Restricting Topical Ocular Chloramphenicol Eye Drop Use in the United States. Did We Overreact?

Abstract

T OPICALOCULARCHLORAMPHENICOL EYEDROPSARE relatively inexpensive and have broad-spectrum coverage of most gram-positive, gram-negative, and anaerobic bacteria. Worldwide, it is estimated that more than 50% of the world use topical chloramphenicol as a first-line agent in the treatment of conjunctivitis. The topical eye drop form of chloramphenicol became available in 1948 and the first fatality from eye drops was reported in 1955. In 1982, Fraunfelder reported another fatality associated with this medication. A subsequent research letter in 1993 reviewed all known case reports of this adverse drug reaction, with 23 blood dyscrasias leading to 12 deaths. In 2007, chloramphenicol eye drops’ relation to aplastic anemia and blood dyscrasias was classified as ‘‘probable’’ according to World Health Organization (WHO) criteria, based on the known published case reports and the spontaneous reports submitted to the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon, USA; www. eyedrugregistry.com). Within 2 years of the 1982 case report of death associated with topical ocular chloramphenicol, sales in the United States declined by 90% and the Physicians Desk Reference placed a black box warning that read: ‘‘.ocular chloramphenicol should not be used unless there is no alternative.’’ However, most countries continued to use the eye drop form of chloramphenicol, and in 2002 England made it the first-line drug of choice for conjunctivitis and it was made available over the counter without the need for a prescription. The rarity of this adverse drug reaction makes it difficult to study with any certainty. Some patients are genetically predisposed to develop blood dyscrasias when they are prescribed chloramphenicol systemically, and it stands to reason that this would hold true for topical administration as well. Published studies from around the world estimate the incidence of idiopathic blood dyscrasia at around 1 in 2 000 000 and drug-related incidence as higher, depending on the medication. What is the incidence of blood dyscrasia or aplastic anemia from topical ocular chloramphenicol? This answer is not known; however, there is an estimation based on population studies published since