Abstract
Keywords
Warfarin, Ascorbic Acid No. 148
Drug Interaction: Warfarin Resistance
A 65-year-old male patient was hospitalized with a 2-day history of pleuritic chest pain associated with shortness of breath, nausea, and diaphoresis. Concurrent medications included amlodipine, ascorbic acid (500 mg twice daily), aspirin, carvedilol, esomeprazole, furosemide, lorazepam, losartan, magnesium, nicotine patch, simvastatin, tiotropium bromide inhalation, and vitamin D. Enoxaparin (60 mg twice daily) and warfarin (5 mg once daily) were started on diagnosis of pulmonary embolism and bilateral deep venous thrombosis. The baseline international normalized ratio was 1, and it remained below the target range of 2 to 3 for 9 days of therapy despite adjustments in warfarin dosage to 20 mg daily. Proteins C and S levels were found to be 98% and 97%, respectively. Levels of factors II and X, measured on day 7, were 105% and 84%, respectively. Free protein S antigen was also normal. Antinuclear antibody and anticardiolipid antibody levels were negative. The albumin concentration remained marginally low throughout admission, with readings of 3.0, 3.2, and 2.9 g/dL on days 0, 4, and 10, respectively. The patient had stable organ function, and noncompliance and diet–drug interactions were ruled out during the hospitalization. After a thorough workup was completed, ascorbic acid was discontinued on day 8. Within 24 hours, the international normalized ratio increased from 1.1 to 2.8. Enoxaparin was discontinued, and warfarin was resumed at a lower dosage (15 mg daily). The international normalized ratio was 12.7 on day 10, with a repeat measurement of 15.4 later that day. Treatment included subcutaneous phytonadione (2 mg 5 hours apart), and warfarin was held due to acuity of the international normalized ratio increase. By day 12, the international normalized ratio had decreased to target range, at 2.7, and the patient was restarted on 3 mg of warfarin daily, and eventually stabilized on a 5 mg daily dose. The patient was discharged on day 15 with an international normalized ratio in the target range.
The authors concluded that there was a drug interaction between ascorbic acid and warfarin. A proposed mechanism of action was the possible chelating agent effect of ascorbic acid resulting in warfarin malabsorption. They concluded that ascorbic acid might have had an inhibitory effect on warfarin, as their patient was unable to achieve anticoagulation during concurrent treatment, but experienced rapidly increasing international normalized ratio values with discontinuation.
Warfarin [“Coumadin”]
Ascorbic Acid [Vitamin C]
Sattar A et al (J Willman, Kindred Hospital Springfield, 701 Walnut Street, Springfield, IL 62702; e-mail:
Colchicine, Sunitinib No. 149
Drug Interaction: Colchicine Toxicity
An 82-year-old male patient with a history of renal cell carcinoma, chronic kidney disease, and gout developed signs of colchicine toxicity 3 days after taking high-dose colchicine (4.8 mg/day) for an acute gout flare concurrently with sunitinib (50 mg/day). The patient began a high-dose colchicine taper (4.8 mg/day for 7 days, 3.6 mg/day for 2 days, then 0.6 mg/day for 1 day) and subsequently began a cycle of sunitinib (50 mg/day for 14 days, off for 7 days) on day 7 of colchicine. He had been taking both colchicine and sunitinib for several years. Other concurrent medications included diltiazem, furosemide, levothyroxine, and rabeprazole (doses not reported). One day after concurrent colchicine and sunitinib use, the patient developed watery diarrhea. Pleuritic right-sided chest pain and shortness of breath occurred 2 days later. The patient was subsequently hospitalized. On day 2 of hospitalization, symptoms included rigors and fever (102.3°F) with continued severe diarrhea leading to metabolic acidosis requiring transfer to the intensive care unit. Additional symptoms included hypotension, requiring norepinephrine (dose not reported), and pneumonia, requiring intubation with mechanical ventilation. Echocardiography showed a decreased left ventricular ejection fraction (30% to 35%) from admission (60% to 65%) and T-wave inversion. Cardiac catheterization was performed showing 90% first obtuse marginal artery stenosis, and a drug eluding stent was placed. Significant laboratory tests included elevated troponin assays (9.83 ng/mL), hypokalemia and hypomagnesemia (levels not reported), leukopenia (white blood cells = 3000-3400/µL), thrombocytopenia (platelets = 92 000/µL), and anemia (hemoglobin = 9.8 g/dL).
