Case Report

The presentation of 6-mercaptopurine overdose in ED

Abstract

6-Mercaptopurine (6-MP), although an effective immu- nosuppressive when used in the treatment of certain cancers, can have devastating effects when ingested accidentally or used in excessive amounts. We report here the case of an unIntentional ingestion of a large amount of 6-MP by a woman with hypothyroidism who was erroneously given this antimetabolic agent by her pharmacist instead the pro- pylthiouracil (PTU) she was actually prescribed. This is one of several documented cases in which 6-MP has been dispensed instead of PTU. Because of the myelosuppressive and hepatotoxic effects of 6-MP, this case reinforces the need for both physicians and patients to understand the importance of examining their medications before ingestion.

CS is a 37-year-old white woman with a medical history significant only for hyperthyroidism who presented to the Stony Brook University Hospital Emergency Department (Stony Brook, NY) for accidental ingestion of 6-mercapto- purine (6-MP). She was diagnosed with hyperthyroidism almost a year ago and was previously being treated with methimazole. Due to hopes of getting pregnant, she was switched to propylthiouracil (PTU) by her endocrinologist and was told to take 100 mg 3 times a day. She, however, was accidentally given 6-MP by her pharmacist at the same dosage of 100 mg 3 times daily. She unknowingly continued to take the medication at the dosage prescribed for 6 days for a total dosage of approximately 1800 mg of 6-MP.

Her symptoms began on day 3 of ingestion in the evening when she began feeling a variety of symptoms such as fatigue, night sweats, headaches, chest pain, hair loss, and body aches in the thighs, neck, and back. She also had nausea and one episode of nonbloody, nonbilious emesis. The most concerning symptom experienced by the patient was drooping of the right eyelid. There was no change in vision or diplopia. She also denied any fevers or diarrhea. Her symptoms progressively worsened, and she was forced to stop on day 6 due to the severity of her symptoms.

This was a healthy appearing young white female who was anxious at times but in otherwise no acute distress. Her vital signs revealed some minor hypertension and tachycardia, but

she was afebrile and in no respiratory distress. The general physical examination of the heart, lungs, and abdomen were unremarkable. On examination of the eyes, the patient was found to have ptosis of only the right eye. The rest of the eye examination was unremarkable. Her thyroid was palpable but was nontender and contained no nodules. Skin exami- nation was remarkable for some darkening of the malar area and an erythematous, diffuse rash in the upper chest.

The patient’s laboratories in the emergency department, approximately 1 week after her initial dose of 6-MP, revealed elevated hepatic aminotransferase levels with an AST of 86, ALT of 141, and Alk Phos of 127. She also had an elevated PT time of 18.1 with an INR of 1.7. Serum electrolytes and complete blood count were within normal range aside from a left shift with 85% neutrophils. She also had a TSH level of

0.296 that was expected given her history of hyperthyroid- ism and because she had not been taking medication for a week. Urinalysis revealed ketones higher than 80 but was otherwise unremarkable.

Patient was kept overnight and given 5 mg of vitamin K. Results of consecutive laboratory examinations of the patient showed improvement of hepatic aminotransferase levels with an AST of 53, ALT of 102, and Alk Phos of 94. Patient’s Coagulation studies also showed improvement with PT of

16.8 and INR of 1.6. The consecutive complete blood count of the patient, however, showed a reduction in white blood cells from 5.5 to 4.6. Patient’s H/H also decreased and went from 13.9/41.7 to 11.0/32.5. Platelets also decreased from 228 to 187. Urine ketones decreased to 15.

