Naranjo Adverse Drug Reactions Probability Scale Research Articles

Causality, severity, and preventability of adverse drug reactions due to multi-drug therapy in leprosy: evidence from a national level institution in Sri Lanka

Objective This study describes the causality, severity, and preventability of adverse drug reactions (ADR) in patients affected by leprosy treated with multi-drug therapy (MDT) at the dermatology and central leprosy clinics of the National Hospital of Sri Lanka. Methods This cross-sectional analytical study consisted of two components (retrospective and prospective). Prospective cases were recruited and followed up for six months. Retrospective data collection was carried out at relevant clinics in the NHSL by extracting data from the clinical records of the patients. When an ADR was suspected, it was confirmed after discussion with the clinic medical officers/consultant dermatologist and scored according to the Naranjo ADR probability scale. The intensity of an individual ADR was evaluated using the modified Hartwig and Siegel Severity Assessment Scale, and preventability assessment was performed using the modified Schumock and Thornton scale. Results One hundred and ninety-seven patients were included for ADR attributable to MDT. Approximately 145 patients (73.6%) developed ADR associated with dapsone. Another 50 cases (25.3%) were associated with rifampicin, and 10 (5.1%) were associated with clofazimine. Of the dapsone related 145 ADRs, 59 (40.7%) were definite, 64 (44.1%) were probable, and 22 (15.2%) were possible. Of the rifampicin-related cases, four (8%) were definite, 35 (70%) were probable, and 11 (22%) were possible. The most common adverse drug reactions detected were haemolytic anaemia and hepatic abnormalities due to MDT. Dapsone was discontinued in 40% (59 out of 145) of these patients, while rifampicin was stopped in 8% (4 out of 50) of patients. Clofazimine was not stopped in any of the patients. Conclusions Adverse drug reactions associated with multidrug therapy in leprosy are common among patients diagnosed with leprosy in Sri Lanka. Most ADRs reported in this study were of mild severity and preventable. Careful monitoring and objective scales are needed to identify ADRs at an early stage.

Adverse Drug Reactions Monitoring in New Patients Admitted to the Cardiac Care Unit in a Tertiary Care Hospital

Background: Adverse Drug Reactions (ADRs) are amongst the commonly occurring event in the intensive care unit where patients are mostly on the polypharmacy. They affect the quality of life of patients and increase the burden on the health care system. Aim and Objectives: The study aimed to estimate the incidence of ADRs and to assess the causality and seriousness of such ADRs by using the Naranjo probability scale. A prospective, observational, longitudinal study was conducted on patients admitted to the cardiac care unit over a period of 10 months. ADRs profile was noted by spontaneous and intensive monitoring. For analysis, descriptive statistics with 95% CI were used. Results: A total of 77 ADRs were reported from the 173 patients, out of which 31 patients suffered from ADRs, with an incidence of 17.9%. The gastrointestinal system was the most common affected system followed by the cardiovascular and respiratory systems. When analyzed on the Naranjo ADR probability scale, the majority of the ADRs (67.5%) were rated as probable followed by possible (32.4%). It was observed that the number of drugs used as well as the duration of stay in the hospital, in patients with ADRs, was significantly higher than those who did not have any adverse effect. The pattern and spectrum of ADRs need to be studied further so that their occurrence can be prevented. Conclusion: The study can be useful in identifying and minimizing preventable ADRs and can be an effort to make the use of drugs more rational and safe

Adverse drug reactions among major depressive disorders: patterns by age and gender

