Many physicians believe it is somet...

Many physicians believe it is sometimes appropriate to prescribe remedys for indications that have not been approved through the U.S. Food and put drugs into Administration (FDA). In this issue of American Family Physician, Stone, Viera, and Parman (1) base their review article onward this premise and discuss more [i]or[/i] less of the unapproved (or, "off-label") uses of selective serotonin reuptake inhibitors (SSRIs).

Off-label use is legal and, with important qualifications, generally embraced at physicians and other health care providers, health care institutions, insurers, pharmaceutical companies, and unruffled the FDA. The FDA has observ that unapproved uses may be appropriate and rational in certain situations, and that advances in medical knowledge and practice inevitably go ahead of labeling revisions.

Off-label prescribing existings a challenge as well as an opportunity involving effectiveness and safety. relate tos include the applicability of labeling for specific uses in notice to administration, contraindications, warnings, precautions, abuse, and staff which were developed for a different use. altercation has surrounded such issues as the authority, wisdom, and risks of off-label prescribing; reimbursement and coverage for off-label uses; physician liability; and the conditions subordinate to which manufacturers can disseminate literature about off-label uses. (2-5)

Physicians who treat children repeatedly prescribe drugs for off-label uses because little information is available from well-controlled studies forward dosage, formulation, effectiveness, and safety in children. novel federal legislation and programs are addressing these vexed questions (6)

Successful patient care requires that physicians be exempt to use drugs according to their best knowledge and conclusion (7) When a physician prescribes a unsalable article for a use not upon the approved label, he or she "has the responsibility to be well informed about the remedy and to base such use forward a firm scientific rationale or upon sound medical evidence." (7,8) The American Medical Association (9) (AMA) and the American Academy of Pediatrics (10) (AAP) have lay opened similar policy statements.

Since the early 1960 the FDA has been required by dint of law to base its approval of remedys and their labels on substantial effectiveness and safety data for a specific use in a particular population based forward well-controlled trials.

Legally, the FDA may not base its approval of a put drugs into solely on anecdotal information or consensus recommendations. The FDA's review of a company's marketing application includes a thorough scientific analysis of the clinical trial data and supporting documentation submitted with the application, and visits to clinical trial sites to inspect and validate data. Before an off-label use can be added to the label of an approved remedy safety and effectiveness must be demonstrated as in the initial application. solitary when the manufacturer receives a supplemental marketing approval from the FDA for a strange use can it advertise or assist the drug for that just discovered use.

Lack of approval for an off-label use can be to be ascribed to many factors. For example, the company may not be interested in pursuing approval for the off-label use for commercial or financial reasons. Another possibility is that the company may have carried disclosed some studies on the off-label use as part of its initial application for marketing approval, nevertheless the FDA did not find that the studies met the required standards for approval.

Considerations in Prescribing for Off-Label Uses

If a physician is considering off-label prescribing for a particular patient, the following information can be helpful in facilitating a decision.

COMPENDIA AND GUIDELINES

Off-label uses appear in a number of compendia that use ready committees to review approved and unapproved uses. (1112) a of these compendia have been recognized in Federal legislation for reimbursement purposes

a certain professional organizations, such as the AAP, have guidelines for prescribing medicines for specific off-label indications, diseases, or population collections under consideration, and their Web sites may yield useful information upon specific off-label uses. (For example, behold www.aap.org/policy/re0112.html.)

FDA AND THE MEDICAL LITERATURE

It can be helpful to review the most numerous recently updated FDA labeling for the unsalable article especially any black-box warnings, contraindications, drug-drug interactions, and side tenors especially as these might pertain to the propos off-label use. In addition, the following should raise interest and be factored into the physician's decision-making: higher doses, use in different populations, use in patients with other underlying diseases, and use in patients taking concomitant medications different from those originally anticipated and appearing forward the label approved by the FDA for a specific disease and population. Information is available from the FDA's Center for unsalable article Evaluation and Research (www.fda.gov/ cder/) the FDA's MedWatch program (www.fda.gov/medwatch/ index.html), and a Web site with the chiefly recent pediatric labeling changes (www.fda.gov/cder/pediatric/labelchange.htm).