Adverse Drug Reaction Probability Scale Research Articles

Profile of drug-induced liver injury due to antibiotics in patients with chronic liver disease

Background: Patients with chronic liver disease (CLD) may be more susceptible to drug-induced liver injury (DILI) through reduced drug clearance, aberrant metabolism, altered excretion, or impaired adaptive responses. The diagnosis of DILI may identify a reversible cause for acute decompensation. Aim: The aim was to study the profile and outcomes of DILI in CLD patients. Patients and Methods: A total of 400 consecutive in patients with CLD who had been received antibiotic therapy between September 2015 and April 2016 were prospectively studied for features suggestive of DILI. The Naranjo Adverse Drug Reaction (ADR) Probability Scale was used for identifying ADRs in CLD patients. Results: Sixty-three (15.8%) patients were identified by Naranjo Scale. The most common etiology of CLD in these patients was alcohol (49.2%); hepatitis C virus (7.9%), NASH (4.3%), cryptogenic (14.3%), and hepatitis B virus (5.6%) were other common causes. DILI was more common in Child class C (52.4%) as compared to Child B (30.2%) and Child A (17.4%). Thirteen (20.6%) patients had hepatitic, 17 (27%) had cholestatic, and 33 (52.45) had a mixed pattern. There were six cases with DILI due to anti-tubercular treatment. Clarithromycin (9 cases), clindamycin (9 cases), amoxicillin-clavulanate (7 cases), and co-trimoxazole (5 cases) were the most common antibiotics causing DILI in CLD patients. Forty-three (68.2%) recovered, 11 (17.4%) expired, 3 (4.7%) developed acute on chronic liver failure, and 2 (3.1%) underwent liver transplant. Conclusions: Definitive diagnosis of DILI in CLD patients is difficult, and it is often a diagnosis of exclusion. Exposure to a potentially hepatotoxic agent, the temporal profile of liver function test changes after initiation and withdrawal of antibiotics is useful pointers. Early diagnosis of DILI, even if not definitive, may help in timely intervention and affect outcomes in CLD patients.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

DRUG UTILIZATION EVALUATION OF BENZODIAZEPINES IN A TERTIARY CARE HOSPITAL

Objective: To assess the rationale use of benzodiazepines among various departments in a multi-speciality hospital.
 Methods: A prospective study was conducted with a sample size of 200 for a period of six months. Data was collected from patients based on inclusion and exclusion criteria. Naranjo Adverse Drug Reaction Probability Scale and Drug Interaction Probability Scale (DIPS) were used as a study tool to measure the causality of adverse drug reactions and drug interactions. Based on the dosage of various benzodiazepines DDD was calculated and compared with WHO Anatomical Therapeutic Chemical (ATC) classification Defined Daily Dose (DDD).
 Results: BZD’s were mostly prescribed in males (74.5%) and married patients (86.5%) were more exposed to benzodiazepines compared to others. Lorazepam (70.1%) was found to be the most commonly used drug, mainly prescribed for sedation, followed by anxiety. DDD was calculated and majority of patients had DDD in accordance with WHO standard. Based on cost analysis, Clobazam was found to be the high cost and Lorazepam being the low-cost drug. The results of drug utilization evaluation of benzodiazepines study were compiled and reported to the respected department physician and their feedback was collected.
 Conclusion: The study showed a rational utilization of benzodiazepines and the negative outcomes of BZDs can be reduced by providing drug-related information to the prescribers and consumers.

Delayed Onset of Central Diabetes Insipidus With Ketamine Sedation: A Report of 2 Cases

Ketamine is being prescribed with greater frequency due to an emphasis on multimodal analgesia. With increasing use, uncommon adverse effects associated with ketamine are likely to surface. Limited reports of transient central diabetes insipidus (DI) occurring early after initiation (ie, within 10 hours) of ketamine have been reported. We present 2 cases of delayed onset (32 hours or more after initiation), ketamine-induced, transient central DI in patients cannulated for venovenous extracorporeal membranous oxygenation. No other causes of central DI were determined based upon physical examination or laboratory data, and both patients responded to treatment with desmopressin/vasopressin. The Naranjo adverse drug reaction probability scale noted a probable causation for each case. These cases demonstrate the possibility of a rare but serious complication of ketamine. Improvement after discontinuation of ketamine and administration of desmopressin/vasopressin appear to support a drug–effect association.

