Plogstedarticle

THE CELIAC DIET, SERIES #5
Carol Rees Parrish, R.D., M.S., Series Editor Medications and Celiac Disease—
Tips From a Pharmacist
Celiac disease is a chronic, generically linked, autoimmune disorder that is also known
as celiac sprue, nontropical sprue, and gluten-sensitive enteropathy. Although celiac
disease primarily affects the small intestine, deleterious effects can occur throughout
the entire body. Patients with celiac disease are unable to tolerate the ingestion of
gluten. Gluten is an insoluble protein found in all cereal grains. The gluten that is found
in wheat, rye, and barley is the offending culprit for celiac disease patients. The preva-
lence in the United States is estimated to effect 1% of the population. The following
article is designed to help identify medications that may contain gluten.
INTRODUCTION
Gluten ingestion in a patient with Celiac Disease Patients who have been diagnosed with celiac dis- causes an immunologically mediated inflammatory
ease (CD) or have a need to follow a gluten-free response, which results in damage to the mucosa of the (GF) diet must be aware of potential sources of small intestine. It requires only a relatively small gluten. In the area of pharmaceuticals, potential amount of the gluten to illicit this response so it is sources of gluten contamination come primarily from the addition of the excipient (filler) ingredients added Excipients form the bulk of the product and are to the active drug in order to make a particular dosage designed to perform several functions. In addition to providing bulk, they may be utilized as lubricants forthe powder, or as in the case of starches, absorb water,which causes the tablet to swell and disintegrate. It isthese starches that provide the potential source of Steven Plogsted, Pharm.D, BCNSP, Clinical Pharma- gluten contamination. These excipients can be obtained cist, Nutrition Support Service, Columbus Children’sHospital, Clinical Assistant Professor of Pharmacy, from any starch source, but are primarily derived from Raabe College of Pharmacy, Ohio Northern Univer-sity, Columbus, OH.
PRACTICAL GASTROENTEROLOGY • JANUARY 2007
Medications and Celiac Disease—Tips From a Pharmacist
THE CELIAC DIET, SERIES #5
Table 1
Common Excipient Ingredients in Medications
made synthetically from benzyl chloride which is derived from toluene (a tar oil) (methylcellulose, hydroxymethylcellulose, microcrystalline, powdered)—obtained from fibrous plant material(woody pulp or chemical cotton) derived from a fat source (spermaceti, which is a waxy substance from the head of the sperm whale) an internally cross-linked sodium carboxymethylcellulose for use as a disintegrant in pharmaceutical formulations. It contains no sugar or starch.
mix of sugars resulting from the controlled enzymatic hydrolysis of starch result from the hydrolysis of starch (primarily corn or potato) by heat or hydrochloric acid. It can also beobtained from wheat, rice or tapioca A sugar that may be obtained from barley malt A sugar that is obtained from corn starch A sugar also known as levulose or fruit sugar Obtained from the skin, white connective and bones of animals (by boiling skin, tendons, ligaments, bones, etcwith water) Historically, glycerin (also known as glycerol), was made the following ways:• Saponification (a type of chemical process) of fats and oils in the manufacturing of soaps• Hydrolysis of fats and oils through pressure and superheated steam• Fermentation of beet sugar molasses in the presence of large amounts of sodium sulfite• Today it is made mostly from propylene (a petroleum product) obtained from fats and oils as byproducts in the manufacture of soaps and fatty acids (may also be listed asmono-glycerides or di-glycerides) Lactose, or milk sugar, is used in the pharmaceutical industry as a filler or binder for the manufacture ofcoated pills and tablets A starch hydolysate that is usually obtained from corn but can also be extracted from wheat, potato or rice derived from monosaccharides (glucose and mannose) A starch that has been chemically or mechanically processed. The starch can come from corn, wheat, potatoor tapioca A natural wax product used in tablet or capsule coating derivative of the fatty acids of coconut oil A starch that is usually obtained from potato but may come from any starch source derived from stearic acid (a fat; occurs as a glyceride in tallow and other animal fats and oils, as well as some vegetables; prepared synthetically by hydrogenation of cottonseed and other vegetable oils) Refined sugar also known as refined sugar, beet sugar or cane sugar PRACTICAL GASTROENTEROLOGY • JANUARY 2007
Medications and Celiac Disease—Tips From a Pharmacist
THE CELIAC DIET, SERIES #5
Table 1 (continued)
chemical not derived from any starch source used as a white pigment derivative of glycerin (acetylation of glycerol) corn, potato and tapioca; however, they have also been potato, tapioca, and wheat. If the product lists starch as known to contain starch from wheat. There are a few “cornstarch” or “starch (corn)” it can be assumed to be products that are clearly labeled as GF, however, the GF. If starch by itself is listed, a call to the manufac- majority of the manufacturers do not provide that infor- turer is the only way to confirm the source of the
mation on either the package or the package insert.
