|
Editorial: Thyroid and Tamiflu!
COMPOUNDING WITH THYROID USP
United States Pharmacopeial (USP) Standards—Changing with the Times
1905: Desiccated Thyroid Glands USP appeared in the 8th edition of the United States Pharmacopeia in 1905 for the first time. Desiccated Thyroid Glands USP was defined as the thyroid glands of the sheep, freed from fat, and cleaned, dried, and powdered. One part of Desiccated Thyroid Glands USP represented approximately five parts of the fresh glands.
1936: 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 man. Thyroid contains not less than 0.17 percent and not more than 0.23 percent of iodine in thyroid combination, and must be free from iodine in inorganic or any form or combination other than that peculiar to the thyroid gland. A desiccated thyroid of higher iodine content may be brought to this standard by admixture with a desiccated thyroid of a lower iodine content, or with lactose or sodium chloride.
1985: 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 man. The active principles of Thyroid USP are iodinated amino acids which on hydrolysis yield not less than 90.0 percent and not more than 110.0 percent each of the labeled amounts of levothyroxine and liothyronine. The sum of the contents of levothyroxine and liothyronine is not less than 0.095 percent and not more than 0.125 percent, by weight, of thyroid, and the ratio of levothyroxine to liothyronine is not less than 5.0. 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 as lactose, sodium chloride, starch, sucrose, or dextrose.
1985: Thyroid Tablets USP "�contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of thyroid and levothyroxine."
2009: 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 as lactose, sodium chloride, starch, sucrose or dextrose."
2009: Thyroid Tablets USP contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of levothyroxine and liothyronine, the labeled amounts being 38 mcg of levothyroxine and 9 mcg of liothyronine for each 65 mg of the labeled content of thyroid.
Commercial Products: Who makes Armour Thyroid?
Armour Thyroid has been produced by numerous different companies in recent years, and it is called "Armour Thyroid." The current (2009) Physicians' Desk Reference lists Forest Pharmaceuticals, Inc. as the manufacturer of Armour Thyroid in strengths ranging from � grain to 5 grain. The description is: Armour Thyroid (thyroid tablets, USP) for oral use is a natural preparation derived from porcine thyroid glands and has a strong, characteristic odor. (T3 or liothyronine is approximately four times as potent as T4 or levothyroxine on a microgram for microgram basis.) The tablets provide 38 mcg levothyroxine (T4) and 9 mcg liothyronine (T3) per grain of thyroid. The inactive ingredients are calcium stearate, dextrose, microcrystalline cellulose, sodium starch glycolate, and opadry white.
The adjustment of thyroid replacement therapy should be based upon patient response and confirmed by appropriate laboratory tests. Since some commercially available thyroid preparations may be standardized according to their iodine content rather than the concentration of levothyroxine (T4) and triiodothyronine (T3) and their ratios, patients generally should not be switched to different products/preparations except under the direction and supervision of a physician. Due to the shortage situation, compounded thyroid preparations may be required to meet patient needs.
Compounding with Thyroid USP: Potency Considerations
When compounding with Thyroid USP, the powder must meet USP standards, as with any other chemical. However, the tolerances of this active ingredient are larger (90 percent to 110 percent) than most pure drug substances (about 98 percent to 102 percent). The tablets also have a requirement of 90 percent to 110 percent potency. This poses a problem.
If the Thyroid USP powder assays at 92 percent, it still meets the USP standard. During compounding, if any of the powder is lost, the final capsules may contain less than 90 percent, even though good technique was used. When working with single ingredient powders with the range of 98 percent to 102 percent potency, this is not as much of a problem. But, with ranges of 90 percent to 110 percent, there may be a problem.
This is similar to compounding using commercial products where the commercial product may have a USP requirement of 90 percent to 110 percent, or 80 percent to 120 percent, or 90 percent to 130 percent, etc. In other words, it poses some difficult situations.
One suggestion is to make an adjustment if the Certificate of Analysis (CofA) is on the low or high end for the Thyroid USP powder. The USP standard for Thyroid Tablets (or in compounding, capsules) is that for each 65 mg of the labeled content of thyroid, the capsules will contain 90.0 percent to 110.0 percent of the combination of 38 mcg of levothyroxine and 9 mcg of liothyronine. In order to accomplish this, the CofA data must be considered.
CAUTION WHEN DISPENSING OUT-OF-DATE TAMIFLU!
On what basis can pharmacists dispense out-of-date Tamiflu? Relying on media reports, interviews, etc. is not a valid way of doing business, regardless of who is making the statements. In health care, everything must be documented. Individual state boards of pharmacy requirements involve dispensing "in-date" products and preparations and having documentation to do so!
In compounding, we use CofA data to ensure the quality of our chemicals.
In dispensing, we rely on the official approved FDA labeling to ensure the quality of the commercial product and the approved expiration date for the product.
The labeling on the Tamiflu that is out-of-date (as some stockpiles of Tamiflu are now beyond their expiration date) cannot be relied upon; it is illegal to dispense it as it is currently labeled. As pharmacists, we rely on the labeling for the quality of the commercial product. In order to dispense it, we must have documentation that ensures its quality for each specific lot. At this point in time, we have NO documentation to prove that the product still meets its potency standard.
If the Tamiflu was tested, and it is still within its specifications, pharmacists should obtain the official documentation for each lot and keep it on file.
If no documentation is on hand and any adverse event occurs, it is difficult to predict what may happen in the future from a professional liability standpoint.
If anyone has requested and received this documentation, please share it. If not, this may be an action item for our professional organizations.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
| 
