Editorial: Three Drug Product Shortages: Opportunities for Compounding

The last two weeks have been busy with pharmacists in all practice settings trying to meet patient needs with drug shortages (and potential shortages) involving erythromycin 0.5% ophthalmic ointment, thyroid tablets/capsules, and Tamiflu oral liquid. Let's briefly look at each of these.

1. Erythromycin 0.5% Ophthalmic Ointment (recommendations from CDC)

1. An acceptable substitute is Azithromycin Ophthalmic Solution 1%.
2. Other acceptable alternatives include Gentamicin Ophthalmic Ointment 0.3% or Tobramycin Ophthalmic Ointment 0.3%. If not available, a fluoroquinolone ophthalmic ointment (Ciprofloxacin Ophthalmic Ointment 0.3%) can be used.
3. Betadine (povidone-iodine) Ophthalmic Solution is not recommended. Note: The CDC gave no reason for not recommending this solution, though a controlled trial was published stating, "A 2.5% ophthalmic solution of povidone-iodine as prophylaxis against ophthalmic neonatorum is more effective than treatment with silver nitrate or erythromycin, and is less toxic and costs less. N Engl M Med 1995; 332: 562-566.

2. Thyroid Tablets are included among the "grandfathered" drugs, or the "pre-1938" drugs that have been allowed to stay on the market as "unapproved drugs" under certain conditions but are now in limited supply. To meet patient needs, thyroid capsules are being compounded so patients can continue their therapy uninterrupted. A few comments on compounding thyroid capsules:

1. Thyroid USP is the cleaned, dried, and powdered thyroid gland previously deprived of connective tissue and fat. It is obtained from domesticated animals that are used for food by humans. On hydrolysis, it yields not less than 90.0 percent and not more than 110.0 percent each of the labeled amounts of levothyroxine and liothyronine, calculated on the dried basis. It is free from iodine in inorganic or any form of combination other than that peculiar to the thyroid gland. It may contain a suitable diluent such lactose, sodium chloride, starch, sucrose, or dextrose. United States Pharmacopeia 32/National Formulary 27 2008; 3735-3736.
2. Thyroid Tablets USP contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of levothyroxine and liothyronin, the labeled amounts being 38 mcg of levothyroxine and 9 mcg of liothyronine for each 65 mg of the labeled content of thyroid. United States Pharmacopeia 32/National Formulary 27 2008; 3736-3737.
3. Refer to the Certificate of Analysis to determine the actual potency of the thyroid powder being used and adjust calculations appropriately.
4. Send samples to an analytical laboratory for quality-control purposes.

3. Tamiflu oral liquid dosage form supply has many pharmacists concerned. There are a number of approaches pharmacists can use to compound this oral liquid form.

1. Directions for compounding the oral liquid using cherry syrup (Humco) or Ora-Sweet SF are provided by Roche Laboratories and can be found at: www.tamiflu.com/hcp/dosing/extprep.aspx
2. The International Journal of Pharmaceutical Compounding has also published stability data and a formulation, which can be searched at: www.ijpc.com and www.compoundingtoday.com
3. Pharmacists are encouraged to obtain a reasonable supply of the necessary vehicles in advance from suppliers so that patient needs can be met.

Propylene Carbonate (PC) is primarily used as a solvent in both oral and topical formulations. It occurs as a clear, colorless, mobile liquid with a faint odor and a sp. gr. of about 1.203-1.210. It is freely soluble in water and miscible with acetone, ethanol, and ether.

1. Topically, PC has been used as a solvent for corticosteroids by dissolving the corticosteroid in the PC and then incorporating the liquid in petrolatum, producing microdroplets in the vehicle.
2. Orally, PC has been used as a nonvolatile, stabilizing, liquid carrier in capsules. The drug is dissolved in the PC first. Then the solution can be sprayed on a diluent (lactose0 and capsules filled, resulting in a uniform distribution of the drug.

Whistleblower Lawsuit Leads to $2.3 Billion Settlement
A Pfizer sales representative in Florida filed a whistleblower lawsuit in 2003, which initiated the federal and state investigations that led to Pfizer's record-breaking $2.3 billion settlement.

John Kopchinski, a West Point graduate and Gulf War veteran, said, "In the Army, I was expected to protect people at all costs. At Pfizer I was expected to increase profits at all costs, even when sales meant endangering lives. I couldn't do that."

$1.8 billion of the settlement is solely due to Pfizer's improper "off-labeling" marketing of Bextra that Kopchinski exposed through his lawsuit. FDA had approved Bextra to treat arthritis as well as menstrual pain in very limited doses. The lawsuit alleged that Pfizer promoted Bextra for uses and in doses that far exceeded what the FDA approved, putting patients at risk for serious health problems such as heart attack, stroke, and pulmonary embolism. In addition, the lawsuit claimed that Bextra paid doctors kickbacks in different ways to influence them to prescribe and endorse Bextra for these "off-label" uses. In 2005, Bextra was withdrawn from the market.

"Even though the FDA rejected Pfizer's application to sell Bextra for certain uses because of serious health risks, Pfizer had the gall to push those uses anyway using misleading information," said Erika A. Kelton, a Washington, DC lawyer whose firm, Phillips & Cohen LLP, represents the whistleblower. "Ignoring serious health risks to increase sales is outrageous."

www.phillipsandcohen.com

http://pharmalive.com/news/index.cfm?articleID=648886&categoryid=43&newsletter=1&premium=1

Dale and Applebe's Pharmacy Law and Ethics
9th Edition
Applebe GE, Wingfield J
London, UK: Pharmaceutical Press
Paperback; 672 pages; $59.99

Since 1976, when the first edition entered the market, this book has established itself as the definitive guide to pharmacy practice law and the use of medicines in Great Britain. This edition is completely revised and updated and contains 27 chapters. It is a great and easy read that covers numerous topics of interest to practitioners. Of special interest is the chapter on veterinary medicines, as well as herbal medicines, etc. Although written for practitioners in Great Britain, it is interesting to compare the practice of pharmacy in the U.S. with the UK.

Medication therapy management (MTM) is an integral part of a compounding pharmacist's activities each and every day. Compounding requires a close working relationship with physicians and patients. Physicians routinely rely on pharmacist's judgment and recommendations.

Team Building
Football season is now in full swing with many opportunities for working with high school and collegiate teams. Get to know the trainers and physicians and let them know how you can work with them to enhance the care for athletes!