The authors concluded that sunitinib is a strong P-glycoprotein inhibitor. It was acknowledged that colchicine toxicity typically depends on the dose given, hepatic and renal function, as well as the coadministration of a P-glycoprotein or CYP 3A4 inhibitor. There are several P-glycoprotein and CYP 3A4 inhibitors, and prescribers should be aware of potential interactions.
Colchicine [“Colcrys”]
Sunitinib [“Sutent”]
Abodunde OA et al (OA Abodunde, Department of Internal Medicine, Abington Memorial Hospital, Abington, PA 19001; e-mail:
Antidepressants No. 150
Venous Thromboembolism
A retrospective, case–control study of Taiwanese patients over a 10-year period was conducted to identify the prevalence of venous thromboembolism associated with antidepressant use. Patients were identified using a nationwide representative database in Taiwan and were included if aged 18 years or older. This study included 1880 cases with a diagnosis of venous thromboembolism between 2001 and 2009 in Taiwan as well as 11 222 matched controls that were randomly selected based on matching demographic criteria for each venous thromboembolism case. Based on the patient data collected, antidepressant users were at 1.24-fold higher risk for venous thromboembolism than nonusers. New antidepressant users had a higher risk for venous thromboembolism than continuous users (adjusted odds ratio = 2.54 and 1.47 respectively). Antidepressants with low 5-HT reuptake inhibition potency had greater risk of venous thromboembolism than high-potency antidepressants (adjusted odds ratio = 1.57 and 1.08, respectively). Venous thromboembolism risk was higher in young and middle-aged adults than in the elderly, especially among women and patients with low disease risk scores or no major medical risk factors.
The authors concluded that there is a small increase in risk for venous thromboembolism in antidepressant users. High-potency 5-HT reuptake inhibition antidepressants may be a better choice for patients already at increased risk for venous thromboembolism. Larger studies may be warranted to discover the true incidence of venous thromboembolism events associated with antidepressant use.
Antidepressants [“Amitriptyline,” “Clomipramine,” “Doxepin,” “Citalopram,” “Paroxetine”]
Wu CS et al (HJ Tsai, Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan; e-mail:
Colchicine, Clarithromycin No. 151
Drug Interaction: Rhabdomyolysis
A 59-year-old male patient developed myalgia, weakness, and fever 9 days after taking clarithromycin (500 mg every 12 hours) and colchicine (0.6 mg every 12 hours) concomitantly. Other medications included a nasal decongestant (medication/dose not reported). The patient was being treated for Behcet disease for 15 months with colchicine (0.6 mg every 12 hours) and methotrexate (dose unknown). Methotrexate was discontinued 3 months prior to the event due to elevated liver enzymes, which subsequently normalized after 2 months. Clarithromycin and a nasal decongestant (medication and dose unknown) were prescribed for the treatment of nasal congestion and chronic cough. On admission to the hospital, all medications were discontinued. Laboratory tests included elevated liver enzymes (alkaline phosphatase = 227 IU/L and alanine aminotransferase = 564 IU/L), elevated creatine kinase (766 IU/L), and elevated myoglobin (1393 ng/mL). Renal function remained normal. A bone scan was performed indicating rhabdomyolysis. Muscle weakness, pain, and laboratory markers resolved over 2 weeks, and the patient was discharged without colchicine.
