Naranjo Adverse Drug Reaction Probability Research Articles

Lenalidomide‐Induced Interstitial Lung Disease

Lenalidomide is a more potent and less toxic oral analog of thalidomide. The drug is indicated for treatment of multiple myeloma and other hematologic disorders and has rarely been associated with pulmonary toxicity. We describe a 73-year-old woman who received lenalidomide therapy for multiple myeloma. Nine weeks after starting the drug, she developed progressive dyspnea, cough, and constitutional symptoms, and was found to be hypoxic. A computed tomography scan of the chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was negative for infection, but transbronchial biopsy showed an organizing pneumonia. The patient was diagnosed with lenalidomide-induced interstitial lung disease after other causes were excluded. Clinical and radiologic resolution occurred after lenalidomide was discontinued and a tapering course of corticosteroids was begun. Use of the Naranjo adverse drug reaction probability indicated a high probability (score of 7) that this adverse drug reaction was caused by lenalidomide. Lenalidomide inhibits prostaglandin E(2) (PGE(2)) secretion by cells. If fibroblast PGE(2) synthesis is impaired in the lung, the mitogenic action of cysteinyl leukotrienes may be unmasked, promoting fibroblast proliferation and collagen synthesis, eventually leading to interstitial lung disease. Another potential mechanism may be an immunologic one similar to that seen in the interstitial pulmonary process in patients with hypersensitivity pneumonitis. To our knowledge, only one other case of lenalidomide-induced pulmonary toxicity has been reported in the literature. Although lenalidomide-induced pulmonary toxicity is uncommon, clinicians should consider this potential adverse drug reaction in the differential diagnosis in patients receiving lenalidomide who present with symptoms of interstitial lung disease for which alternative causes have been excluded.

Amiodarone‐Induced Loculated Pleural Effusion: Case Report and Review of the Literature

Pleural effusion is an uncommon manifestation of amiodarone toxicity and is usually associated with amiodarone-induced interstitial pneumonitis. We describe a 70-year-old woman who came to the emergency department with bilateral pleuritic chest pain and malaise 4 weeks after her amiodarone dose was increased from 200 mg/day to 600 mg/day. She had bilateral exudative pleural effusions without associated pneumonitis. She was diagnosed with amiodarone-induced pleural effusions after a thorough workup during her hospitalization excluded other causes for the effusions. Due to intractable arrhythmias, the patient's amiodarone was not discontinued, and she was discharged home. Four days later at a follow-up visit at the pulmonary clinic, the patient complained of worsening chest pain as well as dyspnea and cough. A computed tomography scan showed left-sided pleural effusion with multiple loculations. She underwent a pulmonary vein isolation procedure, and amiodarone was discontinued. She was treated with prednisone 40 mg/day, tapered over the next 2 weeks. Three weeks after the amiodarone was stopped, the patient was asymptomatic, and a chest radiograph showed complete resolution of the effusions. Review of the patient's medical records revealed that she had experienced similar symptoms and exudative pleural effusions 2 years earlier after a similar dose escalation of amiodarone; the symptoms and pleural effusions resolved after the amiodarone dosage was reduced. Use of the Naranjo adverse drug reaction probability scale indicated that the association between the pleural effusions and amiodarone was highly probable (score of 9). This case report emphasizes that amiodarone should be considered in the differential diagnosis of patients with exudative effusions after a thorough workup has excluded other causes. Amiodarone should be replaced with alternative antiarrhythmic therapy if clinically feasible, and corticosteroids may be beneficial.

Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation.