BackgroundAlthough a significant crisis of adverse drug reaction (ADR) among major depressive disorders (MDDs) is not uncommon, research in Ethiopia has been limited. As a result, the goal of this study was to estimate the prevalence rate of ADRs among MDD patients by age and gender at the outpatient department of Amanuel mental specialized hospital (AMSH) in Addis Ababa, Ethiopia. MethodThe study was conducted on 129 (61 men and 68 women) volunteers at the outpatient department of AMSH, Addis Ababa, Ethiopia, from November 2020–March 2021. A longitudinal cross-sectional study design was employed. All participants were between 35 and 72 years old, with a mean age of 49.5 (SD = 18.8). Patients who had been taking an antidepressant for at least one month and had a follow-up within the first three months after diagnosis and treatment initiation were included in the study. Antidepressant-related ADRs were assessed using the Naranjo ADR probability scale. Antidepressant side-effect checklist (ASEC) as all ADRs have been listed on it was also used to classify a mental state examination (MSE) into mild, moderate, and severe. ResultsAccording to this study, the overall prevalence of antidepressant-related adverse reactions among MDD patients was 69%, with females having a higher prevalence rate. One of the study's unexpected findings was that ADR was significantly (p = 0.039) higher in young study subjects than in the elderly (73.1% versus 66.2%, respectively). ADRs were shown to be substantially more common in patients taking polypharmacy than in mono-pharmacy (72.5% versus 65%, respectively). The bulk of the ADRs reported were likely, moderate, and probably avoidable. The most common adverse effects reported by patients in the current study were weight gain in TCAs, followed by sexual dysfunction with SSRIs, nausea or vomiting in MAOIs, and headache in SNRIs. The prevalence of ADRs was higher in MAOIs (80%), while SSRIs had the lowest (62.5%). The prevalence of ADRs varies depending on comorbidities: 62.7 % in the absence of comorbidities versus 74.3% in the presence of comorbidities (those with one or more comorbidities). ConclusionADRs that occur in MDD patients are considerable, and gender and age are associated with their occurrence. These findings underscore the importance of monitoring ADRs in mental outpatients frequently to recognize and decrease the risks posed by ADRs earlier. As a result, the quality of care may increase, total health care expenses may decrease, and adherence among patients with depression may improve.

ADHERENCE AND ASSOCIATED ADVERSE DRUG REACTION WITH ANTIDEPRESSANTS MEDICATION AMONG DEPRESSION PATIENTS IN PSYCHIATRIC HOSPITAL IN POKHARA, NEPAL

Background: The present study determined the prescription pattern of antidepressants, adverse drug reactions (ADRs), the level of adherence, and factors affecting it.
 Methods: This prospective cross-sectional study was conducted with depression patients (n=174; 55.74% female) from August 2019 to November 2019 at a psychiatric hospital of Pokhara, Kaski, Nepal. The Naranjo ADR Probability Scale was employed to assess the ADRs. The rate of medication adherence (MA) was determined using Morisky MA Measurement Scale-Eight. Descriptive statistics (median, interquartile range, frequency, and percentage), bivariate analysis, and Chi-square test were used; p<0.05 was taken as significant in multivariate analysis.
 Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be the most commonly prescribed antidepressants (58.04%) followed by serotonin and noradrenaline reuptake inhibitors (SNRIs; 13.79%). More than half of the patients had a low level of adherence (52.29%) and about 74.13% experienced ADR. The most common ADRs were insomnia (17.05%) and anxiety (17.05%). Female were found to be more non-adherent compared to male (odds ratio 1.011; 95% confidence interval; 0.507–1.832). The level of adherence was found to be associated with the probability and severity of ADR.
 Conclusion: The majority of patients used SSRIs. ADRs were more prevalent. However, adherence to medications was extremely poor in the hospital, which was attributed to factors such as gender, occupation, education, and ADRs.

Parallel Assessment of Chemotherapy Adherence and Supportive Therapy Adherence on Occurrence and Minimization of Adverse Drug Reactions Among Cancer Patients: A Clinical-Based Observational Study.

