Severe manifestations of coricidin intoxication

Brief Reports

Severe Manifestations of Coricidin Intoxication THOMAS J. KIRAGES, MD,* HARSH P. SULE´, MD,* AND MARK B. MYCYK, MD† CoricidinHBP (Schering-Plough Health Care Products, Inc, Memphis, TN) is a popular over-the-counter product abused by teenagers for its potent euphoric properties. Clinically significant signs and symptoms after ingestion are usually short-lived and commonly include tachycardia, hypertension, somnolence, and agitation. We report 2 cases of severe toxicity from CoricidinHBP in adolescents that required prolonged hospitalization. The first case demonstrates prolonged anticholinergic complications from a suicidal attempt with CoricidinHBP. The second case demonstrates significant acetaminophen-induced hepatotoxicty from recreational use of CoricidinHBP Maximum Strength Flu. Adolescent abuse of these products is encouraged because of the easily accessible medium of the Internet. The significant morbidity seen in our cases clearly demonstrates the need for vigilance by health care professionals regarding the abuse of over-the-counter products. (Am J Emerg Med 2003;21:473-475. © 2003 Elsevier Inc. All rights reserved.)

In recent years, several regional poison centers have recognized a steady increase in teenage abuse of over-thecounter (OTC) cough and cold products.1 CoricidinHBP (Schering-Plough HealthCare Products, Inc, Memphis, TN) seems to be a popular OTC product abused by teenagers for its potent euphoric properties. Although complications from CoricidinHBP abuse are generally mild, we describe 2 cases illustrating severe complications from CoricidinHBP abuse that required prolonged hospitalization. These 2 cases from our growing case series of complications from CoricidinHBP abuse demand increased vigilance by healthcare providers for OTC product abuse. CASE REPORTS Case No. 1 A 16-year-old girl was found sleeping on the lawn in front of her home at 7:00 AM. It had been a cold, winter night in Chicago with a low temperature of ⫺12°C. The patient was last seen by her mother at 4:00 AM. The patient admitted to ingesting 20 tablets of CoricidinHBP Cough and Cold, a single tablet of 40 mg fluoxetine and a single tablet of 25 mg diphenhydramine at that time. The mother’s examination of From the *Department of Emergency Medicine, †Section of Toxicology/Toxikon Consortium, Cook County Hospital, Chicago, Illinois. Received July 16, 2002; accepted July 16, 2002. Address reprint requests to Harsh P Sule´, MD, 1900 West Polk Street, 10th Floor, Chicago, IL 60612. E-mail: [email protected] Key Words: Concidin, dextromethorphan, chlorpheniramine, acetaminophen, toxicity/poisoning, nonprescription drugs/poisoning. © 2003 Elsevier Inc. All rights reserved. 0735-6757/03/2106-0006$30.00/0 doi:10.1016/S0735-6757(03)00168-Z