Mercaptopurine‐Induced Fever: Hypersensitivity Reaction in a Patient with Acute Lymphoblastic Leukemia

The antimetabolite mercaptopurine is commonly used as part of treatment regimens for acute lymphoblastic leukemia and as treatment for inflammatory bowel diseases. Adverse effects associated with mercaptopurine include myelosuppression, hepatotoxicity, and hyperpigmentation. We describe a 36-year-old man with Philadelphia chromosome-negative pre-B-cell acute lymphoblastic leukemia who experienced a serious mercaptopurine-induced hypersensitivity reaction requiring prolonged hospitalization and extensive laboratory testing and imaging. He was treated with a multiagent chemotherapy regimen. Mercaptopurine 60 mg/m(2)/day orally was started as part of his third course of chemotherapy. On day 9 of mercaptopurine therapy, the patient developed persistent fevers, skaking chills, and rigors that persisted in the absence of documented infection, consistent with drug fever. All symptoms and signs resolved after discontinuation of mercaptopurine. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of fever and mercaptopurine therapy. Mercaptopurine-induced fever has been reported in patients with inflammatory bowel diseases, but this case report is the first, to our knowledge, in a patient with acute lymphoblastic leukemia. Health care professionals should be aware of the possible development of fever as a hypersensitivity reaction in patients with acute lymphoblastic leukemia treated with mercaptopurine.

Sudden Sensorineural Hearing Loss Associated with Vardenafil

The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and tadalafil-are used primarily in erectile dysfunction, but sildenafil is also indicated for pulmonary hypertension. Common adverse effects of vardenafil include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently, PDE-5 inhibitors have been associated with adverse vision effects, and emerging evidence now indicates that they may also be responsible for hearing changes and hearing loss. We describe a patient who developed unilateral sudden sensorineural hearing loss possibly related to the use of vardenafil for erectile dysfunction. To our knowledge, only one other case of hearing loss related to this drug class has been published. Our patient was a 57-year-old man who came to the emergency department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz range, confirmed by audiogram, that occurred after ingestion of vardenafil. The patient was hospitalized 2 days later for administration of intravenous dexamethasone, followed by oral prednisone. He reported that his hearing had improved on the fourth hospital day and was discharged 3 days later, continuing to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was within normal limits. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3) adverse reaction of sudden sensorineural hearing loss associated with vardenafil consumption. We also performed an analysis of hearing loss cases related to PDE-5 inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System database to compare the characteristics of our patient with those of other reported adverse event cases. Based on the temporal relation of the sudden sensorineural hearing loss to this patient's drug consumption, we propose that the vardenafil is a likely cause of the hearing loss. This case provides further evidence that PDE-5 inhibitor consumption should be considered as a possible cause in patients presenting with sudden sensorineural hearing loss.

Probable Warfarin Interaction with Menthol Cough Drops

Warfarin is a widely used and effective oral anticoagulant; however, the agent has an extensive drug and food interaction profile. We describe a 46-year-old African-American man who was receiving warfarin for a venous thromboembolism and experienced a decrease in his international normalized ratio (INR). No corresponding reduction had been made in his warfarin dosage, and no changes had been made in his concomitant drug therapy or diet. The patient's INR fell from a therapeutic value of 2.6 (target range 2-3) to 1.6 while receiving a weekly warfarin dose of 50 mg. His INR remained stable at 1.6 for 3 weeks despite incremental increases in his warfarin dose. The patient reported that he had been taking 8-10 menthol cough drops/day due to dry conditions at his workplace during the time period that the INR decreased. Five days after discontinuing the cough drops, his INR increased from 1.6 to 2.9. Over the subsequent 5 weeks, his INR was stabilized at a much lower weekly warfarin dose of 40 mg. Use of the Naranjo adverse drug reaction probability scale indicated that the decreased INR was probably related to the concomitant use of menthol cough drops during warfarin therapy. The mechanism for this interaction may be related to the potential for menthol to affect the cytochrome P450 system as an inducer and inhibitor of certain isoenzymes that would potentially interfere with the metabolism of warfarin. To our knowledge, this is the second case report of an interaction between warfarin and menthol. Patients receiving warfarin should be closely monitored, as they may choose to take over-the-counter products without considering the potential implications, and counseled about a possible interaction with menthol cough drops.

