Does the Incidence of Rhabdomyolysis Induced by Doxylamine Overdose Increase in the Elderly?

BACKGROUND: Doxylamine is an over-the-counter drug that is popular in the treatment of insomnia. Doxylamine is relatively safe but can cause rhabdomyolysis. The aim of this study was to evaluate whether the incidence of rhabomyolysis increased in elderly patients (age> or =65 years) with doxylamine overdose. METHODS: This study included 108 patients admitted to an Emergency Department after doxylamine overdose between January 1, 2000, and March 31, 2013. Age, sex, time ingested before admission, amount of drug ingested, gastric lavage, tachycardia, vomiting, hematuria, blood urea nitrogen, blood creatinine, urine pH, and alcohol ingestion were investigated for the risk factors of rhabdomyolysis. RESULTS: Forty-three patients (47.6%) developed rhabdomyolysis. Of 16 elderly patients, 11 developed rhabdomyolysis. Of the 92 patients <65 years-of-age, 34 developed rhabdomyolysis. Advanced age, alcohol ingestion, and increased blood creatinine level were significantly associated with the development of rhabdomyolysis. CONCLUSION: In elderly patients with doxylamine overdose, the incidence rate of rhabdomyolysis may be increased. A high index of suspicion and evaluation of rhabdomyolysis is warranted in elderly patients with doxylamine overdose.

Revisión sistemática de la seguridad y eficacia de la combinación de doxilamina + piridoxina para el tratamiento de la náusea y el vómito durante el embarazo / Systematic review of the safety and efficacy of the combination of doxylamine + pyridoxine for the treatment of nausea and vomiting during pregnancy

Justificación: Más del 80% de las mujeres embarazadas experimentan en algún momento del embarazo náusea y vómito de magnitud variable que puede producir complicaciones importantes, tales como la deshidratación, el incremento de la frecuencia de hospitalizaciones y la alteración de la calidad de vida. Existe controversia sobre la seguridad de la combinación doxilamina + piridoxina para el tratamiento de la náusea y vómito durante el embarazo. Objetivos: A través de una revisión sistemática de la evidencia con metaanálisis, evaluar la seguridad y eficacia de la combinación de doxilamina + piridoxina para el tratamiento de la náusea y el vómito durante el embarazo. Material y métodos: Se incluyeron estudios de casos y controles, estudios de cohorte, ensayos clínicos o ensayos clínicos controlados, de adecuada calidad metodológica, realizados en mujeres embarazadas con náusea y vómito en quienes, dada la frecuencia y gravedad de la sintomatología, se hubiera decidido el tratamiento con doxilamina + piridoxina, al menos en una de las ramas de inclusión al estudio. Se consideraron como variables de desenlace el número de malformaciones congénitas totales observadas, así como el número de malformaciones congénitas ajustadas por tipo. Se efectuó revisión de las bases de datos PubMed (1966 a mayo de 2009), Embase (1988 a mayo 2009), LILACS (1990 a mayo 2009), ARTEMISA (Revisión de la 11ª edición hasta diciembre de 2004), Cochrane controlled trials register, Bandolier y DARE. Estadísticamente, se efectuó el cálculo de riesgo relativo a través de un modelo de efectos fijos de Mantel-Hanezel, en el caso de desenlaces binarios, y diferencia estandarizada de los promedios (SMD), en el caso de desenlaces continuos. Para todos los estimados se efectuó cálculo del intervalo de confianza al 95% (IC95%); se realizó en todos los casos prueba de heterogeneidad, utilizando prueba de Chi cuadrada de Pearson, con un valor de p < 0.05 como sinónimo de significancia. Resultados: No identificamos incremento del riesgo con el uso combinado de doxilamina + piridoxina en mujeres embarazadas con NVP para malformaciones globales con un RR ponderado de 0.97 (IC95% de 0.92 a 1.02), p 0.168, ni para malformaciones cardiovasculares [RR 0.92 (IC95% 0.80 a 1.05), p no significativa (NS)], del sistema nervioso central [RR 1.0 (IC95% 0.87 a 1.15), p NS)], defectos del tubo neural [RR 0.99 (IC95% 0.78 a 1.26), p NS)], alteraciones de extremidades [RR 1.10 (IC95% 0.88 a 1.37), p NS)], labio y paladar hendido [RR 0.85 (IC95% 0.70 a 1.03), p NS)] o malformaciones de la vía urogenital [RR 0.99 (IC95% 0.82 a 1.20), p NS)]. Desde el punto de vista de eficacia, la administración de doxilamina + piridoxina redujo significativamente el riesgo de persistir con náusea y vómito durante el embarazo [RR 0.55 (IC95% 0.41 a 0.74), p 0.0001)]. Conclusiones: Los resultados obtenidos en la actual revisión sistemática señalan un efecto significativamente benéfico de la doxilamina + piridoxina para la reducción de la náusea y el vómito del embarazo (NAVP). Al correlacionar el beneficio del medicamento con su elevado perfil de seguridad (como lo demuestran los cinco metaanálisis en donde el desarrollo de defectos cardiovasculares, del sistema nervioso central, del tubo neural, de las extremidades y genitourinario es similar al del grupo control), permite establecerlo como una alternativa farmacológica eficaz para el tratamiento de la náusea y el vómito presentes durante el embarazo y con riesgo no significativo de teratogenicidad.

