Naranjo Adverse Drug Reaction Probability Research Articles

Nephrogenic Diabetes Insipidus Induced by Two Amphotericin B Liposomal Formulations

Immunocompromised patients are at risk for invasive molds and resistant fungal infections for which amphotericin B may be the only feasible treatment. Nephrogenic diabetes insipidus (DI) and renal tubular acidosis are known adverse effects of conventional amphotericin B; however, nephrogenic DI has been uncommonly associated with liposomal amphotericin B formulations. We describe an 18-year-old woman with aplastic anemia who developed invasive aspergillosis. She began treatment with high-dose (10 mg/kg/day) liposomal amphotericin B at home; however, her condition worsened, and she was hospitalized. Therapy with liposomal amphotericin B was continued until the patient began having symptoms consistent with nephrogenic DI. These symptoms resolved after discontinuation of liposomal amphotericin B; however, after rechallenge with lipid complex amphotericin B (5 mg/kg/day), the symptoms returned. The patient's nephrogenic DI was successfully treated with diuretics. Use of the Naranjo adverse drug reaction probability scale score indicated a probable relationship between liposomal amphotericin B and the development of nephrogenic DI. To our knowledge, this is the third report of nephrogenic DI induced by liposomal amphotericin B. This adverse effect is one of many severe adverse effects caused by all formulations of amphotericin B. A clear understanding of these adverse effects is vital for the clinician to successfully weigh the risks and benefits of antifungal therapy.

Severe Rash Associated with Dexmedetomidine Use During Mechanical Ventilation

Dexmedetomidine, a sedative administered by continuous infusion, is used to facilitate mechanical ventilation through alpha(2)-receptor activation. The drug's most common adverse reactions include hypotension, hypertension, nausea, bradycardia, and dry mouth. However, to our knowledge, no reports of dermatologic allergic reactions from dexmedetomidine use have been published. We describe a 22-year-old man who was intubated after being injured in a motor vehicle collision. He had been receiving propofol and fentanyl infusions for sedation during mechanical ventilation and was transitioning to dexmedetomidine. Within 4 hours of receiving dexmedetomidine 0.2 microg/kg/hour, the patient developed a wheal-and-flare rash encompassing 60% of his body surface area. The infusion was immediately discontinued; over the next 24 hours most of the rash receded, and within 48 hours of drug discontinuation the rash had completely resolved. According to the Naranjo adverse drug reaction probability scale, the likelihood that this rash was induced by dexmedetomidine was probable. Clinicians should be aware of this potential dermatologic adverse effect from dexmedetomidine, and patients receiving the drug should be closely monitored.

Class Effect of Erythropoietin Therapy on Hemoglobin A1c in a Patient with Diabetes Mellitus and Chronic Kidney Disease Not Undergoing Hemodialysis

In patients with diabetes mellitus, hemoglobin A(1c) (A1C) is commonly interpreted as a measure of long-term glycemic control, reflecting a mean glucose level over the previous 2-3 months. Although some reports suggest that treatment with recombinant erythropoietin may affect A1C values in patients undergoing hemodialysis, we know of no evidence to support this interaction in patients with chronic renal insufficiency who are not undergoing hemodialysis. In addition, we know of no evidence specific to the treatment effect of epoetin alfa and/or darbepoetin alfa on A1C. We describe a 64-year-old man with diabetes, chronic kidney disease, and anemia who was treated consecutively with epoetin alfa and darbepoetin alfa and experienced a temporal reduction in A1C level to a nadir of 4.4%. Throughout approximately 3 years of treatment with these erythropoietin analogs, the patient's total daily dose of insulin was reduced in response to his decreasing A1C values, despite elevated blood glucose levels and the absence of patient-reported hypoglycemic events. Five months after the patient's erythropoietin therapy was discontinued, his A1C value increased to 8.8%, leading us to conclude that management of the insulin dose may have been different without the falsely lowered A1C levels. Use of the Naranjo adverse drug reaction probability scale indicated a probable association between this patient's reduced A1C levels and erythropoietin therapy. This case demonstrates that both epoetin alfa and darbepoetin alfa may artificially lower A1C levels in a patient with diabetes who is not undergoing dialysis, and therefore this finding can be interpreted as a class effect. Clinicians should be aware of factors that affect A1C values, specifically erythrocyte life span. In patients receiving erythropoietin, therapeutic decisions should be based on A1C and glucose levels, as well as patient symptoms suggestive of hypo- or hyperglycemia, to avoid therapy changes that could complicate disease management.