Clinically Significant Adverse Events from a Drug Interaction Between Quetiapine and Atazanavir‐Ritonavir in Two Patients

Clinicians caring for patients infected with the human immunodeficiency virus (HIV) and diagnosed with psychiatric comorbidities must be aware of potential drug-drug interactions, particularly with protease inhibitor-based antiretroviral therapy. Although possible interactions can be predicted based on a drug's pharmacokinetic parameters, the clinical significance is often unknown. We describe two patients who experienced serious quetiapine adverse effects potentially mediated through an interaction with ritonavir-boosted atazanavir. The first patient was a 57-year-old man with HIV and bipolar disease who developed rapid and severe weight gain when quetiapine was added to a stable atazanavir-ritonavir-based antiretroviral regimen. After the patient discontinued both quetiapine and ritonavir, his weight returned to its baseline value. The second patient was a 32-year-old woman with HIV, anxiety disorder, and a history of intravenous drug abuse who developed increased sedation and mental confusion when an atazanavir-ritonavir-based antiretroviral regimen was added to her stable antianxiety drug regimen, which included quetiapine. Her symptoms resolved promptly after discontinuation of the quetiapine. Use of the Naranjo adverse drug reaction probability scale indicated that the adverse effects experienced by the two patients were possibly related and probably related, respectively, to an interaction between quetiapine and atazanavir-ritonavir. Quetiapine is primarily metabolized by cytochrome P450 (CYP) 3A4, and ritonavir is a potent inhibitor of CYP3A4. Thus, it is reasonable to theorize that quetiapine concentrations will increase when these drugs are used concurrently, which would be the likely cause of the toxicities in these two patients. To our knowledge, these are the first published reports of a clinically significant interaction between atazanavir-ritonavir and quetiapine. Clinicians should be aware of the potential for this interaction, and extreme caution should be used when prescribing quetiapine and other atypical antipsychotic agents in HIV-positive patients who are receiving antiretroviral therapy.

Kaposi's sarcoma in a patient treated with imatinib mesylate for chronic myeloid leukemia

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder primarily characterized by the presence of the Philadelphia chromosome resulting from a reciprocal translocation between the long arms of chromosomes 9 and 22. This translocation determines a fusion gene, bcr-abl, which encodes a constitutively active protein, tyrosine kinase, resulting in decreased apoptosis, defective adhesion, and genomic instability in transformed cells. The tyrosine kinase activity and its effects represent a potential pharmacologic target of tyrosine kinase inhibitors, such as imatinib. Flare of Kaposi's sarcoma (KS) is well described in immunosuppressed patients treated with corticosteroids and rituximab, but has not yet been reported during treatment with imatinib. Objective: We report a case of cutaneous KS lesions in a patient affected by CML treated with imatinib. Case summary: A 61-year-old white male patient (weight, 90 kg) was diagnosed with CML in March 2006 at the Division of Hematology, University of Rome “Tor Vergata,” Rome, Italy. He was treated with imatinib 400 mg/d, which improved his general condition with few adverse effects. After 12 months of treatment, molecular biology showed an important reduction in the peripheral blood of the fusion oncoprotein bcr-abl p210-b3a2. However, at the same time, multiple cutaneous violaceous papular-nodular lesions appeared on his left forearm. A punch biopsy showed the presence of KS, whereas a polymerase chain reaction assay documented the presence of human herpes virus type 8 (HHV8) DNA in the skin lesion. Serologic HIV was negative and HHV8 viremia was under the limit of quantitation of the assay. Total body computed tomography scan did not reveal any mucosal or visceral lesion. Conclusions: We present a case of a patient with CML who developed KS 12 months after starting treatment with imatinib 400 mg/d. The mechanism behind the development of the cutaneous lesions is unclear, and could have either a casual clinical association or be related to the study drug. According to the Naranjo adverse drug reaction probability scale, the development of KS in this case was probably associated with the imatinib treatment (score, 5–8).

