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Top Ten Drug Drug Interactions

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Clinical pharmacy department , MUST Dean assistant for experts council, scientic conferences and continuous education Manager of CTC ( pharmacy , Must )

Coordinator of pharmaceutical association of MUST Consultant at CCH

 

List of Top Ten Drug Interactions in Long-Term Care Medications chosen for the Top Ten list were based on their frequency of use in older adults in the long-term care setting, and on the potential for adverse consequences if used together. Due to individual variability, not every older adult who takes these medications together will experience an adverse reaction. owever, these combinations have the potential to produce harmful effects.

1.

Warfarin — NSAIDs* 2. Warfarin — Sulfa drugs 3. Warfarin — Macrolides 4. Warfarin — Quinolones** 5. Warfarin — !en"toin 6. AC# in!i$itors — otassium supplements  supplements  7. AC# in!i$itors i n!i$itors — Spironolactone 8. Digo%in — Amiodarone 9. Digo%in — &erapamil 10. T!eop!"lline — Quinolones** ! "#$%D class does not include &'(-) inhibitors !! *uinolones that interact include+ ciprofloxacin, enoxacin, norfloxacin, and ofloxacin. ofloxacin . Warfarin

NSAIDs

&oumadin, warfarin

$leve, $naprox, $naprox D#, $nsaid, $rthrotec, &ataflam, &linoril, Daypro, diclofenac, diclofenacmistoprostrol diclofenacmist oprostrol,, diflunisal, Dolobid, etodolac, eldene, flurbiprofen, ibuprofen, %ndocin, %ndocin #, indomethacin, ketoprofen, ketorolac, /odine, /odine (/, mefenamic acid, meloxican, Mobic, Motrin, nabumetone, "aprelan, "aprosyn, naproxen, 'rudis, 'ruvail, oxapro0in, piroxicam, 1onsel, D#, tolmetin,elafen, Toradol,sulindac, 2oltaren,Tolectin, 2oltarenTolectin (

IMACT' 1otential IMACT'  1otential for serious gastrointestinal bleeding M#C(ANISM ) INT#+ACTI)N+ INT#+ACTI)N+ "#$%Ds increase gastric irritation and erosion of the protective lining of the stomach, assisting in the formation of a 3% bleed. $dditionally, "#$%Ds decrease the cohesive properties of platelets necessary in clot formation. +#&#NTI)N' $void concomitant +#&#NTI)N' $void concomitant use of of an "#$%D with wa warfarin. rfarin. %den %dentify tify reason for "#$%D therapy. %f anti-pyretic effects are desired, then consider acetaminophen. $cetaminophen in doses less than )gday on a short-term basis does not appear to affect the %". /ong-term use of acetaminophen for anti-pyretic and analgesic effects is controversial. %f antiinflammatory effects are necessary, then consider cyclooxygenase-) 4&'(-)5 inhibitor therapy. The minimi0ation of gastric irritation with these agents combined with the lack of antiplatelet action, support the cautious use of &'(-) inhibitors in anticoagulation patients. There are some case reports discussing the elevation of %"s with &'(-) inhibitors. %f analgesic effects are desired, caution should also be exhibited with the use of tramadol6 there are a few

 

case reports describing an elevation of the %" with concomitant administration of tramadol with warfarin. MANA,#M#NT' 1rothrombin time and %" should be monitored every week with coadministration of warfarin with an "#$%D. #igns and symptoms of an active bleed should be monitored with particular attention to the appearance and patterns of bruises. #igns of an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, or black, tarry stools 4hemoccult positive5. Warfarin

Sulfa Drugs

&oumadin,, warfarin &oumadin

7actrim D#, 7actrim ##, &otrim D#, &otrim ##, erythromycinsulfisoxa0o erythromy cinsulfisoxa0ole, le, 3antanol, 3antanol, 3antrisin, 1edia0ole,, #eptra D#, #ulfatrim, sulfamethi0ole, 1edia0ole sulfamethi0ole, sulfamethoxa0ole, sulfamethox a0ole, sulfisoxa0ole, Thiosulfil orte, trimethoprimsulfamethoxa0ole

