Compounding with Esters: Dosing Issues

As discussed last week, if the incorrect salt or base form is used in a compounded preparation, the patient will get an incorrect dose with potential clinical consequences. This week, we will discuss the topic of the many drugs that are available as the "base" form or as an "ester" and their doses, which may be determined on the total ester form or just the base form of the drug. If this is not considered, the final compounded preparation may not fall within the strength requirements (e.g., 90% to 110%) for compounded preparations or the United States Pharmacopeia (USP) monographs.

Some drugs are esters by virtue of their internal chemical structure (e.g., atropine, cocaine, many local anesthetics) and others are esters by the addition of a moiety that will form an ester for certain purposes, including solubility, stability, resistance to degradation after administration, use as prodrugs, etc.

One cannot simply look at the drug title and determine whether or not the drug is a salt or an ester. For example, "acetate salts" include:

• Calcium acetate
• Chlorhexidine acetate
• Desmoppressin acetate
• Flecainide acetate
• Gonadorelin acetate
• Guanabenz acetate
• Leuprolide acetate
• Lysine acetate
• Mafenide acetate
• Zinc acetate

"Acetate esters" include:

• Cortisone acetate
• Desoxycorticosterone acetate
• Dexamethasone acetate
• Fludrocortisones acetate
• Fluorometholone acetate
• Hydrocortisone acetate
• Isoflupredone acetate
• Medroxyprogesterone acetate
• Megestrol acetate
• Melengestrol acetate
• Methylprednisolone acetate
• Norethindrone acetate
• Paramethasone acetate
• Prednisolone acetate
• Trenbolone acetate
• Betamethasone acetate

Further, "succinate salts" include:

• Sumatriptan succinate
• Doxylamine succinate
• Loxapine succinate
• Metoprolol succinate

"Succinate esters" include:

• Chloramphenicol sodium succinate
• Hydrocortisone sodium succinate
• Hypromellose acetate succinate
• Methylprednisolone sodium succinate
• Prednisolone sodium succinate

An interesting example of ester forms is dexamethasone, as its labeled strengths pose an interesting problem because they are not consistent in naming either the base or the ester form. For example:

"Dexamethasone" dosage form monographs are based on the labeled amount of "dexamethasone."

"Dexamethasone Acetate" dosage form monograph is based on the labeled amount of "dexamethasone."

"Dexamethasone Sodium Phosphate" dosage form monographs are based upon the labeled amount of "dexamethasone phosphate," not "dexamethasone."

Since some drugs may occur as salt forms, ester forms, and/or salt-ester forms, it is important to document what form is being used and whether it is a salt, ester, or combination. An example of a drug that occurs both as salt and ester forms is the drug erythromycin: Erythromycin estolate is a salt; Erythromycin ethylsuccinate is an ester; Erythromycin gluceptate is a salt; Erythromycin lactobionate is a salt; and Erythromycin stearate is a salt.

There are a number of important sources of information that can be used to determine the "form" of the drug (base or ester) to be used, including the package insert and the USP-National Formulary dosage form monograph.

For further information, see IJPC 2010; 14(5): 416-418.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

IMPORTANT NOTICE! USP General Chapter <800>

The USP Compounding Pharmacy Expert Committee is revising General Chapter <800>. The revised General Chapter proposal will reflect new and revised guidance documents, response to stakeholder input, and improved clarity of the proposed General Chapter. The revised proposal is tentatively projected to be published in Pharmacopeial Forum 41(2) [Mar-Apr 2015].

IMPORTANT NOTICE! Ophthalmic Drug Book

The 1st edition of a book titled Compounding Guide for Ophthalmic Preparations (2013), published by the American Pharmacists Association, contains errors that have now been corrected on PDFs of the replacement pages. To request the PDFs of those pages, you may send a request to aphabooks@aphanet.org. A revised edition is expected to be available at the end of this year.

