Physicians, advocates call for expanding indications for off-label drugs

Federal law prohibits manufacturers from promoting off-label uses. A large specialty group urges manufacturers to support clinical trials on new indications.

As leading manufacturers of medications used off-label in cataract surgery revise their marketing and sampling procedures, which many surgeons see as a reduction in the samples provided by the companies, clinicians are taking a renewed look at off-label uses and the need to expand approved indications for some drugs.

“The perception by many surgeons is that the new policies are based upon concerns by the companies that providing a high volume of samples to physicians could be misconstrued as promoting the off-label use of these products in cataract surgery,” John A. Hovanesian, MD, FACS, wrote in a recent blog post on OSNSuperSite.com.

Federal law prohibits manufacturers of drugs, devices and biologic products from promoting the off-label use of products approved for specific indications. Meantime, many ophthalmologists use samples of U.S. Food and Drug Administration-approved drugs in off-label surgical applications, which is not prohibited.

Leading advocates for the drug and device industries support the distribution of information about products to clinicians but maintain the illegality of marketing products for off-label uses.

The Alliance of Speciality Medicine, which includes the American Society of Cataract and Refractive Surgery, calls for expanding indications for approved drugs that are currently used off label.

A clinician’s perspective

Daniel S. Durrie, MD, OSN Refractive Surgery Section Editor, characterized recent changes in the market environment as an impetus for continued research for drugs that are commonly used off label.

“I think that this may be a positive in the long run. Increasingly over the past 10 years, many surgeons have been relying on the bundle of antibiotic, nonsteroidal, steroid and ocular lubricant that came together from one company,” Dr. Durrie said. “It gives us the opportunity to really discuss what we should be using. … We are not really tied to one company now to take their package. We can use what is the best combination.”

Researchers and the FDA need to help drug companies design cost-efficient clinical trials to test drugs that are routinely used off-label for surgical applications, he said.

“We need to have a cost-effective study to show that these are safe for our patients. I hope that the FDA itself does not block the ability of the companies willing to do new studies and get FDA approval,” Dr. Durrie said. “We should be able to develop a system that is good for the clinicians and provides specific data on surgical outcomes.”

Corporate procedures

Alcon has altered its call and sampling procedures for Vigamox (moxifloxacin), a fourth-generation fluoroquinolone approved by the FDA for the treatment of bacterial conjunctivitis.

Doug MacHatton, Alcon’s vice president of treasury, investor and public relations, stated the company’s intention to continue sampling and promoting drugs specifically indicated for use in cataract surgery.

“Alcon continues to sample and promote Nevanac (nepafenac ophthalmic suspension 0.1%) and Durezol (difluprednate ophthalmic emulsion 0.05%) to ophthalmologists for their indicated uses in cataract surgery,” Mr. MacHatton said. “Nevanac is indicated to treat inflammation and pain following cataract surgery, and Durezol is indicated to treat pain and inflammation associated with ocular surgery. We recently altered our call and sampling procedures for Vigamox. Vigamox is indicated for the treatment of bacterial conjunctivitis.”

Allergan provides samples of Zymaxid (gatifloxacin ophthalmic solution 0.5%) and Acuvail (ketorolac tromethamine ophthalmic solution 0.45%) via a third-party organization, Crystal Muilenburg, Allergan’s director of corporate communications, said in an interview with Ocular Surgery News.

“Upon request, samples are still available to physicians as they always have been,” Ms. Muilenburg said. “Physicians request samples, and instead of the sales force providing those samples upon request, our third-party organization is providing the samples.”

Allergan contracted a third party to ensure that sales and marketing of established products such as Restasis (cyclosporine ophthalmic emulsion, 0.05%) thrive amid the launch of two new products: Lumigan (bimatoprost ophthalmic solution 0.01%) and Lastacaft (alcaftadine ophthalmic solution 0.25%). The FDA approved both drugs in 2010.