IMACT' %ncreased IMACT'  %ncreased effects of warfarin, with potential for bleeding M#C(ANISM ) INT#+ACTI)N' &urrently, the mechanism for interaction with sulfa drugs is unknown6 however, clinicians hypothesi0e that warfarin8s activity is prolonged due to a decreased production production of vitamin 9 by intestinal flora affected by systemic antibiotic administration. +#&#NTI)N' $void concomitant +#&#NTI)N' $void concomitant use of of a sulfa drug with warfari warfarin, n, particularly particularly sulfamethoxa0ole-trimethoprim. %dentify microbial pathogen prior to initiation of antibiotic therapy. &onsider culture sensitivity screening as research indicates cautious use of any antibiotic with warfarin. %f use of a sulfa drug is imperative, then reduce warfarin dose by :;< during antibiotic administration and for one week following completion of the antibiotic. %f sulfamethoxa0ole-trimethoprim therapy is required, then monitor %" every other day for elevating trends. MANA,#M#NT' 1rothrombin time and %" should be monitored every week during coadministration of warfarin with a sulfa drug. #igns and symptoms of an active bleed should be monitored daily with particular attention to the appearance and patterns of bruises. #igns of an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools 4hemoccult positive5. Warfarin

Macrolides

&oumadin, warfarin

a0ithromycin, 7iaxin, clarithromycin, clarithromyc in, Dynabac, dirithromycin, =-Mycin, erythromycin base, ==#, erythromycin ethyl succinate, =ry-Tab, =ryc, =ry1ed, =rythrocin, erythromycin stearate, %losone, erythromycin estolate, 1edia0ole, erythromycinsulfisoxa0ole, Tao, troleandomycin, >ithromax

IMACT' %ncreased IMACT'  %ncreased effects of warfarin, with potential for bleeding M#C(ANISM ) INT#+ACTI)N' =rythromycin inhibits the metabolism and subsequent clearance of warfarin from the body. The activity of warfarin may also be prolonged due to alterations in the intestinal flora and its production of vitamin 9 for clotting factor production.

 

+#&#NTI)N' The interaction between warfarin and macrolide antibiotics is highly probable and often delayed. &oncomitant use of a macrolide with warfarin should be avoided6 switch to an alternative antibiotic. Microbial pathogen identification prior to antibiotic initiation will decrease the prevalence of unnecessary drug interaction risk. &onsider culture sensitivity screening as research indicates cautious use of any antibiotic with warfarin. MANA,#M#NT' %f use of a macrolide is imperative, then monitor %" every other day and ad?ust warfarin dosing as necessary. #igns and symptoms of an active bleed should be monitored daily with particular attention to the appearance and patterns of bruises. #igns of an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools 4hemoccult positive5. "'T=+ $lthough caution may be warranted when using warfarin with all quinolones, Drug Interaction Facts notes that problems have been documented especially with ciprofloxacin, ofloxacin, and norfloxacin. %n addition, the Medication Management 1ro?ect committee has received a number of reports of %" elevations with levofloxacin. Warfarin

Quinolones

&oumadin, warfarin

alatrofloxacin, alatrofloxaci n, $velox, &ipro, ciprofloxacin, ciprofloxaci n, enoxacin, loxin, gatifloxacin, /evaquin, levofloxacin, lomefloxacin, Maxaquin, Maxaquin, moxifloxacin,, "oroxin, norfloxacin, ofloxacin, moxifloxacin 1enetrex, sparfloxacin, Tequin, trovafloxacin, Trovan, Trovan %2, >agam

