CASE REPORT clonidine, poisoning, patch; poisoning, clonidine, patch

Clonidine Transdermal Patch Poisoning

A case of infant clonidine poisoning from a transdermal patch that had been worn for five days by an adult and then discarded is described. The infant became hypotensive with a systolic blood pressure of 38 m m Hg, and a dopamine infusion was required for six hours to maintain adequate blood pressure. The infant was discharged 24 hours after admission. Clonidine tox- icity, transdermal delivery system pharmacokinetics, and poison prevention are discussed. [Caravati EM, Bennett DL: Clonidine transdermal patch poi- soning. Ann Emerg Med February 1988;17:175-176.]

I N T R O D U C T I O N Clonidine hydrochloride is a potent, widely used antihypertensive drug. It

recently has been released in the transdermal delivery system dosage form, which supplies 0.1, 0.2, or 0.3 mg per day of the drug.] We report what we believe to be the first case of a life-threatening infant poisoning from a clonidine patch that was wom for five days and then discarded.

CASE REPORT A 9-month-old boy was found sucking on a clonidine transdermal patch by

his father at home. His grandmother was undergoing treatment for hyperten- sion with Catapress TTS-2 ® {0.2 mg per day of clonidine) and, because of skin irritation, had recently removed a patch she had been wearing for five days, folded it in half, and discarded it in the trash. Approximately 1.5 hours after exposure, the child became pale and listless and was transported to an emergency department.

On arrival, the patient was pale and lethargic. Vital signs were blood pres- sure, 92/62 mm Hg; pulse, 100; respirations, 24; and temperature, 37.3 C, rectally. An IV of DsW 15 mL/min was established and the patient was ob- served for apnea, hypotension, and any further decrease in mental status. The complete blood count and urinalysis were normal.

After two hours of monitoring, the systolic blood pressure suddenly dropped to 38 mm Hg. A 100-mL fluid challenge was ineffective, and a dopa- mine infusion was begun at 5 ~g/kg/mm to maintain the systolic blood pres- sure at 80 to 90 mm Hg. The patient was admitted to the intensive care unit and weaned from the dopamine over the next six hours. His mental status retumed to normal and no other signs of toxicity were noted. He. was dis- charged the next day in good condition and without signs of rebound hyper- tension.

DISCUSSION Clonidine (2-[(2,6-dichlorophenyl)amino]-2-imidazoline) is a central al-

pha-2 adrenergic agonist that acts at the alpha-adrenergic receptors in the medulla. This results in a decreased sympathetic outflow that lowers blood pressure by decreasing heart rate and cardiac output. At high doses, it may act as a peripheral partial alpha-1 agonist and cause an increase in blood pressure and heart rate.2 The minimum toxic dose has not been established, but severe symptoms have been reported in children taking as little as 0.2 reg.* It is rapidly absorbed by the oral route, and antihypertensive effects are noted 30 to 60 minutes after ingestion, peaking in two to four hours. The mean serum half-life is 13 hours, with a range of six to 24 hours. 4

The signs and symptoms of toxicity vary and reflect both the central and

E Martin Caravati, MD, FACEP* Don L Bennett, RPht Salt Lake City, Utah

From the Division of Emergency Medicine, University of Utah School of Medicine,* and Intermountain Regional Poison Control Center, t Salt Lake City, Utah.

Received for publication February 27, 1987. Accepted for publication May 18, 1987.

Address for reprints: E Martin Caravati, MD, University Hospital, Emergency Department, 50 North Medical Drive, Salt Lake City, Utah 84132.

17:2 February 1988 Annals of Emergency Medicine 175/107

CLONIDINE POISONING Caravati & Bennett

peripheral effects of the drug. The mos t c o m m o n signs are depressed level of consciousness, hypotension, bradycardia, respiratory depression, and miosis. 3-s This symptom complex may mimic opiate overdose. Initially, hypertension may be present but is usually transient. Recurrent apnea is somet imes seen, especial ly in chil- dren. 4 In addit ion, pallor, hypother- mia, hypotonia , seizures, and heart block may occur. 3,5,6 The toxic effects may persist up to 48 hours. 4