More than 80% of the pregnant women, in one moment of the gestation have nausea and vomiting, than can produce important complications like deshydratation, hospital internment, and affectation of the quality of life. There are controversies about the safety of the combination of doxylamine + pyridoxine for the treatment of the nausea and vomiting of pregnancy (NVP). Objective: To evaluate the efficacy and safety of the combination of doxylamine + pyridoxine for the treatment of NVP using the methodological tool of a systematic review. Materials and methods: For the systematic review we include case-control studies, cohort's studies, and controlled trials, performed in pregnant women with NVP and that were treatment with doxylamine + pyridoxine. We considered the number of congenital defects as the principal outcome variable. We made the systematic review using the following data bases: PubMed (1966 to may 2009), Embase (1988 to may 2009), LILACS (1990 to may 2009), ARTEMISA (review of the 11ª edition to December 2004), Cochrane controlled trials register, Bandolier y DARE. The statistical analysis was made with the calculation of relative risk (RR) and 95% confidence interval (CI 95%) with the Mantel-Hanezel model. Results: There was no risk increase of congenital defects in children born of women with NVP treated with the combination of doxylamine + pyridoxine. The RR identified for all congenital defects was 0.97(IC95% de 0.92 a 1.02), p = 0.168; for cardiovascular defects the RR was 0.92 (CI95% 0.80-1.05), for neural tube defects the RR was 0.99 (CI95% 0.78-1.26), and for urinary defects the RR was 0.99 (CI95% 0.8-1.20). The administration of doxylamine + pyridoxine reduced the risk of NVP persistence with a RR of 0.55 (CI95% 0.41-0.74), p < 0.01). Conclusions: The systematic review showed that the administration of doxylamine + pyridoxine has a beneficial effect on the reduction of NVP manifestations, with a high safety to be used during pregnancy.

The Relationship between Rhabdomyolysis and Alcohol Ingestion in Doxylamine Intoxicated Patients

PURPOSE: Doxylamine is commonly used for relief of insomnia; in addition, it is also a drug that is freguently used for intoxication in Korea. This drug is relatively safe; however, it is known to occasionally induce rhabdomyolysis. We have seen many cases of alcohol ingestion in doxylamine intoxications; however, few previous studies have documented the effects of alcohol on rhabdomyolysis. Therefore, the purpose of this study is to determine the effect of alcohol on rhabdomyolysis in doxylamine intoxicated patients. METHODS: This study was conducted on 91 patients admitted to an emergency department after doxylamine intoxication during the period from January 2001 to March 2012. Using the protocol developed beforehand, the amount of drug ingestion, past history, laboratory results, and whether or not alcohol was ingested were recorded. Rhabdomyolysis was defined as serum creatine kinase (CK) over 1,000 U/L. The SPSS package with logistic regression, t-test, and Fisher's test was used for analysis of data. RESULTS: Alcohol ingestion was detected in 52% of the study patients. The presence of hematuria and alcohol ingestion showed a significant association with development of rhabdomyolysis. CONCLUSION: Doxylamine intoxicated patients with alcohol ingestion may have a high rate of incidence of rhabdomyolysis. Therefore, doxylamine intoxicated patients who drink alcohol at the same time should be aware of rhabdomyolysis.

