Unknown Risks of Pharmacy-Compounded Drugs

To the Editor: In August 2006, the United States Food and Drug Administration (FDA) announced that warning letters had been issued to three pharmacies that were producing and distributing thousands of doses of compounded inhalation medications not approved by the FDA.¹ These inhalation medications were used to treat patients with such respiratory diseases as asthma, bronchitis, cystic fibrosis, and emphysema.¹

Pharmacy compounding traditionally involves such practices as manipulating an FDA-approved dosage form, such as a tablet or capsule, to prepare a solution or suspension for individual patients who have difficulties in swallowing.² Traditional pharmacy compounding may also involve preparing an FDA-approved medication excluding a specific ingredient to which an individual patient may have a hypersensitivity.² The FDA permits such traditional practices by pharmacies.

By contrast, nontraditional practices of pharmacy compounding—such as those that prompted the FDA warnings—include the mass production of drug combinations from bulk substances that are sometimes of unknown origin.¹ These drug combinations may be exact copies or slightly modified versions of FDA-approved pharmaceutical products.² The FDA has expressed concern that such nontraditional practices of pharmacy compounding may expose patients to unnecessary health risks.^1,2

The true extent of nontraditional pharmacy compounding in the United States is unknown. However, the FDA and many state public health authorities have expressed serious concerns about quality and safety issues regarding compounded inhalation drugs.^2,3 For example, minutes from the May 2007 meeting of the Ohio State Board of Pharmacy reveal disciplinary action against one pharmacy-compounding facility.³ According to our calculations based on numbers provided in these minutes, between July 2005 and November 2005, the pharmacy in question compounded and dispensed 119 prescriptions for an estimated 7530 doses of inhalation medications, including five different drug-combination products.³ Two of the five compounded products were identical to FDA-approved medications, while three were unapproved combinations.³ Of the seven drug substances that were used to produce the combinations, five were available as FDA-approved inhalation medications, while two (betamethasone and dexamethasone) were not.³

The Ohio State Board of Pharmacy minutes reveal that when quality tests were performed on some of the compounded products, the potency of the tested drugs ranged from approximately 27% to 85% of the amounts of active ingredients listed on the products' labels.³ The board's minutes also indicated that 4530 doses of these compounded combination products had not undergone terminal sterilization or testing for sterility, fungi, or endotoxins before they were dispensed to consumers.³ Test results showed fungal contamination in 1380 doses that had been prescribed to 23 patients.³ After these test results became known, the pharmacies advised these patients to discard the medications.

Many physicians and patients may not be aware that pharmacy-compounded inhalation medications are not approved by the FDA. Physicians may be surprised to learn that their patients are receiving these unapproved drugs from pharmacies. Similarly, patients may be surprised to learn that their pharmacies are dispensing unapproved drugs to them.

In light of the potential health risks to patients of pharmacy-compounded inhalation medications—and considering the availability of comparable FDA-approved products—we strongly suggest that physicians and patients avoid using pharmacy-compounded medications, except in those rare instances when an FDA-approved product may not be an acceptable therapeutic option. Under those circumstances, the physician and patient need to be provided with reliable quality-control testing data to confirm the safety and effectiveness of the compounded product.