Orthopedics

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Pharmacology Update 

Lactose: The Hidden Culprit in Medication Intolerance?

Barbara Magnuson, PharmD; Sommer D. Zarbock, PharmD; Kenneth E. Record, PharmD; Lora Hoskins, RD; Kelly M. Smith, PharmD

Abstract

Although reports are rare, lactose-containing medications may cause patient discomfort and subsequently affect medication adherence.

Lactose (b galactose 1, 4 glucose), a disaccharide also known as milk sugar, is found in many products including dairy foods, infant formula, bakery products, confections, and even pharmaceuticals.1 Hippocrates noted that many Southern Europeans became ill after ingesting milk.2 Only within the past 50 years has the condition been recognized fully, and now it can be medically managed. Clinicians of all specialties should understand the impact of lactose intolerance, particularly as the substance may be the cause of a variety of medication intolerance reactions. This article provides an overview of the condition, as well as implications in the practice of orthopedic surgery. A particular focus is given to orthopedic medication selection and prescribing based on lactose content of specific drug products.

Lactose is not directly absorbed as a dietary nutrient but is broken down by the lactase enzyme. Located in the enterocytes of the small bowel on the brush-border membrane, lactase (D-galactosidase galactohydrolase) selectively acts on lactose, cleaving it into the monosaccharides glucose and galactose.3 “Lactose intolerance” is best defined as the reduced or absent activity of the enzyme lactase. Inability to digest lactose is not life-threatening; however, it often leads to painful and persistent gastrointestinal symptoms such as abdominal bloating, flatulence, and diarrhea. Gastrointestinal symptoms result when undigested lactose reaches the large intestine. In the colon it osmotically draws fluid and ferments due to the actions of enteric bacteria. Thus, lactose may serve as an osmotic laxative. The fermentation process produces lactic acid, carbon dioxide, methane, and hydrogen that result in the common abdominal discomfort and distention.4

Lactose intolerance is a fairly common condition, affecting between 30 and 50 million Americans.3,5 Certain ethnic and racial groups are more affected than others. American Indians, Asians, and African Americans have the highest incidence of lactose intolerance, while 40% to 55% of Northern Europeans are affected or at risk for the condition. Little or no difference exists between affected males and females.

Three types of lactose intolerance or lactase deficiency exist. The two most common types are primary and secondary lactose intolerance. Hypolactasia, a rare condition in which lactase is deficient beginning at birth, will not be addressed in this article.3 Primary lactose intolerance typically develops between ages 2 to 20 years. Affected patients begin to produce less lactase after age 2 years, yet symptoms commonly are not displayed until years later. Secondary lactose intolerance, the most common type, generally develops as lactase levels naturally diminish during natural aging. In addition, secondary lactase deficiency may occur after injury to the small intestine or as a result of certain digestive diseases that hamper lactase production. Examples of the latter include celiac disease, inflammatory bowel disease, and Crohn’s disease. In patients with the human immunodeficiency virus, the virus damages the intestinal mucosa and results in a deficiency of the lactase enzyme.4

Lactose intolerance also has a genetic link. Possession of the common autosomal recessive gene results in decreased lactase activity into and throughout adulthood.6 Lactose intolerance may be temporary or permanent in nature. The condition also may develop in patients who have intestinal problems such as gut infection or gastric surgery, or are receiving certain medications (eg, antibiotics).4

Treatment of lactose intolerance centers on dietary modification and over-the-counter lactase supplementation (eg, LactAid [McNeil Consumer Products, Ft Washington, Pa], Lactrase [Schwarz Pharma Kremers Urban, Mequon, Wis], SureLac [Caraco, Detroit, Mich], or Dairy Ease [Sterling Health, New York, NY]). Patients may require a “trial and error” period before identifying the most effective product for their condition. Some patients incubate lactose-containing…

Although reports are rare, lactose-containing medications may cause patient discomfort and subsequently affect medication adherence.

Lactose (b galactose 1, 4 glucose), a disaccharide also known as milk sugar, is found in many products including dairy foods, infant formula, bakery products, confections, and even pharmaceuticals.1 Hippocrates noted that many Southern Europeans became ill after ingesting milk.2 Only within the past 50 years has the condition been recognized fully, and now it can be medically managed. Clinicians of all specialties should understand the impact of lactose intolerance, particularly as the substance may be the cause of a variety of medication intolerance reactions. This article provides an overview of the condition, as well as implications in the practice of orthopedic surgery. A particular focus is given to orthopedic medication selection and prescribing based on lactose content of specific drug products.