IMACT' %ncreased IMACT'  %ncreased effects of warfarin, with potential for bleeding M#C(ANISM ) INT#+ACTI)N' The exact mechanism for the warfarin-quinolone drug interaction is unknown. eduction of intestinal flora responsible for vitamin 9 production by antibiotics is probable as well as decreased metabolism and clearance of warfarin. +#&#NTI)N' &ulture and identify microbial pathogen prior to initiation of antibiotic therapy. &onsider culture sensitivity screening. The metabolism of warfarin may be delayed in patients administered enoxacin, ciprofloxacin, norfloxacin, or ofloxacin6 thus, quinolone selection should focus on one of the newer agents that has not demonstrated significant impairment of warfarin metabolism. $dditionally, microbial pathogen identification and sensitivity prior to antibiotic initiation will decrease the prevalence of unnecessary drug interaction risk. MANA,#M#NT' 1rothrombin time and %" should be monitored during co-administration of warfarin with a quinolone. %f use of ciprofloxacin is imperativ imperative, e, then monitor %" every other day and ad?ust warfarin dose as necessary. #igns and symptoms of an active bleed should be monitored daily with particular attention to the appearance and patterns of bruises. #igns of an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools 4hemoccult positive5.

Warfarin &oumadin, warfarin

!en"toin Dilantin, phenytoin

 

IMACT' %ncreased IMACT'  %ncreased effects of warfarin andor phenytoin M#C(ANISM ) INT#+ACTI)N' &urrently unknown, but one theory suggests a genetic basis involving liver metabolism of warfarin and phenytoin. +#&#NTI)N' 'btain baseline phenytoin levels 4 . . @  @ ); mirogram ml 5 prior to initiation of warfarin. Monitor %" during co-administration. Target %" should be towards the lower end of  the therapeutic range. MANA,#M#NT' 1rothrombin time, %" , and phenytoin levels should be monitored during co-administration. #igns and symptoms of an active bleed should be monitored daily with particular attention to the appearance and patterns of bruises. #igns of an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools 4hemoccult positive5. AC# In!i$itors

otassium Supplements

 $ccupril, $ceon, $ltace, bena0epr bena0epril, il, &apoten, captopril,, enalapril, captopril enalapril, fosinopril, lisinopril, /otensin, Mavik, moexipril, Monopril, perindopril, 1rinivil, quinapril, ramipril, trandolapril, Anivasc, 2asotec, >estril

9B &are =T, 9aon, 9-dur, 9lor-&on, 9-1hos, Micro-9, potassium acetate, potassium acid phosphate, potassium bicarbonate, potassium chloride, potassium citrate, potassium gluconate, Arocit-9

IMACT' =levated IMACT'  =levated serum potassium M#C(ANISM ) INT#+ACTI)N' %nhibition of $&= results in decreased aldosterone production and potentially decreased potassium excretion. +#&#NTI)N' Draw +#&#NTI)N'  Draw potassium level prior to initiation of $&=-inhibitor in a patient. MANA,#M#NT' 1otassium levels greater than : meq  / should be monitored carefully due MANA,#M#NT' 1otassium to risk of severe hyperkalemia and =93 changes. Catch renal function 47A", #&r5 also.  $d?ust potassium potassium supplementation supplementation if le levels vels increase increase.. AC# In!i$itors

Spironolactone

 $ccupril, $ceon, $ltace, bena0epr bena0epril, il, &apoten,  $ldactone, spironolactone spironolactone captopril,, enalapril, captopril enalapril, fosinopril, lisinopril, /otensin, Mavik, moexipril, Monopril, perindopril, 1rinivil, quinapril, ramipril, trandolapril, Anivasc, 2asotec, >estril IMACT' =levated IMACT'  =levated serum potassium levels M#C(ANISM ) INT#+ACTI)N' Anknown, possibly an additive effect. +#&#NTI)N' Draw potassium level prior to initiation of spironolactone in a patient. MANA,#M#NT' 1otassium levels greater than : should be monitored carefully due to risk of severe hyperkalemia and =93 changes. Catch renal function 47A", #&r5 also. $void potassium supplements in patients taking this combination of medications, unless the need is documented and the patient is monitored closely for hyperkalemia. o Top TopDigo%in 7ack tto

Amiodarone

digoxin, /anoxin

amiodarone, &ordarone

 

