A Male Enhancement Pill Laced With a Diabetes Drug — Virginia, 2019

Products sold over the counter as dietary supplements sometimes contain undeclared prescription drugs approved by the Food and Drug Administration (FDA), putting people who think them harmless at real risk. In 2019, one such product caused an outbreak of severe hypoglycemia — dangerously low blood sugar — in Virginia.

The first two cases

On August 13, 2019, an emergency physician at an academic medical centre called the Virginia Poison Center about a 57-year-old man without diabetes. The day before, his wife had noticed him sweating heavily and agitated. His symptoms eased after lunch but came back, and after 12 hours of confusion he was taken to an emergency department, where his blood glucose was 48 mg/dL (normal is 70–100). He recovered with intravenous dextrose and octreotide, a drug that blocks insulin release and serves as an antidote to recurring low blood sugar from sulfonylurea poisoning.

He had taken no insulin or diabetes medicine. But because health insurance problems had kept him from filling his usual prescription for sildenafil, used to treat erectile dysfunction, he had bought "V8," an oral male enhancement supplement, at a convenience store in the Richmond area and taken one tablet each night from August 10 to 12. Recalling a 2009 outbreak of hypoglycemia linked to counterfeit sildenafil, the physician and poison centre suspected a sulfonylurea — a type of diabetes drug — and sent the product for testing.

On August 22, the Blue Ridge Poison Center heard about a 50-year-old man in Lynchburg, also without diabetes, who was sweating, shaky and confused, with a blood glucose of 32 mg/dL. Oral glucose brought it back to normal by the time he reached the emergency department, but it fell again an hour later, and overnight it dropped as low as 42 mg/dL despite dextrose by infusion and repeated doses. He spent 3 days in hospital. He too had taken V8, bought at a service station. Tests found glyburide and sildenafil in his blood and urine.

The outbreak

The Virginia Department of Agriculture and Consumer Services (VDACS) and the Virginia Department of Health (VDH) opened an investigation on August 14. A case was defined as severe hypoglycemia within 48 hours of taking an over-the-counter male enhancement supplement, in a man with no history of using insulin or other blood sugar medicine.

In the 3 months after the first two cases, 15 more men were hospitalised — 17 in all, aged 33 to 73.

• Their average blood glucose at first evaluation was 30 mg/dL; the lowest recorded was 11 mg/dL.
• Three men were hospitalised twice.
• All received intravenous dextrose, and seven also received octreotide.
• No deaths were found.

The men said V8 was sold in service stations and convenience stores in clear jars, with no ingredient list or warning label. The blue tablets looked very like prescription sildenafil, and the product spread by word of mouth as a way to boost sexual performance.

What was in the pills

Tablets from the men's own supplies and from stores across Virginia were tested independently by the state public health laboratory and by the University of Virginia's pathology laboratories. Every tablet contained sildenafil, from 55 to 156 mg. Most also contained 90 to 100 mg of glyburide — a sulfonylurea used to treat diabetes and known to cause prolonged low blood sugar in overdose — 5 to 10 times the dose used for diabetes. Blood from three patients and urine from a fourth confirmed exposure.

The response

• August 14: the Virginia Poison Center alerted the Richmond City Health Department, and VDH and VDACS began investigating the stores and seizing or quarantining the product.
• August 22: VDACS warned consumers of potentially life-threatening hypoglycemia from V8.
• August 26 and September 12: the Blue Ridge Poison Center urged people not to use it.
• September 16: VDH alerted other states through CDC's Epidemic Information Exchange (Epi-X), followed by a statewide press release the next day.
• November 6: the last confirmed case.

Cases were reported to MedWatch, the FDA's adverse event reporting program, as they occurred. VDACS seized the product at 23 locations across Virginia, and the FDA began investigating where it came from.

Why glyburide?

A 2009 outbreak in Singapore, affecting 150 people, was also linked to counterfeit sildenafil containing glyburide. Why it was in V8 is unclear. One idea is that it was used as a convenient filler, but the tablets held normal therapeutic amounts of sildenafil, which makes that less likely. Another is that it gave the tablets their blue colour, to look like the real prescription drug.

Lessons

People can buy such products without knowing the danger, and without prompt medical care, the resulting low blood sugar could kill. The quick response, the authors write, came from cooperation among poison centres, hospitals, health departments, public health laboratories and the state university health system. Supplements containing undeclared prescription drugs should be taken off the market as soon as they are found, and consumers and clinicians should be warned about them.

Sources

Based on "Outbreak of Severe Hypoglycemia After Ingestion of a Male Enhancement Supplement — Virginia, August–November 2019," by Jennifer A. Ross and colleagues (University of Virginia School of Medicine; Virginia Poison Center, Virginia Commonwealth University Health System; Virginia Department of Health; Virginia Division of Consolidated Laboratory Services), Morbidity and Mortality Weekly Report 69(24), published by the Centers for Disease Control and Prevention.

• The report gives the first patient's octreotide dose in milligrams, a unit that does not fit the drug; the dose is left out here.
• The report's photograph of the product is not reproduced.
• Words on this page from people and organisations outside the federal government are paraphrased; rewritten in hubnx's own words.