Fatal Toxic Epidermal Necrolysis Associated with Minoxidil

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this is the first case report of fatal TEN associated with minoxidil. This case report emphasizes the importance of monitoring for serious dermatologic reactions in patients receiving minoxidil therapy.

Severe Allergic Reaction to Hydrochlorothiazide Mimicking Septic Shock

Hydrochlorothiazide (HCTZ) is a sulfonamide-containing drug with commonly reported adverse effects that include electrolyte abnormalities, orthostatic hypotension, hyperglycemia, and photosensitivity. A few reports have described rare but serious drug complications such as interstitial pneumonitis, angioedema, and aplastic anemia. We describe a patient who experienced a serious HCTZ-induced adverse event that, to our knowledge, has not yet been reported in the literature. A 78-year-old woman came to the emergency department with dyspnea and severe fatigue; her signs and symptoms were suggestive of septic shock from pneumonia. She was treated accordingly, her condition improved, and she was discharged home. During the next 2 months, the patient returned to the emergency department 2 more times and was hospitalized each time with the same diagnosis. During her third admission, it was discovered that the patient's primary care physician had restarted her HCTZ for hypertension after it had been discontinued during each of the first two hospitalizations. The patient's symptoms began within hours of the first and second hospitalizations and almost immediately after taking a dose of HCTZ on the day of the third hospitalization. Her medical history revealed documented allergic reactions to sulfonamide drugs and penicillin; thus a hypersensitivity reaction to HCTZ was suspected. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's hypersensitivity reactions and HCTZ therapy. Because of a lack of evidence showing cross-reactivity among the different classes of sulfonamides, the mechanism of the allergic reaction to HCTZ was unlikely to be cross-sensitivity between sulfonamide antibiotics and sulfonamide nonantibiotic drugs. Although the mechanism is not clear, evidence shows that the allergy to the HCTZ (sulfonamide nonantibiotic) may be due to a predisposition to drug allergies rather than sulfonamide cross-sensitivity. Clinicians should be aware of the potential for these types of allergic reactions.

Antipsychotic Induced Bruxism Treated with Clozapine

Antipsychotic Induced Bruxism Treated with Clozapine

Effect of concomitant administration of meropenem and valproic acid in an elderly chinese patient

Background: Meropenem is a carbapenem with a broad spectrum of activity against β-lactamase-producing organisms. Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. Concomitant administration of meropenem and valproic acid reportedly leads to a rapid decline in serum concentrations of valproic acid, which is sometimes associated with seizures. Case summary: This report describes an 85-year-old Chinese male inpatient who twice received concomitant administration of meropenem and valproic acid for the treatment of pneumonia and poststroke epilepsy, respectively. Rapid declines in valproic acid concentrations were observed both times after meropenem administration. No seizures occurred in the first treatment period; however, when the patient suffered pneumonia again 3 months later, the same concomitant therapy was prescribed, and seizures occurred. It is difficult to identify a single etiology of the seizures. Based on a score of 7 on the Naranjo adverse drug reaction probability scale, the seizures were considered to be probably related to the concomitant administration of meropenem and valproic acid. Conclusions: Various factors make the effect of concomitant administration of meropenem and valproic acid unpredictable, even in the same patient. Caution should be used when administering meropenem and valproic acid concomitantly, especially in elderly patients with central nervous system disorders, even if the patient has had a successful prior experience with these 2 drugs. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

Falsely Low Hemoglobin A1c Levels in a Patient Receiving Ribavirin and Peginterferon alfa‐2b for Hepatitis C

The effect of treatment for hepatitis C viral infection on hemoglobin A(1c) (A1C) levels is not well described in the literature. We describe a 59-year-old man with type 2 diabetes mellitus whose A1C level became falsely low when ribavirin and peginterferon alfa-2b therapy were started for treatment of hepatitis C. After treatment was discontinued, the patient's A1C returned to its previous baseline value. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's low AIC level and his ribavirin-peginterferon alfa-2b therapy. Clinicians should be aware that combination therapy for hepatitis C may affect A1C values. To maintain accurate glucose control in patients with diabetes who are receiving treatment for hepatitis C, it is important that they self-monitor their blood glucose levels in conjunction with A1C data, especially when A1C values become falsely low.

