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Intraocular Hemorrhages Due to Warfarin Fluconazole Drug Interaction in a Patient With Presumed Candida Endophthalmitis
Arch Ophthalmol. 2002;120:94-95.
Fluconazole is a triazole antifungal effective against Candida endophthalmitis. It potentiates the anticoagulant effect of
warfarin sodium.1
Report of a Case
A 44-year-old man experienced worsening vision and floaters in both
eyes for 1 month. His medical history included alcoholism and pancreatitis.
He had been admitted to another hospital for parenteral hyperalimentation
via a central line, complicated by a deep venous thrombosis of his internal
jugular vein requiring anticoagulation with warfarin. His visual acuity without
correction was 20/400 OD and counting fingers at 3 ft OS. Slitlamp examination
revealed mild anterior chamber cells and anterior vitritis in both eyes. Funduscopic
examination revealed vitreous haze and multiple fluffy cotton-ball chorioretinal
opacities predominantly in the left eye (Figure 1). A diagnosis of bilateral Candida
endophthalmitis was made. The patient received an intravitreous injection
of 5 µg of amphotericin B in the left eye after vitreous biopsy, and
was administered 400 mg of oral fluconazole daily by the infectious disease
service. Vitreous biopsy revealed leukocytes on Gram stain, but fungal culture
revealed no growth.
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Figure 1. A, Fundus photograph of the right
eye showing mild vitreous haze, a small preretinal hemorrhage, and a few fluffy,
white chorioretinal infiltrates. B, Left fundus photograph showing multiple
chorioretinal infiltrates and marked vitreous haze.
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Two weeks later, he had decreased vision in his left eye. Medications
included 2.5 mg of warfarin daily, 400 mg of fluconazole daily, and 1% prednisolone
acetate 4 times daily in both eyes. Visual acuity decreased to counting fingers
at 7 ft OD and light perception OS. Funduscopic examination of his right eye
revealed decreased vitritis, cotton-ball opacities at the posterior hyaloid
near the disc, a new preretinal hemorrhage over the disc and the papillomacular
nerve fibers, and macular striae (Figure 2). Examination of the left eye revealed a massive hemorrhagic choroidal
detachment confirmed by B-scan ultrasound (Figure 3). Laboratory evaluation revealed a markedly elevated prothrombin
time of 67.8 seconds (normal range, 9.9-13.0 seconds). The warfarin was discontinued
and the medicine service was consulted. The patient declined surgical drainage
of the choroidal hemorrhage in the left eye.
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Figure 2. Fundus photograph of the right
eye showing an increased preretinal hemorrhage extending from the optic nerve
to the macula and an improvement in vitreous haze and chorioretinal infiltrates.
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Figure 3. B-scan ultrasound of the left
eye, showing massive choroidal hemorrhage.
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Two months later, the patient's visual acuity further decreased to counting
fingers at 2 ft OD. Funduscopic examination of his right eye revealed a dense
vitreous hemorrhage with ochre staining of the posterior hyaloid. He underwent
pars plana vitrectomy in that eye, and postoperative visual acuity improved
to 20/20 OD without correction (Figure 4).
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Figure 4. Fundus photograph of the right
eye following pars plana vitrectomy, showing a mild epiretinal membrane and
fibrovascular tissue at the optic nerve.
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Comment
Massive subretinal and vitreous hemorrhages have been reported as complications
of anticoagulation in patients with age-related macular degeneration (ARMD).2-3 El Baba et al3
reported that 19% of the patients with ARMD who developed massive intraocular
hemorrhages were taking warfarin or aspirin. Histopathological analysis revealed
that rupture of choroidal vessels in disciform scars accounted for the massive
hemorrhages.2 Our patient's preretinal and
vitreous hemorrhage in his right eye and the choroidal hemorrhage in his left
eye probably resulted from the coagulopathy due to the warfarin-fluconazole
interaction. Abnormal vessels of chorioretinal scars caused by Candida endophthalmitis may be the source of the hemorrhages in our
patient. The cytochrome P4502C9 enzyme metabolizes many drugs, including warfarin.4 Fluconazole significantly inhibits cytochrome P4502C9
and potentiates the coumadin effect.4 Since
1990, the nonophthalmic literature has contained reports of the adverse effects
of warfarin-fluconazole drug interaction.1
To our knowledge, this is the first reported case of intraocular hemorrhages
related to warfarin-fluconazole drug interaction. Prothrombin times must be
monitored closely when fluconazole is coadministered with warfarin.
AUTHOR INFORMATION
V. Vinod Mootha, MD;
Mark L. Schluter, MD;
Arup Das, MD, PhD
Albuquerque, NM
Corresponding author: V. Vinod Mootha, MD, University of New Mexico
Health Sciences Center, 2211 Lomas Blvd NE, Albuquerque, NM 87131-5341 (e-mail: vmootha{at}salud.unm.edu).
REFERENCES
1. Seaton TL, Celum CL, Black DJ. Possible potentiation of warfarin by fluconazole. DICP. 1990;24:1177-1178.
ABSTRACT
2. Brown GC, Tasman WS, Shields JA. Massive subretinal hemorrhage and anticoagulant therapy. Can J Ophthalmol. 1982;17:227-230.
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3. El Baba F, Jarrett WH, Harbin TS, et al. Massive hemorrhage complicating age-related macular degeneration: clinicopathologic
correlation and role of anticoagulants. Ophthalmology. 1986;93:1581-1592.
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4. Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998;45:525-538.
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