pill bottles and Coricidin packaging at home corroborated the patient’s stated ingestion history. The patient had a medical history significant for depression and bipolar disorder. Daily medications included olanzapine (Zyprexa, Eli Lilly & Co, Indianapolis, IN) and fluoxetine (Prozac, Eli Lilly & Co). On presentation to the ED, the patient was somnolent and confused. Vitals signs were normal core temperature, heart rate 150 beats/min, blood pressure 170/ 100 mm Hg, and respiratory rate 18 breaths/min. Significant physical findings included 5-mm reactive pupils with horizontal nystagmus, tachycardic heart sounds, hypoactive bowel sounds, normal extremity tone without rigidity, and non flushed skin. Laboratory results demonstrated a normal complete blood count, chemistry panel, and urinalysis. The pregnancy test was negative, and the urine drug screen was also negative. Acetaminophen (APAP) and salicylate levels were undetectable. Head computed tomography was normal. The patient received activated charcoal, intravenous fluids, and was admitted to a monitored bed. The patient required 72 hours of inpatient monitoring until her vital signs and mental status returned to baseline. She was then discharged to her home with outpatient follow-up. Case No. 2 A 16-year-old girl, an honor roll high school student, presented to a community ED with nausea, vomiting, abdominal discomfort, and urinary retention. She reported using CoricidinHBP Cough and Cold recreationally to “get high” on multiple occasions. Over the past 72 hours, she reported ingesting 50 tablets of a different Coricidin preparation, CoricidinHBP Maximum Strength Flu. The patient denied other coingestants and denied alcohol use. Her medical history was significant for depression and recreational cigarette and marijuana use. Daily medications included venlafaxine (EffexorSR, Wyeth Pharmaceuticals, Madison, NJ) and clonazepam (Klonopin, Hoffmann-La Roche Inc., Nutley, NJ). On presentation to the ED, she was normothermic with a heart rate of 105 beats/min and blood pressure of 115/75 mm Hg. Physical examination was significant for diffuse abdominal tenderness without rebound or guarding, and a distended bladder. No other anticholinergic signs were noted. A postvoid residual of 1 L of urine was obtained by Foley catheterization and her abdominal discomfort resolved. Initial laboratory results obtained 24 hours after her last ingestion of Coricidin included acetaminophen 33 ␮g/mL, ALT 775 IU/L, AST 616 IU/L, PT 34.8 sec, INR 2.5, and Cr 0.8 mg/dL. Urine drug screen was positive for cannabinoids. 473

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Salicylate was undetectable. Oral N-acetylcysteine (NAC) therapy was initiated and the patient was admitted. Over the next 24 hours, the patient developed increasing right upper quadrant abdominal pain, a palpable and tender liver edge, asterixis, extremity clonus, and increasing anxiety. Laboratory results 48 hours after her last ingestion of Coricidin included ALT 9000 IU/L, AST 8001 IU/L, PT 42.6 sec, INR 4.6, Cr 0.7 mg/dL, NH325 ␮g/dL, venous pH 7.45, and undetectable acetaminophen. As a result of her worsening condition, she was transferred to a pediatric tertiary care center where she was evaluated for a liver transplant. NAC was continued, and lactulose and 2.4 L of fresh-frozen plasma were administered. The patient’s clinical symptoms and laboratory abnormalities slowly improved over the next 60 hours, and a liver transplant was avoided. After a 7-day hospital stay, the patient was discharged. DISCUSSION The morbidity associated with the teenage abuse of illegal drugs such as gamma- hydroxybutyrate (GHB) and MDMA (Ecstasy) has been well documented in the medical literature and the mass media. However, the morbidity associated with the abuse of OTC products such as CoricidinHBP is still underrecognized and underreported. CoricidinHBP is legal and easily available to adolescents in any pharmacy or convenience store. CoricidinHBP is currently marketed in 3 different formulations2: (1) CoricidinHBP Cold and Flu 325 mg acetaminophen, 2 mg chlorpheniramine maleate; (2) CoricidinHBP Cough and Cold 30 mg dextromethorphan HBr, 4 mg chlorpheniramine maleate; and (3) CoricidinHBP Maximum Strength Flu 500 mg acetaminophen, 15 mg dextromethorphan HBr, 2 mg chlorpheniramine maleate. The recreational user might refer to Coricidin products as “Triple C” or “Red Hots” because of the 3 Cs on the red tablet. These products are popular because of the euphoric and stimulant effects obtained when ingesting more than the manufacturer’s recommended dose.2,3 Each ingredient in the CoricidinHBP products can result in significant toxicity when used in inappropriate doses. Dextromethorphan is a common antitussive agent found in many OTC cough and cold preparations. It is the disomer of 3-methoxy-N-methylmorphine, a synthetic analogue of codeine. Dextromethorphan antagonizes N-methylD-aspartate (NMDA) glutamate receptors and inhibits the reuptake of serotonin. These effects could account for the acute and chronic abuse potential. Symptoms of mild intoxication include tachycardia, miosis or mydriasis, ataxia, clumsiness, hyperexcitability, nystagmus, restlessness, hallucinations, and dystonic reactions. Severe poisoning can result in stupor, coma, seizures, toxic psychosis, and respiratory depression.4,5 Naloxone has been reported to be an effective antidote in some cases.6 Chlorpheniramine maleate is an H1-receptor antagonist. Overdose results in anticholinergic toxicity: warm, dry, and flushed skin, mydriasis, dry mouth, delirium, tachycardia, gastrointestinal dysmotility, and urinary retention. Seizures, hyperthermia, and rhabdomyolysis have been reported in severe cases of chlorpheniramine ingestion.7,8 In pure antihistamine overdoses with life-threatening anticholinergic symptoms, physostigmine has been used as an effective antidote.9

