Varenicline overdose in a teenager

Varenicline (Chantix®) is a selective partial agonist of α₄β₂ nicotinic acetylcholine receptor subtypes. It is approved in the United States to aid with smoking cessation. The maximum recommended dose is 2 mg administered twice daily.¹ We report an acute ingestion of 15 mg in a teenager.

A 16-year-old woman intentionally ingested 30 tablets of 0.5 mg varenicline belonging to her mother. After admitting to the ingestion, the patient was taken to an emergency department but refused to give an exact time of exposure. Upon arrival, she vomited spontaneously, but her physical examination was otherwise unremarkable. Her initial vital signs revealed: blood pressure 135/90 mmHg, pulse 129 beats/minute, respirations 22 breaths/minute. The patient received a single dose of oral activated charcoal and subsequently vomited once more. Monitored observation was continued and, four hours later, her vital signs improved to a blood pressure of 104/64 mmHg, pulse 73 beats/minute, and respirations 15 breaths/minute. She remained symptom-free for four more hours and was discharged.

Varenicline is a partial agonist for α₄β₂ nicotinic acetylcholine receptors found in the central nervous system and is derived from the alkaloid plant product cytisine. Cytisine, derived from the plant Cytisus laburnum, has been used in Eastern Europe to aid in smoking cessation for over forty years and is currently being sold under the brand name Tabex®.^2,3 Varenicline has been modified to have greater bioavailability and selectivity for the α₄β₂ receptor subtype, but to a lower level than nicotine. The highest concentration of α₄β₂ nicotinic receptors can be found on the dopamine and γ-aminobutyric acid–containing neurons, and with its agonist activity varenicline both blocks the nicotine receptor as well as stimulates dopamine release.^2,4 The effects of this receptor activation are thought to be of importance in dependence, thereby reducing the craving for nicotine.⁴

Currently, there are no published reports of varenicline overdose. Reported adverse effects with therapeutic doses of varenicline include gastrointestinal disturbances, sleep dysfunction and headache, with cardiovascular effects appearing to be minimal.¹ Nicotine causes initial stimulation then subsequent blockade of the various nicotinic receptors in the brain, autonomic ganglia, and neuromuscular junction with reported symptoms including hypertension, tachycardia and tachypnea, followed by hypotension, bradycardia and bradypnea.⁵ It is unclear whether varenicline loses specificity for the α₄β₂ subtype in large doses, but the brief hyperadrenergic symptoms seen in our patient are consistent with those reported with nicotine poisoning. Future experience involving supratherapeutic doses of varenicline may better depict at what point selectivity for α₄β₂ nicotinic acetylcholine receptors may be lost.