Survival after varenicline and phentermine overdose with documented serum blood concentrations.

Abstract

Objective: Varenicline is a partial agonist of alpha-4 beta-2 nicotinic receptors used to treat nicotine withdrawal. It is renally eliminated, with an elimination half-life of 24-hours (range 10-54). In overdose, vomiting, hypertension, tachycardia and tachypnoea are seen. Phentermine is a sympathomimetic amine anorectic agent. Phentermine overdose results in central and peripheral adrenergic stimulation with cardiovascular and central nervous system toxicity. To date, there are no published cases reporting serum drug concentrations in patients surviving varenicline overdose. We report a case of varenicline and phentermine overdose confirmed by high performance liquid chromatography-mass spectrometry (HPLC-MS) blood analysis. Case report: A 13-year-old female presented to the emergency department 13 hours after ingesting her mother's varenicline (15 x 1 mg) and phentermine (15 x 30 mg). She began vomiting within 30 minutes of ingestion and this continued every 15-30 minutes throughout the night. On arrival, she complained of light-headedness, palpitations, anxiety and bilateral leg weakness. Initial observations were: pulse 125 bpm, sinus tachycardia, BP 123/72 mmHg, respiratory rate 24/min, saturation 97% (room air), temperature 36.7degreeC. On examination, pupils were 4 mm, equal and reactive, and she had sweaty palms. There was no clonus or tremor. She was able to stand unaided but complained of subjective left-sided weakness. There was no focal weakness on objective neurological testing. Serum electrolytes, acid-base and renal function were normal. Symptoms resolved rapidly. She was observed for 22 hours and discharged well the next day. Serum concentrations of phentermine and varenicline were assayed by HPLC-MS at 13, 17 and 22 hours post-ingestion. Phentermine concentrations were 0.16 mg/L, 0.23 mg/L and 0.16 mg/L (therapeutic range 0.18-0.51). Varenicline concentrations were 4.2 ng/mL at 13-hours and 3.5 ng/mL 22-hours post-ingestion with calculated elimination half-life of 3-hours. Therapeutic concentration associated with reduced nicotine craving is reported to be approximately 8 ng/mL. Conclusion(s): Our patient described rapid onset of recurrent vomiting and palpitations at home, 30-minutes post-overdose which are consistent with early features of varenicline intoxication. Other than sinus tachycardia, she did not exhibit signs of significant adrenergic toxicity in hospital and, most likely, presented after peak toxicity occurred. We theorise that early vomiting, induced by varenicline, reduced drug absorption and mitigated toxicity of both agents and resulted in lower than expected serum drug concentrations post-overdose. Treatment for intoxication with either agent is symptomatic and supportive.