Treatment consists of decontamina- t ion of the gut and support of vital signs. Induction of emesis with syrup of ipecac may not be advisable be- cause lethargy and coma may occur wi thin 30 minutes of ingestion. Respi- ratory depression may require tracheal intubation. Initially, hypertension may be marked, bu t is u sua l ly t rans ien t and gives way to hypotension, s Ag- gressive t reatment of initial hyperten- sion should only be undertaken when end-organ damage is evident, s Brady- cardia responds to atropine; hypoten- sion is managed with volume expan- s ion and, if needed , d o p a m i n e . 3-s Naloxone has been reported to reverse the opioid-like effects z and hypoten- s ion associated wi th c lon id ine tox- icity.8, 9 H y p e r t e n s i o n has been re- ported as a complication of naloxone treatment in three children3 o Tolazo- line, an imidazol ine compound, has alpha-adrenergic inhibitory effects and has been r e c o m m e n d e d as an anti- dote. t~ Due to discrepant reports as to its efficacy and the po ten t ia l com- p l i ca t ions assoc ia ted w i th i ts use, tolazoline should be reserved for hypo- t e n s i o n u n r e s p o n s i v e to the above measures.3-s

Our pa t i en t mani fes ted CNS de- pression and hypo tens ion after oral

exposure to a patch that was thought to be i n n o c u o u s by the parents be- cause it had been used for almost a week. The t r ansdermal sys tem is a tan-colored flexible multilayered film, 0.2 m m thick, that provides systemic delivery of clonidine for seven days at an approximately constant rate. The a m o u n t of drug released is direct ly proportional to the area of the patch. To ensure a constant release of drug, the total drug content of the system is greater than the total amount of drug de l ive red . T h r e e d i f f e r e n t dosage forms exist that deliver 0.1, 0.2, or 0.3 mg per day of c lonidine . The total amount of drug in each patch is 2.5 mg, 5.0 mg, and 7.5 rag, respectively. The a m o u n t of residual drug in the system after seven days of use may vary from 20% to 75% and after 11 days m a y be as h igh as 40%. 12 A patch designed to deliver 0.2 rag/day of clonidine after seven days of use may still contain 1.0 to 3.7 mg of ac- tive drug. ]2

SUMMARY Used transdermal drug-delivery sys-

tems clearly represent another source of potentially life-threatening poison- ing to the child in the home. A child does not necessarily require oral ex- posure to the patch and may manifest signs of toxicity after applying used ones to the skin. 13 Physic ians who prescribe this dosage form should in- form their patients of this potential hazard and counsel them as to a safe means of disposal of the patch, Pa- t ients should also be ins t ruc ted to make frequent "patch checks" to ver- ify their placement. At tempts to lo- cate lost patches should be especially thorough in homes with children.

The authors thank Wanda Updike, MD, for review of the manuscript; Darla Taylor for preparation of the manuscript; and Elmo Gruwell, .MD, and Douglas Hack- ing, MD, for their cooperation in this case.

REFERENCES 1. Physicians Desk Reference. Oradel, New Jersey, Medical Economics Company Inc, 1987, p 712-713.

2. Lowenstein J: Clonidine. Ann Intern Med 1980;92: 74-77.

3. Olsson JM, Pruitt AW: Management of clonidine ingestion in children. J Pediatr 1983; 103:646-650.

4. Conner CS, Watanabe AS: Clonidine over- dose: A review. Am J Hosp Pharm 1979;36: 906-911. 5. Anderson RJ, Hart GR, Crumpler CP, et ah Clonidine overdose: Report of six cases and re- view of the literature. Ann Emerg Med 1981;10: 107-112. 6. Williams PL, Krafcik JM, Potter BB, et ah Cardiac toxicity of clonidine. Chest 1977;72: 784-785.

7. Kulig K, Duffy JP, Rumack BH: Naloxone for treatment of clonidine overdose (letter). lAMA 1982;247:1697. 8. Niemann JT, Getzug T, Murphy W: Reversal of clonidine toxicity by naloxone. Ann Emerg Med 1986;15:1229-1231. 9. North DS, Peterson CD: Efficacy of naloxone in clonidine poisoning. Am J Dis Child 1983; 137:807-808. 10. Gremse DA, Artman M, Boergh RC: Hyper- tension associated with naloxone treatment for clonidine poisoning, l Pediatr 1986; 108:776-778.

11. Schieber RA, Kaufman ND: Use of tolazoline in massive clonidine poisoning. Am [ Dis Child 1981;135:77-78.

12. MacGregor TR, Matzed KM, Keirns II, et al: Pharmacokinetics of transdermally delivered clonidine. Clin Pharmacol Ther 1985;38: 278-284.

13. Reed MT, Hamburg EL: Person-to-person transfer of transdermal drug-delivery systems: A case report (letter). N Engl I Med 1986;314: 1120.

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