Click on the drug interaction of
interest to see more details.
- Warfarin
NSAIDs*
- Warfarin
Sulfa drugs
- Warfarin
Macrolides
- Warfarin
Quinolones**
- Warfarin
Phenytoin
- ACE inhibitors
Potassium supplements
- ACE inhibitors
Spironolactone
- Digoxin
Amiodarone
- Digoxin
Verapamil
- Theophylline
Quinolones**
* NSAID class does not include
COX-2 inhibitors
** Quinolones that interact include: ciprofloxacin, enoxacin,
norfloxacin, and ofloxacin
|
Warfarin |
NSAIDs |
| Coumadin,
warfarin |
Aleve,
Anaprox, Anaprox DS, Ansaid, Arthrotec, Cataflam,
Clinoril, Daypro, diclofenac, diclofenac/mistoprostrol,
diflunisal, Dolobid, etodolac, Feldene, flurbiprofen,
ibuprofen, Indocin, Indocin SR, indomethacin,
ketoprofen, ketorolac, Lodine, Lodine XL, mefenamic
acid, meloxican, Mobic, Motrin, nabumetone, Naprelan,
Naprosyn, naproxen, Orudis, Oruvail, oxaprozin,
piroxicam, Ponsel, Relafen, sulindac, Tolectin, Tolectin
DS, tolmetin, Toradol, Voltaren, Voltaren XR |
IMPACT: Potential for
serious gastrointestinal bleeding
MECHANISM OF INTERACTION:
NSAIDs increase gastric irritation and erosion of the protective
lining of the stomach, assisting in the formation of a GI bleed.
Additionally, NSAIDs decrease the cohesive properties of
platelets necessary in clot formation.
PREVENTION: Avoid
concomitant use of an NSAID with warfarin. Identify reason for
NSAID therapy. If anti-pyretic effects are desired, then
consider acetaminophen. Acetaminophen in doses less than 2g/day
on a short-term basis does not appear to affect the INR.
Long-term use of acetaminophen for anti-pyretic and analgesic
effects is controversial. If anti-inflammatory effects are
necessary, then consider cyclooxygenase-2 (COX-2) inhibitor
therapy. The minimization of gastric irritation with these
agents combined with the lack of anti-platelet action, support
the cautious use of COX-2 inhibitors in anticoagulation
patients. There are some case reports discussing the elevation
of INRs with COX-2 inhibitors. If analgesic effects are desired,
caution should also be exhibited with the use of tramadol; there
are a few case reports describing an elevation of the INR with
concomitant administration of tramadol with warfarin.
MANAGEMENT: Prothrombin
time and INR should be monitored every week with
co-administration of warfarin with an NSAID. Signs and symptoms
of an active bleed should be monitored with particular attention
to the appearance and patterns of bruises. Signs of an active
bleed include: coughing up blood in the form of coffee grinds
(hemoptysis), gum bleeding, nose bleeds, cola- or tea-colored
urine (hematuria), or black, tarry stools (hemoccult positive).
|
Warfarin |
Sulfa Drugs |
| Coumadin,
warfarin |
Bactrim DS,
Bactrim SS, Cotrim DS, Cotrim SS,
erythromycin/sulfisoxazole, Gantanol, Gantrisin,
Pediazole, Septra DS, Sulfatrim, sulfamethizole,
sulfamethoxazole, sulfisoxazole, Thiosulfil Forte,
trimethoprim/sulfamethoxazole |
IMPACT: Increased effects
of warfarin, with potential for bleeding
MECHANISM OF INTERACTION:
Currently, the mechanism for interaction with sulfa drugs is
unknown; however, clinicians hypothesize that warfarins
activity is prolonged due to a decreased production of vitamin K
by intestinal flora affected by systemic antibiotic
administration.
PREVENTION: Avoid
concomitant use of a sulfa drug with warfarin, particularly
sulfamethoxazole-trimethoprim. Identify microbial pathogen prior
to initiation of antibiotic therapy. Consider culture
sensitivity screening as research indicates cautious use of any
antibiotic with warfarin. If use of a sulfa drug is imperative,
then reduce warfarin dose by 50% during antibiotic
administration and for one week following completion of the
antibiotic. If sulfamethoxazole-trimethoprim therapy is
required, then monitor INR every other day for elevating trends.
MANAGEMENT: Prothrombin
time and INR should be monitored every week during
co-administration of warfarin with a sulfa drug. Signs and
symptoms of an active bleed should be monitored daily with
particular attention to the appearance and patterns of bruises.