starch. Other common terms include pregelatinizedstarch and sodium starch glycolate. Both products are ROLE OF THE FOOD AND DRUG ADMINISTRATION
starches derived from corn, wheat, potato, or rice,however, they have been chemically treated or The United States Food and Drug Administration processed. Despite manipulation, some gluten can (FDA) is responsible for overseeing the safe manufac- turing of drug products. While they maintain strict reg- There are also the four “Dex-ingredients” derived ulations for the active ingredient of the drug product, from starch (dextrans, dextrose, dextrates, dextrins).
they provide minimal over-site for what excipients can Dextrans come from corn and potato starch; dextrose be added. The drug manufacturers must utilize only comes from corn. These Dex-ingredients are not a prob- FDA approved excipients, but the quantity and type of lem for CD patients. Dextrates and Dextrins can come excipient is not specifically regulated. This is impor- from any starch source so a call to the manufacturer is tant to understand, especially in the manufacturing of the only way to know if it contains gluten. It is impor- generic drug products, since generic product does not tant to know that other ingredients are derived from have to contain the same excipients as the brand name wheat, but are not hazardous because of the process in product. The generic drug manufacturers must demon- which they are made; conversely, just because a product strate certain absorption characteristics when they is processed does not mean all gluten has been removed.
reproduce a drug, but all other aspects can differ.
For instance, some alcohols are derived from wheat.
Because the alcohol is purified, the alcohol contains no WHEN TO CALL THE DRUG MANUFACTURER
protein (gluten) making it safe for CD patients. On the Where can a consumer or health care professional other hand, a product may originally start without obtain the necessary drug information? Can this infor- glutens, but in the manufacturing process, may become mation be trusted? The consumer or health care pro- cross-contaminated. This is exactly the reason that a fessional needs to consider two questions when an pharmacist should call the manufacturer as the second inquiry is made about the gluten content of a drug. The step even after reviewing the inactive ingredients in the first question is what are the inactive ingredients or package insert. This step should be taken as a safeguard excipients? Excipients are listed in the package insert whenever possible. Patients with CD often receive edu- and should be the first place a pharmacist looks for cation about the GF diet from a dietitian because they information (Table 1). Once the excipients are read the are the experts in the field. It is the same case with med- second question that should be asked is, what is the ications. Pharmacists are the experts in drug informa- source of the ingredient? Again, the package insert tion, which includes knowing if excipients contain provides the pharmacist with the starting point. One of gluten. Patients are referred to pharmacists for that the first key words to look for in the inactive ingredi- information just like they are referred to dietitians to get ents section is starch. As mentioned previously, starch information about diet. Unfortunately, many pharma- can be derived from several sources including corn, cists are not well-versed enough about CD and the PRACTICAL GASTROENTEROLOGY • JANUARY 2007
Medications and Celiac Disease—Tips From a Pharmacist
THE CELIAC DIET, SERIES #5
appearance,” or “new manufacturer” should be a sign that the GF status of the product must be reestablished. Gluten Free Pharmaceuticals Resources*
One of the most common problems encountered when trying to obtain the gluten status from the drugmanufacturer is the manufacturers lack of information.