“The impetus of it is a reprioritization on the marketing and sales side,” she said. “Lumigan was approved by FDA late last year, Lastacaft is just being launched, and Restasis is taking a big priority as well. So, we have reprioritized the products that the sales force supports directly to physicians and reassigned requests for other products such as Zymaxid and Acuvail to a third party so we can continue to address physicians’ needs in a timely manner.”

Allergan complies with sampling guidelines included in the Prescription Drug Marketing Act of 1987 and amendments implemented in 1992, Ms. Muilenburg said.

Officials at Bausch + Lomb and Ista Pharmaceuticals declined to comment about drug sampling or off-label uses of existing drugs.

PhRMA and AdvaMed statements

In a statement issued in mid-February, John Castellani, Pharmaceutical Research and Manufacturers of America (PhRMA) president and CEO, noted the vital role of pharmaceutical manufacturers in disseminating information on prescription drugs and emphasized the illegality of promoting off-label uses.

“Providing physicians with timely information about the medicines they prescribe clearly benefits patients and advances health care throughout the United States,” Mr. Castellani said. “That being said, promotion of off-label uses of medicines is illegal and should not be done. Though there are often good therapeutic reasons for using medicines off-label to treat patients, each physician should decide the right course of treatment case-by-case.”

The PhRMA Code on Interactions “reinforces our intent that interactions be professional, ethical, informational exchanges designed to benefit patients and to enhance the practice of medicine,” Mr. Castellani said. “The code recognizes that physician prescription decisions are based on various factors, including individual patient medical needs and the health care professionals’ medical knowledge and experience.”

Khatereh Calleja, JD, vice president, technology and regulatory affairs for the Advanced Medical Technology Association (AdvaMed), also issued a statement.

“AdvaMed has always believed treatment decisions should be made between physicians and patients. In their practice of medicine, physicians can prescribe medical technologies for uses other than their approved indications. This is inherent to the medical profession’s ability to use their best knowledge and judgment for the best interests of patients,” the statement said. “While medical technology companies are prohibited from marketing FDA approved devices for off-label use, the medical community can administer and prescribe legally marketed products for such use in advancing the care of their patients and the overall public health.”

Specialty medicine’s stance

In a position statement, the Alliance of Specialty Medicine, which encompasses the ASCRS and various other physician groups, recognized that physicians may prescribe or administer approved products for off-label uses provided they use sound medical judgment and act in the best interest of patients. In addition, physicians should be well-informed about the product, base its use on firm scientific and medical evidence, and maintain awareness of the product’s use and effects.

Specialty physicians should counsel patients about the benefits and risks of a proposed treatment and alternative treatments, and notify the relevant agency or institution of adverse events related to the off-label use of medical products.

The statement said that physicians who receive compensation from industry or are engaged in product development and/or testing should disclose those relationships. Physicians should avoid interactions or activities in which discussions of off-label use may be considered promotional.

The alliance also encouraged manufacturers to seek to expand indications for which products are approved. – by Matt Hasson

• Daniel S. Durrie, MD, can be reached at Durrie Vision, 5520 College Blvd., Suite 200, Overland Park, KS 66211; 913-491-3330; fax: 913-491-9650; e-mail: ddurrie@durrievision.com.
• John A. Hovanesian, MD, FACS, can be reached at Harvard Eye Associates, 24401 Calle De La Louisa, Suite 300, Laguna Hills, CA 92653; 949-951-2020; fax: 949-380-7856; e-mail: drhovanesian@harvardeye.com.
• Doug MacHatton can be reached at Alcon Laboratories, 6201 South Freeway, Fort Worth, TX 76134; 817-551-8974; e-mail: doug.machatton@alconlabs.com.
• Crystal Muilenburg can be reached at Allergan, 2525 Dupont Drive, Irvine, CA 92612-1599; 714-246-5842; fax: 714-246-4800; e-mail: muilenburg_crystal@allergan.com.
• Disclosure: Dr. Durrie is a clinical investigator for Alcon and Abbott Medical Optics. Dr. Hovanesian is a consultant for Bausch + Lomb, Allergan and Ista Pharmaceuticals.