Signs of an active bleed include: coughing up blood in the form
of coffee grinds (hemoptysis), gum bleeding, nose bleeds, cola-
or tea-colored urine (hematuria), and black, tarry stools
(hemoccult positive).
|
Warfarin |
Macrolides |
| Coumadin,
warfarin |
azithromycin, Biaxin, clarithromycin, Dynabac,
dirithromycin, E-Mycin, erythromycin base, EES,
erythromycin ethyl succinate, Ery-Tab, Eryc, EryPed,
Erythrocin, erythromycin stearate, Ilosone, erythromycin
estolate, Pediazole, erythromycin/sulfisoxazole, Tao,
troleandomycin, Zithromax |
IMPACT: Increased effects
of warfarin, with potential for bleeding
MECHANISM OF INTERACTION:
Erythromycin 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 K for clotting factor production.
PREVENTION: The
interaction between warfarin and macrolide antibiotics is highly
probable and often delayed. Concomitant use of a macrolide with
warfarin should be avoided; switch to an alternative antibiotic.
Microbial pathogen identification prior to antibiotic initiation
will decrease the prevalence of unnecessary drug interaction
risk. Consider culture sensitivity screening as research
indicates cautious use of any antibiotic with warfarin.
MANAGEMENT: If use of a
macrolide is imperative, then monitor INR every other day and
adjust warfarin dosing as necessary. Signs and symptoms of an
active bleed should be monitored daily with particular attention
to the appearance and patterns of bruises. Signs of an active
bleed include: coughing up blood in the form of coffee grinds
(hemoptysis), gum bleeding, nose bleeds, cola- or tea-colored
urine (hematuria), and black, tarry stools (hemoccult positive).
NOTE: Although
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. In addition, the M3 Project committee has
received a number of reports of INR elevations with
levofloxacin.
|
Warfarin |
Quinolones |
| Coumadin,
warfarin |
alatrofloxacin, Avelox, Cipro, ciprofloxacin, enoxacin,
Floxin, gatifloxacin, Levaquin, levofloxacin,
lomefloxacin, Maxaquin, moxifloxacin, Noroxin,
norfloxacin, ofloxacin, Penetrex, sparfloxacin, Tequin,
trovafloxacin, Trovan, Trovan IV, Zagam |
IMPACT: Increased effects
of warfarin, with potential for bleeding
MECHANISM OF INTERACTION:
The exact mechanism for the warfarin-quinolone drug interaction
is unknown. Reduction of intestinal flora responsible for
vitamin K production by antibiotics is probable as well as
decreased metabolism and clearance of warfarin.
PREVENTION: Culture and
identify microbial pathogen prior to initiation of antibiotic
therapy. Consider culture sensitivity screening. The metabolism
of warfarin may be delayed in patients administered enoxacin,
ciprofloxacin, norfloxacin, or ofloxacin; thus, quinolone
selection should focus on one of the newer agents that has not
demonstrated significant impairment of warfarin metabolism.
Additionally, microbial pathogen identification and sensitivity
prior to antibiotic initiation will decrease the prevalence of
unnecessary drug interaction risk.
MANAGEMENT: Prothrombin
time and INR should be monitored during co-administration of
warfarin with a quinolone. If use of ciprofloxacin is
imperative, then monitor INR every other day and adjust warfarin
dose as necessary. Signs and symptoms of an active bleed should
be monitored daily with particular attention to the appearance
and patterns of bruises. Signs of an active bleed include:
coughing up blood in the form of coffee grinds (hemoptysis), gum
bleeding, nose bleeds, cola- or tea-colored urine (hematuria),
and black, tarry stools (hemoccult positive).
|
Warfarin |
Phenytoin |
| Coumadin,
warfarin |
Dilantin,
phenytoin |
IMPACT: Increased effects
of warfarin and/or phenytoin
MECHANISM OF INTERACTION:
Currently unknown, but one theory suggests a genetic basis
involving liver metabolism of warfarin and phenytoin.
PREVENTION: Obtain
baseline phenytoin levels prior to initiation of warfarin.
Monitor INR during co-administration. Target INR should be
towards the lower end of the therapeutic range.
MANAGEMENT: Prothrombin
time, INR , and phenytoin levels should be monitored during
co-administration. Signs and symptoms of an active bleed should
be monitored daily with particular attention to the appearance
and patterns of bruises. Signs of an active bleed include:
coughing up blood in the form of coffee grinds (hemoptysis), gum
bleeding, nose bleeds, cola- or tea-colored urine (hematuria),
and black, tarry stools (hemoccult positive).
|
ACE Inhibitors |
Potassium Supplements |
| Accupril,
Aceon, Altace, benazepril, Capoten, captopril,
enalapril, fosinopril, lisinopril, Lotensin, Mavik,
moexipril, Monopril, perindopril, Prinivil, quinapril,
ramipril, trandolapril, Univasc, Vasotec, Zestril
|
K+ Care ET,
Kaon, K-dur, Klor-Con, K-Phos, Micro-K, potassium
acetate, potassium acid phosphate, potassium
bicarbonate, potassium chloride, potassium citrate,
potassium gluconate, Urocit-K |
IMPACT: Elevated serum
potassium
MECHANISM OF INTERACTION:
Inhibition of ACE results in decreased aldosterone production
and potentially decreased potassium excretion.
