DRUG INTERACTIONS

1 D REMOVAL

1.1 URINE IS NO 1: URINE IS MOSTLY WTAER, D , D METABOLITES

NEED TO BE WATER SOLUBLE TO HAVE A HIGH DEGREE OF RENAL
EXCRETION
1.1.1 MANY DS ARE LIPID SOLUBLE (NON POLAR, UNCHARGED) AND
WILL NEED TO BE CONVERTED TO MORE WATER SOLUBLE( POLAR,
CHARGED) CPD IN ORDER TO CONCENTRATE IN RENAL FILTRATE (
URINE)

1.1.2 RENAL EXCRETION IN URINE

PHASE 1 AND PHASE 2 METABOLISM REFERS TO WNZYME CATALYZED
TRANSFORMATION RXS TAKE PLACE IN INTESTINE AND LIVER
PHASE 1 METABOLISM: OXIDATION RXS
PHASE 2 METABOLISM" PRimarily involves #CONJUGATION RXS, WHICH FURTHER
INCREASES A COMPOUNDS WATER SOLUBILITY , SOME CPDS REQUIRE BOTH PHASE
1 AND PHASE 2 RXS FOR ADEQUATE RENAL EXCETION (NON POLAR , LIPID
SOLUBLE---CONVERTED TO POLAR, WATER SOLUBLE)
THE DRUG THAT IS SUBJECT TO THE RX IS CALLED THE SUBSTRATE
THIS IS CALLED #FIRST PASS METSBOLISM, WHICH RESULTS IN THE #INACTIVATIO
OF SOME PERECENTAGES OF 75% OF ORAL DS
NON POLAR DRUG GOES PHASE 1 OXIDATION RXS(CYP 40 RXS ARE PHASE 1 RXS)--IF
NOT POLAR ENOUGH PHASE 2 CONJUGATION RXS ( CONVERT NON POLAR LIPID
SOLULE TO POLAR, WATER SOLUBLE)

1.2 FECES 2

1.3 MINOR ROUTES SKIN, TEARS, BREAST MILK, LUNGS

1.4 BLOODS SUPPLY FROM GUT GOES DIRECTLY TO LIVER, WITH

WHTAEVER SWALLOWED FOOD/DINKS RIDING ALONG

1.5 NUTRIENTS ARE ABSORBED AND SUBSTANCES THAT ARE NOT

NEEDED INCLUDING DRUGS, ARE EXCRETED
2 CYTOCHROME P 450 ENZYMES

2.1 CYP ENZYMES ARE POLYMORPHIC

2.1.1 CYP 50 ENZYMES ARE POLYMORPHIC, WHICH MEANS THERE
ARE DIFFERENT FORMS OF SAME ENZYME, THE CHANGES ARE DUE
TO #SINGLE NUCLEOTIDE POLYMORPHISM(SNP) IN DNA THAT
CODES FOR THE ENZYMES, A SNP CAN CAUSE THE ENZYME
PRODUCTION IN AN INDIVIDUAL TO #INCREASE OR DECREASE,
WHICH WILL INCREASE OR DECREASE RATE OF D METABOLISM
AND CONSEQUENTLY SERUM LEVEL OF THE SUBSTRATE DRUG

2.2 CYP P 450 ENZYMES

2.2.1 NORMAL METABOLIZER

2.2.2 ULTRA RAPID METABOLIZER UM

2.2.3 EXTENSIVE METABOLIZER EM

2.2.4 INTERMEDIATE METABOLIZER IM

2.2.5 POOR METABOLIZER PM

2.2.6 CYP ENZYMES VARY BY ETHNICITY AND AMONG INDIVIDUALS

2.3 PRODRUGS
2.3.1 CYP 450 METABOLISM
ACTIVE D --DECREASE ACTIVE DRUG
INACTIVE PRODRUG---INCREASE ACTIVE DRUG

2.3.2 INDUCER( LAG TIME)

W MOST DS, INDUCERS MAKE MORE ENZYMES, WHICH: DECREASE ACTIVE DRUG
W PRODRUGS, MORE ENZYME DUE TO AN INDUCER WILL MAKE : INCREASE ACTIVE
DRUG
LAG TIME: TO SEE EFFECT
EFFECTS REMAIN AFTER DRUG IS DC UNTIL ENZYMES DEGRADE