Lactose Intolerance

Lactose is not directly absorbed as a dietary nutrient but is broken down by the lactase enzyme. Located in the enterocytes of the small bowel on the brush-border membrane, lactase (D-galactosidase galactohydrolase) selectively acts on lactose, cleaving it into the monosaccharides glucose and galactose.3 “Lactose intolerance” is best defined as the reduced or absent activity of the enzyme lactase. Inability to digest lactose is not life-threatening; however, it often leads to painful and persistent gastrointestinal symptoms such as abdominal bloating, flatulence, and diarrhea. Gastrointestinal symptoms result when undigested lactose reaches the large intestine. In the colon it osmotically draws fluid and ferments due to the actions of enteric bacteria. Thus, lactose may serve as an osmotic laxative. The fermentation process produces lactic acid, carbon dioxide, methane, and hydrogen that result in the common abdominal discomfort and distention.4

Lactose intolerance is a fairly common condition, affecting between 30 and 50 million Americans.3,5 Certain ethnic and racial groups are more affected than others. American Indians, Asians, and African Americans have the highest incidence of lactose intolerance, while 40% to 55% of Northern Europeans are affected or at risk for the condition. Little or no difference exists between affected males and females.

Three types of lactose intolerance or lactase deficiency exist. The two most common types are primary and secondary lactose intolerance. Hypolactasia, a rare condition in which lactase is deficient beginning at birth, will not be addressed in this article.3 Primary lactose intolerance typically develops between ages 2 to 20 years. Affected patients begin to produce less lactase after age 2 years, yet symptoms commonly are not displayed until years later. Secondary lactose intolerance, the most common type, generally develops as lactase levels naturally diminish during natural aging. In addition, secondary lactase deficiency may occur after injury to the small intestine or as a result of certain digestive diseases that hamper lactase production. Examples of the latter include celiac disease, inflammatory bowel disease, and Crohn’s disease. In patients with the human immunodeficiency virus, the virus damages the intestinal mucosa and results in a deficiency of the lactase enzyme.4

Lactose intolerance also has a genetic link. Possession of the common autosomal recessive gene results in decreased lactase activity into and throughout adulthood.6 Lactose intolerance may be temporary or permanent in nature. The condition also may develop in patients who have intestinal problems such as gut infection or gastric surgery, or are receiving certain medications (eg, antibiotics).4

Treatment of lactose intolerance centers on dietary modification and over-the-counter lactase supplementation (eg, LactAid [McNeil Consumer Products, Ft Washington, Pa], Lactrase [Schwarz Pharma Kremers Urban, Mequon, Wis], SureLac [Caraco, Detroit, Mich], or Dairy Ease [Sterling Health, New York, NY]). Patients may require a “trial and error” period before identifying the most effective product for their condition. Some patients incubate lactose-containing milk overnight with a lactase enzyme. Adding 5 to 10 drops of lactase preparation to a glass of milk hydrolyzes about 70% to 100% of the lactose.7 This option provides the patient with an alternative if they are unable to tolerate, swallow, or digest the enzyme-replacement products. In addition, several lactose-free food items can be found in the supermarket dairy aisle.

Drug Intolerance: The Hidden Culprit?

The lactose molecule is slightly sweet to the taste, anhydrous, and water soluble but relatively insoluble in alcohol, chloroform, and ether. These physical properties make lactose a desirable diluent for soluble drugs, as well as a filler or bulking agent used in preparing capsules, tablets, or other solid oral dosage formulations (eg, chewable or orally disintegrating tablets). The presence of lactose in medications may not be trivial to a patient with a known intolerance to the compound. The link between lactose-containing medications and gastrointestinal reactions was not formally identified until the observations of Lieb and Kazienko8 in 1978. A limited number of case reports have since described the onset of diarrhea following medication initiation in the presence of otherwise lactose-free diets. Although the reports are rare, lactose-containing medications may cause patient discomfort and subsequently affect medication adherence. Health care practitioners should be cognizant of medications that contain lactose if their patients experience serious intolerance reactions. Alternative medications or different routes of drug administration may be necessary.