Acetaminophen is a common analgesic and antipyretic found in over 100 OTC cold preparations. It is the most common analgesic implicated in reported cases of poisonings.1 Therapeutic ingestions are easily handled by glutathione detoxification in the liver, but in overdoses the glutathione capacity is overwhelmed by the toxic metabolite n-acetyl-p-benzoquinonemine (NAPQI). Initial symptoms are usually mild and nonspecific, and evidence of hepatic toxicity is delayed by 24-48 hours postingestion. The antidote N-acetylcysteine (NAC) is virtually 100% hepatoprotective when initiated within 8 hours of an acute overdose.10 Adolescent abuse of dextromethorphan cough syrups for a phencyclidine-type “high” has been well described.6 Although cough syrups have traditionally been the preparation of choice among adolescents, the convenience of the tablet form of Coricidin has made it increasingly popular.11 One tablet contains the equivalent of 3 teaspoons (15 mL) of dextromethorphan syrup. The additional euphoric properties associated with the anticholinergic properties of the chlorpheniramine in CoricidinHBP tablets make it a favored OTC product, over dextromethorphan syrup alone, among young adults.11-13 Reports in the medical literature regarding the escalating abuse of Coricidin have been limited to poison center case series presented at toxicology meetings.12,13 It has been reported that patients generally abuse Coricidin for its central nervous system effects and not as a means of suicide. Toxicity from OTC products has been described from appropriate dosing over chronic periods of time and in accidental overdoses.7 Therefore, it makes sense that intentional abuse of these products would also result in toxicity. Symptoms commonly demonstrated in these poison center cases include tachycardia, hypertension, somnolence, and agitation. Most reports of Coricidin ingestion have described the anticholinergic effects of CoricidinHBP, because CoricidinHBP Cough and Cold (dextromethorphan and chlorpheniramine) seems to be the favored preparation of the 3 Coricidin products among young adults.14 Our second case demonstrates the complication of acetaminophen toxicity when either of the Coricidin Flu products is abused. A review of some popular websites used by adolescents to gain information on these easily and legally available drugs of abuse also demonstrates an increase in testimonial reporting of fatal and near fatal overdoses of Coricidin products, not to mention “bad trips”.15,16 Anonymous authors have chronicled their experimentation with Coricidin, documenting the quality of their experience with escalating doses.17,18 One author describes his formula for synthesizing dextromethorphan at home. At another site, a father writes how his son died while abusing Coricidin tablets. The information available on the Internet about Coricidin is easy to obtain and greater in volume than the information in the toxicology or EM literature. From a healthcare financing and public health standpoint, these OTC products represent ever-increasing morbidity and mortality. In the first case, the patient had been outside on a cold, Chicago winter night for several hours before presenting to the ED. Although she was normothermic on presentation, if she had been in her home and not in a hypothermic environment, she might have been significantly hyperthermic, adding to her morbidity. In both cases, the patients had lengthy hospital stays, 3 days and 7 days.