The authors concluded that drug–drug interactions that affect the pharmacokinetics of colchicine are major contributors to colchicine toxicity. Many colchicine-related deaths occur in patients taking therapeutic doses of colchicine while also taking a potent CYP 3A4 inhibitor such as clarithromycin. Dose reduction may be useful in the presence of CYP 3A4 and P-glycoprotein inhibitors.
Colchicine [“Colcrys”]
Clarithromycin [“Biaxin”]
Kim JB et al (JB Kim, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea) Colchicine-induced rhabdomyolysis caused by interaction with clarithromycin in a patient with Behcet disease. J Clin Rheumatol 19:108–109 (Mar) 2013
Amitriptyline No. 152
Substance Abuse
Two case reports of amitriptyline misuse were described.
Patient 1. A 45-year-old female patient with a history of alcohol and benzodiazepine abuse developed confusion that required multiple hospital admissions while taking amitriptyline (~600 mg/day) at more than twice the prescribed daily dose and additional 50 mg tablets as needed for anxiety. She reported a numbed, pleasant, more social state and felt more at ease with people. Despite counseling and the patient’s attempts to quit abusing amitriptyline, she exhibited drug-seeking behavior and required multiple hospital admissions for injuries due to falls while intoxicated with the drug.
Patient 2. A 46-year-old male patient with a history of alcohol, sedative-hypnotic, stimulant, and opiate drug abuse developed confusion after taking amitriptyline (dose unknown). The patient purchased amitriptyline from the “street” and from a friend prescribed the medication. He reported “high” that included hallucinations, euphoria, confusion, and a distorted sense of time. He was admitted to the hospital or emergency department 6 times for altered mental status due to amitriptyline overdose.
The authors concluded that tricyclic antidepressants have abuse potential. Many psychiatrists and other physicians may not be aware of the abuse potential of tricyclic antidepressants and should be attentive to the risk in their patients. The mechanism of action for abuse is unclear, but may be related to the anticholinergic and antihistaminergic properties of tricyclic antidepressants.
Amitriptyline [“Elavil”]
Shenouda R & Desan PH (PH Desan, Department of Psychiatry, Yale University School of Medicine, New Haven, CT; e-mail:
Fondaparinux No. 153
Hepatotoxicity
A 5-year-old (12 kg) patient with a history of axillary veno-lymphatic malformation developed nausea, vomiting, and clinically significant signs of hepatitis 30 hours after the initiation of fondaparinux (2 mg/day) for the treatment of thrombosis. Concurrent medications included paracetamol (200 mg/day) and codeine (0.6 mL/kg). Laboratory tests drawn after the initiation of fondaparinux included elevated liver function enzymes (aspartate aminotransferase = 720 IU/L, alanine aminotransferase = 509 IU/L, and γ-glutamyl transferase = 161 IU/L). Alkaline phosphatase and total bilirubin remained normal. Screenings for infectious etiologies were negative. Fondaparinux was immediately discontinued, and clinical resolution of symptoms and laboratory signs of liver injury occurred over the next 5 days with complete resolution.
The authors concluded that fondaparinux was the likely cause of hepatotoxicity. The mechanism of fondaparinux hepatotoxicity is not known, but is likely not related to drug metabolites as it is not metabolized by the liver. Direct toxicity should not be ruled out, but it is possible that inflammatory mediators may have helped sensitize hepatocytes to fondaparinux. Monitoring liver function tests in the first few days of therapy may be useful in patients with unknown tolerance.