Simultaneous determination of clobutinol hydrochloride and doxylamine succinate from syrups by RP HPLC using a new stationary phase containing embedded urea polar groups

A new, simple, fast, reproducible and sensitive reversed phase HPLC method, using a new stationary phase containing embedded urea polar groups, has been developed and validated for the simultaneous determination of clobutinol hydrochloride (CLO) and doxylamine succinate (DOX) in syrups. The determination was carried out on a C8 urea column (125 mm x 3.9 mm i.d., 5 µm particle size) synthetized at the Liquid Chomatography Laboratory (LabCrom) of the Chemistry Institute of Unicamp. The mobile phase consisted of a mixture of acetonitrile:methanol:phosphate buffer (pH 2.5) in the gradient mode. The diode array detector (DAD) was operated at 230 nm for CLO and 262 nm for DOX. The method showed adequate precision, with relative standard deviations (RSD) less than 1%. The presence of the excipients did not interfere in the results of the analysis. Accuracy was determined by adding standards of the drugs to a placebo and good recovery values were obtained. The analytical curves were linear (r² 0.9999 for CLO and 0.9998 for DOX) over a wide concentration range (2.4-336 µg mL-1 for CLO and 2.3-63 µg mL-1 for DOX). The solutions were stable for at least 72 hours at room temperature. The criteria for validation using the ICH guidelines were fulfilled.

Um novo método simples, fácil e reprodutível, de fase reversa para CLAE, usando uma fase estacionária contendo um grupo polar, uréia, embutido, foi desenvolvido e validado para determinação simultânea de cloridrato de clobutinol (CLO) e succinato de doxilamina (DOX) em xarope. A determinação foi realizada em uma coluna C8 uréia (125 mm x 3,9 mm d.i., 5 µm tamanho de partícula) sintetizada em nosso laboratório (LabCrom). A fase móvel consistiu de mistura de acetonitrila:metanol:tampão fosfato pH 2,5, em eluição por gradiente. O detector por arranjos de diodo (DAD) foi utilizado a 230 nm para CLO e a 262 nm para DOX. O método apresentou precisão adequada, com desvio padrão relativo menor que 1%. A presença de excipientes não interferiu nos resultados obtidos. A exatidão foi realizada pela adição dos padrões dos fármacos ao placebo e valores de recuperação aceitáveis foram obtidos. As curvas analíticas mostraram-se lineares (r² 0,9999 para CLO e 0,9998 para DOX) em uma ampla faixa de concentração (2,4-336 µg mL-1 para CLO e 2,3-63 µg mL-1 para DOX). A solução padrão foi estável por 72 horas a temperatura ambiente. Os parâmetros de validação foram realizados conforme o guia ICH.

Clinical Features of the Patients with Seizures after Doxylamine Succinate Overdose / 대한간질학회지

PURPOSE: Doxylamine succinate is an over-the-counter drug commonly used in the treatment of insomnia. It is in the ethanolamine class of antihistamine and is frequently involved in intentional overdoses. Seizures are uncommon, but there are potentially serious complications, making early recognition and treatment essential. METHODS: We reviewed retrospectively the medical records of patients admitted for seizures after a doxylamine succinate overdose from Jan. 1, 1992 to Dec. 31, 2008. We evaluated them with respect to age, sex, amount ingested, clinical symptomatology, time from ingestion to seizure, complication, and prognosis. RESULTS: Among the 146 doxylamine overdose patients, 11 patients developed seizures. Females accounted for 9 (81.8%) patients and the number aged between 20 and 40 years was also 9 cases (81.8%). The average time from ingestion to emergency room visit was 170 minutes (60-360). The average time from ingestion to development of seizures was 188 minutes (60-480). The amount of doxylamine succinate ingested was 750-4,750 mg (mean = 2,425 mg). The frequent anticholinergic symptoms were tachycardia (63.6%), vomiting (45.5%), mydriasis (36.4%), and hypertension (36.4%). Rhabdomyolysis and drug induced hepatitis were observed in 7 cases (63.6%) and 6 cases (54.5%), respectively. Primary treatment included administration of benzodiazepine and conservative care. After more than a 6 month follow-up, no patients developed further seizure. CONCLUSIONS: The incidence of seizure after doxylamine succinate overdose is uncommon and prognosis is good. However, other serious symptoms are commonly combined, and we have to be aware that seizures are a potential complication and should be actively investigated and vigorously treated.