PREVENTION: Draw potassium
level prior to initiation of ACE-inhibitor in a patient.
MANAGEMENT: Potassium
levels greater than 5 should be monitored carefully due to risk
of severe hyperkalemia and EKG changes. Watch renal function
(BUN, SCr) also. Adjust potassium supplementation if levels
increase.
|
ACE Inhibitors |
Spironolactone |
| Accupril,
Aceon, Altace, benazepril, Capoten, captopril,
enalapril, fosinopril, lisinopril, Lotensin, Mavik,
moexipril, Monopril, perindopril, Prinivil, quinapril,
ramipril, trandolapril, Univasc, Vasotec, Zestril
|
Aldactone,
spironolactone |
IMPACT: Elevated serum
potassium levels
MECHANISM OF INTERACTION:
Unknown, possibly an additive effect.
PREVENTION: Draw potassium
level prior to initiation of spironolactone in a patient.
MANAGEMENT: Potassium
levels greater than 5 should be monitored carefully due to risk
of severe hyperkalemia and EKG changes. Watch renal function
(BUN, SCr) also. Avoid potassium supplements in patients taking
this combination of medications, unless the need is documented
and the patient is monitored closely for hyperkalemia.
|
Digoxin |
Amiodarone |
| digoxin,
Lanoxin |
amiodarone,
Cordarone |
IMPACT: Digoxin toxicity
MECHANISM OF INTERACTION:
Multiple theories exist, but actual mechanism is unknown.
Amiodarone 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.
PREVENTION: Obtain digoxin
level prior to initiation of amiodarone therapy. Then, decrease
dose of digoxin by 50% and monitor digoxin levels once weekly
for several weeks.
MANAGEMENT: Maintain
digoxin level between 1-2. Monitor for signs and symptoms of
digoxin toxicity (abdominal pain, anorexia, bizarre 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 weakness).
|
Digoxin |
Verapamil |
| digoxin,
Lanoxin |
Calan, Calan
SR, Covera-HS, Isoptin, Isoptin SR, verapamil, Verelan
|
IMPACT: Digoxin toxicity
MECHANISM OF INTERACTION:
Synergistic effect of slowing impulse conduction and muscle
contractility, leading to bradycardia and possible heart block.
PREVENTION: Monitor heart
rate and EKGPR interval. Evaluate selection of verapamil and
digoxin. If patient has CHF, note that verapamil has no proven
benefit in reducing mortality or morbidity; furthermore, digoxin
offers no additional benefit in mortality, but does improve
symptomatology.
MANAGEMENT: Monitor heart
rate and EKGPR interval. Monitor for signs and symptoms of
digoxin toxicity (abdominal pain, anorexia, bizarre 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 weakness).
NOTE: Although 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.
|
Theophylline |
Quinolones |
|
aminophylline, Choledyl SA, oxtriphylline, Phyllocontin,
Slo-Bid, Slo-Phyllin, Slo-Phyllin 125, Theo-24, Theo-Dur,
Theolair, theophylline, Uniphyl, Uniphyl CR |
alatrofloxacin, Avelox, Cipro, ciprofloxacin, enoxacin,
Floxin, gatifloxacin, Levaquin, levofloxacin,
lomefloxacin, Maxaquin, moxifloxacin, Noroxin,
norfloxacin, ofloxacin, Penetrex, sparfloxacin, Tequin,
trovafloxacin, Trovan, Trovan IV, Zagam |
IMPACT: Theophylline
toxicity
MECHANISM OF INTERACTION:
Inhibition of hepatic metabolism of theophylline by the
quinolones.
PREVENTION: Obtain
theophylline level prior to initiation of a quinolone. Of the
quinolones, enoxacin and ciprofloxacin reduce theophylline
clearance by 30-84%. Consider switching to gatifloxacin,
levofloxacin, moxifloxacin, or trovafloxacin; these agents
appear not to inhibit theophylline metabolism.
MANAGEMENT: Monitor
theophylline levels. Maintain level within targeted range of
5-15mcg/mL; however, theophylline toxicity may result even when
the level is within the targeted range. Signs and symptoms of
theophylline toxicity include seizures, nausea, and vomiting.
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Content developed by: Karen E. Brown, PharmD
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