Probable levetiracetam-associated depression in the elderly: Two case reports

Background: Compared with traditional antiepileptic drugs, levetiracetam has a unique mechanism of action and unique properties, including predominant renal excretion and lack of drug-drug interactions. In the elderly, depression associated with levetiracetam has not been reported. Case summaries: A 73-year-old black man (height, 172.7 cm; weight, 92.7 kg; body mass index [BMI], 31 kg/m 2) with stage 4 kidney disease was taking levetiracetam 500 mg BID for partial complex seizures. After 5 months of taking medication, new-onset depression, evidenced by depressed mood, weight loss, fatigue, and appearing withdrawn, was noted in this patient. Levetiracetam was discontinued by order of the patient's primary care physician. At a follow-up appointment 4 weeks later, the depressive symptoms had nearly resolved. The patient's Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating levetiracetam to be a probable cause of depression in this patient. In a second case, a 92-year-old white woman (height, 154.9 cm; weight, 54.5 kg; BMI, 22.7 kg/m 2) with existing chronic kidney disease and new-onset partial seizure, likely due to a meningioma, was initiated on levetiracetam 500 mg once daily. Depressive symptoms (eg, anhedonia, hypersomnolence, decreased appetite) were noted within 5 weeks. Cessation led to improvement in mood and cognition within 8 days. Based on this patient's Naranjo Adverse Drug Reaction Probability Scale score of 6, levetiracetam was a probable cause of depression in this patient. Conclusions: Levetiracetam was a probable cause of depression in these 2 elderly patients. Cautious use and additional monitoring may be necessary when prescribing levetiracetam to elderly patients, especially when prescribing to those with a history of renal impairment.

Hyperkalemia‐Induced Paralysis

Hyperkalemia is an electrolyte abnormality that can lead to severe consequences. Paralysis induced by hyperkalemia has been described in only a few reports. We describe a 60-year-old man who experienced paralysis presumably due to hyperkalemia. He presented to the emergency department with severe weakness in all extremities. The patient's serum potassium concentration was greater than 8 mEq/L and his serum creatinine concentration was 7 mg/dl. Findings on electrocardiography were abnormal. Of note, his drug therapy included lisinopril and naproxen. After treatment for hyperkalemia, the patient's symptoms resolved; however, he was admitted for further workup for renal failure. The patient was discharged after approximately 1 week with a diagnosis of end-stage renal disease. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's paralysis and hyperkalemia. Although hyperkalemia as a cause of paralysis is extremely rare, clinicians should be aware of this potentially life-threatening, noncardiac toxicity.

A novel strategy for managing clopidogrel-induced adverse skin reactions

We conducted a prospective observational study using a course of steroids and antihistamines to treat a cohort of patients who developed skin reactions to clopidogrel, to assess whether dual antiplatelet therapy could be continued in an outpatient setting. This study included 2,701 patients who underwent percutaneous coronary intervention (PCI) at our centre over a 23 month period. Patients with skin reactions to clopidogrel were identified and then commenced on five days oral prednisolone (30 mg/od) and chlorpheniramine (4 mg/tds) for seven days. A subsequent telephone survey was performed to evaluate a number of variables. The probability of the adverse reaction being secondary to clopidogrel was assessed using the Naranjo adverse drug reaction probability scale. Twenty (0.7%) patients were identified who developed adverse skin reactions to clopidogrel. There was complete resolution seen in the majority (89%) of patients within an average of 3.2 days following treatment. One patient had partial resolution, and one had no response to treatment, but both were able to continue clopidogrel. We propose a novel, safe and effective way of managing clopidogrel-induced skin reactions using a short course of prednisolone and chlorpheniramine, without stopping or substituting clopidogrel.