The Relationship of Plasma Concentration of Doxylamine and Rhabdomyolysis in Doxylamine Overdose

PURPOSE: The relationship between plasma concentration of doxylamine and rhabdomyolysis in doxylamine overdose has not yet been reported. The aim of this study was to determine if the plasma concentration of doxylamine can predict the occurrence of rhabdomyolysis. METHODS: We reviewed the medical records of patients whose plasma concentration of doxylamine were checked during a state of doxylamine overdose. Variables, including the measured concentration (Ct) of drug, were compared between the rhabdomyolysis and the non-rhabdomyolysis group. We calculated the hypothetical initial concentration (C0) based on first order pharmacokinetics and measurement of each patient's plasma concentration of doxylamine (Ct). C0 values were compared based on the occurrence of rhabdomyolysis. RESULTS: A total of 41 blood samples were taken; all were taken more than two hours after the ingestion of doxylamine. Of the 41, 14 of the subjects showed rhabdomyolysis and 15 of the subjects did not. The rest were excluded from the study. Average values of Ct and C0 in the rhabdomyolysis and non-rhabdomyolysis groups were, respectively, 4.18+/-5.17 mg/L Vs 4.18+/-2.23 mg/L, for Ct; 6.21+/-7.92 mg/L Vs 15.53+/-17.97 mg/L for C0. Ct levels between the two groups were not different (p=1.00), but the difference in C0 was marginally significant (p=0.08). Blood sampling time showed a significant difference between the two groups (p=0.03). CONCLUSION: We can not confirm a relationship of plasma doxylamine concentration and rhabdomyolysis but it appears that the development of rhabdomyolysis in doxylamine overdose has a tendency to increase at high plasma concentration.

Comparative Analysis of Overdose with Common Sleep-aid Medications: Doxylamine vs Diphenhydramine

PURPOSE: The previous studies on H1 antihistamine overdose have generally been limited to cases of acute doxylamine succinate (DS) poisoning, yet there have been some studies on diphenhydramine (DPH) overdosing. But many clinicians consider the two drugs to be very similar and to have similar ingredients. The purpose of this study was to clarify the toxicologic characteristics and clinical outcomes between DS and DPH poisoning/overdose. METHODS: We reviewed the medical and intensive care records of the patients with acute DS or DPH poisoning and who admitted to our emergency department from January 2008 and April 2010. We collected patient information regarding the features of the poisoning and the clinical and demographic characteristics. The patients were assessed for the clinical outcomes, the GCS, the PSS (Poisoning Severity Score) and the SOFA (Sequential Organ Failure Assessment). RESULTS: Fifty seven patients (45 cases of DS poisoning and 12 cases of DPH poisoning) were enrolled. Compared with the DS group, the DPH group had higher incidences of intubation, serious mental change, QTc prolongation and ECG conduction abnormality (p=0.041, <0.001, 0.014 and 0.044, respectively). The DPH group had a higher PSS and a longer ICU stay. The peak CPK time and the CPK normalization time were longer for the patients with rhabdomyolysis due to DS poisoning. CONCLUSION: Two common H1 antihistamines, doxylamine and diphenhydramine, are in the same ethanolaminestructural class, but the toxico-clinical outcomes are different according to many aspects. Therefore, clinicians could take a careful approach for the differential diagnosis and management between DS and DPH poisoning.