2.3.3 INHIBITORS(RAPID EFFECT)

W MOST DS, INHIBITORS MAKE ENZYMES INACTIVE WHICH INCREASE ACTIVE
DRUD
W PRODRUGS, LESS ENZYME DUE TO AN INHIBITOR WILL MAKE : DECREASE DRUG
RAPID EFFECT: COMPETITIVE BINDING OR CHANGE IN BINDING SITE TO DECREASE
AFFINITY
ONSET IS QUICK AND EFFECTS STOP WHEN D IS DICONTINUED
2.4 PRODRUGS TO EXTEND DOSING INTERVALS

2.4.1 A DRUG THAT HAS 50% BIOAVAILABILITY ( WRITTEN AS F=0.5)

LOSES HALF OF DOSE TO FIRST PASS METABOLISM

2.4.2 A PRODRUG VERSION COULD BE DESIGNED TO THE USE CYP

ENZYMES TO CATALYZE A REACTION THAT CONVERTS AN INACTIVE
D TO AN ACTIVE FORM, INSTEAD OF CONVERTING AN ACTIVE D TO
AN INACTIVE METABOLITE, THIS WOULD INCREASE THE DRUGS
ORAL BIOAVAILABILITY , WHICH COULD MAKE LONGER DOSING
INTERVAL FEASIBLE

2.4.3 VALACYCLOVIR---ACYCLOVIR

2.4.4 HERPES SIMPLEX VIRUS (HSV) , GENITAL INFECTION, CHRONIC

SUPPRESSION(ACYCLOVIR 400 MG BID, VALACYCLOVIR 500 MG -1 G
DAILY)

2.5 PRODRUG TO PREVENT D ABUSE

2.5.1 LISDEXAMFETAMINE(VYVANSE) PRODRUG ----L LYSINE+D
AMPHETAMINE( ACTIVE)

2.6 PRODRUG AND TOXICITY RISK: BREAST FEED MOTHER AKE

CODIENE, RAPIDLY CONVERTED MRPHINE , INFANT SUFFERED FATAL
RESPIRATRY DEPRESSION, WAS FOUND UM CYP2D6, SEVERLA
CHILDREN UMS OF CYP 2D6 SUFFERED FATAILTY FROM CODEINE FOR
POST TONSILLECTOMY /ADENOCTOMY PAIN, THIS IS THE MOST
COMMON OPERATION IN CHILDREN, CODEINE WOULD HAVE RISK W
OTHER PROCEDURES IN CYP 2 D6 UMS
2.6.1 CYP 2D6 METABOLIZERS MANY ANTIDEPRESSANTS,
ANTIPSYCHOTICS, AND PIAN MEDICTAIOINS

2.6.2 CYP 2 D6 INHIBITORS:DULOXETIENE, FLUOXTETINE,

PAROXETINE

2.6.3 BW;LIFE THREATENING ESPIRATORY DEPRESSION AND DEATH

IN CHILDREN RECEIVED CODEINE, MOST CASES OCCURED
FOLLOWING TONSILLECTOMY,FOR ADENIOCTOMY AND MANY OF
CHILDREN HAD EVIDENCE BEING UM AND CODIENE DUE CYP 2 D6
POLYMORPHISM, CODEINE IS CI IN PEDIARTIC PTS <12 YRS AND IN
PEDIATRIC PTS <18 YRS AFTER TONSILLECTOMY ,FOR ADENCTOMY,
AVOID CODEINE PEDITRIAC PTS 12-18 YRS OF AGE WHO HAVE
OTHER RISK FACTORS THAT MAY INCREASE SENSITIVTY TO
RESPIRATORY DEPRESSANT EFFECT OF CODEINE

2.7 enzyme inducer decrease the concentration of the substrate drugs

2.7.1 PS PORCS
PHENYTOIN, SMOKING, PHENOBARBITAL AND PRIMIDONE, OXACARBAZEPINE,
RIFAMPIN, RIFABUTIN, RIFAPENTINE, CARBAMEZEPINE, ST JOHN WORT