Clozapine-Induced Pulmonary Embolism: A Case Report and Literature Review

Purpose To report a case of pulmonary emboli induced by clozapine in a patient who was also using nicotine gum. This case is presented to alert health care providers of this rare adverse effect, to call attention to the risks associated with thromboembolism, and to enable prompt recognition of symptoms so that morbidity and mortality may be decreased in future cases. Summary A 51-year-old white woman was admitted to the psychiatric ward of a hospital for depression. She had suicidal ideation, was experiencing ethanol abuse relapse, and had had auditory hallucinations caused by concomitant medication nonadherence for 2 weeks prior to admission. The patient smoked 2 packs of cigarettes per day and was adhering to a smoking cessation program that included the use of nicotine gum. She developed diffuse pulmonary emboli 15 days after clozapine initiation. Application of the Naranjo Adverse Drug Reaction Probability Scale to this case indicated a probable relationship between initial clozapine titration and the development of pulmonary emboli in the patient. Clozapine was discontinued without tapering, and the patient was discharged with prescriptions for fluphenazine and warfarin. Discussion The exact mechanism by which clozapine causes pulmonary emboli is unclear, but there have been some hypotheses. This case is similar to previously reported cases because pulmonary embolism was seen on the initiation of clozapine therapy; however, it is unclear whether the concurrent use of nicotine gum increased the risk of developing pulmonary embolism. Conclusion Based on previous case studies and the literature, it was concluded that clozapine alone was the cause of pulmonary embolism in this patient. The role of nicotine remains questionable.

Acalculous Cholecystitis in a Patient with Metastatic Renal Cell Carcinoma Treated with Sunitinib

A 62-year-old woman was treated with sunitinib as a second-line therapy for metastatic clear-cell renal carcinoma. She was given oral sunitinib 50 mg once daily, 4 weeks on followed by 2 week off. During the fourth week of her first cycle, the patient was admitted to our hospital because of an acute-onset, right upper quadrant pain associated with nausea and vomiting. She was diagnosed with acute acalculous cholecystitis, which was treated with broad-spectrum antibiotics, and sunitinib therapy was discontinued. A follow-up computed tomography scan of the abdomen revealed a complete resolution of gallbladder changes. Our patient did not have major risk factors for developing an acalculous cholecystitis except for a relative immunosuppressed state secondary to her advanced renal cancer. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 5, indicating a probable association of the event with sunitinib. Because the use of sunitinib is expanding in clinical practice, we want to alert the oncology community about this uncommon and life-threatening complication in patients receiving sunitinib or another agent with antiangiogenic activity.

P03-118 Valacyclovir-associated psychosis and manic symptoms in an adolescent female with genital herpes simplex: A case report

We report the first case of valacyclovir-induced psychosis with symptoms of mania in an adolescent female with no psychiatric history. the patient presented with irritable mood, decreased need for sleep, auditory hallucinations, and grandiose delusions 72 hours after starting oral valacyclovir for newly acquired genital herpes. She was on no other medications. Delirium was ruled out by history and physical, urine toxicology was negative, head CAT scan was unremarkable, as were thyroid hormones and basic laboratories. the symptoms continued after stopping the valacyclovir, but improved with risperidone. after withdrawal of risperidone, the patient has been symptom free for 4 months. According to the Naranjo Adverse Drug Reaction (ADR) probability scale, this case report scores as a possible drug reaction. Although there are no reports of neuropsychiatric side effects with valacyclovir, there are for the medications structural analogs, acyclovir and ganciclovir. These cases were primarily in elderly patients who are immunocompromised, have renal dysfunction and receive the medication by the intravenous route. other anti-viral medications, such as interferon, have also been shown to induce mood symptoms, including depression and mania. Genital Herpes is a common and painful infection, with no known cure. Three medications, acyclovir, valacyclovir and famciclovir, have been shown to reduce the duration and severity of the disease. Clinicians should be aware that Valacyclovir and its analogs may induce psychosis with manic symptoms in young, healthy patients with no previous psychiatric history. Further research is needed to demonstrate a clear association, causal relationship and possible mechanism for the reaction.