The Clinical Features and Risk Factors of Seizure After Doxylamine Intoxication

PURPOSE: Doxylamine is antihistamine drug that is used as a hypnotic. It is also used for suicidal attempts because it can be easily purchased at the pharmacy without a prescription. There were many articles about the complications after doxylamine intoxication such as a rhabdomyolysis, but only a few articles have reported on seizure. We reviewed the cases of doxylamine intoxication with seizure that were treated in the emergency department. METHODS: We reviewed the medical records of the patients who were over 15 years old and who were intoxicated by doxylamine at 3 emergency medical centers from January 2006 to June 2010. We reviewed the patients' age, gender, the dose of doxylamine ingested, if gastrointestinal decontamination was done, the time from intoxication to hospital arrival, the seizure history, treatment of seizure, the electroencephalography (EEG) results, the brain computed tomography (CT) results and the blood test results. RESULTS: There were 168 patients who were intoxicated by doxylamine during the study period. Twelve patients had a seizure episode. The differences between the patients who developed seizure and the patients who did not were the dose and the serum levels of sodium and creatinine. The only clinically meaningful difference was the amount of doxylamine. The amount of doxylamine ingested (>29 mg/kg) predicted the development of seizure with a sensitivity of 75% and a specificity of 92% on the ROC curve. One patient among the seizure patients expired in the emergency department. CONCLUSION: In case of doxylamine intoxicated patients, there is close relationship between seizure and ingested amount, so close observation needs to be done for the patients who ingest too much because doxylamine can cause death. Further prospective studies are needed for doxylamine intoxicated patients with a seizure episode.

The Predictive Factors of the Serum Creatine Kinase Level Normalization Time in Patients with Rhabdomyolysis due to Doxylamine Ingestion

PURPOSE: Doxylamine succinate (DS) is frequently used to treat insomnia and it may induce rhabdomyolysis in the overdose cases. The purpose of this study is to evaluate the factors that can predict the serum creatine kinase (CK) level normalization time for patients with rhabdomyolysis due to DS ingestion. METHODS: This study was conducted on 71 patients who were admitted with rhabdomyolysis after DS ingestion during the period from January 2000 to July 2009. Rhabdomyolysis was defined as a serum CK level over 1,000 U/L. The collected data included the general characteristics, the anticholinergic symptoms, the ingested dose, the peak serum CK level, the time interval (TI) from the event to the peak CK level and the TI from the event to a CK level below 1,000 U/L. We evaluated the correlation between the patients'variables and the TI from the event to the peak CK level time and the time for a CK level below 1,000 U/L. RESULTS: The mean ingested dose per body weight (BW) was 30.86+/-18.63 mg/kg and the mean TI from the event to treatment was 4.04+/-3.67 hours. The TI from the event to the peak CK level was longer for the patients with a larger ingestion dose per BW (r=0.587, p<0.05). The CK normalization time was longer for the patients with a larger ingested dose per BW (r=0.446, p<0.05) and a higher peak CK level (r=0.634, p<0.05). CONCLUSION: The ingested dose per BW was correlated with the TI from the event to the peak CK level, and the ingested dose per BW and the peak CK level have significant correlations with the CK normalization time. These factors may be used to determine the discharge period of patients who had rhabdomyolysis following a DS overdose.

The Relation between Rhabdomyolysis and Microscopic Hematuria in Doxylamine Ingested Patients / 대한신장학회잡지

BACKGROUND: Doxylamine is the most commonly intoxicated drug in the emergency room. This drug is relatively safe but is known to induce rhabdomyolysis and acute renal failure in rare occasions. We found the presence of microscopic hematuria in doxylamine intoxicated patients. But no previous studies have documented this hematuria. Our objectives of this study were to determine the incidence of microscopic hematuria after doxylamine overdose and to find the prognostic factors that contribute to this complication. METHODS: This study was conducted from 22 patients admitted to Kyung Hee Medical Center after doxylamine intoxication during the period from January 2001 to December 2003. Using the protocol made beforehand, the amount ingested, past history and laboratory results were recorded. Rhabdomyolysis was defined as serum myoglobin over 300 ng/mL or serum creatine phosphokinase (CK) over 1, 000 IU/L. Data were analyzed using SPSS program with t- test, Fisher's exact test and discriminant analysis. RESULTS: The microscopic hematuria was detected in 63.6% of patients. The amount ingested per body weight, presence of rhabdomyolysis and the time when the muscle enzymes reach highest level were related to the hematuria. CONCLUSION: The incidence of microscopic hematuria was higher when more than 30 mg per body weight of doxylamine was ingested than less this amount. Microscopic hematuria suggests the presence of kidney and urinary tract injury. Urine pH of hematuria is over 7.5. Our findings provide no support for the belief that the ferrihemate injures the kidney of doxylamine ingested patients.

