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Published: March 2004
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Visual Disturbances with COX-2 Inhibitors

Prescriber Update 25(1): 8–9.
March 2004

Dr David Coulter, Research Associate Professor; Dr David Clark, Senior Research Fellow, Intensive Medicines Monitoring Programme, New Zealand Pharmacovigilance Centre, Dunedin

Acute, temporary, and sometimes severe, visual disturbances have been reported with celecoxib and rofecoxib use.  The eyesight changes appear to be completely reversible on withdrawal of the COX-2 inhibitor.  Similar events have occurred with the non-specific non-steroidal anti-inflammatory agents (NSAIAs).  In patients who develop acute visual disturbance while on a COX-2 inhibitor or NSAIA, prompt withdrawal is recommended followed by monitoring for resolution of symptoms.

A range of visual disturbances are described

The Pharmacovigilance Centre in Dunedin has received nine reports of visual changes associated with the use of celecoxib and rofecoxib.  Six of the reports were for celecoxib (from a total of 726 reports), and three for rofecoxib (out of 487 reports).  Two of the case reports are detailed below, while others have been published elsewhere.1  In all but one of the visual disturbance cases the duration to onset from first taking the COX-2 inhibitor was within four weeks.  The eyesight changes were bilateral in eight of the cases.  To date, there have been no reports received for the newer COX-2 inhibitors available, probably because of the early stage of monitoring.

The following adverse reactions were reported: blurred vision, abnormal vision, scintillating scotomata, visual field defect and temporary blindness.  The World Health Organisation's (WHO) adverse reactions database contains similar reports for celecoxib and rofecoxib.  There is one other published report2 of visual disturbance with celecoxib; and two reports3,4 of visual disturbance associated with ibuprofen involving a total of four patients, suggesting that visual changes can also occur with the non-specific non-steroidal anti-inflammatory agents (NSAIAs).  Blurred vision, cataract, conjunctivitis, eye pain and glaucoma are listed as adverse effects in the celecoxib (Celebrex®) data sheet5; while blurred vision is included in the rofecoxib (Vioxx®) data sheet.6

New Zealand case reports provide further detail

Case 1: A man aged 78 took a first dose of rofecoxib 50mg one night and two doses of 25mg the next day for shoulder pain.  The following morning he had reduced vision with blurring.  He was seen later that morning by his doctor who found no useful vision in one eye and reduced visual acuity of 6/18 in the other.  He took no further rofecoxib.  Later the same day he was reviewed by an ophthalmologist and his vision was assessed as having returned to normal.  This event was recorded as temporary blindness.

Case 2: A man aged 81 was taking celecoxib 100mg daily following knee replacement surgery for osteoarthritis.  Three weeks after commencing celecoxib he developed jellybean-shaped loss of vision centrally in each eye.  This occurred every day after his morning dose and lasted for a few hours.  The celecoxib was stopped and there was no recurrence of the visual disturbance.

Symptoms resolved on prompt discontinuation

In the eight reports where the outcome is known, the patients recovered quickly on withdrawal of the COX-2 inhibitor.  Two had experienced similar problems with non-specific NSAIAs; one with indomethacin and the other agent unknown.  However, for the other seven patients the acute visual changes were first-time symptoms.  The visual disturbances did not recur during periods of observation of up to seven months following withdrawal.  None of the patients were re-exposed to celecoxib or rofecoxib.

A plausible mechanism exists

There is evidence that the cyclo-oxygenase enzymes COX-1 and COX-2 are involved in the regulation of retinal blood flow.7  Interference with the action of these enzymes by either COX-2 inhibitors or conventional NSAIAs may therefore cause acute, temporary disturbance of vision.  The clinical picture seen in the reported cases is consistent with this mechanism, although there may be other possible explanations.

Consider iatrogenic eyesight changes in presenting patients

This case series shows acute, reversible and sometimes severe disturbances of vision in close association with the use of celecoxib and rofecoxib.  This signal is strengthened by reports held in the WHO database.  Prescribers should be aware of these adverse reactions, which are possible with both COX-2 inhibitors and conventional NSAIAs.  If eyesight changes occur, the anti-inflammatory medicine should be immediately withdrawn and the patient assessed for response, in particular, resolution of visual symptoms.  For patients in whom a severe visual disturbance has occurred, avoiding future exposure to the causative agent and other NSAIAs is recommended.

Competing interests (authors): Unconditional programme grants have been received from various pharmaceutical companies, including Merck Research Laboratories USA. Merck Sharp & Dohme (NZ) Ltd is the sponsor of Vioxx™ (rofecoxib).

Correspondence to Dr David Coulter, NZ Pharmacovigilance Centre, PO Box 913, Dunedin. E-mail: david.coulter@stonebow.otago.ac.nz

References
  1. Coulter DMC, Clark DWJ, Savage RL. Celecoxib, rofecoxib, and acute temporary visual impairment. BMJ 2003;327:1214-1215.
  2. Lund BC, Neiman RF. Visual disturbance associated with celecoxib. Pharmacotherapy 2001;21(1):114-115.
  3. Tullio CJ. Ibuprofen-induced visual disturbance. American Journal of Hospital Pharmacy 1981;38:1362.
  4. Nicastro NJ. Visual disturbances associated with over-the-counter ibuprofen in three patients. Annals of Ophthalmology 1989;29:447-450.
  5. Pharmacia. Celebrex Data Sheet 12 March 2002. www.medsafe.govt.nz/profs/Datasheet/c/Celebrexcap.pdf
  6. Merck Sharp & Dohme (New Zealand) Limited. Vioxx Data Sheet 30 September 2003.
  7. Haefliger IO, Meyer P, Flammer J, Lüscher TF. The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology? Survey of Ophthalmology 1994;39(2):123-132.

 

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