LENALIDOMIDE-INDUCED ACUTE EOSINOPHILIC PNEUMONIA

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: MDS/MPD (Myelodysplastic Syndrome/Myeloproliferative disorder) overlap syndrome is characterized by dysplasia and cytopenias which prevalence is not known. Lenalidomide is an immunomodulatory drug analogous to thalidomide that is frequently used in myelodysplastic syndrome and also used in cases of Polycythemia Vera. Pulmonary side effects are rare. We present a case of lenalidomide induced acute eosinophilic pneumonia. CASE PRESENTATION: A 76-year-old male with a history of MDS/MPD overlap syndrome, primary and secondary hemochromatosis (transfusion dependent) who recently started lenalidomide was admitted for shortness of breath. He had 2 days of respiratory distress, desaturation (83% room air), new onset of cough and nasal congestion. No history of fever, chills, chest pain, palpitations, no sick contacts. He had chronic fatigue but not worse than baseline. The physical exam was positive for a respiratory distress, a flow systolic murmur and rales at the pulmonary bases. Work up included a negative procalcitonin, negative respiratory viral panel, negative blood cultures. Chest x-ray showed diffuse hazy interstitial and airspace opacity. Chest CT showed ground glass pulmonary infiltrates. His initial management included blood transfusions, diuretics, broad spectrum antibiotics and coverage for PCP and atypical pneumonia, oxygen by nasal canula with 2 Litters. Diuretics were given for suspected pulmonary edema. His Echo showed an ejection fraction of 60-65% and despite effective diuresis, symptoms did not improve. Patient underwent a bronchoalveolar lavage which showed 27% eosinophils, negative gram stain, negative bacterial and fungal cultures. Cytology was negative for malignancy. PCP DFA was negative. A new diagnosis of acute eosinophilic pneumonia was made and patient was treated with steroids and lenalidomide was stopped as well as antibiotics. DISCUSSION: Lenalidomide is becoming a frequently used medication in the last few years due to its new multiple uses approved by the FDA. Pulmonary side effects are rare and acute eosinophilic pneumonia is added to this list. The Naranjo Drug Adverse Drug Reaction Probability Scale was positive for 8 points in our case, making it a probable drug reaction. This is the first case to our knowledge ever reported in MDS/MPD treatment with Lenalidomide. CONCLUSIONS: Lenalidomide is a pharmacologic agent that is linked to multiple but rare pulmonary side effects. Providers should be aware that acute eosinophilic pneumonia can be one of this rare side effects. Reference #1: Toma, Andrew & P. Rapoport, Aaron & Burke, Allen & Sachdeva, Ashutosh. (2017). Lenalidomide-induced eosinophilic pneumonia: Lenalidomide and eosinophilic pneumonia. Respirology Case Reports. 5. e00233. 10.1002/rcr2.233 Reference #2: Mankikian J, Lioger B, Diot E, et al. 2014. Pulmonary toxicity associated with the use of lenalidomide: case report of late-onset acute respiratory distress syndrome and literature review. Heart Lung 43(2):120–123. Reference #3: Naranjo CA, Busto U, Sellers EM, et al. 1981. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 30(2):239–245. DISCLOSURES: No relevant relationships by Mohamad Bitar, source=Web Response No relevant relationships by Fernando Fuentes, source=Web Response No relevant relationships by Shahla Mallick, source=Web Response

Efavirenz-Induced Vanishing Bile Duct Syndrome: A Case Report

Background: Efavirenz (Sustiva®) is used for the treatment of human immunodeficiency virus (HIV) type 1 infection. Hepatoxicity is a known potential adverse drug event with efavirenz; however, to our knowledge, vanishing bile duct syndrome (VBDS), a type of liver injury, has not been reported with this therapy. Case Presentation: We report the case of a 48-year-old male with HIV and VBDS secondary to antiretroviral therapy. The patient was started on efavirenz, emtricitabine, and tenofovir disoproxil fumarate (Atripla®). Four weeks later, the patient presented with complaints of poor appetite, nausea with emesis, dark urine, and malaise. Labs obtained supported the diagnosis of acute hepatitis, and a liver biopsy confirmed a diagnosis of VBDS. The Naranjo adverse drug reaction probability scale showed that it was probable (score of 7) that the VBDS was related to drug therapy. Efavirenz was assessed to be the most likely cause of VBDS, end-stage liver disease, and the eventual need for liver transplantation. Conclusion: To our knowledge, this is the first reported case of probable efavirenz-induced VBDS in a patient living with HIV. Recognition and awareness of this adverse drug reaction by clinicians for quick diagnosis, discontinuation of therapy, and management are important in patients receiving this regimen.