IMACT' Digoxin IMACT'  Digoxin toxicity M#C(ANISM ) INT#+ACTI)N' Multiple theories exist, but actual mechanism is unknown.  unknown.    $miodarone  $miodaro ne may decr decrease ease the clearance clearance of of digoxin, resu resulting lting in prolonged prolonged digoxin digoxin activity. activity. There may also be an additive effect on the sinus node of the heart. +#&#NTI)N' 'btain digoxin level prior to initiation of amiodarone therapy. Then, decrease dose of digoxin by :;< and monitor digoxin levels once weekly for several weeks. MANA,#M#NT' Maintain digoxin level between -). Monitor for signs and symptoms of digoxin toxicity 4abdominal pain, anorexia, bi0arre mental symptoms in the elderly, blurred vision, bradycardia, confusion, delirium, depression, diarrhea, disorientation, drowsiness, fatigue, hallucinations, halos around lights, reduction in visual acuity, mydriasis nausea, neuralgia, nightmares, personality changes, photophobia, restlessness, vertigo, vomiting, and weakness5.   Digo%in

&erapamil

digoxin, /anoxin

&alan, &alan #, &overa-#, %soptin, %soptin #, verapamil, 2erelan

IMACT' Digoxin IMACT'  Digoxin toxicity M#C(ANISM ) INT#+ACTI)N' #ynergistic effect of slowing impulse conduction and muscle contractility, leading to bradycardia and possible heart block. +#&#NTI)N' Monitor heart rate and [email protected] interval. =valuate selection of verapamil and digoxin. %f patient has &, note that verapamil has no proven benefit in reducing mortality or morbidity6 furthermore, digoxin offers no additional benefit in mortality, but does improve symptomatology. MANA,#M#NT' Monitor heart rate and [email protected] interval. Monitor for signs and symptoms of  digoxin toxicity 4abdominal pain, anorexia, bi0arre mental symptoms in the elderly, blurred vision, bradycardia, confusion, delirium, depression, diarrhea, disorientation, drowsiness, fatigue, hallucinations, halos around lights, visual acuity, mydriasis, nausea, neuralgia, nightmares, personality changes, photophobia, restlessness, vertigo, vomiting, and weakness5. "'T=+ $lthough caution may be warranted when using theophylline with all quinolones, Drug Interaction Facts notes that problems have been documented especially with ciprofloxacin, enoxacin, and norfloxacin.

T!eop!"lline

Quinolones

aminophylline, &holedyl #$, oxtriphylline, alatrofloxacin, $velox, &ipro, ciprofloxacin, 1hyllocontin, #lo-7id, #lo-1hyllin, #lo-1hyllin ):, enoxacin, loxin, gatifloxacin, /evaquin, /evaquin, Theo-)E, Theo-Dur, Theolair, theophylline, levofloxacin, lomefloxacin, levofloxacin, lomefloxacin, Maxaquin, Maxaquin, Aniphyl, Aniphyl & moxifloxacin, moxifloxaci n, "oroxin, norfloxacin, ofloxacin, 1enetrex, sparfloxacin, Tequin, trovafloxacin, Trovan, Trovan %2, >agam IMACT' Theophylline IMACT'  Theophylline toxicity M#C(ANISM ) INT#+ACTI)N' %nhibition of hepatic metabolism of theophylline by the quinolones.

 

+#&#NTI)N' 'btain theophylline level prior to initiation of a quinolone. 'f the quinolones, enoxacin and ciprofloxacin reduce theophylline clearance by F;-GE<. &onsider switching to gatifloxacin, levofloxacin, moxifloxacin, moxifloxacin, or trovafloxacin6 trovafloxacin6 these agents appear not to inhibit theophylline metabolism. MANA,#M#NT' Monitor theophylline levels. Maintain level within targeted range of :MANA,#M#NT' Monitor :mcgm/6 however, theophylline toxicity may result even when the level is within the targeted range. #igns and symptoms of theophylline toxicity include sei0ures, nausea, and vomiting.

!ith my "est #ishes $hmed $"uelhana

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