FREQUENTLY ENCOUNTERED DRUG INTERACTIONS

DDIs

Amiodarone & Simvastatin:

Mechanism: Amiodarone may decrease the metabolism of HMG-CoA
Reductase Inhibitors (Lexicomp 2009)
Concurrent use of AMIODARONE and SIMVASTATIN may result in an
increased risk of myopathy or rhabdomyolysis. (Micromedex 2009)

Recommendation: Dose of Simvastatin should not exceed 20 mg/day

(Lexicomp 2009)

Amiodarone & Warfarin:

Mechanism: The primary mechanism of these interactions is likely
related to the ability of Amiodarone to inhibit the CYP isoenzymes
responsible for warfarin and acenocoumarol metabolism (Lexicomp
2009)
Monitor for altered anticoagulant effect if inhibitor is initiated,
discontinued, or changed in dosage. Amiodarone-induced inhibition may
require several weeks to develop (HANSTEN & HORN 2009)

Recommendation: Contact Anticoagulation Clinic when Warfarin or

Amiodarone are INITIATED. Disregard if maintained on combo.

Amiodarone & Digitalis:

Mechanism: Concurrent use of DIGOXIN and AMIODARONE may
result in digoxin toxicity (nausea, vomiting, cardiac arrhythmias).
(Micromedex 2009)

Recommendation: Decrease digoxin dose by 1/3-1/2 (Lexicomp 2009).

If maintained on combination take into account age, renal function and
dose of digoxin

Sulfamethoxazole & Warfarin:

Mechanism:
Use alternative or monitor anticoagulation carefully an adjustment of
warfarin dosage may be needed (HANSTEN & HORN 2009)

Recommendation: Contact Anticoagulation Clinic when

Sulfamethoxazole is INITIATED. Disregard if maintained on combo.

Metronidazole & Warfarin:

Mechanism: Use alternative antibiotic if possible. If not, monitor
anticoagulation carefully, an adjustment of warfarin dosage may be
needed (HANSTEN & HORN 2009)
The hypoprothrombinemic effects of the S-isomer of warfarin were
increased approximately 100% (and the half-life increased 60%)

Recommendation: Contact Anticoagulation Clinic when Warfarin or

Metronidazole is INITIATED.

Hydrochlorothiazide & Lithium:

Mechanism: Concurrent use of HYDROCHLOROTHIAZIDE and
LITHIUM may result in increased lithium concentrations and lithium
toxicity (weakness, tremor, excessive thirst, confusion). (Micromedex
2009)

Recommendation: Consider reducing the dosage of lithium by 50%

upon initiation of a thiazide diuretic. Monitor for increased
therapeutic/toxic effects of lithium if a thiazide is initiated/dose
increased, or decreased effects if a thiazide is discontinued/dose
decreased. (Lexicomp 2009)

Carbamazepine & Warfarin:

Mechanism: Concurrent use of CARBAMAZEPINE and WARFARIN
may result in decreased anticoagulant effectiveness. (Micromedex 2009)

Recommendation: Contact Anticoagulation Clinic when Carbamazepine

INITIATED/STOPPED/CHANGED.
Disregard if maintained on combo.

Clarithromycin & Simvastatin:

Mechanism: Concurrent use of SIMVASTATIN and
CLARITHROMYCIN may result in an increased risk of myopathy or
rhabdomyolysis. (Micromedex 2009)

Recommendation: Hold Simvastatin during Clarithromycin therapy,

alternatively Azithromycin may be considered if it is an acceptable
alternative depending on indication. Hansten & Horn 2009

Nitroglycerin & Vardenafil:

Mechanism: Both nitrates and PDE 5 inhibitors exert their effects
through potentiation of the vasodilatory effects of cGMP -- nitrates by
stimulating cGMP production, and PDE 5 inhibitors by inhibiting an
enzyme responsible for the metabolism of cGMP.
Concurrent use of VARDENAFIL and ORGANIC NITRATES may
result in potentiation of hypotensive effects. (Micromedex 2009)
Recommendation: Avoid combination (HANSTEN & HORN 2009)

Simvastatin & Cyclosporine:

Mechanism: Concurrent use of SIMVASTATIN and CYCLOSPORINE
may result in an increased risk of myopathy or rhabdomyolysis
(Micromedex 2009)

Recommendation: Dose of Simvastatin should not exceed 20 mg/day

(P&T 2009)

Dofetilide & Moxifloxacin:

Mechanism: Concurrent use of DOFETILIDE and MOXIFLOXACIN
may result in an increased risk of cardiotoxicity (QT prolongation,
torsades de pointes, cardiac arrest). (Micromedex 2009)

Recommendation: Consider alternative antibiotic. The concomitant use

of Moxifloxacin and Dofetilide may be acceptable if an ECG lacks
significant QTc prolongation.