Drug-Induced Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Background: Acute kidney injury (AKI) is a severe kidney disease. Drug-induced AKI (D-AKI) is one type of AKI, which is difficult to be diagnosed. The incidence of D-AKI in China has rarely been studied. This study aims to explore the disease burden, related drugs and diagnosis status of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in mainland China. Suspected AKI was screened based on serum creatinine changes according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury and patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. D-AKI was firstly evaluated by pharmacists using Naranjo Adverse Drug Reaction Probability Scale and further confirmed by nephrologists through carefully reviewing the medical records. Findings: Altogether 280,255 hospitalized patients were screened and 1960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as D-AKI (37.50%, 735/1960) with a hospital mortality rate of 13.88% and 54.34% of the survivors not achieving full renal recovery. 1642 drugs were related to AKI in these 735 D-AKI patients. Anti-infectives (34.35%, 564/1642), diuretics (21.80%, 358/1642) and proton pump inhibitors (PPIs) (10.48%, 172/1642) were the top 3 types of drugs relavent to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitutes and carbapenems related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Interpretation: In China, D-AKI has caused a substantial medical burden. Chinese pharmacists and nephrologists should bear the major responsibility of leading the campaign of managing D-AKI. Funding Statement: This study is supported by Medical Policy and Administration Department, National Health and Family Planning Commission of China, 2015. The National Natural Science Foundation of China (No.91742205 and No.81625004), the Beijing Young Scientist Program (BJJWZYJH01201910001006), and Peking University Clinical Scientist Program by the Fundamental Research Funds for the Central Universities. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of Xuanwu Hospital of Capital Medical University.

Dermatomyositis associated with omalizumab therapy for severe asthma: a case report

BackgroundOmalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characterized. Delayed anaphylactoid and serum sickness-like reactions have also been described; however, their relationship to the drug remains uncertain, and the frequency is unknown.Case presentationWe present a case of a 59-year old female who developed amyopathic dermatomyositis (DM) after receiving omalizumab infusions for steroid-refractory severe asthma. After 6 months of omalizumab, the patient developed an erythematous, intensely pruritic cutaneous eruption. Skin biopsy indicated nonspecific features of dermatitis. However, neither topical corticosteroids nor gabapentin and maximal doses of multiple antihistamines gave her relief. On follow-up clinical exam 8 months later, she had classic cutaneous features of dermatomyositis, with confirmatory repeat skin biopsy. Laboratory investigations revealed negative myositis specific antibodies, positive antinuclear antibody, and negative anti-histone antibodies. Creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase levels and C-reactive protein were also within normal limits. These findings supported the clinical impression of amyopathic DM. The patient’s symptoms improved with oral corticosteroid therapy. A malignancy screen was negative. There was no evidence of end organ dysfunction.ConclusionsDermatomyositis is not a known adverse effect of omalizumab therapy. DM has a low incidence, but potentially life threatening consequences. Amyopathic DM may represent up to 21% of cases of DM, with similar risks of malignancy and end organ dysfunction. DM has been associated with biologic therapy. Using the Naranjo adverse drug reaction (ADR) probability scale, our patient had a “probable” omalizumab related ADR. A more likely explanation is that the patient had underlying DM that remained occult due to chronic corticosteroid therapy. Our case highlights the need for clinical vigilance and maintenance of a broad differential when patients on biologic therapies present with cutaneous eruptions. In our patient, the cutaneous clinical features of DM became pronounced over serial assessments. Laboratory markers may be deceptively normal, as in amyotrophic DM, or confounded by ongoing corticosteroid therapy. There are important clinical implications of prompt diagnosis, given the association of DM with end organ disease including interstitial lung disease, and possible concomitant malignancy.