Predictors of High Peak Serum CK Levels in Doxylamine Intoxication

BACKGROUND: Because doxylamine succinate (DS) is an over-the-counter medicine, it can be obtained easily and is frequently used in suicidal attempts. Patients usually recover without serious complications, but occasionally rhabdomyolysis and even death can occur in DS intoxication. In this study, the authors tried to find out the independent predictors of high peak serum CK levels, i.e. probable rhabdomyolysis in DS intoxication. METHODS: The medical records of 41 patients who visited a hospital for DS intoxication from January 1, 2002 to April 30, 2003, were reviewed retrospectively. RESULTS: In the group of DS only, initial occult blood of urine (P=0.003), initial WBC count (P=0.003) and confusion (P=0.007) were the best predictors of the peak serum CK level (2=0.724). In the group of DS with other drugs intoxication, initial creatinine level (P=0.003) and initial occult blood of urine (P=0.007) were the best predictors of the peak serum CK level (r2=0.784). In the cases of rhabdomyolysis patients, the time taken for the CK level to be increased over 1,000 IU/L was 1.9level to be increased over 1,000 IU/L was 1.9+/-0.6 days. CONCLUSION: In DS only intoxication, occult blood in initial urine analysis, initial high WBC count and confusion can be thought of as useful clinical predictors for high peak serum CK level case. In DS with other drugs intoxication, initial creatinine level and initial occult blood of urine can be considered as the best predictors. More than 2 days will be needed for the observation of serious complications in DS intoxication.

A Case of Non-traumatic Rhabdomyolysis after Doxylamine Overdose

Doxylamine is an antihistamine of the ethanolamine class. It is used primarily as a sleep-inducing agent. Clinicians should be aware of the complications in rhabdomyolysis patients who ingest doxylamine succinate and over-the-counter antihistamines. The easy availability of these substances increases the potential not only of intentional overdose by adults but also of inadvertent ingestion by children. Prompt intervention and careful assessment of renal function, urinary output, and serum creatine kinase levels may represent the difference between an uncomplicated and acute renal failure. Recognition of the potential for rhabdomyolysis and institution of vigorous treatment may prevent acute renal failure in patients who have taken an overdose of the drug. A 14-year-old male was found to have hematuria and oliguria. Evaluation of the patient revealed myoglobinuria, and a creatine kinase(CK) level of 117,563 IU/L. He was recovered by massive fluid administration, urine alkalization and mannitol infusion. We report a case of a suicide attempt in a child where ingestion of the doxylamine complicated by non-traumatic rhabdomyolysis with brief review related literatures.

A Case of Severe Rhabdomyolysis with Acute Renal Failure after Doxylamine Overdose / 대한신장학회잡지

Doxylamine succinate is an over-the-counter drug widely used for treating insomnia. We experienced a case of severe rhabdomyolysis complicating acute renal failure after doxylamine overdose in a 24-year- old male. The maximum values of creatine kinase and creatinine level during hospitalization were 264,141 IU/L and 8.4 mg/dL, respectively. Oliguria and severe dyspnea occurred on the sixth hospital day and were treated with hemodialysis. Then, he recovered without any sequelae. To the best of our knowledge, the maximum creatine kinase level of 264,141 IU/L in the present case is the highest value among the case reports on doxylamine-induced rhabdomyolysis and this is the first case report in Korea of doxylamine-induced severe rhabdomyolysis accompanying oliguric acute renal failure and requiring treatment with hemodialysis.