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

Thrombocytopenia from Combination Treatment with Oseltamivir and Probenecid: Case Report, MedWatch Data Summary, and Review of the Literature

The possibility of an avian flu pandemic has spurred interest in preventive treatments with antivirals such as oseltamivir. Combining treatment with probenecid to delay excretion may extend limited supplies of oseltamivir. We previously conducted a pharmacokinetic study of oseltamivir plus probenecid among healthy volunteers. In this article, we describe a 68-year-old woman who, during the pharmacokinetic study, developed severe thrombocytopenia 2 weeks after starting oseltamivir plus probenecid. She was receiving no other drug therapy at the time. Her platelet count decreased from 200 to 15 x 10(3)/mm(3), although no clinically evident bleeding abnormalities were noted. The two drugs were discontinued. One week later, without any therapeutic intervention, her platelet count returned to normal. By using the Naranjo adverse drug reaction probability scale to assess the strength of the association between the drugs and the adverse event, a score of 7 was derived for both drugs, indicating that the association was probable. We found no previous literature reports of thrombocytopenia associated with either drug. However, a review of the United States Food and Drug Administration's Adverse Event Reporting System database found 93 cases of thrombocytopenia and/or decreased platelet counts associated with oseltamivir and 24 cases associated with probenecid administration. Signal detection analyses were significant for oseltamivir (p=0.001), but not probenecid. The underlying mechanism of thrombocytopenia with these drugs is unknown. Clinicians should be aware that the use of oseltamivir and probenecid has been reported to be associated with thrombocytopenia.

Acute Profound Thrombocytopenia Associated with Readministration of Eptifibatide: Case Report and Review of the Literature

The glycoprotein IIb-IIIa inhibitor eptifibatide has been shown to be beneficial in the treatment of acute coronary syndromes and during percutaneous coronary intervention (PCI). Case reports of acute profound thrombocytopenia have been reported with eptifibatide, yet the true incidence of this reaction is unknown. We describe a 50-year-old woman with severe coronary artery disease who developed acute profound thrombocytopenia after readministration of eptifibatide. Eptifibatide was administered through hospital day 3, when it was discontinued in preparation for coronary angiography and PCI; the drug was restarted on day 5. On hospital day 6, she was noted to have a platelet count below 5 x 10(3)/mm,(3) indicating a profound decrease from a baseline of 456 x 10(3)/mm(3) on admission. Eptifibatide, heparin, vancomycin, and clopidogrel were potential causative agents. Anticoagulation and vancomycin were stopped, and her platelet count increased to 30 x 10(3)/mm(3) on day 7. Subsequent reexposure to heparin and vancomycin yielded no adverse effects. The patient's platelet count increased over the remainder of her hospitalization, and she was discharged home on day 19. Based on clinical presentation and negative heparin platelet factor 4 antibody test, eptifibatide was the most likely cause of thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated that eptifibatide was the probable cause of thrombocytopenia (score of 5); scores of 1 (possible) or 0 (doubtful) were derived with heparin, vancomycin, and clopidogrel. We conducted a literature search and compiled information from published case reports to describe the pattern of onset and recovery of eptifibatide-induced thrombocytopenia. In all patients receiving eptifibatide, routine platelet counts should be monitored at baseline and within 2-6 hours after starting the drug.