Fondaparinux [“Arixtra”]
Orostegui L et al (L Orostegui, Service de Pharmacologie Clinique, Hopital de Bicetre, Cedex, France; e-mail:
Clozapine No. 154
Fatal Venous Thrombosis
A 22-year-old male patient developed fatal, multisystem venous thromboembolism after 2 years of clozapine therapy (500 mg daily) for the treatment of schizophrenia. No other concurrent medications were reported. The patient was hospitalized with tonic–clonic seizures in a coma. A neurological exam revealed bilateral papilla edema, negative meningeal signs, and a positive left Babinski sign. A contrast-enhanced magnetic resonance image showed hemorrhagic infarctions in the bilateral frontoparietal lobes with enhancement around the thrombi in the right transverse and superior sagittal sinuses. Venography studies revealed evidence of thrombosis involving superior sagittal sinus, right transverse sinus, and right sigmoid sinus. Lower extremity Doppler sonography revealed deep venous thrombosis in his bilateral common femoral veins, deep femoral veins, and superficial femoral veins with partial recanalization. Ultrasonography of the abdomen showed portal vein thrombosis with cavernous transformation. A triphase liver computed tomographic scan showed decreased opacification in the major portal vein, right and left portal veins, the splenic vein, and the superior mesenteric vein. Routine biochemical, hepatic, renal, and thyroid profiles; sedimentation rate; tumor markers; echocardiogram; chest x-ray; and transthoracic echocardiography were normal. Plasma levels of homocysteine (reference range = 3.30-20.30 µmol/L) and low-density lipoprotein (0-3.12 µmol/L) were elevated at 50 µmol/L and 3.17 µmol/L, respectively. An extensive coagulation profile was completed to identify the predisposing factors of thrombosis. However, only the plasma levels of D-dimer (0-500 ng/L) were found to be elevated at 4008 ng/mL. Initially, the patient was started on full-dose, low-molecular-weight heparin and nicoumalone 2.5 mg daily for treatment of thrombosis. Simultaneously, antiepileptic drugs were given and clozapine was discontinued. On hospital day 9, he developed intermittent bleeding of the upper gastrointestinal tract with an international normalization ratio of 2.1. Despite resuscitation efforts, the patient developed multisystem organ failure and died.
The authors concluded that this patient experienced clozapine-associated multisystem venous thromboembolism. Although multiple theories exist, the exact mechanism of clozapine-induced venous thromboembolism remains unknown.
Clozapine [“Clozaril”]
Hu Q et al (S Zhu, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; e-mail:
Denosumab No. 155
Severe Hypocalcemia
A 61-year-old female patient experienced severe, symptomatic hypocalcemia 1 month after treatment with denosumab (120 mg) for bone metastases from stage IV infiltrating ductal breast carcinoma. Her concurrent medications included amlodipine, aspirin, levothyroxine, metoprolol, calcium carbonate, calcitriol, anastrozole, oxycodone, glipizide, and atorvastatin. On admission to the emergency department, she was experiencing involuntary shaking of both lower and upper extremities resulting in a fall and a 3-day history of watery diarrhea. Physical examination revealed carpopedal spasm and perioral paresthesias. Laboratory results showed an ionized calcium of 2.3 mg/dL, serum creatinine of 3.3 mg/dL, sodium of 140 mmol/L, potassium of 3.0 mmol/dL, chloride of 107 mmol/dL, carbon dioxide of 17 mmol/dL, phosphorus of 5.4 mg/dL, and a parathyroid hormone level of 778 pg/mL. An electrocardiogram showed a prolonged QTc interval of 520 milliseconds, compared to her baseline of 445 milliseconds. She was treated aggressively with intravenous fluid and calcium gluconate for chronic kidney disease with denosumab-induced severe hypocalcemia. Her creatinine returned to baseline, and ionized calcium level increased to 4.3 mg/dL over her hospitalization stay.
The authors concluded that the patient experienced severe hypocalcemia from denosumab therapy, possibly related to her underlying renal dysfunction. It is hypothesized that chronic kidney disease patients are at a higher risk of hypocalcemia due to a pharmacodynamic effect, including a dependence on parathyroid hormone–mediated bone turnover and inhibition of osteoclastic activity.
Denosumab [“Prolia”]
Ungprasert P et al (P Ungprasert; e-mail:
Etanercept No. 156
Anaphylaxis
Two case reports of etanercept-associated anaphylaxis were described in pediatric juvenile idiopathic arthritis patients.
