Arens A1,2; Vo K1,2; Van Wijk X3,; Lemos N3; Olson K2,4; Smollin C1,2!!

1 Department of Emergency Medicine, University of California San Francisco; 2 California Poison Control System, San Francisco Division; 3 Department of Laboratory Medicine, University of California San Francisco; 4 Departments of Medicine & Clinical Pharmacy, University of California San Francisco!

!!

Introduction !!

Illicit drugs can be adulterated, or substituted with alternative medications, which can result in outbreaks of poisoning.!

A series of patients in the Bay Area, including two fatalities, were referred to the San Francisco division of the California Poison Control System (CPCS) for complications after ingesting adulterated ‘Xanax’ tabs purchased illegally off the street. !

Analysis of the initial pills found large quantities of fentanyl and etizolam. !!

Index Cases!

Three patients were evaluated by EMS after drinking alcohol, using cocaine, and ingesting ‘Xanax’ purchased off the street. !Patient 1. 34F last seen normal at midnight was found unresponsive by friends at 0800. Patient was asystolic on EMS arrival with rigor of the jaw. A ‘Xanax’ tablet found in patient’s purse was sent to the medical examiner’s office.

Patient 2. 37F with a h/o Crohn’s Disease presented to the ED with complaints of right lower extremity weakness. !VS: T 37.1, BP 90/50, HR 112, RR 16, SpO2 100% RA!Neuro: A&Ox3, CN II-XII intact!

! Decreased motor strength and sensation in RLE ! ! distal to the knee.!

Comprehensive drug screen: Cocaine, Benzoylecgonine, Cocaethylene, Fentanyl, Norfentanyl, Levamisole, Diphenhydramine!!Patient 3. 27M with no past medical history presented to the ED with complaints of left upper extremity weakness. !VS: T 37.8, BP 96/76, HR 124, RR 11, SpO2 sat 96% RANeuro: A&Ox3, CN II-XII intact!

! Decreased motor strength and sensation in LUE ! ! distal to the elbow.!

Comprehensive drug screen: Cocaine, Benzoylecgonine, Cocaethylene, Fentanyl, Norfentanyl, Levamisole, Cotinine!!

!!

!

Public Health Alert!!Within one week of the presentation and identification of the first patients, CPCS and the San Francisco Department of Public Health issued a health advisory and press release to alert both health care providers and potential consumers of this potential life-threatening adulterated product. !

!!!!!!

Discussion! The SF division of the California Poison Control System and the SF medical examiner’s office identified ten patients and two fatalities exposed to an adulterated ‘Xanax’ product identified to contain potentially lethal concentrations of fentanyl and etizolam. !!A health advisory and press release were created to alert both health care providers and potential consumers of this potential life-threatening adulterated product. !!

Conclusion!!Clusters of patients with unexpected effects after ingestion of illicit or illegally obtained substances should alert health care providers of a potential epidemic of adulterated products. !!!

Pill Analysis!!

21M was found down “in a wheelbarrow” by friends!after using ‘Xanax’ purchased off the street. !!A friend arrived with the ‘Xanax’ tab (Image 1a). !

•  Pill was sent for analysis at the Zuckerberg San Francisco General (ZSFG) Clinical Chemistry Laboratory!

•  Liquid Chromatography - Mass Spectrometry !! was used to determine the contents. !

!!!!

!

Adulterated Xanax: A Case Series From San Francisco!

Cases to Date !!

Image 1a. Pill submitted for analysis to the ZSFG Clinical Chemistry Laboratory: white rectangular pill stamped ‘2’ on one side and ‘XANAX’ on the other with 3 score marks on each side. Total weight: 212 mg. !

!

Image 1b. Image of commercially available 2mg Xanax® tab. !

Table 1. Patients referred to CPCS – San Francisco Division!

•  All cases were referred from 10/15 –12/31/2015!

•  Five patients were treated at ZFSG!

•  Biological samples were analyzed at the ZSFG Clinical Chemistry Laboratory!

Date! Age! Sex! Clinical ! Serum levels ! Comprehensive Drug Screen!

10/15! 27! M! Demand cardiac ischemia, rhabdomyolysis, compression neuropathy, acute kidney injury!

Fentanyl 1.55 ng/mL Etizolam 0.60 ng/mL!

Cocaine, Benzoylecgonine, Cocaethylene, Norfentanyl, Levamisole, Cotinine!

10/15! 38! F! Demand cardiac ischemia, rhabdomyolysis, compression neuropathy!

Fentanyl 0.61 ng/mL Etizolam <0.24 ng/mL!

Cocaine, Benzoylecgonine, Cocaethylene, Norfentanyl, Levamisole, Diphenhydramine!

10/15! 34! F! Found deceased by friends after ingesting ‘Xanax’! Pending autopsy! Pending autopsy!

!

10/17! 21! M!

Obtundation requiring intubation, cardiogenic pulmonary edema, and biventricular heart failure. Symptoms improved after 5 days.!

Fentanyl 1.39 ng/mL Etizolam 0.26 ng/mL! Benzoylecgonine, Norfentanyl!

10/26! 42! M! Found deceased on scene with pills marked ‘Xanax’ found nearby! Pending autopsy! Pending autopsy!

!

10/26! 45! M! Lethargy after ingesting chlordiazepoxide, alcohol and 3 ‘Xanax’ bought from a friend! Etizolam 22 ng/mL! Chlordiazepoxide, Demoxepam!

11/4! 19! M! Lethargy and ataxia after ingesting ‘Xanax’!Fentanyl 0.15 ng/mL!Etizolam 55 ng/mL!Alprazolam 101 ng/mL !

Norfentanyl, Cotinine!

11/15! 19! M! CNS/resp depression requiring naloxone! Fentanyl 2.6 ng/mL!Norfentanyl, Cotinine, Diphenhydramine, Naloxone, Sertraline!

11/28! 8mo! M! CNS depression requiring intubation ! Urine only – Fentanyl identified!

Norfentanyl, Midazolam, Alpha-hydroxymidazolam, Atropine, Lorazepam!

12/31! 25! M!Cardiac arrest after ingesting ‘Xanax’ purchased on the street (recovered fully after 2 days)!

Fentanyl 1.4 ng/mL!

Norfentanyl, Diazepam, Nordiazepam, Temazepam, Oxazepam, Naloxone, Acetaminophen!

Contents: Fentanyl 3.4 mg! Etizolam 10.6 mcg!