Ondansetron‐Induced Aminotransferase Level Elevation: Case Report and Review of the Literature

Elevation of aminotransferase levels is a rarely reported adverse effect of ondansetron. Increased aminotransferase levels, however, have been observed in patients receiving concurrent cisplatin chemotherapy and ondansetron. We describe a 44-year-old woman with no oncologic history or treatment with chemotherapy who received intravenous ondansetron on three separate occasions in the emergency department and subsequently experienced aminotransferase level abnormalities. Her baseline aspartate aminotransferase levels were within normal limits on each occasion, but increased to several times the upper limit of normal within 1 day of admission. After a diagnostic evaluation and drug review were performed, ondansetron appeared to be the most likely cause. On discontinuation of ondansetron, her aminotransferase levels trended downward, and the patient was discharged in stable condition. The Naranjo adverse drug reaction probability scale score for this event was 9, indicating that ondansetron was a definite cause of the elevated aminotransferase levels. Some studies describe a higher rate of increased aminotransferase levels in patients with cancer who are treated with ondansetron compared with those receiving metoclopramide. These elevations are not dose related and have not been associated with liver injury. Furthermore, the chemotherapeutic agent administered may play a role in aminotransferase level elevations. Since cisplatin was administered in most of these studies and is known to independently cause hepatotoxicity, the overall contribution of ondansetron to aminotransferase level elevation is not fully known. With the increased use of ondansetron outside of oncologic medicine, it is important that clinicians are aware of this rare adverse effect when determining the cause of elevated aminotransferase levels.

Antibiotic Allergies in the Medical Record: Effect on Drug Selection and Assessment of Validity

To determine the frequency with which reported antibiotic allergies alter drug selection and to assess the validity of these allergies. Retrospective medical record review, with concurrent interviews conducted in a selected subgroup of patients. Tertiary care academic medical center. Three hundred patients with at least one documented antibiotic allergy and who received an antibiotic while hospitalized. Data were collected to determine the patients' allergies documented in the medical record. The first antibiotic regimen that each patient received while hospitalized was evaluated for deviation from the standard of care as determined from institutional protocols, recommendations in the literature, and expert opinion. A total of 416 allergies to antibiotics were reported. Penicillins were the agents most commonly reported (198 reports), followed by sulfonamides, cephalosporins, macrolides, and fluoroquinolones. The reported allergies altered antibiotic therapy in 91 (30.3%) patients. Report of a penicillin or cephalosporin allergy and use of antibiotics for prophylaxis were strong predictors of altered therapy. The subgroup consisted of 100 patients who were interviewed to determine the specific details of their reported allergic reactions. For 22 of the 100 patients, major discrepancies were found between their verbal reports and medical record documentation. The Naranjo adverse drug reaction probability scale was used to determine the validity of their reactions. Among these 100 patients, 109 (78.4%) of 139 reported reactions to antibiotics were deemed to be allergic in nature. For 55 (50.5%) of the 109 allergic reactions, the Naranjo score was 5 or greater, which correlates with probable to definite validity. Discrepancies between the medical record and in-depth allergy histories are common, and the validity of reported allergic reactions is frequently questionable. Because documentation of an antibiotic allergy frequently alters therapy, increased effort to verify these reactions may be beneficial.

Heparin‐Dependent Antibodies and Thrombosis without Heparin‐Induced Thrombocytopenia

Although heparin-dependent antibodies (HDAs) typically manifest with thrombocytopenia as in heparin-induced thrombocytopenia (HIT), they may also manifest with preserved platelet counts. We describe a 35-year-old woman who developed severe thrombotic complications due to heparinization and unrecognized HDAs. She had received subcutaneous heparin as prophylaxis for deep vein thrombosis during a 5-day hospitalization for postpartum cardiomyopathy. Five days after discharge (day 1), she developed bilateral lower extremity arterial thrombi and underwent heparinization and successful lower extremity thrombectomies. A pulmonary embolus and hepatic and renal infarcts were then found. On days 2-6, the patient experienced a myocardial infarction, ischemic cerebrovascular accident, recurrent lower extremity arterial thrombus, and splenic infarct. On day 7, blood obtained on day 4 was found to be strongly positive for HDAs. In the interim, the patient had been transitioned to warfarin. Her platelet counts were never less than 75% of baseline and were consistently above 200 x 10(3)/mm(3). Hypercoagulability studies were negative. The patient's score on the Naranjo adverse drug reaction probability scale indicated that the relationship between this adverse reaction and heparin was probable. An extensive MEDLINE search located 22 other reports of patients who developed HDAs, sometimes associated with thrombosis, but whose platelet counts did not decrease. As with our patient, many of these case reports described clinicians who overlooked thrombosis due to HDAs because the patients did not have HIT. Clinicians should be cognizant of this possibility and consider a diagnosis of HDAs in patients with ongoing thrombosis who are receiving heparin therapy. It is strongly recommended that heparin be substituted with another anticoagulant in such cases until the presence of HDAs can be definitively ruled out.