Omalizumab as a Provoking Factor for Venous Thromboembolism

A 43-year-old man with a history of severe extrinsic allergic asthma treated with once-monthly omalizumab (600 mg) for the last 15 months. He presented to the emergency room with a 2-week history of right lower limb pain and chest pleuritic pain. Computed tomography pulmonary angiography showed bilateral pulmonary embolism with right-sided pulmonary infarction and ultrasound of right lower limb confirmed distal deep vein thrombosis. No other known risk factors were identified. Treatment with omalizumab was stopped during hospitalization. The Naranjo Adverse Drug Reaction (ADR) Probability Scale classifies this as a probable ADR (score of 6). Omalizumab is a humanized monoclonal anti-IgE antibody indicated for the treatment of persistent moderate-to-severe asthma and certain chronic refractory urticaria. The EXCELS study (The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma), a postmarketing observational cohort study to assess clinical safety profile of omalizumab, showed a significant increase in venous thromboembolism. In conclusion, omalizumab has been associated with arterial and venous thromboembolic events, although the evidence is not definitive.

A Study on Adverse Effects of Antidepressants in a tertiary care teaching hospital

Objective: To identify the adverse effects of antidepressants at the initiation of therapy. To make causality assessment of the adverse effect identified using WHO ADR probability scale. Materials and Methods: Patients prescribed with at least one antidepressant were randomly selected and monitored for adverse drug reactions (ADRs), irrespective of their age and gender. Results: Of the 100 patients who received antidepressants, 33 patients experienced 10 ADRs. Selective serotonin receptor inhibitors (SSRIs) were the most common therapeutic class of drugs associated with ADRs. Gastrointestinal system was most commonly affected system organ class. Gastritis and dry mouth were the most frequently reported ADRs. Majority of the ADRs were ‘mild’ in their severity. Conclusion: In this study, incidence of adverse reaction to antidepressants was 32% and the most common group of Antidepressants implicated are SSRIs.

A case of carbamazepine-induced vitamin B12 deficiency and neuropathy

Drug induced Neuropathy is seen commonly in patients undergoing treatment with drugs like phenytoin, dapsone, isoniazid etc. Carbamazepine is a drug used in the treatment in the treatment of focal seizure, generalized tonic - clonic seizure and trigeminal neuralgia. It is presented a case of carbamazepine induced vitamin B12 deficiency and neuropathy. A 21 year old male presented to our hospital with complaints of history of slipping of footwear while walking, numbness, impairment of balance and unsteadiness of gait in both lower limbs. Detailed history revealed the patient was on treatment with carbamazepine for tonic - clonic seizure for three months. He is non- smoker, non -alcoholic, not on treatment with other drugs and there is no family history of diabetes mellitus/ sensory neuropathy. On examination power was normal on both lower limbs, vibration sensation was decreased in both lower limbs, sensation was reduced, joint position was affected in bilateral toe and ankle reflex was absent. Vitamin B12 level was found to be 83pg/ml. The patient was discontinued from carbamazepine and started on vitamin B12 therapy and the symptoms subsides slowly. Causality assessment done by WHO- UMC probability method and Naranjo Adverse Drug Reactions Probability Scale showed “Probable” association.

STUDY OF ADVERSE DRUG REACTIONS OF ANTI-NEOPLASTIC AGENTS IN DIFFERENT STAGE OF CANCER

STUDY OF ADVERSE DRUG REACTIONS OF ANTI-NEOPLASTIC AGENTS IN DIFFERENT STAGE OF CANCER Dr. Joel Thomas*, Dr. Joshin Sara Cherian, Dr. Monica John, Dr. Jeffy Abraham, Dr. Vijay M C Padmavathi College of Pharmacy and Research Institute, Periyanahalli, Dharampuri, Tamilnadu, India ABSTRACT To evaluate the clinical adverse drug reactions (ADRs) reported in cancer patients taking anticancer drugs in different stage of cancer. Adverse drug reactions (ADRs) are a global problem in different stages of cancer. Anti-cancer drugs are prone to cause ADRs and there is lack of Pharmacovigilance data on such drugs. Therefore the present prospective observational study was undertaken to monitor possible ADRs in the chemotherapy of different stage of cancer. Adverse drug interactions may enhance or diminish the antitumor effects and result in improvement or treatment failure; drug interactions may also increase or decrease the side-effect profile of the anti-neoplastic drug. Precaution must be taken when prescribing other therapeutic agents to patients undergoing active anticancer therapy. The study is the clinical assessment of adverse drug reaction in cancer patients by Naranjo’s ADR probability scale after the clinical pharmacist intervention of a government hospital. We have conducted the prospective study to analyze the ADRs in the oncology department for the period of six months from December 2015 to May 2016 in Government Headquarters, Krishnagiri by the Doctor of Pharmacy (Pharm D) students. The study population consists of 150 patients in total. Among them 54.6 % (n=82) of the patients were females. On classifying the patients on age 32 % (n=48) of the patients were of age group 50-59. From the total prescription 34.66% (n=52) patients were diagnosed as stage II cancer. From this clinical study it may be concluded that chemotherapeutic agents have a narrow therapeutic index and dosage needed to achieve a therapeutic response usually proves toxic to the bodies rapidly proliferative cells. However, early detection of drug toxicity helps to modify the doses or the drug regimen to minimize toxic effects. Keywords: Adverse drug reaction, Chemotherapy, Clinical Pharmacist, Naranjo’s, ADR Probability scale, Oncology, Stages of cancer, Pharm D Full Text Article

