Risk Management

Responding to “Dear Healthcare Provider” Letters

Anne M. Menke, RN, PhD, OMIC Risk Manager

Digest, Winter 2007

Within the last several months, ophthalmologists have received two “Dear Healthcare Provider” letters from drug manufacturers informing them of “important safety information” about medications they administer regularly. Bristol-Myers Squibb sent the first letter on November 22, 2006 at the urging of the food and Drug Administration (FDA).[1] Consistent with a prior warning on the prescribing information, the letter again reminded ophthalmologists that Kenalog^TM(triamcinolone acetonide) is not approved for intraocular administration. In response to reports of endophthalmitis, eye inflammation, increased intraocular pressure, and visual disturbances including vision loss— all known side effects about which ophthalmologists routinely inform patients—the company added additional prescribing information recommending against administering Kenalog^TM by intraocular, intraturbinal, subconjunctival, sub-Tenons, retrobulbar, nasal turbinate, and intralesional (about the head) routes. The second “Dear Healthcare Provider” letter was distributed by genentech Inc., manufacturer of Avastin^TM (bevacizumab) and Lucentis^TM(ranibizumab), drugs both widely used for the treatment of age-related macular degeneration (AMD). In its January 24, 2007 letter, the company informed ophthalmologists that the ongoing SAILOR clinical study revealed a higher incidence of stroke in the 0.5-mg  Lucentis^TM dose group compared with the 0.3-mg dose group (1.2% versus 0.3% respective- ly; P = 0.02).[2]  These letters have prompted numerous calls to OMIC’s risk management hotline.

Q  Can I still administer Kenalog^TM ?

A  It is OMIC’s opinion that, despite the manufacturer’s warning, it remains legal for ophthalmologists to administer Kenalog^TM (TA) by the routes mentioned in the letter as part of “the practice of medicine.” In the event of a lawsuit, ophthalmologists who are challenged about their use of TA will continue to rely upon expert witnesses, peer-reviewed literature, and well-documented efforts to provide quality care. Moreover, OMIC feels that the ophthalmologist is in the best position to determine how to treat an individual patient and recognizes that “off-label” use of approved medications is a legal and necessary part of the practice of medicine. Accordingly, our professional liability policy provides coverage for such off-label use, including ongoing use of TA.

Q  Do I need to tell my patients about the letter?

A  Yes. Patients should be informed of TA’s off-label status and told that the manufacturer has recommended against ophthalmic use, but that the FDA and attorneys have confirmed that ongoing use is legal as part of the practice of medicine. They should also be advised of the long-standing and widespread use of TA to treat ocular conditions as described in many peer-reviewed articles, and that the National Eye Institute is conducting clinical trials on its use. OMIC has prepared a sample consent form for TA, available at www.omic.com.

Q  The letter from Genentech did not provide any guidance. Am I required to assess a patient’s risk of stroke before I administer Lucentis^TM? Should some patients get the lower dose, even though only the higher dose has been approved by the FDA?

A  The label produced when Lucentis^TM was approved warns of the theoretical risk of thrombo- embolic events with intravitreal inhibitors of VEGF,[3] a drug class that also includes Macugen and Avastin. Accordingly, the risk management recommendations that precede OMIC’s revised sample consent form advise physicians to consider conditions that increase the risk for such complications. Now that ophthalmologists have been warned of the higher risk of a second stroke in patients with a stroke history, they should specifically elicit and document any history of stroke. The need for a stroke risk consultation with an internist and the dosage amount both depend upon the patient’s overall health, extent of AMD, and risk tolerance. faced with the certainty of visual loss from AMD, some elderly patients may prefer to assume the risk of stroke in order to best preserve their vision. Others may refuse the medication at any dose. Carefully determine and document the patient’s clinical findings and preferences, and ensure that patients who refuse the medication understand the consequences of their refusal. Consider giving patients written instructions about how to contact you and a list of eye symptoms that should be immediately reported to you. Patients considered at high risk for stroke should be educated on its symptoms and directed to call 911 or to proceed to the nearest emergency room if they suspect they are having a stroke.

1. Lewis-Hall, Freda, MD, Senior VP for Medical Affairs, Bristol-Myers Squibb CO. Dear Healthcare Provider. 22 Nov. 2006.

2. Barron, Hal, MD. Senior VP Development, CHief Medial Officer, Genentech, Inc. 24 Jan 2007.

3. The full prescribing information for Lucentis^TM is available at http://www.gene.com/gene/products/information/pdf/lucentis-prescribing.pdf