Background: Cancer is a disease that is inevitably treated using chemotherapy, but the cytotoxic drugs used in the treatment have the potency to cause adverse drug reactions (ADRs). Thus, supportive therapy plays an essential role in managing the untoward effects of the cancer drugs in patients. This highlights the importance of medication adherence in managing the disease, mitigating and preventing the occurrence of chemotherapy-induced ADR without compromising the health status of the cancer population. Objective: To assess the adherence to chemotherapy and supportive therapy and to evaluate type and degree of causality of ADRs observed in cancer patients. Methods: On ethics committee approval, a 6-month observational study was conducted among recruited cancer patients undergoing chemotherapy in a tertiary care hospital. Morisky Medication Adherence Measurement Scale-8 was employed to assess the medication adherence, and ADR causality was determined using Naranjo ADR Probability Scale. Results: Ninety cancer patients participated in the study, out of which females were 61.11%. Chemotherapy adherence in comparison to supportive drugs was observed to be more (21.11%). Twelve different combination of ADR were reported in the subjects with variability in the degree of causality assessment. Conclusion and Relevance: The distinction of adherence to the medication used in cancer management with marked level of ADR was well depicted in the study, implicating the necessity of prudent symbiotic practice of an oncology pharmacist, patient, and physician relationship in optimizing the quality of life of cancer patients by imparting vigilant efforts in medication adherence.

TheAssociation between Metformin Therapy and Lactic Acidosis.

There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally evaluate the association between metformin therapy and lactic acidosis in published case reports using two causality scoring systems, (2) to determine the frequency of pre-existing independent risk factors in published metformin-associated lactic acidosis cases, (3) to investigate the association between risk factors and mortality in metformin-associated lactic acidosis cases, and (4) to explore the relationship between prescribed metformin doses, elevated metformin plasma concentrations and the development of lactic acidosis in cases with chronic renal impairment. A systematic review was conducted to identify metformin-associated lactic acidosis cases. Causality was assessed using the World Health Organisation-Uppsala Monitoring Centre system and the Naranjo adverse drugreaction probability scale. Compliance to dosing guidelines was investigated for cases with chronic renal impairment as well as the association between steady-state plasma metformin concentrations prior to admission. We identified 559 metformin-associated lactic acidosis cases. Almost all cases reviewed (97%) presented with independent risk factors for lactic acidosis. The prescribed metformin dose exceeded published guidelines in 60% of cases in patients with impaired kidney function. Metformin steady-state plasma concentrations prior to admission were predicted to be below the proposed upper limit of the therapeutic range of 5mg/L. Almost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range.

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.

CASE REPORT ON DOCETAXEL-INDUCED INTERSTITIAL LUNG DISEASE

Docetaxel belongs to taxane family of antineoplastic agents that are indicated for the treatment of locally advanced or metastatic non-small-cell lung cancer. Docetaxel is associated with many adverse effects, and pulmonary reaction has an incidence of 41%. However, interstitial pulmonary disease is found to occur only in <1% of the population as per the post-marketing surveillance reports. Here, we report a case of docetaxel-induced interstitial lung disease (ILD). The patient information and details were collected using the hospital information system. The adverse drug reaction (ADR) of ILD occurred after 5 cycles of chemotherapy with docetaxel at a dose of 60 mg/m2 that is 80 mg IV. The causality of the event in our case was assessed using the Naranjo ADR probability scale which marked a score of 7 (probable). It is necessary that all physicians be aware of the reaction and to closely monitor clinicoradiological and functional status of the patients at regular intervals after administration of docetaxel.

Hypomagnesemia and exposure to romidepsin: A Research on Adverse Drug events and Reports (RADAR) project.

