Richard L. Gorman, M.D., FAAP and Paul V. Williams, M.D., FAAP

Patients with asthma and other chronic lower respiratory illnesses often rely on nebulized medicines to give them relief. Bronchodilators, mucolytics, antibiotics, anticholinergics, steroids and other immune modulators are converted from liquid medications into an aerosol mist that is inhaled into patients' airways. Recently, however, what health care providers are prescribing and what patients have been getting may be substantially different.

Three firms, RoTech Health Care, CCS Medical and Reliant Pharmacy Services, have been warned by the Food and Drug Administration (FDA) to stop distributing millions of doses of compounded, unapproved drug units nationwide. The concerns motivating the FDA to issue these warning letters include patient safety, drug effectiveness and violation of FDA regulations.

Compounding by pharmacists traditionally is allowed when a unique medicine is needed for an individual patient. Legitimate pharmacy compounding occurs when a patient is allergic to an ingredient in a commercially available drug or needs a concentration or dosing form that is not commercially available.

Pediatric health care providers often turn to compounding pharmacies to compound liquid formulations of medications available only as tablets or capsules. This kind of compounding is initiated after a conversation between a health care clinician and the patient. The FDA permits this type of compounding.

The three firms that have been warned have been acting more like pharmaceutical manufacturers than pharmacies involved in compounding. The companies are manufacturing an unapproved copy or "knockoff" of an FDA approved, commercially available drug. Drugs approved by the FDA are examined for both safety and efficacy. These unapproved copies have not been tested for either. These mass compounded drugs also have not been subjected to the FDA scrutiny for good manufacturing processes, sterility, stability, purity or concentration of the active ingredient. A deficiency in any of these areas could put patient care at risk.

Particle size is another important consideration when delivering nebulized medication. Budesonide is a good example of some of the issues that surround particle size. Budesonide has a low solubility and is difficult to keep in solution. Different nebulizers generate different particle sizes that lead to different patterns of lung deposition of the drug. An unapproved copy of this medication may have characteristics that change the particle distribution pattern in patients' lungs.

There are several ways to identify vials of FDA-approved medications for nebulizers. All approved vials will have the expiration date, lot number, medication name, dose and pharmaceutical manufacturer name embossed on the vial. Unapproved copies will have paper labels affixed to the outside of the vial and will not have lot numbers or expiration date. Since at this time there are no FDA-approved generic forms of Pulmicort Respules, Xopenex or DuoNeb, any generic substitution for these medications is an unapproved copy.

Pediatric prescribers can write "dispense as written" on their prescriptions. A brief discussion with patients that unapproved copies of the medication are being distributed in the United States is warranted. This discussion could highlight specific risk to the individual patient and how to identify potentially fraudulent vials.

Pediatricians or patients can notify the FDA of complaints or concerns about these compounded drugs by contacting the agency's voluntary reporting program, MedWatch, at 800-FDA-1088 (800-332-1088) or www.fda.gov/medwatch/report.htm.

Dr. Gorman is chair of the AAP Section on Clinical Pharmacology and Therapeutics executive committee and Dr. Williams is chair of the AAP Section on Allergy and Immunology executive committee.

Reprinted with permission from American Academy of Pediatrics News, Vol. 27 No. 12, December 2006. © 2006 American Academy of Pediatrics