Statin‐Associated Adverse Cognitive Effects: Survey Results from 171 Patients

To characterize the adverse cognitive effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Patient survey-based analysis. One hundred seventy-one patients (age range 34-86 yrs) who self-reported memory or other cognitive problems associated with statin therapy while participating in a previous statin effects study. Patients completed a survey assessing statin-associated, cognitive-specific adverse drug reaction (ADR) characteristics, relation of the ADR to specific statin and dose (or potency), and time course of symptom onset and recovery. Visual analog scales were used to assess the effect of the cognitive ADRs on seven quality-of-life domains. Demographic and clinical data were also collected. To target cognitive ADRs with a probable or definite causal relationship to statins, the Naranjo adverse drug reaction probability scale was used: 128 patients (75%) experienced cognitive ADRs determined to be probably or definitely related to statin therapy. Of 143 patients (84%) who reported stopping statin therapy, 128 (90%) reported improvement in cognitive problems, sometimes within days of statin discontinuation (median time to first-noted recovery 2.5 wks). Of interest, in some patients, a diagnosis of dementia or Alzheimer's disease reportedly was reversed. Nineteen patients whose symptoms improved or resolved after they discontinued statin therapy and who underwent rechallenge with a statin exhibited cognitive problems again (multiple times in some). Within this vulnerable group, a powerful relationship was observed between potency of the statin and fraction of trials with that agent resulting in cognitive ADRs (p<0.00001). Quality of life was significantly adversely affected for each of the seven assessed domains (all p<0.00000001). Findings from the survey suggest that cognitive problems associated with statin therapy have variable onset and recovery courses, a clear relation to statin potency, and significant negative impact on quality-of-life. Administration of a patient-targeted questionnaire is a feasible approach that provides a useful complement to other ADR surveillance approaches.

Worsening Psychosis Induced by Varenicline in a Hospitalized Psychiatric Patient

Varenicline is a novel treatment for smoking cessation; however, the agent has not been well studied in a population with severe mental illness. Varenicline can reportedly cause neuropsychiatric adverse effects, some resulting in hospitalizations and/or suicides. We describe a case of clinician-observed, worsening psychotic symptoms in a patient with chronic mental illness who was receiving varenicline. A 45-year-old woman with bipolar disorder, mixed type with psychotic features, was admitted to a psychiatric hospital due to acute decompensation after she discontinued her drug therapy. Because of the facility's smoke-free policy, the patient was not permitted to smoke cigarettes during her hospitalization. Over the next several weeks, her condition was stabilized with psychotropic drugs. Her symptoms improved, and plans were made for her discharge. Varenicline was prescribed to manage her nicotine cravings. After 2 days of treatment, staff members noted worsening of the patient's psychotic symptoms and agitation. Varenicline was discontinued, the patient's mental status returned to baseline, and she was subsequently discharged. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's worsening psychosis and her varenicline therapy. This case report provides valuable support of previously published cases that demonstrate the risk of exacerbation of psychotic symptoms with varenicline use in patients with severe mental illness. With proper assessment and management of varenicline-induced neuropsychiatric effects, health care professionals can provide an important role in helping to prevent and manage worsening psychiatric symptoms.

Vancomycin‐Induced Leukocytoclastic Vasculitis

Vancomycin is well recognized as causing the nonallergic skin reaction known as red man syndrome; however, it is rarely suspected as causative in the setting of an immune-mediated skin reaction. We describe a 76-year-old Caucasian woman with a history of penicillin and sulfa allergies who was transferred to our medical center while receiving vancomycin for treatment of persistent methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. After admission, the patient's pacemaker was explanted; cultures from the pacemaker grew MSSA. Based on the culture data and her allergy to penicillin, vancomycin was continued. On day 4 of therapy, the patient developed a papular rash with small blisters on her distal upper extremities. Furosemide, which she was receiving intermittently to maintain fluid balance, was initially suspected as the likely cause. Furosemide was withheld; however, the rash worsened and spread to her neck and torso. Results of skin biopsy confirmed a severe leukocytoclastic, necrotizing small-cell vasculitis that met the criteria for a hypersensitivity vasculitis associated with drug therapy. Five days after discontinuation of vancomycin, the vasculitis was resolving and continued to resolve throughout the remainder of her hospitalization. Furosemide was readministered without worsening of the vasculitis. Use of the Naranjo adverse drug reaction probability scale indicated that the likelihood of vancomycin being the cause of the vasculitis was probable (score of 5). Clinicians should be aware of vancomycin as a potential cause of small-vessel vasculitis.

