
Azole antifungals except isavuconazonium
Lefamulin
Macrolides
FQ
Azole antifungals increase risk of QT prolongation EXCEPT ____
isavuconazonium
Which antidepressants increase risk of QT prolongation?
SSRIs: highest risk with citalopram, escitalopram
TCAs
Others: mirtazapine, trazodone, venlafaxine
Which SSRIs have highest risk of QT prolongation?
Citalopram and escitalopram
Which Antipsychotics increase risk of QT prolongation?
First-gen (e.g. haloperidol, thioridazone)
Seond-gen: highest risk with ziprasidone
Which second-gen antipsychotic has highest risk of QT prolongation?
Ziprasidone
Which antiemetics increase risk of QT prolongation?
5-HT3 receptor antagonists (e.g. ondansetron)
Others: droperidol, metoclopramide, promethazine
Which oncology meds increase risk of QT prolongation?
Androgen deprivation therapy (e.g. leuprolide)
Tyrosine kinase inhibitors (e.g. nilotinib)
Other: oxaliplatin
What are some misc meds that increase risk of QT prolongation?
Cilostazol, donepezil, fingolimod, hydroxyzine, loperamide, ranolazine, solifenacin, methadone, tacrolimus
What are some drug/drug classes that increase risk of CNS depression?
Opioids
Skeletal muscle relaxants
Antiepileptic drugs
Benzodiazepines
Barbiturates
Hypnotics
Antidepressants: mirtazapine, trazodone,
AntiHTN: propranolol, clonidine
Cannabis-related drugs: dronabinol, nabilone
Sedating antihistamines
Cough syrups with antihistamine or opioid
Some NSAIDs
Which combo of drugs has highest risk for fatality d/t CNS depression?
Opioids + benzodiazepines or other CNS depressants (including alcohol)
S/sx of CNS depression
somnolence, dizziness, confusion/cognitive impairment, altered consciousness/delirium, gait instability/imbalance/risk of falls/accidents
Benzodiazepines are drugs of abuse and often prescribed inappropriately (for anxiety or insomnia). What are some appropriate indications?
Status epilepticus, alcohol withdrawal, as an antidote for stimulant overdose, prior to medical procedures, in acute high-anxiety situations for anticipatory emesis with chemo
What are some patient counseling points for meds that can cause CNS depression?
Do NOT use alcohol
Do not operate car or other vehicles/machiens
Can increase risk of falls, confusion
Do ER or IR formulations of opioids have greater risk of fatality when taken with alcohol?
ER formulations have higher risk – several become shorter-acting when taken with alcohol
Avoid ____ (opioid) if pharmacogenomic profile is unknown (highest risk with CYP2D6 UMs)
Codeine
Which drugs increase risk of ototoxicity?
Aminoglycosides: gentamicin, tobramycin, amikacin, others
Cisplatin
Loop diuretics (esp rapid IV admin): furosemide, bumetanide, ethacrynic acid
Salicylates: aspirin, salsalate, magnesium salicylate, others
Vancomycin
Consider audiology consult at start of treatment for baseline and monitor
Avoid using multiple ototoxic drugs at the same time if possible
S/sx otoxicity
hearing loss, tinnitus, vertigo
Which drugs increase risk of nephrotoxicity?
Anti-infectives: aminoglycosides, amphotericin B, polymyxins, vancomycin
Cisplatin
CNIs: cyclosporin, tacrolimus
Loop diuretics: furosemide, torsemide, bumetanide, eythacrynic acid
NSAIDs
Radiographic contrast dye
If using cisplatin, use ___ to protect kidneys
amifostine (Ethyol)
What are anticholinergic symptoms?
CNS depression, including sedation, and peripheral anticholinergic side effects of dry mouth, dry eyes, blurry vision, constipation, urinary retention
Highest risk in elderly
Which drugs have anticholinergic toxicity risk?
Antidepressants/antipsychotics: paroxetine, TCAs, first-gen antipsychotics
Sedating antihistamines: diphenhydramine, brompheniramine, chlorpheniramine, doxylamine, hydroxyzine, cyproheptadine, meclizine
Centrally-acting anticholinergics: beztropine, trihexyphenidyl
Muscle relaxants: baclofen, carisprodol, cyclobenzaprine
Antimuscarinics (for urinary incontinence): oxybutynin, darifenacin, tolterodine
Others: atropine, belladonna, dicyclomine
What is the risk of taking PDE-5i (sildenafil, tadalafil, avanafil, vardenafil) with CYP3A4 inhibitors?
Decreased PDE-5 inhibitor metabolism = increased side effects (headache, dizziness, flushing = increased risk of falls/injury)
If taking CYP3A4i, start with 50% of usual starting dose of PDE-5i
What is the risk of taking PDE-5i with nitrates or alpha-1 blockers (non-selective (e.g. doxazosin, terazosin) or selective (e.g. tamsulosin))?
All cause vasodilation
Additive effects can cause to hypotension/orthostasis, dizziness and falls
With nitrates, severe hypotension can cause chest pain and CV events which can be fatal
What is your recommendation for PDE-5i and nitrates?
Do NOT use together (contraindicated)
What is your recommendation for PDE-5i and alpha-1 blockers?