2.7.2 INDUCERS=DECREASED LEVELS/EFFECTD OF SUBSTRATE

,UNLESS IT IS A PRODURG

2.8 ENZYME INHIBITORS INCREASE CONCENTRATION OF THE

SUBSTRATE DRUGS
2.8.1 G LOVE PACMAN
GRAPEFRUIT, PROTEASE INHIBITIORS:RITONAVIR, AND OTHERS, AZOLE
ANTIFINGALS: FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, POSACONAZOLE,
VORICONZOLE, ISAVUCONAZONIUM, CYCLOSPORINE, CCOBICICSTAT, CIMETIDINE,
MACROLIDES( CLARITHROMYCIN, ERYTHROMYCIN, BUT NOT AZITHROMYCIN),
AMIODARONE AND RDRONEDARONE, NON DHP CCB: DILITIAZEM, VERAPAMIL
2.8.2 iNHIBITORS: NCREASED EFECTS/LEVELS/ADR/TOXICITIES OF
SUBSTRATES, UNLESS IT IS A PRODRUG

3.1 lag time for enzyme inductions

3.1.1 INHIBITION OF AN ENZYME IS FAST, EFFECTS ARE SEEN
WITHIN A FEW DAYS AND WILL END QUICKLY WHEN THE
INHIBIITOR IS IS DISCONTINUED

3.1.2 INDUCTION MOST OFETN REQUIRES ADDITIONAL ENZYME

PRODUCTION, WHICH TAKES TIME

3.1.3 THE FULL EFFECT ON DRUG LEVELS DUE TO ENZYME

INDUCTION MAY NOT BE SEEN FOR UP TO 4 WEEKS

3.1.4 WHEN THE INDUCER IS STOPPED IT COULD TAKE 2-4 WEEKS

FOR THE INDUCTION TO DISAPPEAR COMPLETELY, THE EXCESS
ENZYMES WILL DEGRADE BASED ON THEIR HLAF LIVES
4 GUT EXCRETION IN THE FECES

4.1 P -GLYCOPROTIEN EFFLUX PUMPS(TRANSPORTERS)

4.1.1 P-GP TRANSPORTS DRUGS AND THEIR METABOLITES OUT F
THE BODY BY PUMPING THEM INTO GUT, WHERE THEY CAN BE
EXCRETED IN STOOL

4.2 OATP IS ANOTHER DRUG TRANSPORTER

4.3 enterohepatic recycling

4.3.1 AFTER A DRUG HAS BEEN METABOLIZED IT CAN BE
TRANSOOTRED THROUGH THE BILE BACK TO THE GUT

4.3.2 FROM THE GUT THE DRUG CAN BE # REABSORBED AGAIN,

ENTER INTO # PORTAL VIEN AND # TRAVEL BACK TO THE LIVER

5 COMOMN DRUG INTERACTIONS

5.1 CARDIOVASCULAR (CVD) DRUGS THAT INTERACT WITH EACH

OTHER
5.1.1 AMIODARONE(FOR RHYTM)+WARFARIN TO REDUCE CLOT
RISK: USED TOGETHER FOR TT OF AFIB, DRONEDARONE HAS
SIMILAR DRUG INTERACTION ISSUES
AMIODARONE CYP2C9 INHIBITOR, METABLOLIZE WARFARIN, IF USE AMIODARONE
IST START WARFRAIN LESS OR EQUAL 5, IF USE WARFARIN 1ST, WHEN START
AMIODARONE DECREASE WARFRAIN 30-50% DEPEND ON INR, BOTH MONTOR INR,
ADJUST AS NEEDED, AMIODARONE INHIBIT CYP AND PGP