KIRAGES ET AL ■ CORICIDIN INTOXICATION

The first patient was nearly intubated for airway protection secondary to somnolence and confusion, and the second patient had potential for liver transplantation. There are significant morbidities and possible mortalities associated with common OTC medications.19 Although this report singles out CoricidinHBP products, several other OTC products are available to adolescents.20 and can be similarly life-threatening. Our responsibility is two-fold: first, to recognize the potential complications, and second, to educate teens and parents regarding the toxic and nontoxic presentations associated with OTC product use and abuse. There is an ever-increasing volume of knowledge that the specialty of EM encompasses, and it is not realistic to expect every EP to know the formulation of every OTC product. However, it is our responsibility to recognize the various toxidromes and be aware of the potential complications. Furthermore, along with our colleagues in other specialties, especially pediatrics, we need to be aggressive about getting the word out on the growing abuse of these OTC remedies. This includes the need for more epidemiologi studies, as well as publicity through the mass media to adolescents, parents, and educators. Finally, as we become entrenched in the Internet era, we must come to terms with a vast fund of knowledge easily accessible to adolescents who are often more Internet-savvy than their parents, teachers, and physicians. It is, therefore, important for medical organizations and the government to be aggressive and quick to publicize the potential risks of the legal drug du jour. This needs to be directed not only to parents and teachers, but also to the adolescent clients themselves through the very media that is the source of information on the latest “high”. REFERENCES 1. Litovitz TL, Klein-Schwartz W, White S, et al: 2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2001;19:337-395 2. CoricidinHBP Products Page. http://www.coricidinhbp.com/ prodinfo.html. Accessed March 2002.

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3. Triple C’s http://koltershock1.net/abyss/. Accessed January 2002. 4. Pender ES, Parks BR: Toxicity with dextromethorphan containing preparations: a literature review and report of two additional cases. Pediatr Emerg Care 1991;1:163-165 5. Roberge RJ, Hirani KH, Rowland PL III, et al: Dextromethorphan and pseudoephedrine-induced agitated psychosis and ataxia. J Emerg Med 1999;17:285-288 6. Nordt SP: DXM: a new drug of abuse? Ann Emerg Med 1998; 31:794-795 7. Gunn VL, Taha SH, Leibelt EL, et al: Toxicity of over the counter cough and cold medications. Pediatrics 2001;108:E52 8. Wogoman H, Steinberg M, Jenkins AJ: Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine. Am J Med Pathol 1999;20:199-202 9. Burns MJ, Linden CH, Graudins A, et al: A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000;35:374-381 10. Jones AL: Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol 1998;36:277-285 11. US OH: Cold Pills ‘A Poor Man’s Ecstasy.’ http://www. dispatch.com/ & http://www.mapinc.org/norml/v01/n1501/a12.htm. Accessed March 2002. 12. Baker SD, Borys DJ: Coricidin use and abuse in Texas during 1998 and 1999. J Toxicol Clin Toxicol 2000;38:533 13. Simone KE, Bottei EM, Siegel ES, et al: Coricidin abuse in Ohio teens and young adults [Abstract]. J Toxicol Clin Toxicol 2000;38:532-533 14. Erowid DXM Vault: Complete Guide to DXM in Non Prescription Drugs. http://www.erowid.org/chemicals/dxm/dxminfo2.shtml# CoricidenCC. Accessed March 2002. 15. Erowid Experience Vaults: DXM [With CPM]—How to Lose a Son With Coriciden. http://www.erowid.org/experiences/exp. php3?ID-5903. Accessed March 2002. 16. The Third Plateau: Coricidin Warnings. http://www.third. plateau.org/coricidin.html. Accessed March 2002. 17. Boyer EW, Shannon M, Hibberd PL: Web sites with misinformation about illicit drugs. N Engl J Med 2001;345:469-471 18. Wax P, Reynolds N: Just a click away: student Internet surfing for recreational drug information. J Toxicol Clin Toxicol 2000; 38:531 19. Pentel P: Toxicity of over-the-counter stimulants. JAMA 1984;254:1898-1903 20. Katcher ML: Cold, cough, and allergy medications: uses and abuses. Pediatr Rev 1996;17:12-17