Cardiac Arrest with Pulseless Electrical Activity Associated with Methylphenidate in an Adolescent with Normal Baseline Echocardiogram

Recent concerns of adverse cardiac events associated with drugs used to treat attention-deficit-hyperactivity disorder (ADHD) have prompted debate over whether these drugs are truly safe. We describe a 17-year-old boy with a normal baseline echocardiogram who had been taking methylphenidate for ADHD for 18 months and experienced cardiac arrest. Emergency personnel attempted to resuscitate him, performing defibrillation twice for ventricular fibrillation, with subsequent pulseless electrical activity. The patient was immediately taken to the hospital where he received continued resuscitation, intravenous boluses of cardiac drugs, and additional defibrillation. A persistent pulsatile rhythm returned about 2 minutes after arrival. Overall, the patient was pulseless for 22 minutes. Emergency cardiac catheterization revealed wall motion abnormalities without coronary lesions. He was mechanically ventilated and was transferred to the intensive care unit, where he remained comatose. Neurologic studies performed the next day revealed diffuse encephalopathy due to anoxic brain injury. An echocardiogram on day 3 showed slightly improved left ventricular systolic function, which improved further by day 15. As the patient did not regain purposeful movement, he was discharged to a rehabilitation facility on day 33. The patient's methylphenidate therapy had been started at an appropriate dose of 18 mg/day and titrated over a period of 3 months up to 36 mg/day, which he continued until the event. The drug had been discontinued on admission, was not restarted, and for the next 2 years, the patient experienced no further cardiac events, although his severe mental deficiencies persisted. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's adverse cardiac event and methylphenidate. To our knowledge, this is the first case report of a patient with documentation of a normal baseline echocardiogram who experienced cardiac arrest with pulseless electrical activity while taking methylphenidate for ADHD. Clinicians should be aware that despite performing a comprehensive cardiac examination before prescribing a stimulant for ADHD, patients may still be at risk for a serious cardiac event. The risks and benefits of using these drugs must be assessed by clinicians, parents, and patients.

Diabetic Ketoacidosis Associated with Aripiprazole

Metabolic adverse effects such as hyperglycemia, alterations in insulin sensitivity, and weight gain are known to be potential complications of atypical antipsychotic therapy. In certain cases, hyperglycemia may be so profound that diabetic ketoacidosis (DKA) or hyperosmolar coma may result. Aripiprazole, approved by the United States Food and Drug Administration in 2002, appears to have fewer metabolic adverse effects than other atypical antipsychotics. We describe a 44-year-old man with no personal or family history of diabetes mellitus who was prescribed aripiprazole for schizoaffective disorder. Two weeks after starting this therapy, the patient developed DKA, which was corrected with insulin therapy and aggressive hydration. According to the Naranjo adverse drug reaction probability scale, aripiprazole was the probable trigger of his DKA. An exhaustive search for other causes of DKA was unrevealing. Administration of aripiprazole or any other atypical antipsychotic should be terminated when impaired glucose tolerance is suspected. Vigilance regarding the potential adverse effects of this class of drugs, including new agents such as aripiprazole, is crucial to preventing potentially life-threatening complications of hyperglycemia.

Development of Unilateral Cervical and Supraclavicular Lymphadenopathy After Human Papilloma Virus Vaccination

A 26-year-old woman developed significant unilateral anterior cervical and supraclavicular lymphadenopathy 3 days after receiving her first dose (of a total of three doses) of human papilloma virus (HPV) vaccine. She had no history of lymphadenopathy after other previous immunizations, and had received no vaccines other than HPV at that time. The left-sided lymphadenopathy developed after she was vaccinated in the left deltoid muscle. The spatial and temporal relationships between the appearance of the lymphadenopathy and receipt of the vaccine in the absence of other causal agents strongly suggest that the HPV vaccine was the causal agent. Use of the Naranjo adverse drug reaction probability scale indicated that the HPV vaccine was a probable (score of 6) cause of the patient's adverse reaction. The patient received her second dose of the HPV vaccine 2 months later without further lymphadenopathy. To prevent unnecessary lymph node biopsies and patient concern, clinicians should be aware that lymphadenopathy may occur after HPV vaccination.