5.1.2 AMIODARONE+DIGOXIN:CAN BE GIVEN TOGETHER FOR

ARRHYTMIA TT:AMIODARONE ( FOR RHYTHM), DIGOXIN ( FOR RATE
CONTROL, DECREASE HR, OR FOR SYMPTOM IMPROVEMENET IN A
PT W HF)
AMIODARONE INHIBIT PGP, DIGOXIN PGP SUBSTARTE, BOTH DECREASE HR, INCR
BRADYCARDIS, ARRYTHMIA, FATATLITY, IF USE AMIODARONE 1ST, START DIGOXIN
AT LOW DOSE AS 0.125 MG DAILY INSTEAD OF 0.25 MG DAILY, IF USINF DIGOXIN 1ST,
DECREASE DIGOXIN DOSE BY 50%, IF ORAL CHANGE 0.25 MG DAILY TO 0.125 MG
DAILY OR CHANGE 0.125 MG DAILY TO 0.125 MG OTHER DAY, BOTH CHECK ENZYME
INHIBITORE CAN INCREASE DIGOXIN LEVEL, MONITOR SX DIGOXIN
TOXICITY:NAUSEA, MONITOR HR, NORAML RATE 60-100(CHECK OTHER DS HR:BB,
DEXEDETOMIDINE(PRECEDX),CLONIDINE), DIGOXIN USED FOR RATE CONTROL,
CONSIDER BB OR NON DHP CCB PREFERRED, CHECK ELECTROLYTES, ADJUST IF
LOW, RENAL IMAPIRMENT DECREASE DIGOXIN DOSE OR FREQUENCY, OR DC

5.1.3 DIGOXIN+LOOP DIURETICS, CAUTION: HF AND RENAL

IMPARIMENT OFTEN CONCUURENT :DIGOXIN IS CLEARED BY P-GP
AND DIRECTLY EXCRETED BY KIDNEYS:RENAL IMPAIRMENT (
DIGOXIN LEVEL AND TOXCIITY RISK)
LOOPS DEC MG,CA,NA, LOW K, MG, CA WORSEN ARHTMIAS, LOW K, MG CAUSE
DIGOXIN TOXIICITY

5.1.4 DILTIAZEM/VERPAMIL+OTHER DRUGS THAT DECREASE HEART

RATE( PREFERRED FOR RATE CONTROL ( OVER DIGOXIN): BETA
BLOCKERS ALSO PREFERRED
ADD EFFECT W OTHER DS DECREASE HR(AMIODARONE, DIGOXIN, BB,
DEMEDDETOMIDINE(PRECEDX),CLONIDINE), MONITOR HR 60-100 BPM

5.1.5 STATINS+CYP 3A4 STRONG INHIBITORS

DILTIAZEM, VERAPMIL, RITONAVIR AND OTHER PIS, COBICSTAT, CLARITHROMYCIN,
ERYTHROMYCIN, AZOLE ANTIFNGALS, VIEKIERA PAK, CYCLOSPORINE,
GRAPEFRUIT JUICE/FRUIT, AMIODARONE, DRONEDRONE
INCREASE EVELS W CYP3A4 SUBSTRATES(SAL SIMV,ATRO,LOVSTATIN CYP3A4
SUBSTRATES), INCREASE MYOPATHY W HIGH CPK, CAUSE RHABDOMYOLYSIS W
ACUTE RENAL FAILURE ARF
W STATINS, (USE RPP, NOT METABOLIZED CYP450) OR USE LOWER DOSE
SIMVASTTAIN 10-20 MG,
GRAPEFRUT JUICE: DO NOT TAKE W CYP 3A4 SUBSTRATES, SNLT NO TAKE W
GRAPEFRUIT
5.2 INHIBITORS INCREASE SUBSTRATE DRUGS

5.2.1 CYP 3A4 INHIBITOR+CYP 3A4 SUBSTRATES(MANY) INCLUDES

THE OPIODS FENTANYL, HYDROCODONE, OXYCODONE,
METHADONE, HYDOCODONE, HYDROMORPHONE (MAJOR)
DECSUBSTRATE, INC ADR(OPIOIDSUBSTRATE:SEDATION,RESPIRATORY
DEPRESSION), MONITOR D , SE

5.2.2 VAPROATE+LAMOTRIGINE:VALPROATE IS AN INHIBITOR OF

LAMOTRIGINE METABOLISM
VALPROATE DEC LAMOTRIGINE, INCREASE LAMOTRIGNE INC SJS/TEN,RISK
HIGHEST PEDIATRICS, INITATE LAMOTRIGINE USE STARTER KIT DOSING BEGINS W
LOWER LAOTRIGINE DOSE,TITRATE Q 2 WKS, COUNSEL RASH