1592. Safety of Oral Trimethoprim/Sulfamethoxazole Prophylaxis in Renal Transplant Recipients

BackgroundTrimethoprim/sulfamethoxazole (TMP/SMX) is the agent of choice for Pneumocystis jirovecii Pneumonia (PJP) prophylaxis in renal transplant (RT) recipients. All other prophylactic agents are considered second-line due to efficacy, drug intolerances, cost, administration requirements, and lack of coverage of Toxoplasma. Anecdotally, alternative agents are commonly used at our institution due to clinician hesitancy and perceived risk of adverse drug reactions (ADRs). Our objective was to assess the safety of TMP/SMX prophylaxis in RT recipients.MethodsRT recipients transplanted at a tertiary US medical center between May 9, 2015 and November 30, 2017 were retrospectively identified. Patient charts were reviewed for antimicrobial agents used for PJP prophylaxis and ADRs due to TMP/SMX. ADRs were classified using the National Institutes of Health, Division of Microbiology and Infectious Diseases (DMID) criteria and were scored for probability of association with TMP/SMX using the Naranjo ADR probability scale.ResultsDuring the study period, 64 of 95 adult RT recipients (67.4%) received TMP/SMX for PJP prophylaxis. Of the patients who received TMP/SMX, 26 (40.6%) had a clinician-documented ADR attributed to TMP/SMX and 24 (37.5%) had the drug discontinued. The most frequent provider-reported ADRs due to TMP/SMX were hyperkalemia (10 patients, 15.6%), neutropenia (nine patients, 14.1%), and elevated liver function tests (LFTs) (three patients, 4.7%). However, when classified using DMID criteria, nine of the 26 ADRs were less severe than Grade 1. Two ADRs were Grade 3 (severe), including 1 case each of neutropenia and elevated LFTs. No ADRs were Grade 4 (life-threatening). All ADRs received a score ≤4 on the Naranjo ADR probability scale, indicating a possible ADR related to TMP/SMX. Often, ADRs did not resolve or other additional medication adjustments were needed following TMP/SMX discontinuation (19 of 26 patients, 73.1%). No cases of PJP occurred.ConclusionTMP/SMX is underutilized in RT recipients at our institution, despite being well-tolerated and efficacious. Clinician hesitancy with TMP/SMX in this population may be unfounded. Internal efforts are underway to increase the use of TMP/SMX in RT recipients.Disclosures All authors: No reported disclosures.

Liposomal Amphotericin B–Associated Cardiac Arrest

Abstract Liposomal amphotericin B (L-AmB) was developed with the intent to minimize the adverse effects associated with amphotericin B deoxycholate, especially nephrotoxicity. Although there has been a substantial decrease in adverse effects with L-AmB compared with its predecessor, there is a small body of evidence suggesting its association with cardiovascular adverse events. We report a case of L-AmB-associated cardiac arrest in a patient with preexisting cardiac-related disease states. In addition, we review currently available literature regarding cardiac-related adverse events associated with L-AmB. When the Naranjo Adverse Drug Reaction Probability Scale was applied to this case, the probability of association was determined as possible. This case adds to a small but important body of literature regarding L-AmB–associated cardiotoxicity. Moreover, a review of the available literature indicates that providers should be aware of the potential for cardiac adverse events with L-AmB.

