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• Filed under: The Hospital Pharmacy, Clinical, Departments

• Keywords: supplement use, diabetes, decision-making, patient care

Head Off Hypoglycemia

From: The Hospitalist, June 2009

by Michele B. Kaufman, PharmD, BSc, RPh

Let’s look at a case: A known diabetic patient has been in good control, with glycosylated hemoglobin (HbA1c) levels lower than 6.5 gm/dL the past two years. Her medication regimen has remained relatively stable during that time. Her daily medications include simvastatin, 40 mg; metformin extended release, 2,000 mg; sitagliptin, 100 mg; glimepiride, 8 mg; quinapril, 20 mg; a multivitamin; calcium carbonate, 1,500 mg; and an 81-mg aspirin.

Her lipid panel, liver and renal function tests, and blood pressure are all within normal limits. However, she was admitted to the hospital with a plasma glucose level of 38 mg/dL.

Upon physical examination, she appears diaphoretic, with weakness, confusion, tremulousness, and palpitations. She is treated with glucose to maintain a level of above 50 mg/dL, and she responds without long-term sequelae.

What precipitated this event?

Drug-Induced Hypoglycemia

Hypoglycemia may represent a lab error or artifactual hypoglycemia due to glycolysis in the collection sample. To determine a pathological cause of hypoglycemia, the triad of low plasma glucose, hypoglycemia symptoms, and symptom resolution with correction of the blood glucose level should be used.1 Hypoglycemia is most often seen in diabetic patients and is the most commonly noted endocrine emergency in the inpatient setting, as well as in the ambulatory setting. Some common causes of hypoglycemia in diabetes patients include alcohol consumption, skipping meals, too much exercise, and intentional or unintentional medication overdoses.2

Treatment is required when the blood glucose level is below 45 gm/dL. Symptoms include anxiety, tremulousness, nausea, sweating, palpitation, and hunger.3 More severe symptoms related to compromised central nervous system function include weakness, fatigue, confusion, seizures, focal neurologic deficits, and coma.

The most common causes of drug-induced hypoglycemia are insulin, ethanol, or sulfonylureas. Risk factors associated with unintentional overdose of sulfonylureas include advanced age, drug-to-drug interactions, and decreased renal or hepatic clearance. Other drugs have been reported to cause hypoglycemia. Some of these include high-dose salicylates, beta-blockers, haloperidol, monoamine oxidase inhibitors, other sulfonamides (particularly trimethoprim-sulfamethoxazole), pentamidine, quinine/quinidine, and quinolone antibiotics (e.g., gatifloxacin or levofloxacin).4

Diabetics use more than 120 natural medicines, either alone or in combination with their prescribed diabetes medications, to lower blood glucose and/or improve HbA1c.5 Some of the most commonly used products are banaba, bitter melon, fenugreek, and Gymnema (hypoglycemics), along with American or panax ginseng, cassia cinnamon, chromium, prickly pear cactus, soy, or vanadium (insulin sensitizers).

Diagnosis

Patient history aids in the clinical diagnosis of hypoglycemia and should be reviewed to determine a potential drug-induced cause. History also might identify a medication dispensing error (e.g., the onset of hypoglycemia following a recent medication refill). Hospitalists should question the patient or the patient’s family as to medication use, including over-the-counter drugs, vitamins, supplements, natural foods, and other related products.

Treatment

Glucose should be administered to maintain a plasma glucose level of at least 50 gm/dL. This may be achieved orally via frequent meals or snacks, or intravenously. The underlying cause should be addressed. In drug- or medication-induced cases, the causative agent should be removed or retitrated to an effective dose that does not cause hypoglycemia.

Upon further questioning, the patient admitted she’d been taking 3,000 mg of a bitter melon product per day. She took this in addition to all her prescribed medications. Because bitter melon has an insulin-like effect, its use in combination with glimepiride led to the clinically significant hypoglycemic reaction, which required hospitalization and treatment. Prior to discharge, the patient promised to discuss the use of alternative and natural products with her pharmacist or physician before trying anything new. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City.

References

1. Guettier JM, Gorden P. Hypoglycemia. Endocrinol Metab Clin North Am. 2006;35:753-766.
2. Holt HH. Drug-induced hypoglycemia: overview. The University of Maryland Medical Center Web site. Available at: www.umm.edu/ency/article/000310.htm. Accessed March 2, 2009.
3. Hurd R. Drug-induced hypoglycemia. Drugs.com Web site. Available at: www.drugs.com/enc/drug-induced-hypoglycemia.html. Accessed March 2, 2009.
4. Mehlhorn AJ, Brown DA. Safety concerns with fluoroquinolones. Ann Pharmacother. 2007; 41:1859-1866.
5. Natural medicines in the clinical management of diabetes. Natural Medicines Comprehensive Database Web site. Available at: www.naturaldatabase.com. Accessed March 3, 2009.
6. Teva announces approval and launch of generic Imitrex tablets. Available at: finance.yahoo.com/news/Teva-Announces-Approval-and-bw-14308223.html/print. Accessed March 2, 2009.
7. Additional strengths of Avinza available. Monthly Prescribing Reference Web site. Available at: www.empr.com/Additional-strengths-of-Avinza-available/article/126905/. Accessed March 2, 2009.
8. Gelnique treatment for overactive bladder. Drugs.com Web site. Available at: www.drugs.com/gelnique.html. Accessed March 2, 2009.
9. Reclast label. The U.S. Food and Drug Administration Web site. Available at: www.fda.gov/cder/foi/label/2008/021817s002lbl.pdf. Accessed March 2, 2009.
10. Clopidogrel bisulfate (marketed as Plavix). The U.S. Food and Drug Administration Web site. Available at: www.fda.gov/medwatch/safety/2009/safety09.htm#plavix. Accessed March 2, 2009.
11. PPI interactions with clopidogrel. Med Lett Drugs Ther. 2009;51 (1303):2-3.
12. PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009;51(1306):13-4.
13. Xigris (Drotrecogin alfa [activated]): early communication about an ongoing safety review. The U.S. Food and Drug Administration Web site. Available at: www.fda.gov/medwatch/safety/2009/safety09.htm#Xigris. Accessed March 2, 2009.