5.2.3 MONOAMINE OXIDASE (MAO) INHIBITORS(PHENELZINE,

ISOCARBOXAZID, TRANYLCYPROMINE AND LINEZOLID,
METHYLENE BLUE) and SLECTIVE MAO-B INHIBITORS
SELEGILINE,RASAGILINE
+DS THAT INCREASE EPINEPHRINE EPI, NOREPINEPHRINE NE, DOPAMINE
DA:PSEUDOEPHEDRINE, PHENYLEPHRINE, EPINEPHRINE, NOEREPINEPHRINE,
DOBUTAMINE, SNRIS, BUPROPION, AND STIMUALNTS INCLUDING AMPHETAMINES
USED FOR ADHD (METHYPHENIDTAE, LISDEXAMFETAMINE, DEXTROAMPHETAMINE
MAO ENZYME METABOLIZES EPI, NE, DA, 5HT, BLOCKING MAO W MAOI WILL
INCREASE EPI, NE,DA,5HT, HIGH E,NE,DA:HTN CRISIS, HIGH 5HT:SS
DO NOT USE TOGETHER, USE 2 WK WASHOUT PERIOD BETWEEN SEROTONERGIC DS,
ANOTHER ANTIDEPRESSANT, CHANGE FLUOXETINE TO MAOI WAIT 5 WEEKS
+DRUGS THAT INCREASE SEROTONIN (5 HT)
ANTIDEPRESSSANTS, SSRIS, SNRIS, TCAS, MAOI, MIRTAZAPINE, TRAZADONE,
OIPIODS, FENATNYL, METHADONE, TRAMADOL,OTHERS( BUSPIRONE,
DEXTROMETHORPHAN( HIGH DOSE TAKEN AS DRUG OF ABBUSE, LITHIUM, ST JOHN
WORT
+TYRAMINE RICH FOODS/DRINKS
MAO METABOLIZES TYRAMINE, IF BLOCKED TYRAMINE CAUSE INCREASE NE, W
RISK OF HYPERTENSIVE CRISIS
TYRAMINERICH FOODS AGED, PICKLED, FERMENTED OR SMOKED, INCLUDE AGED
CHEESE, AIR DRY MEATS, WINE, BBERS, DO NOT EAT FOODS RICH TYRAMINE

5.2.4 CYP 2D66 INHIBITORS(AMIODARONE, FLUOXETINE,

PAROXETINE, FLUVOXAMINE)+ CYP 2 D6 SUBSTRATES(FFAP)
DEC D METABOLISM, INCR ADRS,TOXICITY, AVOID USE TOGETHER OR DECR DOSE
OF SUBSTRATE

5.2.5 CYP3A4, P-GP INHIBITORS+CALCINEURIN INHIITORS(CNIS)

TACROLIMUS, CYCLOSPORINE, SIROLIMUS
DER D METABOLISM INCRADRS, TOXICITY (INCREASE BP, NEPHROTOXIC,
METABOLIC SYNDROME), AVOID USE TOGETHER OR DECR DOSE CNI , MONITOR
TRANSAPLNT D (TROUGH)
5.3 INDUCERS DECREASE SUBSTRATE DS

5.3.1 ANTIEPLIEPTIC DS AEDS:PHENYTOIN,

PHENOBARITAL,PRIMIDONE, CARBAMAZEPNINE,
OXACARBAZEPINE+ OTHER DS METABOLIZED BY CYP ENZYMES,
INCLUDING ORAL CONTRACEPTIVES,OTHER AEDS AND ABZ(AUTO
INDUCER, INDUCES OWN METABOLISM)
DECREASE SUBSTRATE D OR CBZ , WITH AEDS LOSS SEIZURE CONTROL
MONITOR CHANGE D LEVELS, TAKEN UP 4 WKS FULL EFFECT, INCREASE DOSE OF
SUBSTRATE D, IF SUBSTRATE IS LAMOTRIGINE, USE STARTER KIT DOSING BEGINS W
HIGHER LAMOTRIGINE DOSE

5.3.2 RIFAMPIN +CYP AND P-GP SUBSTRATES(MOST DS)

CONCENTRATION OF SUBSTRATE DS DECREASE
MONITOR D LEVELS, OR MONITOR PARAMTERE SUCH AS INR W WARFRAIN,
INCREASE DOSE OF SUBSTRATE D