Ofloxacin-induced maculopapular rash in the infant

Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in countries having limited healthcare resources. The ofloxacin is an antimicrobial used for treating several bacterial infections. The ofloxacin, belonging to quinolone group of drugs, is bactericidal and acts by inhibition of bacterial DNA gyrase. Among the adverse drug reaction of ofloxacin, skin rashes are rare. An ofloxacin-induced maculopapular rash is the unique rare condition in the infant. The present case report was assessing the causality in ofloxacin induced maculopapular rash in the infant. Naranjo Adverse Drug Reaction Probability Scale and World Health Organization and Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment were used for assessing the causality. According to the Naranjo and WHO-UMC, ofloxacin scaled as the probable/likely cause of this ADR in infant. So, authors can conclude that the ofloxacin should be used cautiously in the pediatric age group.

Doxycycline induced fixed drug eruption: a case report

Fixed drug eruption (FDE) is an adverse drug reaction seen with various groups of drugs are antibiotics such as trimethoprim -sulphamethoxazle, pencillin, tetracyclines, non steroidal anti- inflammatory drugs like ibuprofen, aspirin etc. Doxycycline belongs to tetracycline groups of antibiotics. We herein present the case of Doxycycline induced fixed drug eruption. A 35-year - old man presented to our hospital, with a 2-day history of itching and hyperpigmentation over the chest. Patient developed skin lesion 2 days after and he started taking Doxycycline 100 mg twice a day for skin infections. Dermatological examination revealed multiple well defined hyperpigmented patches seen over the anterior aspect of the chest. Doxycycline was discontinued immediately, and the skin lesions resolved spontaneously within 2 weeks. Causality assessment by using Naranjo adverse drug reaction probability scale and WHO Uppsala monitoring scale categorize the reaction as Doxycycline was the probable cause for the adverse drug reaction. Severity assessment by using modified Hartwig and Siegel ADR severity assessment scale labelled the reaction as mild-level 2. The causative drug or drugs and cross reactants should be avoided in future to prevent recurrence of similar skin reactions.

Unusual Cause of Acute Drug-Induced Hepatitis

Rivaroxaban is an oral anticoagulant used in non-valvular A-fib, as well as treatment and prevention of DVT and pulmonary embolism (PE). We present a case of reversible acute liver injury; a rare adverse reaction of rivaroxaban. A 62-y.o. female presented to ER with a 2-week history of nausea, early satiety, dull aching RUQ pain, dark urine and normal colored stool. She has history of GERD and recurrent PE, the latest was a month earlier and she was started on rivaroxaban. She has no history of alcohol/acetaminophen use, substance abuse, liver disease, blood transfusion, recent travel or infection. The only positive physical exam finding was mild RUQ tenderness. Initial work up showed markedly elevated LFTs (table). Acute hepatitis profile, monospot test, acetaminophen/alcohol levels, EBV, CMV, CPK, TSH, urine/blood drug screen, autoimmune workup, liver ultrasound with Doppler, CT and MRI abdomen; all were negative. The patient was discharged home with GI follow-up. Few days later, she presented with worsening symptoms including dizziness, poor appetite and nausea. Repeat blood test showed worsening LFTs. Patient was admitted and started on supportive therapy while efforts to determine the cause of elevated LFTs continued. Rivaroxaban-induced acute liver injury was entertained. The drug was stopped and she was switched to enoxaparin for anticoagulation. Her LFTs and symptoms continued to improve over few months after her discharge. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between rivaroxaban use and acute liver injury. Rivaroxaban is a direct factor Xa inhibitor that may cause bleeding, rash and liver injury. Rivaroxaban is associated with moderate ALT elevation in 1.5% to 3% of patients. Most cases have an onset within 1 to 8 weeks of starting therapy. All patients recover 2 to 4 weeks after stopping rivaroxaban. Cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome due to rivaroxaban have not been reported in the literature. The exact mechanism of liver injury is unknown, but may be idiosyncratic or immunologic. Rivaroxaban is metabolized in the liver mainly by CYP3A4 and is susceptible to drug-drug interactions. Clinicians should be made aware of this rare side effect as early discontinuation of the drug is essential to prevent morbidity and even mortality. Future research is needed to determine if routine follow up of LFTs is advised in patients on rivaroxaban.2173 Figure 1 No Caption available.