Erythromycin & Simvastatin:

Mechanism: Concurrent use of SIMVASTATIN and ERYTHROMYCIN
may result in an increased risk of myopathy or rhabdomyolysis.
(Micromedex 2009)

Recommendation: Hold Simvastatin during Erythromycin therapy,

alternatively Azithromycin may be considered if it is an acceptable
alternative depending on indication. Hansten & Horn 2009

Fluconazole & Warfarin:

Mechanism: Fluconazole has been shown in vitro to be a potent
inhibitor of CYP2C9, the enzyme primarily responsible for metabolism
of S-warfarin (the more active enantiomer), a potent inhibitor of
CYP2C19, and a moderate inhibitor of CYP3A4 (Lexicomp 2009)

Recommendation: Contact Anticoagulation Clinic when Fluconazole is

INITIATED.

Methotrexate & Trimethoprim:

Mechanism: Concurrent use of COTRIMOXAZOLE and
METHOTREXATE may result in an increased risk of Methotrexate
toxicity (myelotoxicity, pancytopenia, megaloblastic anemia).
(Micromedex 2009)
Recommendation: Due to the potential severity of this interaction,
consider avoiding concomitant use of Methotrexate and either
Sulfamethoxazole or Trimethoprim. (Lexicomp 2009)

Primidone & Warfarin:

Mechanism: Concurrent use of PRIMIDONE and WARFARIN may
result in decreased anticoagulant effectiveness. (Micromedex 2009)
Recommendation: Contact Anticoagulation Clinic when Primidone is
INITIATED/STOPPED. Disregard if maintained on combo.

Rifampin & Warfarin:

Mechanism: Concurrent use of RIFAMPIN and WARFARIN may result
in decreased anticoagulant effectiveness of warfarin. (Micromedex 2009)

Recommendation: Contact Anticoagulation Clinic when Rifampin is

INITIATED/STOPPED. Disregard if maintained on combo.

Dofetilide & Hydrochlorothiazide:

Mechanism: Thiazide Diuretics may increase the serum concentration of
Dofetilide by 30%. (Lexicomp 2009)

Recommendation: The concomitant use of hydrochlorothiazide and

Dofetilide is contraindicated by the manufacturer of Dofetilide.
(Lexicomp 2009)

Allopurinol & Mercaptopurine OR Azathioprine:

Mechanism: Concomitant Allopurinol and Azathioprine therapy has
been reported to impair the conversion of 6-mercaptopurine (the first
metabolite of Azathioprine) to inactive products by inhibiting xanthine
oxidase, resulting in higher blood levels of 6-mercaptopurine.
(Micromedex 2009)

Recommendation: Dose reductions of 67% to 75% of the normal dose

of Azathioprine are warranted in the presence of concomitant Allopurinol
therapy (Micromedex 2009)

Nefazodone & Simvastatin:

Mechanism: Due to the potential severity of this interaction, the
concomitant use of Nefazodone and HMG-CoA reductase inhibitors that
undergo CYP3A4 metabolism (simvastatin/atorvastatin/lovastatin)
should be avoided. (Lexicomp 2009)

Recommendation: Neither fluvastatin, pravastatin, nor rosuvastatin

would likely be affected by Nefazodone. (Lexicomp 2009)
Atazanavir & PPIs:
Mechanism: The AUC of unboosted Atazanavir was decreased 94% in
normal subjects when coadministered with omeprazole or lansoprazole.
(Lexicomp 2009)

Recommendation: Avoid Proton Pump Inhibitors.

Simvastatin & Gemfibrozil:

Mechanism: When given with gemfibrozil, the AUC of simvastatin
increases 35% and of simvastatin acid 185%. Elimination half life:
Simvastatin increases 74% and simvastatin acid 51% (Micromedex
2009)

Recommendation: Dose of Simvastatin should not exceed 20 mg/day

(P&T 2009)

(Lexicomp 2009)
(HANSTEN & HORN 2009)
(Micromedex 2009)