Patient 1. A 10-year-old male experienced an anaphylactic allergic reaction within 24 hours of receiving his fifth weekly etanercept (25 mg) injection. Concurrent medications included methotrexate weekly subcutaneous injections. His medical history included long-standing antinuclear antibody(+) polyarticular juvenile idiopathic arthritis and linear scleroderma. He noticed itching and mild periorbital swelling immediately after the injection and awoke the next morning with a rash, nausea, and difficulty breathing. He had no known drug allergies at the time. Physical exam revealed generalized urticarial, diffuse facial edema, and mild angioedema. Respiratory distress and swelling resolved with 2 doses of epinephrine, a normal saline intravenous bolus, prednisolone, and ranitidine. Despite continued treatment with steroids and antihistamines, his facial rash persisted throughout his hospitalization. Etanercept was stopped and the patient was started on adalimumab injections every other week. The patient has reported no adverse events with current therapy for over 2 years.
Patient 2. A 15-year-old girl developed a generalized urticarial rash and dyspnea within minutes after her third etanercept (20 mg) injection. She had no known drug allergies at the time. Antihistamines and prednisone led to a prompt and sufficient improvement of symptoms, and therapy was changed from etanercept to adalimumab. Methotrexate was later added due to persistent arthralgia, and the patient has tolerated this therapy well for at least 1.5 years.
The authors concluded that these cases describe anaphylaxis, a severe hypersensitivity reaction, to etanercept therapy. Standard therapy resolved both reactions.
Etanercept [“Enbrel”]
Crayne CB et al (RQ Cron, Children’s of Alabama, 1600 7th Avenue S, Children’s Park Place, Suite M210, Birmingham, AL 35233-1711; e-mail:
Varenicline No. 157
Memory Impairment
Thirteen case reports of memory impairment in patients treated with varenicline for smoking cessation were described. The patients were identified through the New Zealand Intensive Medicines Monitoring Programme, a pharmacy dispensing database. Four of the 13 cases were coded as severe, with 1 patient experiencing periods of total memory loss, 1 patient forgetting to collect her children on different occasions, and 1 patient reporting memory loss affecting her ability to work. Eleven patients were less than 57 years old at the time of the event. Factors considered included the time between starting varenicline and onset of adverse event; possible confounders, such as smoking status, concomitant medicines, and medical history; and any dechallenge response. In 9 of the 13 cases, varenicline was withdrawn due to memory impairment, and an additional patient reduced the dose. Of the 10 patients who were dechallenged, 9 reported a definite improvement after stopping varenicline. The relationship of memory impairment with varenicline was assessed as “probable.” The relationship was determined as “possible” for 3 other cases, with insufficient information available on the last patient to perform causality assessment. Because psychiatric events, including depression, poor concentration, anxiety, and sleep disturbance, may affect memory, the authors also reviewed all reports of these events in the varenicline New Zealand Intensive Medicines Monitoring Programme data sets; none were found.
The authors concluded that a causal relationship is suggested between varenicline and memory impairment in 12 of the 13 reports in this series.
Varenicline [“Chantix”]
Tan M & Harrison-Woolrych M (M Tan, Intensive Medicines Monitoring Programme, New Zealand Pharmacovigilance Centre, Department of Preventative and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin 9054, New Zealand; e-mail:
Metronidazole, Disulfiram No. 158
Psychosis
A 48-year-old male patient developed psychotic symptoms after receiving combined treatment with disulfiram (400 mg once daily) and metronidazole (500 mg 3 times daily). Concurrent medications at the time of admission included omeprazole, disulfiram, and oral vancomycin. His medical history included alcohol dependence, and a recent Clostridium difficile infection. He presented to the emergency department with persistent paranoid delusions, believing that his relatives and spouse were after his life. A urine drug screen showed no evidence of methamphetamine, cocaine, or ethanol use. The initial differential included a psychotic disorder due to a medical condition. Delirium was excluded as a diagnosis, as consciousness and orientation were not compromised, withdrawal signs were absent, and the psychotic symptoms were stable. It was later found that the patient had been admitted 7 days prior to this episode for Clostridium difficile colitis, and treated with metronidazole, later switching to oral vancomycin. The paranoid delusions started at the last day of the 4-day metronidazole schedule. As vancomycin has not been associated with psychotic symptoms, it was excluded as an etiologic cause. Disulfiram was discontinued, and the paranoia resolved over a course of several days with benzodiazepine treatment. After a total of 5 admission days, he came to fully trust his relatives and spouse, realizing that his mistrust was unjustified. On discharge, he was advised to decrease his dose to a half-tablet of disulfiram daily for 5 days, and then increase to the full tablet thereafter.