Bicalutamide‐Associated Fulminant Hepatotoxicity

Abstract Bicalutamide is a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We describe a 59-year-old man with metastatic prostate carcinoma treated with bicalutamide as part of androgen deprivation therapy before starting chemotherapy. At baseline, his liver function test results and serum creatinine concentration were within normal limits, and an abdominal computed tomographic scan did not demonstrate liver metastasis. After 4 days of bicalutamide therapy, the patient came to the emergency department with complaints of abdominal pain, distension, and tenderness. His liver function tests were abnormal, and bicalutamide was discontinued. After 2 days of increasing liver function tests and symptoms of hepatotoxicity, the patient developed tachycardia and hypotension that was resistant to fluid resuscitation. Multiorgan damage was manifested by an alanine aminotransferase level greater than 40 times the upper limit of normal, serum creatinine concentration of 4.2 mg/dl, and troponin I level of 18 ng/ml. The patient died 8 days after bicalutamide therapy was begun secondary to multiorgan failure, most likely as a result of fulminant hepatotoxicity. The Naranjo adverse drug reaction probability scale showed a probable (score of 5) causal relationship between bicalutamide and fulminant hepatotoxicity. Fulminant hepatotoxicity is a rare but potentially fatal adverse effect of bicalutamide. Liver function tests should be monitored before and during bicalutamide therapy, even for patients who have previously completed a course of this therapy with no signs or symptoms of toxicity.

Sunitinib‐Related Fulminant Hepatic Failure: Case Report and Review of the Literature

Drug-induced hepatotoxicity is an infrequent but life-threatening complication. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma and gastrointestinal stromal tumor. However, results from preapproval clinical trials suggest an equivocal hepatic risk profile for sunitinib. We describe a 75-year-old woman with renal cell carcinoma who was admitted to the intensive care unit after experiencing fulminant hepatic failure during sunitinib therapy. The patient's hepatic and renal chemistries had been within normal limits throughout four previous cycles of sunitinib therapy spanning 9 months. After the fifth cycle, she complained of a 3-day history of severe diarrhea and dehydration. Her abnormal laboratory test results included the following: total bilirubin level 5.9 mg/dl, aspartate aminotransferase level 3872 U/L, alanine aminotransferase level 3332 U/L, ammonia level 897 microg/dl, and an international normalized ratio of 4.8. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between sunitinib and hepatotoxicity. Supportive care including aggressive intravenous hydration and reversal of coagulopathy was successful. The patient was discharged home on hospital day 7 without apparent longstanding sequelae. Clinicians should be aware of this possible adverse effect of sunitinib, and continued pharmacovigilance is imperative to accurately quantify the possible risk of sunitinib-related hepatotoxicity.

Cesium‐Induced QT‐Interval Prolongation in an Adolescent

Alternative medicine is becoming increasingly popular, especially with terminally ill patients. Most alternative remedies have not been adequately studied or proven effective for the diseases for which they are promoted. In the worst cases, these therapies are harmful. We describe a 16-year-old girl with metastatic hepatocellular carcinoma who experienced cesium-induced QT-interval prolongation after the start of a cesium chloride-based alternative treatment regimen. She had received seven courses of chemotherapy, with a cumulative doxorubicin dose of 500 mg/m(2) over 5 months, resulting in minimal tumor regression. Against the advice of her oncologist, she abandoned traditional therapy and started an alternative regimen that included cesium chloride supplements. Two weeks later, the patient went to a local emergency department after experiencing two brief syncopal episodes. An electrocardiogram revealed occasional premature ventricular contractions, a QTc interval of 683 msec (normal range for females 450-460 msec), and R on T phenomenon. She was admitted to the hospital and later experienced monomorphic ventricular tachycardia, which resolved spontaneously. Lidocaine therapy was started, and the patient was transferred to a cardiac intensive care unit at our hospital. Her plasma cesium level was 2400 microg/dl (normal < 1 microg/dl), and her family was told to stop her alternative treatment regimen. On hospital day 5, as no additional arrhythmias had occurred, lidocaine was discontinued. Two days later, the patient's QTc interval had decreased to 546 msec, and she was discharged home. Two months later, at a follow-up visit, her serum cesium level was 1800 microg/dl, and her QTc interval was 494 msec. According to the Naranjo adverse drug reaction probability scale, cesium was the probable cause of the patient's arrhythmia. In animal models, cesium chloride has induced cardiac arrhythmias, including torsade de pointes. It inhibits delayed rectifier potassium channels in the myocardium, causing delayed repolarization and QT-interval prolongation. Patients with cancer should be aware that alternative remedies may be harmful and ineffective. Because patients may be unlikely to self-report alternative remedies, health care providers should specifically ask their patients about any alternative treatments they may be taking and should be knowledgeable about their toxicities.