5.3.3 CYP 3A4 INDUCERS+OPIOIDS THAT ARE SUBSTRATES OF CYP

3A4:FEBTANYL, HYDROCODONE, OXYCODONE, METHADONE,
HYDROCODONE,HYDROMORPHONE:MAJOR
INCREASE METABOLISM, DECREASE OPIOIDSS, ANAGLESIA(PAIN RELIEF) WILL
DECREASE
ASSESS PT BREAKTHROUGH PAIN TO DETERMINE INCREASE DOSE NECESSARY,
CAUTION OPIOIDS CAUSE REPIRATORY DEPRESSION, WHEN OVERDOSED
INDUCTION HAS LAG TIME

5.3.4 CYP 2D6 UMS+PRODRUGS CODEINE,TRAMADOL(IN CYP 2D6

UM:SIMILAR EFFECT TO AN INDUCER OF CYP 2D6
NO CYP2D6 INDUCER, HOWEVER W CYP2D6 UMS(PRODUCE TWICE AS MANY
ENZYMES, EFFECT SIMILAR TO INDUCER, THE ACTIVE D CONC WILL INCREASE,
CAUSE TOXICITY ,RISK FATTALITY
DO NOT USE CODEINE OR TRAMADOL PTS<12 YRS AND CHILDREN <18 YRS FOLLOW
TONSILLECTOMY OR ADENOCTOMY, DO NOT USE OPIOID PRODRUG METABOLIZED
BY CYP2D6 (CODIENE,TRAMADOL) IN BREAST FED MOTHER UNLESS KNOWN SHE IS
NOT 2D6UM, NEVER CRUSH OR CHEW ANY ER OPIOID INCLUDE PRODRUGS

5.3.5 CYP 3A4, P-GP INDUCERS+CALCINUERIN INHIBITORS(CNIS),

TACROLIMUS, CYCLOSPORINE,SIROLIMUS
DECREASE CNI LEVEL, WITH INCREASE RISK OF TRANSPALNT ORAGN REJECTION
RISK TRANSPALNT REJECTION, AVOID USE TOGETHER OR INCREASE DOSE CNI
CAREFULLY, MONITOR CNI LEVEL TROUGH FOR EFFICACY

5.3.6 SMOKING+SOME ANTIPSYCHOTICS, ANTIDEPRESSANTS,

HYPNOTICCS, ANXIOLYTICS, CAFFEINE, THEOPHYLLINE, INSULIN,
WARFRAIN(R ISOMER), SMOKING INDUCES CYP 1A2
SMOKERS WHO QUIT: WHEN INDUCER:CIGRAETTES STOPPED, D CONC CYP1A2 WILL
INCREASE , CAUSE TOXICITY, ACTION: COUNSEL SMOKING CESSATION, WHEN
SMOKER QUITS MONITOR INR, R ISOMER OF WARFARIN LESS POTENT ISOMER
METABOLIZED CYP1A2, BUT THERAPEUTIC RANGE NARROW , AFFECTED
CURRENT SMOKER: SUBSTRATE DS(CYP1A2 SUBSTRATE) WILL DECREASE LEVELS,
ACTION: WHEN CURRENT SMOKER STARTS A DRUG(PRIMARILY CYP1A2
SUBSTRATES) A HIGHER DOSE REQUIRED, WHEN NSMOKER QUITS A LOW DOSE D
NEEDED, IF NOT REUCED TOXICITY RESULT, NICOTINE REPLACEMENT AS
PATCH,GUM, DO NOT INDUCE CYP ENZYMES

