Clinical pharmacy department ,

MUST
Dean assistant for experts council,
scientifc 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$itors otassium supplements
7. AC# in!i$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.
Warfarin NSAIDs
&oumadin, warfarin $leve, $naprox, $naprox D#, $nsaid, $rthrotec,
&ataflam, &linoril, Daypro, diclofenac,
diclofenac,mistoprostrol, diflunisal, Dolobid,
etodolac, -eldene, flurbiprofen, ibuprofen, %ndocin,
%ndocin #., indomethacin, ketoprofen, ketorolac,
/odine, /odine (/, mefenamic acid, meloxican,
Mobic, Motrin, nabumetone, "aprelan, "aprosyn,
naproxen, 'rudis, 'ruvail, oxapro0in, piroxicam,
1onsel, .elafen, sulindac, Tolectin, Tolectin D#,
tolmetin, Toradol, 2oltaren, 2oltaren (.
IMACT' 1otential for serious gastrointestinal bleeding
M#C(ANISM )* INT#+ACTI)N+ "#$%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' $void concomitant use of an "#$%D with warfarin. %dentify reason for "#$%D
therapy. %f anti-pyretic effects are desired, then consider acetaminophen. $cetaminophen in
doses less than )g,day on a short-term basis does not appear to affect the %".. /ong-term
use of acetaminophen for anti-pyretic and analgesic effects is controversial. %f anti-
inflammatory effects are necessary, then consider cyclooxygenase-) 4&'(-)5 inhibitor
therapy. The minimi0ation of gastric irritation with these agents combined with the lack of anti-
platelet action, support the cautious use of &'(-) inhibitors in anticoagulation patients. There
are some case reports discussing the elevation of %".s with &'(-) inhibitors. %f analgesic
effects are desired, caution should also be exhibited with the use of tramadol6 there are a few
case reports describing an elevation of the %". with concomitant administration of tramadol
with warfarin.
MANA,#M#NT' 1rothrombin time and %". should be monitored every week with co-
administration of warfarin with an "#$%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 7actrim D#, 7actrim ##, &otrim D#, &otrim ##,
erythromycin,sulfisoxa0ole, 3antanol, 3antrisin,
1edia0ole, #eptra D#, #ulfatrim, sulfamethi0ole,
sulfamethoxa0ole, sulfisoxa0ole, Thiosulfil -orte,
trimethoprim,sulfamethoxa0ole
IMACT' %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 of vitamin 9 by intestinal flora affected by systemic antibiotic
administration.
+#&#NTI)N' $void concomitant use of a sulfa drug with warfarin, 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 co-
administration 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, Dynabac,
dirithromycin, =-Mycin, erythromycin base, ==#,
erythromycin ethyl succinate, =ry-Tab, =ryc,
=ry1ed, =rythrocin, erythromycin stearate,
%losone, erythromycin estolate, 1edia0ole,
erythromycin,sulfisoxa0ole, Tao, troleandomycin,
>ithromax
IMACT' %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, $velox, &ipro, ciprofloxacin,
enoxacin, -loxin, gatifloxacin, /evaquin,
levofloxacin, lomefloxacin, Maxaquin,
moxifloxacin, "oroxin, norfloxacin, ofloxacin,
1enetrex, sparfloxacin, Tequin, trovafloxacin,
Trovan, Trovan %2, >agam
IMACT' %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. $dditionally, microbial pathogen identification and sensitivity prior to
antibiotic initiation will decrease the prevalence of unnecessary drug interaction risk.
MANA,#M#NT' 1rothrombin time and %". should be monitored during co-administration of
warfarin with a quinolone. %f use of ciprofloxacin is imperative, then monitor %". every other
day and ad?ust warfarin dose as necessary. #igns and symptoms of an active bleed should be
monitored daily with particular attention to the appearance and patterns of bruises. #igns of
an active bleed include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum
bleeding, nose bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools
4hemoccult positive5.
Warfarin !en"toin
&oumadin, warfarin Dilantin, phenytoin
IMACT' %ncreased effects of warfarin and,or phenytoin
M#C(ANISM )* INT#+ACTI)N' &urrently unknown, but one theory suggests a genetic
basis involving liver metabolism of warfarin and phenytoin.
+#&#NTI)N' 'btain baseline phenytoin levels 4 -. @ ); mirogram, ml 5 prior to initiation of
warfarin. Monitor %". during co-administration. Target %". should be towards the lower end of
the therapeutic range.
MANA,#M#NT' 1rothrombin time, %". , and phenytoin levels should be monitored during
co-administration. #igns and symptoms of an active bleed should be monitored daily with
particular attention to the appearance and patterns of bruises. #igns of an active bleed
include+ coughing up blood in the form of coffee grinds 4hemoptysis5, gum bleeding, nose
bleeds, cola- or tea-colored urine 4hematuria5, and black, tarry stools 4hemoccult positive5.
AC# In!i$itors otassium Supplements
$ccupril, $ceon, $ltace, bena0epril, &apoten,
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
IMACT' =levated serum potassium
M#C(ANISM )* INT#+ACTI)N' %nhibition of $&= results in decreased aldosterone
production and potentially decreased potassium excretion.
+#&#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
to risk of severe hyperkalemia and =93 changes. Catch renal function 47A", #&r5 also.
$d?ust potassium supplementation if levels increase.
AC# In!i$itors Spironolactone
$ccupril, $ceon, $ltace, bena0epril, &apoten,
captopril, enalapril, fosinopril, lisinopril, /otensin,
Mavik, moexipril, Monopril, perindopril, 1rinivil,
quinapril, ramipril, trandolapril, Anivasc, 2asotec,
>estril
$ldactone, spironolactone
IMACT' =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.
7ack to TopDigo%in Amiodarone
digoxin, /anoxin amiodarone, &ordarone
IMACT' Digoxin toxicity
M#C(ANISM )* INT#+ACTI)N' Multiple theories exist, but actual mechanism is unknown.
$miodarone may decrease the clearance of digoxin, resulting in prolonged digoxin 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 D-). 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
IMACT' 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 =93@1. 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 =93@1. 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,
1hyllocontin, #lo-7id, #lo-1hyllin, #lo-1hyllin D):,
Theo-)E, Theo-Dur, Theolair, theophylline,
Aniphyl, Aniphyl &.
alatrofloxacin, $velox, &ipro, ciprofloxacin,
enoxacin, -loxin, gatifloxacin, /evaquin,
levofloxacin, lomefloxacin, Maxaquin,
moxifloxacin, "oroxin, norfloxacin, ofloxacin,
1enetrex, sparfloxacin, Tequin, trovafloxacin,
Trovan, Trovan %2, >agam
IMACT' 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, or trovafloxacin6 these agents appear not to inhibit
theophylline metabolism.
MANA,#M#NT' Monitor theophylline levels. Maintain level within targeted range of :-
D: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