Consider systemic medications in otherwise unexplained ocular conditions
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Prescription systemic medications indicated for non-ocular conditions can cause patients of all ages to experience ocular side effects. Because adverse drug events (ADEs) from such agents range from conjunctivitis to permanent vision loss, these patients just may end up in the optometrist’s chair.
While the Food and Drug Administration receives more than 300,000 adverse drug event reports annually, Paul Seligman, MD, FDA director of the Office of Pharmacoepidemiology and Statistical Science, said in a Washington Times interview, “We have always estimated we receive 10% of all reports.”
Unrecognized ADEs are often discovered after FDA approval of new medications. The Physicians Desk Reference’s (PDR’s) safety warnings are often inconsistent and delayed in publication, and 20% of new drugs either have labeling changes with additional warnings or are withdrawn from the market due to major side effects after FDA approval (Lasser KE et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002;287(17)2215-2220).
A sampling of commonly prescribed systemic medications and their ocular ADEs, based on reports from the Oregon Health Sciences University’s Casey Eye Institute in Portland, world literature and the FDA, appears in the accompanying charts.
Topamax and glaucoma
Casey professor of ophthalmology, F.T. Fraunfelder, MD, author of Drug-Induced Ocular Side Effects and Drug Interactions, is associated with the Casey Eye Institute’s national registry of drug-induced ocular side effects. His research on the anti-seizure medication, Topamax (topiramate, Ortho-McNeil), found 115 reports of acute secondary angle-closure glaucoma at his institute. Combining reporting systems from the FDA, pharmacological manufacturers and world literature, along with further study of these cases, he found 83 bilateral and three unilateral glaucoma cases, 17 cases of acute bilateral myopia up to -8.75 D, nine cases of supra-choroidal effusions, three cases of periorbital edema and four cases of scleritis. Each of these findings is reversible if recognized early enough and drug use is discontinued.
Additionally, according to the FDA’s Medwatch, Topamax caused abnormal eye and vision disorders, lacrimation, diplopia and myopia in a sample of 291 patients.
Osteoporosis, arthritis agents
According to the Casey registry, the bisphosphonate Fosamax (alendronate sodium, Merck) is indicated for osteopenia and osteoporosis, inhibiting bone resorption but causing episcleritis. According to F.W. Fraunfelder and F.T. Fraunfelder (Bisphosphonates and ocular inflammation. N Engl J Med. 2003;348(12):1187-1188), episcleritis and uveitis were resolved when the medication was discontinued.
Potential Ocular Side Effects of Systemic Drugs |
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German and New Zealand researchers cited these ocular ADEs from arthritis COX-2 anti-inflammatory inhibitor, Celebrex (celecoxib, Pfizer): severe, acute visual field defects and blurred or abnormal vision. Onset of the field loss occurred 1 week or sooner, lasted a few hours after each dose and prevented the patient from reading until the medication was discontinued (Coulter DM, Clark DW, Savage R. Celecoxib, rofecoxib, and acute temporary visual impairment. Br Med J. 2003;327:1214-1215).
Another COX-2 inhibitor, Vioxx (rofecoxib, Merck), is believed to have caused branch retinal vein occlusion (Coulter DM, Clark DW, Savage R. Retinal vein occlusion in patients treated with rofecoxib (Vioxx). Br Med J. 2004;327:1214-1215). Patients taking these systemic arthritis medications need to be closely monitored for acute or permanent visual disturbances.
The statins and ocular myasthenia
According to international literature, statins can cause ocular myasthenia (Parmar B, Francis PJ, Ragge NK. Statins, fibrates, and ocular myasthenia. Lancet. 2002;60(9334):717).
Interferon and retinopathy
In a French ophthalmology journal, S. Sommer and colleagues stated that multiple sclerosis treatment with interferon beta-1b caused a bilateral retinopathy (Interferon beta-1b retinopathy during a treatment for multiple sclerosis. J Fr Ophtalmol. 2001;24(5):509-512).
Post-marketing labeling changes
Pre-marketing ocular side effects for Imitrex (sumatriptan, Glaxo Wellcome), a systemic migraine medication, included scleral, accommodation and extra-ocular muscle disorders; mydriasis; ocular hemorrhage; eye pain; keratitis; conjunctivitis; ocular edema and irritation; corneal opacities and corneal epithelial defects; while post-marketing ADEs included: ischemic optic neuropathy, retinal artery occlusion, retinal vein thrombosis and loss of vision.
Zyrtec (cetirizine HCl, Pfizer) is indicated for seasonal and perennial ocular pruritis and tearing related to allergies. According to Medwatch, the ocular ADEs for Zyrtec are: ocular melanoma, glaucoma, ocular hemorrhage, loss of accommodation, xerophthalmia, headache and visual field defect.
Ocular ADE-Causing Drugs |
Cardiovascular Diseases
Middle Age to Geriatric Diseases/Conditions
All Ages, Brain Diseases and Disorders
Milder Conditions
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The FDA ordered post-marketing labeling revisions for Aralen (chloroquine phosphate, Sanofi), a chloroquine anti-malarial agent, to cite irreversible retinal damage with long-term or high doses. The retinopathy is dose related, and eye care practitioners are advised to establish a baseline and conduct periodic follow-up examinations to include visual acuity, slit-lamp, funduscopic and visual field tests. If the patient experiences any light flashes, streaks, accommodation difficulties or corneal opacities, Aralen should be discontinued. These patients should be closely observed for possible progression and retinal changes, and visual disturbances may progress even after cessation of the therapy. Melanin accumulation occurred in ocular tissues of fetal mice eyes 5 months after the drug was eliminated from the rest of the body (Ullberg S. Lindquist NG, Sjostrand SE. Accumulation of chorioretinotoxic drugs in the foetal eye. Nature. 1970;227:1257).
Cancer, GI disorders, depression
Some post-menopausal women who took AstraZeneca’s Arimidex (anastrozole) tablets for early breast cancer developed cataracts during the clinical trials, says the FDA’s Center for Drug Education and Research (CDER). Cataracts also frequently developed in patients taking Pfizer’s Aricept (donepezil HCl) for mild to moderate dementia associated with Alzheimer’s disease. Glaucoma and retinal hemorrhage occurred with Aricept, as did milder ocular side effects of conjunctival hemorrhage, eye irritation, blepharitis, dry eyes and floaters.
Also according to the CDER, changes in the ocular lens and retina were reported following the use of Lamisil (terbinafine HCl, Novartis) for nail fungus.
The CDER says that one of two delayed-release heartburn and acid reflux disease capsules, TAP Pharmaceutical’s Prevacid (lansoprazole), can cause diplopia, while the use of AstraZeneca’s frequently advertised “purple pill,” Nexium (esomeprazole magnesium) can cause conjunctivitis and abnormal vision.
Wyeth’s Effexor XR (venlafaxine HCl), an anti-depressant, commonly causes abnormal vision, but it may also cause sudden, unexpected eye pain, redness and changes in vision as possible indications of increased intraocular pressure, according to the CDER. Use of Pfizer’s Zoloft (sertaline HCl), another antidepressant, can cause eye pain, scotoma and visual field defects, xerophthalmia, photophobia, diplopia and lacrimation.
For your information:
- Clinicians can report ocular side effects at the National Registry of Drug-Induced Ocular Side Effects or call Dr. Fraunfelder at (503) 494-5686 for information about reported drugs.
- Adverse drug events can also be reported to the Medwatch program at (800) FDA-1088; fax: (800) FDA-0178; Web site: www.fda.gov/medwatch.
- Patients can access drug information at the FDA Center for Drug Evaluation and Research Web site.