Adverse events have been reported in hospitals and elsewhere where children have received a compounded tacrolimus oral liquid that may be subpotent. Testing, however, showed that the compounded preparations were of the correct strength according to the laboratory standards available. However, it appears that the pharmacists compounded the preparation according to routine procedures, and the problem may be traceable to the lack of appropriate "potency" labeling for the tacrolimus bulk powder. Without a "potency" description on the label, the child may not have received the required amount of drug per dose.

The labeling in the PDR for Prograf states, "Prograf is available for oral administration as capsules (tacrolimus capsules) containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous tacrolimus." It also states that "tacrolimus" has an empirical formula of C₄₄H₆₉NO₁₂�H₂O with a formula weight of 822.03.

The pharmacists involved apparently used tacrolimus bulk powder in compounding the formulation, which is routine and customary, and the best procedure in compounding because you do not have to deal with excipients. The label on the bulk powder does not mention anything about activity, as many other microbiological-derived drugs do, but the empirical formula does show that it contains one molecule of water in each molecule of drug. That is equivalent to about a 2.2% difference in the quantity of drug present in the hydrate vs the anhydrous form. The commercial product is anhydrous. Although not mentioned in the labeling, there is an activity or potency equivalent that must be considered.

If tacrolimus had a USP monograph, it would have been a source of labeling and potency information. Why hasn't a USP monograph been established as a source of standard potency information for the drug? Since tacrolimus is not a USP monographed item, the pharmacist would have no real indication that an "activity coefficient" of tacrolimus should be considered. As an example, if one looks at other bacterial-derived drugs, such as gentamicin sulfate, there is a statement in the USP that it has a potency equivalent to not less than 590 mcg of gentamicin per mg, calculated on the dried basis, and the actual potency equivalent is stated on the label of the bulk substance. Pharmacists use this labeled potency equivalent in their compounding calculations.

However, if the bulk chemical produced in an FDA-registered facility cannot be appropriately labeled at its origin, then the pharmacist does not have the required information to practice as a professional. The bulk powder may be mislabeled if tacrolimus does not have a requirement for a potency designation. It appears that the manufacturer submitted an incomplete label, the FDA approved an incomplete label, and the manufacturer has not submitted information to the United States Pharmacopeial Convention for a monograph standard to be developed. Apparently, the bulk manufacturer was not required to list a potency designation on the bulk chemical label as is required with other similar drugs. It appears that the manufacturer, the FDA, and the bulk chemical synthesizer all share responsibility here.

Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief

IACP's 2006 Annual Meeting & Compounders on Capitol Hill is only 3 weeks away! The dates are June 3 through 6, 2006 and the location is the J. W. Marriott on Pennsylvania Avenue in Washington, D.C. If you haven't already registered for IACP's Annual Meeting, REGISTER TODAY! Don't miss this exciting chance to network with colleagues, receive continuing education on important developments affecting the compounding profession, meet with your Members of Congress, and party at the Rx Mixer. Now is a critical time for the compounding profession. Fight to protect your practice. Be in Washington, D.C. from June 3rd through the 6th this year!

For more information on the meeting and to register, visit www.iacprx.org/RegisterNow.

Also, if you haven't already made your hotel reservations, rooms are going fast. View current lodging options on the IACP website at www.iacprx.org/site/PageServer?pagename=Hotels.

Below are just some of the topics discussed this week on IJPC's Compounders' Network List:

• Compounding for pandemic flu threat
• FDA audits
• Fillers and Naltrexone
• Ideas for scar tissue treatments
• Libido Cream
• Malarone oral liquid
• Seborrhea

Join the CNL today at www.ijpc.com/Editorial/Listserve.cfm and read what others have to say and/or contribute, and what questions are posted. It's easy, free, and informative.

PCAB Accepting Applications
Accreditation Gives Compounding Pharmacies Competitive Advantage

WASHINGTON, DC- The Pharmacy Compounding Accreditation Board (PCAB) is now accepting applications for accreditation from all compounding pharmacies. The initial class of nearly sixty pharmacies has begun the documentation process and the first in-pharmacy surveys are complete. Based on the successful inauguration of the accreditation program, PCAB is now inviting all compounding pharmacies to apply at www.pcab.info. PCAB accreditation is a voluntary program for compounding pharmacies which was founded and continues to be lead by the American College of Apothecaries, the American Pharmacists Association, the International Academy of Compounding Pharmacists, the National Association of Boards of Pharmacy, the National Community Pharmacists Association, the National Alliance of State Pharmacy Associations, the National Home Infusion Association, and the United States Pharmacopeia.

As a part of the accreditation process, PCAB will provide accredited pharmacies with advertising and marketing material designed to provide an advantage in a very competitive field.

Ken Baker, PCAB Executive Director, noted several advantages that can be gained by pharmacies that become PCAB Accredited� compounding pharmacies. "Accreditation will not only provide assurance to patients and prescribers that this pharmacy has been tested against very strict quality and safety standards, but it will also identify it as one of the preeminent compounding pharmacies." Baker adds, "A compounding pharmacy now has a way of proving its adherence to high standards, not only patients and physicians, but also to insurance companies and regulators."

With so many sensationalized stories concerning compounding being highlighted in the news, accreditation provides a positive, quality based message to patients, prescribers and the public. PCAB believes accreditation has other benefits. By answering payors demands for proof from pharmacies that they are following quality standards, PCAB believes that accreditation will lead to an increase in the number of insurance companies willing to write policies for compounding pharmacies. "Accreditation should also help hold the line on insurance premiums for accredited compounders," says Baker. "Insurers understand that adherence to strict quality standards helps minimize errors and risks which leads to fewer liability claims."

"Compounding is a critical component of the healthcare industry." said PCAB Board President John A. Gans, PharmD., "because ultimately, PCAB accreditation is for the patient." Dr. Gans, who holds the dual role of being APhA Executive Vice President, added that pharmacists must ensure that the process is driven and controlled by the profession. He believes that this will improve pharmacy practices and thereby improve patient care.

Analyze Your Triturations
If you use triturations in compounding with high-potency, low-dosage drugs, it is advisable to have your triturations analyzed to confirm they are of the proper strength. If the analytical results show a variation from what is expected, an adjustment can be made and the trituration re-analyzed for confirmation. Then, when an aliquot is removed, you can have a greater assurance of obtaining the correct quantity of active drug for the formula.