e14072 Background: Romidepsin (R) is indicated for cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma. Hypomagnesemia (HM) is common in these patients and is also listed in the Full Prescribing Information (FPI) for R. Moreover, since cardiac arrhythmias are associated with HM, patients exposed to R may be at higher risk. This study assessed whether HM was causally related to R exposure and to what extent magnesium (M) supplementation was undertaken in those with HM. Methods: We searched a large, U.S. patient data repository to detect all patients (aged 20-94 years) exposed to R (10/2010-01/2017). For these patients, serum M, as well as M supplementation data, was collected. Baseline M was assessed at initial R exposure, and HM was defined as either, a decline in M to < 1.8 mg/dL after R exposure or, in those with baseline M < 1.8 mg/dL, a decline in M by ≥0.1 mg/dL after R exposure. For each patient with HM after R exposure, the validated Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to determine the probability that HM was caused by R. Results: Of 51 R-exposed CTCL (or other lymphoma) patients, 25 (49.0%) had HM. Of these 25, NADRPS scores yielded: 1 doubtful, 16 possible, 8 probable and 0 definite. Additionally, 24 of 25 patients with HM had documentation for presence or absence of M supplementation: 9 (37.5%) had supplementation with M agents considered to be bioavailable, 12 (50%) received M agents considered to have low bioavailability, and 3 (12.5%) had no M supplementation. Conclusions: In this study population, 25 of 51 (49.0%) patients had HM after R exposure, which appears to nearly double the percentage of patients described in the FPI. Moreover, 8 of 25 (32%) patients with HM had causality attributed to R exposure. In addition, 15 of 24 (63%) patients with HM received M supplementation with agents considered to have low bioavailability or received no M supplementation. These findings support the need for ongoing monitoring of R-exposed patients with low M, as well as the importance of repleting M with agents considered to be adequately bioavailable. Also, given that HM appears to be more frequent in this study population compared to pre-marketing data in the FPI, further studies are warranted.

A clinical study of severe cutaneous adverse drug reactions and role of corticosteroids in their management

Background: Various medications are used for the treatment of various diseases. Ironically, adverse drug reactions (ADRs) also accompany the use of these medications and are as old as the medicine itself. These drug reactions can range from mild transient erythema at one end of the spectrum to severe cutaneous ADRs (SCADRS) that include Steven–Johnson syndrome (SJS), toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aim: This study aims to study the clinical and epidemiological aspects of severe cutaneous adverse drug reactions (SCADRS) at a referral center of Jammu region, with special reference to the role of corticosteroids in the management. Materials and Methods: The study was carried out between July 2015 and December 2015, at a tertiary hospital after permission from Ethical Committee of the institution. A total of 44 patients were included in the study which included outpatients as well as inpatients admitted after written informed consent. The Naranjo ADR probability scale was applied to indicate the causality of the drug with the SCADRS. Results: In the study, a total of 44 patients were included in the study. Males outnumbered the females, and maximum patients were in the age group of 21–40 years. SJS was the most common SCARD found followed by DRESS. Antiepileptic class of drug was found to be most commonly implicated. Immediate withdrawal of the culprit drug and administration of systemic steroids reverted the SCARD in maximum patients. Conclusion: Severe cutaneous adverse drug reactions can be associated with serious morbidity as well as mortality. Their knowledge and prompt recognition are essential for clinicians as early recognition, and immediate withdrawal of the culprit drug/drugs with adequate management can be lifesaving.

Self-Reported Adverse Drug Reactions, Medication Adherence, and Clinical Outcomes among Major Depressive Disorder Patients in Ethiopia: A Prospective Hospital Based Study.

Background There is paucity of data on prevalence of Adverse Drug Reactions (ADRs) and adherence and clinical outcomes of antidepressants. The present study determined the magnitude of ADRs of antidepressants and their impact on the level of adherence and clinical outcome. Methods A prospective cross-sectional study was conducted among depression patients from September 2016 to January 2017 at Gondar University Hospital psychiatry clinic. The Naranjo ADR probability scale was employed to assess the ADRs. The rate of medication adherence was determined using Morisky Medication Adherence Measurement Scale-Eight. Results Two hundred seventeen patients participated in the study, more than half of them being males (122; 56.2%). More than one-half of the subjects had low adherence to their medications (124; 57.1%) and about 186 (85.7%) of the patients encountered ADR. The most common ADR was weight gain (29; 13.2%). More than one-half (125; 57.6%) of the respondents showed improved clinical outcome. Optimal level of medication adherence decreased the likelihood of poor clinical outcome by 56.8%. Conclusion ADRs were more prevalent. However, adherence to medications was very poor in the setup. Long duration of depression negatively affects the rate of adherence. In addition, adherence was found to influence the clinical outcome of depression patients.