Rhabdomyolysis Complicating Doxylamine Overdose / 대한신장학회잡지

BACKGROUND: Because of its ready availability in over-the-counter sleep preparations, doxylamine succinate is used frequently for suicidal attempts. Non-traumatic rhabdomyolysis is known to be a rare complication of doxylamine succinate but its pathogenesis and dose dependent effect are not known. The purpose of this study is to examine the frequency of various complications, especially rhabdomyolysis in doxylamine overdose and also to examine the effect of dose on the occurrence of these complications. METHODS: Medical records of patients who ingested doxylamine succinate from July 1996 to June 2000 were reviewed. Their age, sex, amount of ingestion and laborotory data are collected and also the occurrence of complication and dose-complication relationship were examined. RESULTS: 1) Total number of patients was 33 and average dose of ingestion was 1,510.6+/-180.7mg(150-5,000). 2) Complication rates were as follows tachycardia 20 patients(66%), hypertension 17 patients(51%), rhabdomyolysis 16 patients(48.4%), generalized seizure 7 patients(21.2%) and hyperthermia 5 patients(15.1%). 3) Tachycardia, seizure and rhabdomyolysis were occured more frequently in high dose groups. CONCLUSION: Rhbdomyolysis is not an infrequent complication in doxylamine overdose. Recognition of potential hazard for rhabdomyolysis and the institution of vigorous treatment to prevent acute renal failure, especially in patients who have taken a large amount of drugs will be required.

Two Cases of Rhabdomyolysis Complicated with Doxylamine Overdose / 대한신장학회잡지

Doxylamine succinate is common over-the-counter sleep medication that is frequently involved in accidental poisonings and suicide attempts. Doxylamine overdose is generally directed at the anticholinergic effect including autonomic,and central nervous system effect and direct cardiac toxicity. Rarely, rhabdomyolysis has been reported with doxylamine overdose. We experienced two cases of rhabdomyolysis with overdose of doxylamine in 17-year-old and 31-year-old male. They were diagnosed with high levels of creatine phosphokinase in serum, myoglobin in serum and urine, and increased radionuclide uptake of muscles in (99m)Tc-MDP bone scan. Patients recovered without any complications with hydration and diuresis. Clinicians should be aware of the possibility of rhabdomyolysis in patients with doxylamine overdose.

A Case of Rhabdomyolysis after Doxylamine Overdose

We report a case of non-traumatic rhabdomyolysis after overdose of doxylamine succinate. A 22-year-old woman with reactive depression had an overdose of doxylamine with suicidal intent. She had decreased mental state, confusion, convulsion, vomiting, tachycardia, pupil dilatation, and ocular flutter. Serum creatine phosphokinase concentra-tion was 6,752 IU/L initially, increased to maximum (165,590 IU/L) at the third day, and then rapidly decreased and returned to normal 2 weeks after intoxication. Acute renal failure occurred but was resolved without hemodialysis. Rhabdomyolysis associated with renal failure is a rare but serious complication after doxylamine overdose.

4 Case of Rhabdomyolysis due to Doxylamine Intoxication / 대한신장학회잡지

Doxylamine is common over-the-counter sleep preparations & frequently involved in overdoses. The clinical course is dominated by the anticholinergic effects, including central nervous system & autonomic effects. We report 4 cases of suicide attempts in adults where ingestion of the doxylamines were complicated by rhabdomyolysis. They ingested doxylamines variable amount & were carried to emergency department. They complained gastrointestinal or central nervous system symptoms. Gastric lavages & administrations of activated charcoal were done. Creatine phosphok inase levels were normal or markedly elevated on arrival, but peaked several days later. Serum creatinine levels were normal. 99mTc-MDP bone scans were showed increased muscle labelling at the regions of muscle injury. They were treated with hydration, urine alkalinization, & supportive measures in hospital. On considering cause of rhabdomyolysis, our patients did not show any evidence of viral illness or coingestion of other potential myopathic toxins to support a secondary cause of rhabdomyolysis. The mechanism of rhabdomyolysis in cases of doxylamine overdose seems to be a direct toxic effect of the drug on striated muscle, but the exact mechanism is not clear. In all cases where such overdoses are suspected, consideration should be given to obtaining a urinalysis & a creatine phosphokinase level on arrival & creatine phosphokinase levels are carefully followed. Primary detoxication included gastric lavage & administration of activated charcoal. The patient's urine output & renal function should be closely monitored.