The authors concluded that this patient experienced psychotic symptoms induced by simultaneous metronidazole and disulfiram. The mechanism of action may involve inhibition of dopamine-β-hydroxylase and monoamine oxidase, the enzymes responsible for dopamine metabolism, resulting in accumulation.
Metronidazole [“Flagyl”]
Disulfiram [“Antabuse”]
Luykx JJ et al (CH Vinkers; e-mail:
Medication Errors No. 159
Home Medication Administration in Pediatric Patients
A prospective observational analysis was performed during 92 home visits to describe errors that occurred during home medication management of children with cancer. Throughout the analysis, 963 medications were reviewed, and 242 medication administrations were observed. The child’s mother was primarily the person responsible for administering medications in the majority of visits (87%), and most parents (97%) scored within the adequate range for health literacy. A total of 72 errors were discovered, 4 of which resulted in injury and 40 had the potential to cause injury. The weighted overall error rate was 70.2 errors per 100 patients (95% confidence interval = 58.9-81.6). Drug administration medication errors most frequently occurred (63.5%). Nonchemotherapy medications were more frequently implicated in errors than chemotherapeutic agents. Forty-seven percent of children experienced a medication error, 8% experienced more than 1 error, and 8% experienced 3 or more errors. Frequently observed errors included administration of wrong dose or frequency (28%), wrong labeling (18%), missed doses (19%), prescribing error (12.5%), and use of expired medication (12.5%).
The authors concluded that errors were common in this study of pediatric oncology patients receiving medications in the home. They stated that parent administration errors were often related to communication failures with the provider or between in-home caregivers.
Medication Errors [Medication Errors]
Walsh KE et al (KE Walsh, Department of Pediatrics, Benedict Second Floor, UMass Medical Center, 55 North Lake St, Worcester, MA 01655; e-mail:
Cytarabine No. 160
Overdose
Two case reports of intrathecal cytarabine overdose in children with cancer were described.
Case 1. A 17-year-old girl received an intended intravenous dose of cytarabine (177 mg) intrathecally rather than the prescribed intrathecal dose (70 mg) for treatment of acute myeloid leukemia. The error was discovered within an hour of administration. Treatment included monitoring and holding the scheduled intravenous cytarabine dose that day. Clinical condition remained stable and the scheduled chemotherapeutic regimen involving cytarabine, daunorubicin, and etoposide was resumed the following day. No neurologic symptoms were noted throughout the following month. Expiration occurred due to progression of acute myeloid leukemia and was not believed to be related to cytarabine overdose.
Case 2. A-4 year-old boy received 175 mg intrathecal cytarabine rather than the prescribed 70 mg for treatment of acute lymphoblastic leukemia. The error was discovered within an hour of administration. Treatment included withdrawal of 12 mL of cerebral spinal fluid to remove excess cytarabine and administration of intrathecal hydrocortisone (24 mg) followed by intravenous dexamethasone. No neurologic symptoms or adverse reactions were apparent and his condition remained stable. The scheduled chemotherapeutic regimen including polyethylene glycol-asparaginase, vincristine, daunorubicin, and oral prednisone was completed as planned. Complications and neurologic sequelae remained absent 2 years and 9 months after the overdose occurred.