News

FDA Gets in the Way by Halting Dallas Hospital from Using Ebola-screening Device
The Dallas hospital that treated Thomas Eric Duncan had a version of the Ebola-screening device used by the U.S. military in West Africa sitting on a shelf, but the FDA guidelines prohibited staff from using it on him. The device is very successful for detecting Ebola in less than one hour; but it sat idly by because current federal guidelines prevented the hospital from obtaining a specific "kit" needed for screening, the military website Defense One reported Thursday.

Promising Experimental Ebola Drug Goes Overlooked
Sarepta Therapeutics, a biotech company in Cambridge, Massachusetts, with a small supply of an experimental Ebola drug that has shown promising preliminary results in laboratory trials for safety and effectiveness, reminded various arms of the U.S. government that the drug, known as AVI-7537, is available in limited quantities. However, so far no response has been received from the U.S. government. Making the situation even more puzzling, the U.S. government in years past funded Sarepta's research on Ebola, until the Department of Defense abruptly cut the program for budgetary reasons in 2012. Sarepta received a $300 million federal contract in 2010 supervised by the Department of Defense as part of a research program targeting Ebola and another deadly viral disease.
http://www.businessweek.com/articles/2014-10-20/ebola-sareptas-promising-experimental-drug-goes-overlooked

CVS Pharmacy Benefits Plan Charges Higher Co-pays at Drugstores Selling Tobacco Products
CVS's new pharmacy benefits unit, Caremark, features copayments that are up to $15 higher on prescriptions filled where tobacco is sold; the plan that could benefit the company's own network of drugstores. The plan gives people covered by such plans an incentive to buy their medications at CVS, which stopped selling tobacco products last month. The company is opening itself up to criticism that it is designing coverage plans that give an advantage to its own pharmacies. David Balto, a former policy director at the U.S. Federal Trade Commission who is now an antitrust attorney, said the tobacco-free network could be problematic if it effectively steers patients to CVS.
http://online.wsj.com/articles/cvs-plays-hardball-with-rivaldrug-chains-1413846855

San Francisco Wants Pharma to Pay for Drug Take-back
The San Francisco Board of Supervisors has introduced a bill that would require drug companies to fully fund and administer a citywide drug take-back program. The bill follows a federal appeals court ruling requiring drug companies to pay for a take-back program that a California county passed into law two years ago. This raises the prospect that other local governments may also pursue similar programs and pass the costs on to the pharmaceutical industry. The purpose of the program is to reduce contaminants in drinking water and lower the threat of drug abuse stemming from drugs that linger in household medicine chests.
http://blogs.wsj.com/pharmalot/2014/10/22/san-francisco-wants-pharma-to-pay-for-a-take-back-program-who-is-next/

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Did You Know ...

�that laws, regulations, and standards must be very carefully and judiciously prepared? They must be well thought out with ALL the implications considered and sufficient time allowed for implementation.

Tip of the Week

The process of developing laws, regulations, and standards requires the input of all different practices of pharmacy; otherwise, we are going to see a loss of medications available to patients that will result in harm, extended illness and disease processes, discomfort, and even death. Sad to say, many laws, regulations, and standards are not based on "science" but opinions and desires of a few to "get their way"! What a price to pay!

Looking Back

He saw the train,
And tried to duck it!
Kicked first the gas,
And then the bucket!
     Burma Shave

ACHC is pleased to announce that the following pharmacies have achieved PCAB Accreditation:

Riverpoint Pharmacy, Spokane, Washington; Catherine Hudek, RPh, chudek@riverpointrx.com. Re-Accreditation for Sterile & Nonsterile Compounding

Brookfield Pharmacy, Brookfield, Connecticut; James Cangelosi, RPh, jimpaincenter@snet.net. Initial Accreditation for Sterile Compounding

Fresenius Medical Care Pharmacy Services, Inc., St. Petersburg, Florida; Pauline Laurendeau, CPhT, Pauline.Laurendeau@fmc-na.com. Re-Accreditation for Sterile Compounding