5.4 ADDITIONAL COMMON, WELL KMOWN DRUG INTERACTIONS

5.4.1 PDE-5 INHIBITORS:SILDENAFIL, VARDENAFIL, TADALAFIL,
AVANAFIL
+CYP 3A4 INHIBITORS
DECREASE ED D METABOLISM, INCRREASE SE INCLUDE HA,DIZZINESS,
FLUSH(INCREASE RISK OF FALLS,INJURY), ACTION: START W HALF USUAL STARTING
DOSE,CHANGE 5O MG SILDENAFIL TO 25 MG, CHANGE 10 MG
VARDENAFIL/TADALAFIL TO 5MG,AVANAFIL 100 MG TO 50 MG
+NITRATES
MAGNIIFED ADVERSE EFFECTS, SIMILAR IN BOTH CLASSES RISK OF SEVERE
HYPOTENSION,DEATH, CONCURRENT USE CI, ACTION:DO NOT USE TOGETHER,
CHECK FILL HISTORY FOR SL NITROGLYCERIN FOR PRN USE W CHEST PAIN, FOR
ACUTE USE(UA/NSTEMI) CAN CONSIDER USE IF 24 HRS AFTER
SILDENAFIL,MONITOR BP
+ ALPHA BLOCKERS
ADDITIVE INCREASED ADVERSE EFFECT, SIMILAR IN BOTH
CLASSES:HYPOTENSION/ORTHOSTASI,DIZZINESS,FALLS,NON SELECIVE ALPHA
BLOCKER HIGHER RISK HYPOTENSION,ORTHOSTASIS, ACTION: WHICHEVER D
CLASS (PDE5 INHIBITOR OR ALPHA BLOCKER) START W LOW DOSE, EG:DO NOT USE
MORE THAN 1 MG DOXAZOSIN (NON SELECTIVE ALPH BLOCKER) OR IF AN ALPHA
BLOCKER INTIALLY USE LOWER DOSE OF PDE5 INHIBITOR

5.4.2 DS PROLONG QT INTERVAL

+ANTIARRHYTHMICS(AMIODARONE, DRONEDARONE, SOTALOL, IBUTILIDE,
DOFETILIDE)
+ANTIBIOTICS/ANTIFUNGALS( QUINOLONES AND MACROLIDES), AZOLE
ANTIFUNGAL, EXCEPT ISAVUCONAZONIUM(CRESEMBA), ANTIDPERESSANTS,
TRICYCLICS, SSRIS,HIGHER RISK: CITALOPRAM, ESCITALOPRAM
+ANTIPSYCHOTICS(MOST):INCLUDING PHENOTHIAZINES( END IN AZINE, SUCH AS
THIORIDAZINE),HALOPERIDOL, ZIPRASISONE
+ANTIEMETIC AGENTS: 5 HT3 RECEPTOR ANTAGONISTS, INCLUDING
ONDAMSETRON, DROPERIDOL AND PHENOTHIAZINES AS PROCHLORPERAZINE
OTHERS: DONEPEZIL, FINGOLIMOD, METHADONE

5.4.3 QUINOLONES, TETRACYCLINES

+ANATCIDS, SUCRALFATE, BILE ACID RESINS, MAGNESIUM, ALUMINUM, CALCIUM,
IRON, ZINC, MULTIVITAMINS, PHOSPHATE BINDERS: SEPARATE ABIC FROM ABOVE
DS REQUIRE #ACIDIC GUT FOR ABSORPTION ARE IN GERD CHAPTER
5.5 DS W SIMILAR SE, WHEN USED IN COMBINATON HAVE MORE SE

5.5.1 CNS DEPRSSION

OPIOIDS, SKELETAL MUSCLE RELXANTS, ANTIEPILEPTIC DS, BENZODIAZEPINES,
BARBITURATES, HYPNOTCS, MIRTAZAPINE, TRAZADONE, DRONABINOL, NABILONE,
PROPRANOLOL, CLONIDINE, SEDATING ANTIHISTAMINES, COUGH SYRUOS WITH
ANTIHISTAMINE OR OPIOID, SOME NSADIS
HIGHEST RISK FOR FATALITY WHEN USED IN COMBINATION: DO NOT USE
TOGETHER: OPIODS+BZDS OR OTHER CNS DEPRESSANTS

5.5.2 ADDITIVE OTOTOXCIITY

AMINOGLYCOSIDES
CISPLATIN
LOOP DIURETICS(ESPECIALLY IV)
SALICYLATES( INCLUDING ASPIRIN, SLASALATE, MAGNESIUM SALICYLATE)
VANCOMYCIN

5.5.3 ADDITIVE NEPHROTOXCIICTY

AMINOGLYCOSIDES, AMPHOTERICIN B, VANCOMYCIN
CISPALTIN, METHOTREXATE W HIGH CHEMO DOSES
CYCLOSPORINE, TACROLIMUS( CALCINEURIN INHIBITORS
LOOP DIURETICS ( ESPECIALLY IV)
NSAIDS: AVOID USE W RENAL IMPAIRMENT