Cardiotoxicity associated with 5-flurouracil - A case series

5-flurouracil (5-FU) is a frequently administered chemotherapeutic drug in various malignant neoplasms. We report four cases of cancer patients who were exposed to 5-FU and which resulted in cardio toxicity. Patients developed supraventricular tachycardia, sinus bradycardia, cardiomyopathy, and acute coronary vasospasms. In all cases, the events were reversible. Except in case of cardiomyopathy the chemotherapy was continued without any further issues. All the observed adverse drug reactions (ADR) were carefully studied and the causality was assessed using Naranjo ADR probability scale.

Adverse drug reaction monitoring of antidepressants in the psychiatry out patient department at a tertiary care teaching hospital in India: A cross-sectional observational study

Background: Antidepressant drugs, though of great benefit in a range of psychiatric disorders, are associated with a wide range of potential adverse effects. There is growing concern among the healthcare personnel to assess these adverse drug reactions (ADRs) of newer psychotropic drugs, which have an impact on long-term compliance and achieving successful treatment. The present study was thus designed to monitor and analyze the pattern of occurrence of ADRs to antidepressant medications in Outpatient Department (OPD) of a tertiary-care hospital. Materials and Methods: A cross-sectional observational clinical study was carried out in the OPD of Psychiatry in Medical College, Kolkata. A total of 190 patients who received antidepressants were studied. 5-8 consecutive previously diagnosed depression patients attending follow-up per day, were screened for suspected ADRs, 2 days (one male OPD and one female OPD) in a week, over 6 months (October 2013 to March 2014). Adverse event history, medication history and other relevant details were captured in a format as adopted in the Pharmacovigilance Programme of India (PvPI). Causality of ADR was assessed by Naranjo's ADR probability scale. The severity of each reported ADR was assessed using Hartwig and Siegel Scale. All the statistical analysis was done by using SPSS-version 20 (SPSS Inc). Results: A total of 190 patients were screened for the study of which males and females represented 43.68% and 56.31% of the cases respectively. The age-group presenting with maximum depressive problems was found to be 30-39 years. A total of 481 ADRs were noted of which dry mouth was the commonest, closely followed by nausea and tremor. Out of 130 ADRs assessed for causality, 89.23% of the ADR cases, were found to be 'probable', while 10.77% were found to be 'possible'. According to Hartwig and Siegel's Scale 83.99% of the cases were found to be mild, 14.97% moderate and 1.04% severe. Conclusion: The study enables to obtain information on the incidence and pattern of adverse drug reactions associated with antidepressants in the local population thereby reducing its occurrence and protecting the user population from avoidable harm.

Adverse drug reactions in elderly patients following discharge from an internal medicine clinic.

The aim of this study was to evaluate the incidence and type of adverse drug reactions (ADRs) and identify risk factors for ADRs in elderly patients within 30 days following discharge from an internal medicine clinic. A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between September 1(st) and November 30(th) 2012. Patients aged ≥ 65 years discharged from the clinic during the study period were eligible for inclusion in the study. The follow-up visit was scheduled ~ 30 days after discharge. During the visit, the patients were assessed for the occurrence of ADRs. Two independent physicians evaluated each possible ADR by using the Naranjo ADR probability scale. Multivariate logistic regression analysis was used to identify predisposing factors for ADRs. There were 209 patients included in this study. A total of 72 ADRs were detected in 63 (30.1%) patients. The most frequent ADRs were bleeding disorders associated with warfarin therapy, followed by hypoglycemia associated with antidiabetics. Five (6.9%) ADRs, which resulted in hospital admission, were classified as serious. Multivariate logistic regression analysis indicated number of prescribed drugs ≥4 and prescription of furosemide and warfarin to be associated with increased risk of ADRs. Our study showed that ADRs are an important cause of morbidity in elderly patients after hospital discharge. Judicious prescription of drugs and careful and frequent monitoring of drug therapy are necessary to reduce the risk of ADRs.