Venlafaxine-induced Thyroiditis: A Case Report

Thyroiditis is the most common inflammatory disorder that affects thyroid gland.The diagnosis is mainly based on clinical findings, in particular the degree of pain and tenderness of thyroid. Confirmatory laboratory test includes presence of thyroid specific autoantibodies. Treatment is based on the severity of symptoms (pain and redness) and aims to restore the normal function of thyroid. Drug-induced thyroiditis has been described previously in the literature. Venlafaxine is an antidepressant agent with an efficacy similar to that of selective serotonin reuptake inhibitors. The dose of this medicine can be adjusted up to 150 mg/day one year after initiation. However, usage of venlafaxine may be limited due to the dose-dependent side effects. Here we describe a patient diagnosed with generalized anxiety disorder and migraine headache who developed venlafaxine-induced thyroiditis following dose adjustment to the maximum of 150 mg/day. The diagnosis was made based on the clinical symptoms and confirmatory laboratory tests according to the Naranjo Adverse Drug Reaction Probability Scale. Thyroiditis symptoms subsided after reducing venlafaxine dose and initiating prednisolone therapy. It should be noted that thyroid function was fully restored to normal only after cessation of venlafaxine administration.

Hepatotoxicity upon using niacin to pass a drug test: A case report

ObjectivesTo report a case of hepatotoxicity when niacin was used by a patient with HIV to pass a drug test. MethodsNiacin is a soluble pyridine derivative widely used in the management of dyslipidemia. Common adverse effects include flushing, nausea, gastrointestinal discomfort, and hepatotoxicity. The use of niacin for nonmedical purposes has been increasing in prevalence in recent years, particularly in attempts to alter or mask results of urine drug tests. Although there is no scientific evidence that niacin can alter a urine drug screen result, easily retrievable information exists on the Internet touting niacin as a potential way to prevent detection of tetrahydrocannabinol (THC). The following report describes a case of hepatotoxicity in an HIV-infected adult who reported using niacin to mask THC in urine drug screen results. ResultsThe patient developed marked elevations in his liver enzymes (aspartate aminotransferase greater than 25 times the upper limit of normal and alanine aminotransferase greater than 3 times the upper limit of normal) that resolved after discontinuation of the drug. Because of the patient’s self-reported use and discontinuation of niacin, the Naranjo Adverse Drug Reaction Probability Scale demonstrated a “definite” relationship between the development of hepatotoxicity and the ingestion of over-the-counter sustained-release niacin. The patient did not develop further clinical abnormalities proposed to be secondary to niacin toxicity in previously published case reports, including glucose abnormalities, coagulopathies, metabolic acidosis, QTc prolongation, and myalgias. ConclusionHealth care providers should be aware of this nonmedical use of niacin to alter or mask a drug test, especially when discerning the cause of hepatotoxicity. In addition, pharmacists in the community setting should be aware of this use of niacin when encountering patients purchasing over-the-counter niacin, particularly in patients who may be more likely to use illicit substances.

Safety and Feasibility of Outpatient Rabbit Antithymocyte Globulin Induction Therapy Administration in Kidney Transplant Recipients.

Kidney transplant induction therapy often includes inpatient administration of rabbit antithymocyte globulin (rATG) over multiple days. To reduce hospital length of stay (LOS) and drug expenditures, the rATG induction course was completed in the outpatient setting via peripheral intravenous administration. The present study assesses early readmission trends ascribable to an outpatient rATG administration protocol to ensure initial reduction in hospital LOS is sustained early after discharge. This was a retrospective study of kidney recipient outcomes for patients transplanted between January 1, 2008, and February 29, 2016, immediately following implementation of an outpatient rATG protocol. Readmission data within 7days of outpatient rATG administration were collected. The relatedness of rATG administration to an adverse drug reaction resulting in readmission was determined by the World Health Organization-Uppsala Monitoring Centre Causality Assessment Scale and the Naranjo Adverse Drug Reaction Probability Scale. A total of 1104 patients received outpatient doses of rATG and were included. An upward trend in kidney transplant volume and outpatient rATG administrations per year was found from 2008-2015. Following protocol implementation, the percentage of overall readmissions ranged from 9% to just over 12% from 2008-2014 and remained less than 10% for 2014 through 2016. The percentage of outpatient rATG infusions that potentially led to rATG-related readmissions was less than 4% per year over the study period. A total of 1124 hospital days were saved, 125days per year on average. Outpatient administration of rATG is feasible, safe, and did not increase readmissions in the period directly following administration. The findings of this analysis support our continued use of the outpatient rATG protocol at our institution.