5.5.4 ADDITIVE: ANTICHOLINERGIC EFFECTS

PAROXETINE, TRICYCLIC ANTIDEPRESSANTS, FIRST GENERATION ANTIPSYCHOTICS
SEDATING ANTIHISTAMINES, NICLUDING: DIPHEHYDRAMINE, BROMPHENIRAMINE,
CHLORPHENIRAMINE, DOXYLAMINE, HYDROXYZINE, CYPROHEPTADINE
ATROPINE, BELLADONNA, DICYCLOMINE, MECLIZINE
BENZTROPINE, TRIHEXYPHENIDYL
MUSCLE RELEXANTS, INCLUDING CARISOPRODOL, CYCLOBENZAPRINE, BACLOFEN
OVERACTIVE BLADDER ANTIMUSCARINICS, SUCH AS TOLTERODINE, OXYBUTYNIN,
DARIFENACIN

5.5.5 serotonergic toxcicity

ANTIDEPRESSANTS:SSRIS,SNRIS,TCAS,MIRTAZAPINE, TRAZADONE
ANTIDEPRESSANTS MAO INHIBITORS: TRANYLCYPROMINE, ISOCARBOXAZID,
PHENELZINE
SELECTIVE MAOI:SELEGILINE, RASAGILINE
OTHER MAOI: LINEZOLID, METAXALONE,METHYLEN BLUE
BUSPIRONE
DEXTROMETHORPHAN: TAKEN IN EXCESS AS D OF ABUSE
DIHDRYERGOTAMINE
LITHIUM
MEPREDINE, METHADONE, TRAMADOL, TAPAENTADOL, FENTANYL, RISK W OTHER
OPIODS USED IN COMBINATIOIN
METOCLOPRAMIDE
TRIPTANS: SEROTONERGIC DS W OCCASIONAL PRN TRITAN USE MAY BE SAFE,
MORE SEROTONERGIC DS INCREASE RISK
NATRUAL PRODUCTS: ST JOHN WORT, L TRYPTOPHAN
5.5.6 BLEEDING RISK
ANTICOAGULANTS:WARFARIN, DABIGATRAN, APXIBAN, BETRIXABAN,
EDOXABAN,RIVAROXBAN, HEPARIN, ENOXAPARIN, DALTEPARIN, FONDAPRINUX,
ARGOTRABAN, BIVALRUIDN
ANTIPLATELETS: SALICYLATE, INCLUDING ASPIRIN, DIPYRIDAMOLE,
CLOPDIOGREL, PRASUGREL, TICAGRELOR
NSADIS, SSRIS, SNRIS
NATRUAL PRODUCTS: 5 GS: GINKGO BILOBA, GARIC, GNIGER, GLUCOASMINE,
GINSENG, VITAMIN E, WILLOW BARK, FISH OILA HIGH DOSE

5.5.7 HYPERKALEMIA RISK

SPRINOLACTONE, EPLERENONOE, HIGHEST RISK
RENIN ANGIOTENSIN ALDOSTERONE DS: ACEI,ARBS,ALISKIREN,
SACBUTRIL/VALSARTAN
AMILORIDE, TRIAMTERENE, SALT SUBSTITUTES KCL, CALCINUERIN INHIBITOR(
TACROLIMUS,CYCLOSPPORINE), CANGALOFLOZIN, PENTAMIDINE, SMX/TMP,
DROSPIRENONE CONATIN ORAL CONTRACEPTIVES

5.6 PRODUG: CLOPIDOGREL(PLAVIX)+CYP2C19 INHIBITORS

5.6.1 CLOPIDOGREL(PLAVIX)
RISK W CYP2C19 INHIBITOS, WHICH MAY BLOCK CONVERSION TO ACTIVE FORM:
DO NOT USE W CYP2C19 INHIBITORS, INCLUDING OMEPRAZOLE AND
ESOMPERAZOLE
RISK W PMS OF CYP2C19 , LOW CONVERSION TO ACTIVE FORM, W REDUCED EFFECT
OF DRUG ON PLATELET ACTIVITY
USE AN ALTERNATIVE P2Y12 INHIBITOR IN PTS IDENTIFIED AS PMS OF CYP 2C19