EPA-0761 – The application of naranjo's adverse drug reaction (ADR) probability scale to elicit the direct correlation between NRG3 consumption and the onset of psychotic symptoms

Background NGR3 substance is usually in the form of a white powder that is consumed by humans to create a legal high; feelings of euphoria and reduce tiredness. It is a GHB analogue and when consumed turns into GHB in the body. A 40year old male patient who ingested NRG3 was admitted thrice with symptoms of hearing voices, hyperactivity, agression and the inability to sleep. Aim and objective To determine the probability of onset of psychotic symptoms as an effect of ingestion of NRG3. Methodology To apply Naranjo's ADR probability scale and on the basis of the weighted questions of the scale, which examine factors such as temporal association of drug administration and event occurrence, alternative causes for the event, drug levels, dose-response relationships and previous patient experience with the substance NRG3. Results Using the scale, the score indicated that there was a definite adverse drug reaction with NRG3. Conclusions A definite adverse drug reaction of psychotic symptoms did occur with the ingestion of NRG3.

Two cases of hallucination in elderly patients due to a probable interaction between flu immunization and tramadol

Annual vaccination against influenza (FluV) is indicated forindividuals at risk of developing medical complicationsbecause of underlying pathological conditions [1]. Most ofthese patients are likely to be exposed to drug treatmentsoccasionally characterised by a narrow therapeutic index.The possible effects of FluV on the metabolism of thesedrugs have not been investigated in detail [2].We report on an adverse drug reaction (ADR) in two elderlypatients, a woman and a man aged 85 and 84 years, respective-ly, highly homogeneous in terms of pathological manifesta-tions, who developed hallucinations after the administration ofFluV (Vaxigrip® and Intanza®, respectively). Both patients atthe moment of vaccination had been receiving treatment withtramadol for several months due to chronic lumbar pain.The female patient had tolerated tramadol (100 mg/day)well, and no interactions were evident with the concomitanttherapy (Table 1). Six days after vaccination she developedhallucinations resulting in equilibrium imbalance and a majorfall. Neurological examinations carried out in the EmergencyDepartment (ED), including computed axial tomography(CAT) scan, did not reveal organic causes. The neurologistsuspecting the iatrogenic nature of the hallucinations,suspended the tramadol treatment and the hallucinationsdisappeared within 36 h. The following day, the patient de-cided to take 100 mg of tramadol and once again developedhallucinations with confusion and amnesic episodes. She wasadmitted again to the ED, and a second neurological examalso did not reveal any organic cause for the symptoms.Tramadol treatment was suspended and the hallucinationsdisappeared once again, this time within 48 h.In the male patient tramadol (25 mg/day) had also beenwell tolerated; no interactions were evident with the con-comitant therapy (Table 1). Five days after vaccination thepatient was hospitalised for hallucinations, psychomotoragitation, hypotension and malaise. Tramadol withdrawalled to an improvement in the severity of the hallucinations,which completely disappeared in 2 days. The neurologicalexaminations including CAT scan did not reveal possibleorganic causes.The Naranjo ADR probability scale indicates a “proba-ble” relationship between the female patient’s developmentof ADRs and therapy with tramadol, and a “possible” rela-tionship for the male patient. In both patients tramadol waswell tolerated, and ADRs developed in both cases only afterimmunisation against influenza. Both patients denied usingherbal remedies.Tramadol is inactivated by cytochrome P450 (CYP) 3A4and CYP2B6 [3, 4] and metabolised by CYP2D6 to itsactive metabolite M1. FluV decreases CYP3A4 activity,with peak inactivation occurring 7 days after vaccination[5, 6]. This reduction in CYP3A4 activity is greater inelderly people [5] and is consistent with the time course of