Our patient presented with 6-MP overdose and was at risk for developing 6-MP toxicities including hepatotoxicity and bone marrow suppression [1,2]. Because there are no specific antidotes available for 6-MP overdose, care usually revolves around minimizing absorption of 6-MP, and careful monitoring of the patients blood counts in case toxicities occurred. Because our patient consumed her last dose of 6-MP 2 days earlier, there was no place for gastric lavage or activated charcoal. These mechanisms are recommended in the acute setting and can be effective particularly if ingestion occurred within 1 hour of presentation. There is no roll for hemodialysis in patients with 6-MP ingestion because it is rapidly distributed intracellularly. Bone marrow harvest is also a possibility and can be beneficial in the event the patient developed prolonged neutropenia or bone marrow aplasia. This was not indicated in our patient. Aside from the aforementioned measures, patients

0735-6757/$ – see front matter (C) 2009

513.e2 Case Report

Fig. 1

should be started on intravenous hydration to optimize urinary excretion of drug metabolites.

It is evident that the patient was already showing some physical symptoms after starting the medication. Whether the symptoms were due simply to 6-MP toxicity or a combination between the toxicity and her hyperthyroidism cannot be determined. However, several of her symptoms including the nausea, vomiting, anorexia, abdominal pain, skin changes, and hair loss are consistent with side effects of 6-MP.

Hepatotoxicty is a concern of patients having 6-MP toxicity. With a 6-MMPN level of 22593, our patient was at severe risk for hepatotoxicty. This was evidenced by her laboratory studies that revealed the elevated with elevated Liver enzymes and prolonged PT and INR. These values were much higher than baseline laboratory results taken before ingestion of the drug.

Hematologic toxicity caused by 6-MP is one of the more worrisome toxicities. Because of its myelosuppressive effects, patients can present with anemia, leukopenia, and thrombocytopenia. These effects usually take place around day 16 after a 5-day regimen of 6-MP. Although initial laboratory results showed no signs of hematologic toxicity, consecutive laboratory results did show a decreasing red blood cell, white blood cell, and platelet count that may be early signs of possible bone marrow suppression. For this reason, it was important to monitor her blood levels in the coming week to determine if these cell counts continue to decrease. Cases of anemia have been shown to respond to iron supplementation and blood transfusions. Thrombocytopenia too can be treated with platelet transfusions. Cases of severe

myelotoxicity can be supported with granulocyte-colony stimulating factor. As stated earlier, bone marrow harvesting for future rescue may be of benefit in some patients but only if performed within several hours of ingestion (Fig. 1).

Fortunately, long-term studies of our patient’s blood counts revealed that both her complete blood count and liver studies had come back to her normal baseline levels. She, however, continued to have ptosis of her right eye almost 1 month after ingestions despite having a normal magnetic resonance imaging. Although neurologic effects are a rare toxicity of 6-MP, it is possible that was the cause.

Having patients present to the emergency department for overdoses and intoxications is not uncommon and can usually be treated by administration of its antidote. However, problems arise when no antidote exists, such as in the case with our patient. With these patients, Treatment protocols generally involve around minimizing absorption of the substance into the blood stream and monitoring for side effects with close follow-up. In the case of our patient, nothing could be done to decrease absorption due to the latency between time of ingestion and presentation to the emergency department. As a result, care for outpatient was done through careful monitoring of blood counts for the emergence of toxicity. Fortunately, despite the excessive amount of 6-MP ingested by our patient, she did not develop any Long-term effects.

Why 6-MP continues to be erroneously dispensed instead of PTU continues to be an issue of concern due to the potentially life-threatening effects 6-MP can cause. The physical similarity between the 2 pills and the fact they sound somewhat similar are likely contributory factors. Regardless, this case reinforces the need for both physicians and patients to understand what medications they are taking and to make sure that the right medication is given to them by their pharmacist.

Neeraj Gupta BS Stony Brook University School of Medicine Stony Brook, NY, USA

Christopher C. Lee MD Tae Ho Lim MD Adam J. Singer MD

Stony Brook University Medical Center Department of Emergency Medicine

Stony Brook, NY, USA E-mail address: [email protected]

doi:10.1016/j.ajem.2008.07.019

References

1. Blum M. Letter to the editor. Alert: 6-mercaptopurine may be erroneously dispensed instead of propylthiouracil. Thyroid 2005;15(11):1315.
2. Chow LL. Toxic ingestion of 6-mercaptopurine by young siblings of pediatric oncology patients. J Pediatr 2004:669-71.