They often will respond that they don’t use any glutenin the manufacturing of their product, but because they buy raw materials (excipients) from outside sourcesthey cannot verify that those excipients are GF. While A Guide Through the Medicine Cabinet, by Marcia Milazzo there is no way to know if a product is GF, having an understanding of the excipients’ origin or how thoseexcipients are produced, the pharmacist can provide an educated assessment of the likelihood of gluten contam- ination. We still need to contact the manufacturers and *The GF status of medications should be confirmed by periodically we can usually trust the information they give us when they state that their product is GF. The ultimate choiceto take the medication, however, lies with the consumer. gluten content of medications to be able to answer ques- Information for prescription medications are more plentiful than for over-the-counter (OTC) drugs. Thegovernment controls are not as tight for OTC drugs onthe market; information regarding the gluten status is HOW YOUR PHARMACIST CAN HELP
often difficult to obtain and less reliable. The con- Pharmacists may often be called upon to determine sumer should always try to find a source for these whether a pharmaceutical product is GF. This can be a products in anticipation of need. The Walmart® chain, challenging task. In a survey performed in 2001, only for example, displays the gluten status of many of their five of 100 pharmaceutical companies had a policy OTC products directly on the package (see Table 3 for ensuring gluten-free status for their medications, although many more stated that they believed their Fortunately, nutritional supplements are now products to be GF (3). One of the problems faced by under the new Food Allergen Labeling and Consumer the pharmaceutical manufacturers is the uncertainty of Protection Act of 2004 that went into effect in January the GF status of the raw materials obtained from out- 1, 2006 and must be labeled if they contain wheat (bar- side sources. Cross contamination during manufactur- ley and rye are not used in the preparation of medica- ing can also occur. A reliable way of determining the tions.) The Act further directs the Food and Drug GF status of the medications that a CD patient is tak- Administration (FDA) to develop and implement a ing is essential to the health of the CD patient. Several plan on GF labeling within the next two years as well books and web sites are available to assist in this as defining the term “gluten-free” for labeling pur- process, but should be thought of as starting places poses for food products but not medications (4).
(Table 2). If possible, inquiries should be made Developing a relationship with your local pharma- directly to the pharmaceutical companies to ensure the cist is one way to make access to drug information GF status of a particular product. Adding to the burden timelier and less intimidating. Although pharmacists of the CD patient is the fact that pharmaceutical man- are experts in their knowledge of medications, they ufacturers frequently change the inactive ingredients may not be as familiar with CD or how the excipients of their products. This can happen without warning, so are produced. Taking the time to explain your condi- the GF status of a product should be re-assessed on a tion and even point them to various sources of infor- regular basis. Any indication that a product is “new mation can be helpful. It is important to understand the and improved,” “new formulation,” “new product PRACTICAL GASTROENTEROLOGY • JANUARY 2007
Medications and Celiac Disease—Tips From a Pharmacist
THE CELIAC DIET, SERIES #5
Common Over-the-Counter Gluten Free Products
Summary of Key Points
1. Gluten can be found as a normal component of a drug prod- uct. When a product contains the word “starch” the source should be identified. Corn, rice, potato and tapioca starch 2. While all product formulations should be checked with the manufacturer, it is not always possible to do so in a timely Aspirin Enteric Coated 325mg (Leiner,code #44/227, Watson) 3. The likelihood of gluten contamination is small for products that do not contain excipients derived from starch. 4. The product package insert is a good place to start in search for gluten in medications, but may not completely 5. Internet resources may also provide some help, but caution Comtrex (tabs/caplets/liquid)Comtrex Deep Chest ColdComtrex Non DrowsyFreeda’s Vitamins time constraints pharmacists are under; allowing them Ibuprofen (manufact. is Pharm Formulations) to obtain this information during non-peak hours will increase their level of cooperation. For more resources MobicMorphine Sulfate Ext Release Tab (Endo)Motrin (Children’s) oral susp CONCLUSION
Motrin Cold DF BerryMotrin DF Oral Susp Berry Obtaining accurate information regarding the gluten status of medications and over-the-counter products can be a difficult and time-intensive process. Lack of understanding of what gluten is and how gluten can fil- ter into our lives is a barrier to retrieving this informa- tion. Proper education of the health care professional can be a valuable tool in combating this problem. For Robitussin Cold & Congestion CapletRobitussin Cold & Cough Liqui-Gels a summary of key points, see Table 4. ■ Robitussin Cold Severe Congestion liqui-gelsRobitussin Cold, Cough & Flu Liqui-Gels References
1. Anon. National Institutes of Health Consensus Development Robitussin Multi Symptom Cold & Flu Caplets Conference Statement. Celiac Disease, 2004; June 28-30.
2. Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac dis- ease in at-risk and not-at-risk groups in the United States: a large Sesame Street Complete Vitamins & Minerals multicenter study. Arch Intern Med, 2003;163: 286-292.
3. Crowe JP, Falini NP. Gluten in pharmaceutical products. Am J Health-Syst Pharm, 2001; 58:396-401.
4. Pietzak M. Gluten-free Food Labeling in the United States. J Ped Gastroenterol Nutr, 2005;41:567-568.
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PRACTICAL GASTROENTEROLOGY • JANUARY 2007

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