Behavioral activation secondary to antidepressant use in an intellectually disabled woman

INTRODUCTION The under-appreciation for and potential lack of recognition of medication-related adverse effects in persons with intellectual disabilities (ID) can be a function of a variety of factors, including under-recognition of the prevalence of psychopathology in those with IDs compared to the general population, rating scales completed by the caregiver rather than the patient, low familiarity of healthcare needs by this special population, and lack of consensus criteria for diagnostic purposes. Recognition and management of unintended medicationrelated effects may represent an area for clinical interventions and quality of life improvement for practitioners, especially pharmacists working with this population. We present a case of a woman with significant intellectual impairment who became increasingly agitated, aggressive, and self-injurious following initiation of an antidepressant.

Quinine-induced bronchiolitis obliterans and organizing pneumonia

Quinine is a vital anti-malarial drug used in the management of resistant Falciparum malaria. There are previous reports of quinine-induced pulmonary edema and infiltrates. We report the first case of biopsy-proven bronchiolitis obliterans organizing pneumonia (BOOP), confirmed by the Naranjo Adverse Drug Reaction Probability Scale (NADRS) of 5 and a severity scale of 5, secondary to intravenous quinine, in a 15-year-old girl with Plasmodium falciparum infection after a visit to Kenya. Clinical course of the patient followed by review of the literature and appropriate medical interventions for quinine-induced BOOP are suggested.

Monitoring of incidence, severity, and causality of adverse drug reactions in hospitalized patients with cardiovascular disease

Background:Patients admitted to cardiology department are mostly on polypharmacy. So drug-drug interactions and adverse effects of drugs are quite common. Yet, there is a paucity of data regarding adverse drug reaction (ADR) monitoring in cardiology department in India. The present study is an effort to fill up these lacunae.Materials and Methods:A prospective, observational study registering 966 indoor cardiology patients according to predetermined inclusion and exclusion criteria was conducted for one year. ADR profile was noted by spontaneous reporting and intensive monitoring. Naranjo ADR probability scale was used to establish the causality.Results:A total of 208 ADRs were reported from 188 patients (19.5%). Of these 188 patients, 62 patients (33%) were hospitalized primarily due to the development of ADRs, while 126 (67%) patients developed ADRs during hospital stay. Nitrates were the most common offender drug group (17.8%).Conclusion:Development of ADR in one of every five cardiac patient points toward a grave situation, but a higher incidence of Type A reactions in cardiology department means that these can be avoided.

Establishing Causality of CNS Depression in Breastfed Infants Following Maternal Codeine Use

We recently reported on a breastfed infant who succumbed to opioid toxicity following exposure to morphine, the active metabolite of codeine, which was prescribed to his mother who was a cytochrome P450 2D6 (CYP2D6) ultrarapid metabolizer. This report is believed to be the first case of neonatal fatality as a direct result of maternal drug excretion into breast milk and, therefore, it is critical to corroborate the causative relationship between maternal codeine use during breastfeeding and neonatal opioid toxicity with other existing evidence. To establish whether maternal use of codeine can be a cause of CNS depression in breastfed infants. A systematic review of the medical literature using several databases was conducted. The Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to examine causality. In addition to our case report, three abstracts and two full-length studies reported adverse drug reactions (ADRs) in infants exposed to codeine in breast milk. In total, 35 infants were identified. Specifically, ADRs were described as unexplained episodes of drowsiness, apnea, bradycardia, and cyanosis in suckling infants. Using the NADRPS, codeine was found to be a definite cause of CNS depression in breastfed infants. The use of codeine by breastfeeding mothers can cause adverse CNS events in breastfed infants. Physicians should recognize codeine use during breastfeeding as a cause of CNS depression in infants, and breastfeeding mothers should be educated on these adverse events before receiving codeine.