Cinacalcet-Induced Leukocytoclastic Vasculitis

An 80-year-old woman on maintenance hemodialysis therapy developed severe hypercalcemia under vitamin D treatment for secondary hyperparathyroidism. To avoid the toxic calcemic effects, cinacalcet was introduced and the dose of vitamin D was substantially decreased. Cinacalcet targets the calcium-sensing receptor and decreases parathyroid hormone levels without increasing calcium and phosphorus levels. Three days after starting cinacalcet therapy, the patient developed palpable purpura on both upper and lower extremities that resolved after discontinuation of cinacalcet and administration of steroids. Skin biopsy of the initial eruption showed leukocytoclastic vasculitis. According to the Naranjo adverse drug reaction probability scale, leukocytoclastic vasculitis probably was caused by cinacalcet introduction. Drug-induced vasculitis is a poorly defined disorder, and, in most cases, no pathogenetic mechanism can be described. An idiosyncratic reaction to the agent often is proposed. Cinacalcet should be considered a causative agent of cutaneous leukocytoclastic vasculitis, and although this is the result of only a clinical observation, further attention is required in the future because cinacalcet recently has been introduced in the treatment of secondary hyperparathyroidism in patients on long-term hemodialysis therapy.

Tigecycline-induced acute pancreatitis: case report and literature review

Tigecycline is a broad-spectrum antimicrobial agent structurally related to minocycline. Pancreatitis has been associated with the tetracycline class of antibiotics and concerns about tigecycline-induced acute pancreatitis have recently been raised. We describe a 69-year-old female who received tigecycline for treatment of a complicated skin and skin-structure infection. Following 7 days of tigecycline she developed severe abdominal pain and elevated pancreatic enzymes suggesting acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of her acute pancreatitis. Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of pancreatitis, including abdominal pain, during treatment with tigecycline.

Fatal acute hepatitis after sequential treatment with levofloxacin, doxycycline, and naproxen in a patient presenting with acute Mycoplasma pneumoniae infection

Background: The diagnosis of drug-induced liver injury relies on comprehensive clinical assessments due to the absence of an established biomarker or pathognomonic features of liver histology. However, prompt recognition of a culprit drug as the cause of liver injury is the most important aspect in the management of hepatotoxicity. Case summary: A 63-year-old white male (85 kg) was admitted because of community-acquired pneumonia with associated pericarditis and subclinical hepatitis, subsequently related to acute Mycoplasma pneumoniae infection (diagnostic positive immuno-globulin M enzyme immunoassay, on hospital days 5 and 20). The patient had received cisplatin and radiotherapy from March to May 2006, as treatment for pharyngolaryngeal squamous cell carcinoma T3N0M0 without subsequent evidence of localized or meta-static recurrent disease (last oncologic consultation, May 17, 2007). He reported alcohol ingestion until March 2006 but no known liver disease, blood transfusion, or exposure to mushrooms or industrial cleaning solvents. Results of serologic tests for viral and nonviral infectious hepatitis, iron and copper studies, and tests for autoantibodies were normal or negative. The patient became initially asymptomatic and fever disappeared following sequential treatment with levo-floxacin (500 mg BID), doxycycline (100 mg BID), and naproxen (500 mg TID). However, on hospital day 10 jaundice and a significant elevation (alanine aminotransferase, 1577 U/L; aspartate amino-transferase, 1754 U/L; alkaline phosphatase, 189 U/L) of serum transaminases appeared. Despite the discontinuation of all medication, the patient gradually deteriorated and died 27 days after admission due to acute fulminant hepatic failure. Autopsy revealed massive hepatic necrosis, inflammatory changes with presence of eosinophils, and cholestasis. An objective causality assessment scale (Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale) suggested that each of the 3 drugs could “probably” (score = 6) be related to the patient's fulminant hepatitis. The Naranjo Adverse Drug Reactions Probability Scale assessment for the same drugs indicated a “possible” causal relation (score = 2). Conclusion: We report a case of lethal hepatitis possibly/probably associated with levofloxacin, doxy-cycline, and naproxen in a patient with acute M pneumoniae infection.