Start with low dose when adding a drug for either class (e.g. if taking an alpha-1 blocker, start at half the usual PDE-5i dose)
Common CYP3A4 substrate: Analgesics
Fentanyl, hydrocodone, methadone, oxycodone
Others: buprenorphine, diclofenac, meloxicam, tramadol
Common CYP3A4 substrate: Anticoagulants
apixaban, rivaroxaban, R-warfarin
Common CYP3A4 substrate: CV drugs
Amiodarone, amlodipine, diltizaem, verapamil
Others: bosentan, eplerenone, ivabradine, nifepdipine, quinidine, ranolazine, tolvaptan
Common CYP3A4 substrate: Immunosuppressants
Cyclosporine, tacrolimus, sirolimus
Common CYP3A4 substrate: Statins
atorvastatin, lovastatin, simvastatin
Common CYP3A4 substrate: HIV drugs
Atazanavir, efavirenz, and other NNRTIs, ritonavir, ripranavir
Common CYP3A4 substrate: PDE-5i
Sildenafil, tadalafil, vardenafil, avanafil
Common CYP3A4 substrate: Misc
Ethinyl estradiol
Others: alfuzosin, aprepitant, aripiprazole, BZDs, brexpiprazole, buspirone, carbamazepine, citalopram, clarithromycin, colchicine, dapsone, dutasteride, erythromycin, escitalopram, felbamate, haloperidol, ketoconazole, levonorgestrel, mirtazapine, modafinil, ondansetron, progessterone, quetiapine, tamoxifen, trazodone, venlafaxine, zolpidem
Common CYP3A4 inducers
PS PORCS: Phenytoin, smoking, phenobarbital, oxcarbazepine, rifampin, carbamazepine, St. John’s wort
Others: efavirenz, etravirine, primidone, rifabutin, rifapentine
Common CYP3A4 inhibitors: anti-infectives
Clarithromycin, erythromycin, azole antifungals
Other: isoniazid
Common CYP3A4 inhibitors: CV drugs
Amiodarone, diltiazem, verapamil
Others: dronedarone, quinidine, ranolazine
Common CYP3A4 inhibitors: HIV drugs
Cobicistat, ritonavir, efavirenz and other protease inhibitors
Common CYP3A4 inhibitors: misc
Grapefruit, cyclosporine
Others: aprepitant, cimetidine, fluvoxamine, haloperidol, nefazodone, sertralien
Common CYP1A2 substrates
Theophylline, R-warfarin
Others: aldosteron, aprepitant, clozapine, cyclobenzaprine, duloxetine, ethinyl estradiol, fluvoxamine, methadone, mirtazapine, olanzapine, ondansetron, pimozide, propranolol, rasagiline, ropinirole, tizanidine, zolpidem
Common CYP1A2 inducers
Carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s wort
Others: ritonavir, primidone
Common CYP1A2 inhibitors
Ciprofloxacin, fluvoxamine
Others: atazanavir, cimetidine, zileuton
Common CYP2C8 substrates
Amiodarone, pioglitazone, repaglinide
Common CYP2C8 inducers
Phenytoin, rifampin
Common CYP2C8 inhibitors
Amiodarone, atazanavir, clopidogrel, gemfibrozil, ketoconazole, SMX/TMP, ritonavir
Common CYP2C9 substrates
S-warfarin
Others: alosetron, carvedilol, celecoxib, diazepam, diclofenac, fluvastatin, glyburide, glipizide, glimepiride, meloxicam, nateglinide, phenytoin, ramelteon, tamoxifen, zolpidem
Common CYP2C9 inducers
Carbamazepine, phenobarbital, phenytoin, rifampin, smoking, St. John’s wort
Others: aprepitant, primidone, rifapentin, ritonavir
Common CYP2C9 inhibitors
Amiodarone, fluconazole, metronidazole, SMX/TMP
Others: atazanavir, capecitabine, cimetidine, efavirenz, etravirine, gemfibrozil, fluvoxamine, fluorouracil, isonazid, ketoconazole, oritavancin, tamoxifen, valproic acid, voriconazole, zafirlukast
Common CYP2C19 substrates
Clopidogrel
Others: phenytoin, thioridazine, voriconazole
Common CYP2C19 inducers
Carbamazepine, phenobarbital, phenytoin, rifampin
Common CYP2C19 inhibitors
Esomepraozle, omeprazole
Others: cimetidine, efavirenz, etravirine, fluoxetine, fluvoxamine, isoniazid, ketoconazole, modafinil, topiramate, voriconazole
Common CYP2D6 substrates
Codeine, meperidine, tramadol, tamoxifen
Others:
Analgesics: hydrocodone, methadone, oxycodone
Antipsychotics/antidepressants: aripiprazole, brexipiprazole, doxepin, fluoxetine, haloperidol, mirtazapine, risperidone, thioridazine, trazodone, TCA, venlafaxine
Others: atomoxetine, carvedilol, dextromethorphan, flecainide, methamphetamine, metoprolol, propafenone, propranolol
Common CYP2D6 inhibitors
Amiodarone, duloxetine, fluoxetine, paroxetine
Others: bupropion, cimetidine, cobicistat, darifenacin, dronedarone, mirabegron, propafenone, quinidine, ritonvair, sertraline