The amount of lactose in oral medications generally is dwarfed by comparison to the lactose content of many dietary substances, particularly dairy products. An 8-oz glass of milk contains 10 to 12 g lactose, while medication amounts are measured in milligrams.4 Nonetheless, these seemingly trivial amounts can be significant in patients with a severe condition. Lactose is a base component of >20% of prescription and 6% of over-the-counter medications; thus, the potential for some patients to have clinically significant reactions exists.3 The product labeling (eg, package insert, Physician’s Desk Reference) and manufacturer are the most reliable sources of information about inert medication ingredients, and should be consulted prior to prescribing or administering oral medications to patients with severe lactose intolerance. Pharmacists also can be consulted to assist in determining lactose-containing compounds. Of note, when a product is listed as containing “sugar” as an inactive ingredient, it more commonly reflects sucrose content, rather than lactose.4 Lactose also should not be confused with lactulose, a synthetic disaccharide and osmotic diuretic that creates reactions that could be easily mistaken for lactose intolerance. Sorbitol, a sugar alcohol that may produce gastrointestinal side effects very similar to lactose intolerance, is another common medication additive. It is important that health care professionals recognize the difference between these substances and treat their patients accordingly, as inaccurately labeling a patient lactose-intolerant may lead to lifestyle or dietary alterations that are subsequently ineffective.

Common Oral Orthopedic Medications Containing Lactose and Possible Alternative Agents

Medication Considerations

The amount of “filler” or lactose used may vary by product, manufacturer, formulation and strength. Generic products often are manufactured by several different companies and the amount of lactose will vary from one generic manufacturer to the next, as well as between different strengths of the same product. These facts, in conjunction with the lack of labeling of lactose quantity in product information, make anticipating concerns about the potential to cause reactions in lactose-intolerant patients more challenging. Select lactose-containing oral medications, as well as corresponding alternative products, that should be considered by orthopedic clinicians are displayed in the Table. In dietary or herbal supplements (eg, glucosamine), the amount of active and inactive ingredients varies by lot and manufacturer. Thus, providing a listing of lactose-free or lactose-containing products is not feasible. The best source of information regarding these product components is each compound’s manufacturer.

The Bottom Line
  • Common gastrointestinal symptoms of lactose intolerance include diarrhea, flatulence, bloating, cramping, and abdominal pain and discomfort.
  • Evaluate lactose, a common drug filler, as the underlying cause of apparent gastrointestinal intolerance reactions to medications.
  • Consider lactose content, and use alternative products accordingly, before prescribing or recommending solid oral dosage forms for use in patients with severe lactose intolerance.
  • Consult package inserts, the Physician's Desk Reference, manufacturers, or pharmacists to identify lactose-containing prescription or nonprescription drugs.

References

  1. Matthews SB, Waud JP, Roberts AG, Campbell AK. Systemic lactose intolerance: a new perspective on an old problem. Postgrad Med J. 2005; 81:167-173.
  2. Campbell AK, Waud JP, Matthews SB. The molecular basis of lactose intolerance. Sci Prog. 2005; 88:157-202.
  3. Rusynyk RA, Still CD. Lactose intolerance. J Am Osteopath Assoc. 2001; 101:S10-S12.
  4. Russette HK, Oh T. In search of lactose. J Pharm Technol. 1996; 12:16-20.
  5. National Digestive Diseases Information Clearinghouse. Lactose Intolerance. Available at: www.digestive.niddk.nih.gov. Accessed April 9, 2007.
  6. Pray WS. Lactose intolerance: the norm among the world’s peoples. Am J Pharm Educ. 2000; 64:205-207.
  7. Lactose Intolerance. Eat to Beat Illness. URL: http://www.indiadiets.com/diets. Accessed April 18, 2007.
  8. Lieb J, Kazienko DJ. Lactose filler as a cause of drug induced diarrhea. N Engl J Med. 1978; 299:314.

Authors

Drs Zarbock, Magnuson, Record, Smith, and Ms Hoskins are from University of Kentucky HealthCare, Lexington, Ky.

Correspondence should be addressed to: Kelly M. Smith, PharmD, University of Kentucky HealthCare, 800 Rose St, H110, Lexington, KY, 40536-0293.

10.3928/01477447-20070801-10

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