The authors concluded that these cases of intrathecal cytarabine overdoses in children demonstrated that measures such as cerebral spinal fluid exchange may not uniformly be required.
Cytarabine [“Cytosar”]
Thienprayoon R et al (R Thienprayoon, Division of Hematology-Oncology, Department of Pediatrics, University of Texas at Southwestern Medical Center, Dallas, TX; e-mail:
Etanercept No. 161
Henoch–Schönlein Purpura
A 61-year-old male developed a nonblanching rash approximately 5 months after initiating etanercept (50 mg subcutaneously weekly) for treatment of ankylosing spondylitis. Concurrent medications included colchicine. Laboratory values revealed a normal serum creatinine (1.1 mg/dL). Treatment included discontinuation of etanercept and initiation of prednisone 20 mg daily. Four weeks after discontinuing etanercept, worsening fatigue, peripheral synovitis, and petechiae on the lower extremities, abdomen, back, and hands developed. Physical examination revealed tender, swollen joints and petechiae with coalescence and lower-extremity edema. Repeat laboratory analysis revealed an elevated serum creatinine (3.3 mg/dL), erythrocyte sedimentation rate (69 mm/h), and C-reactive protein (3.9 mg/dL). Urinalysis revealed proteinuria and microscopic red blood cells. Additional laboratory analyses revealed a spot urine protein and creatinine ratio of 2.4, serum IgA of 430 mg/dL, antinuclear antibody 1:80 speckled pattern, and antihistone antibody 6.3 units. Renal biopsy revealed diffuse mesangial proliferative glomerulonephritis. Immunofluorescence staining revealed granular global mesangial deposits positive for IgA and C3 and confirmed the diagnosis of Henoch–Schönlein purpura. Additional treatment included intravenous methylprednisolone (1 g per day for 3 days) followed by a slow prednisone taper. At 7 months, synovitis and skin rash had resolved, and serum creatinine had normalized (1.2 mg/dL).
The authors concluded that the Henoch–Schönlein purpura experienced by this patient was likely due to etanercept and was the first report of tumor necrosis factor inhibitor–induced Henoch–Schönlein purpura in a patient with ankylosing spondylitis. The proposed mechanism was immune dysregulation induced by etanercept resulting in an altered balance of cytokine function and uninhibited TH2 cytokines.
Etanercept [“Enbrel”]
Rolle AS et al (AS Rolle, 110 Dunlop Village Circle, PO Box 189, Colonial Heights, VA 23834; e-mail:
Rifaximin No. 162
Toxic Epidermal Necrolysis (First Report*)
A 62-year-old female developed a diffuse, erythematous, maculopapular, and desquamating reaction on the chest, arms, and legs 12 days after initiation of rifaximin (550 mg twice daily) for management of hepatic encephalopathy secondary to end-stage liver disease. Two doses of intravenous rifaximin (400 mg every 8 hours) were administered 20 days earlier. Concurrent medications included oral lactulose (20 mg every 6 hours), intravenous vancomycin (750 mg daily), and oral spironolactone (100 mg daily). A review of medical history revealed no allergies or autoimmune conditions. Treatment included discontinuation of rifaximin and administration of intravenous diphenhydramine (25 mg once), intravenous methylprednisolone (60 mg every 12 hours), and topical triamcinolone cream (0.1%). The reaction improved over the subsequent few days and was completely resolved after 1 week. Expiration due to respiratory arrest occurred weeks later and was believed to be unrelated to the previous skin reaction.
The authors concluded, via assessment with the Naranjo scale, the toxic epidermal necrolysis experienced by this patient was possibly due to rifaximin. They concluded that this was the first report of toxic epidermal necrolysis associated with rifaximin use. The authors did not propose a mechanism of reaction occurrence.
Rifaximin [“Xifaxan”]
Patel AS et al (EM Supan, Methodist Willowbrook Hospital, 18220 Tomball Parkway, Houston, TX 77070; e-mail: