Pharmacovigilance and assessment of drug safety reports during COVID 19.

The speed and volume of clinical research to discover effective drug against novel corona virus has been remarkable. To address the unmet medical need, the regulations are made flexible and convenient without any relaxation in drug safety reporting. The pharmacovigilance activities, especially adverse event reporting regardless of clinical trials or clinical practice should continue as usual because patient safety is the priority. The exposure to experimental drugs with limited evidence of risk - benefit makes it more crucial to adapt robust safety monitoring, accuracy in adverse event reporting, and timely assessment. With the current restriction on physical contact, travel and free movements, isolation, quarantine, and huge clinical workload during pandemic, causality assessment will be more challenging. It may not be possible to capture details of all adverse events, thereby affecting completeness and quality of safety reports. A substantial number of COVID 19 patients will receive investigational drugs along with multiple other medications for clinical manifestations and drug therapy for lifestyle diseases. Causality assessment will be a challenge due to overlapping toxicities, multiple confounding, contributory factors, and insufficient data on safety and risk profile of combining drugs. Assessment will be unable to precisely determine the causality as certain or unlikely, although, it will be valuable in categorizing the causal association as "possible" adverse drug reactions and their scientific basis. Several of these detailed reports, when collated, can identify risk factors for possibilities of prevention or avoid harm. In the current situation of pandemic and uncertainty of experimental new and old repurposed drugs, causation needs to be viewed for the study drug with a public health perspective. After all, this is the best time tested approach to generate evidence and drug evaluation to prevent damage to prospective patients.

Early treatment outcome of bedaquiline plus optimised background regimen in drug resistant tuberculosis patients.

AIMS: Bedaquiline (BDQ) has been recently approved for drug resistant tuberculosis with active drug safety monitoring under programmatic condition. The present study was conducted to evaluate safety, tolerability and efficacy of bedaquiline plus optimised background regimen. METHODS: A prospective study was conducted on cohort of pre-extensively drug resistant (XDR) and XDR pulmonary TB patients. Eligible patients were closely monitored for cardiac safety, adverse events (AEs), clinical and microbiological improvement during BDQ (6 months) and post BDQ phase for twelve months. RESULTS: Of 127 patients enrolled, a significant increase in mean QTc interval was observed on 13th day and 3rd week as compared to baseline (p < 0.0001). Mean maximum increase of QTc was 37.92ms (95% CI, 14.1-61.74ms). Concomitant anti-TB medications, age, gender, low body mass index (BMI) had significant effect on QTc prolongation (p < 0.0001, p < 0.05). However, none of the patient required discontinuation of BDQ. Majority of AEs (86.3%) were non-serious and not preventable 108 (87.1%). The median time for sputum-culture conversion was 40.89 ± 3.5 days (95% CI, 34-48 days) and the treatment outcome was successful in 102 (80.3%) patients with negative sputum culture conversion. CONCLUSIONS: Bedaquiline containing regimen achieved favourable outcome. Although, bedaquiline along with concomitant anti-TB medications has the potential to prolong QTc interval, the benefit certainly outweighs the risk. This calls for a through pre-treatment cardiovascular and biochemical evaluation as a preventive measure and appropriate selection of patients for safe use of BDQ and successful outcome.

An analysis of the use of antimicrobial agents in outdoor patients of ophthalmology.

OBJECTIVES: The study was aimed to analyze commonly used antimicrobials in outdoor patients of ophthalmology department. MATERIALS AND METHODS: The study was an observational, cross-sectional study carried out in the Department of Pharmacology and Ophthalmology after approval from the head of departments and Institutional Ethics Committee. All the patients age 18 years and above who were prescribed antimicrobials and gave consent were included in study. Data were recorded in a case study form containing relevant patient information and results of general, ocular, and special examinations along with the details of antimicrobials prescribed. Data were analyzed according to the World Health Organization/International Network for Rational Use of Drugs indicators and appropriate statistical tests. RESULTS: A total of 900 patients who were prescribed antimicrobial agents (AMAs) were included in the study. The most common chief complaint was diminution of vision (25.78%). The most common indication of use of AMAs was for treating ocular infections (50.22%). The most commonly prescribed antimicrobial group was fluoroquinolone (FQ) (63.8%) and the most common drug was moxifloxacin (35.95%). The most common dosage form of AMAs was eye drops (68.55%). The average number of drugs per encounter was 4.41. The percentage of encounters with injectables prescribed was 0.67%. The percentage of use of antibiotics was 100%. The percentage of total drugs and AMAs prescribed by generic name was 41.5 and 11.92, respectively. The percentage of antimicrobial drugs prescribed from essential drugs list was 34.24%. The mean duration of antimicrobial therapy was 7.2 ± 4.54 days. CONCLUSION: More than half of the patients are prescribed multiple AMAs. Moxifloxacin, a newer generation FQ , was the most commonly prescribed AMA in our study. Educational interventions and strict adherence to hospital antimicrobial use policy are needed to restrict the use of AMAs and increase rational prescribing.

A safety analysis of different drug regimens used in human immunodeficiency virus-positive patients.

BACKGROUND: Long-term toxicity of antiretroviral agents is rarely addressed in initial clinical trials. Effective pharmacovigilance is essential for long-term safety of antiretroviral therapy (ART). MATERIALS AND METHODS: All adverse drug reactions (ADRs) reported due to ART between January 2014 and September 2016 were analyzed as per different drug regimens used. ADRs were also analyzed for system organ classification, seriousness, time relationship of ADRs with drug therapy, causality (as per the World Health Organization-Uppsala Monitoring Centre scale and Naranjo algorithm), and severity (Hartwig and Siegel scale). Comparison was done between (tenofovir + lamivudine + efavirenz [TLE]) and (zidovudine + lamivudine + nevirapine [ZLN]) regimens. RESULTS: During a study period, 2983 patients were on ART. The most common drug regimen prescribed was TLE (1805) followed by ZLN (326). A total of 325 (10.89%) ADRs were reported in which 150 ADRs were reported in TLE regimens (46%) and 130 in ZLN regimens (40%). The mean age of patients with ADRs was 40 ± 12.56 years and men (58.1%) were more affected than women (41.8%). The most common system organ involved in ZLN regimen was blood (50, 39%) and skin (35, 27%), while it was neurological (63, 42%) and renal disorder (27, 18%) in TLE regimen. Most of ADRs were observed after 1 month of therapy (79.5%) and showed possible causal relation with drug therapy (78.15%). Majority of ADRs were mild in nature (86.7%). The serious ADRs were reported more in ZLN (18%) regimen as compared to TLE (9%) (P < 0.05). CONCLUSION: Both ART regimens are associated with ADRs affecting all body system; however, the frequency and severity of ADR are high with ZLN regimen.

An Evaluation of Efficacy and Safety of Commonly Prescribed Drugs and Effect of These Drugs on Quality of Sleep in Patients Suffering From Zoster-Associated Pain.

This observational, prospective, single-center study was conducted to evaluate the efficacy and safety of commonly prescribed drugs for zoster-associated pain and their impact on quality of sleep at a tertiary care hospital in western India. Patients ≥18 years of age, newly diagnosed with zoster-associated pain were evaluated on days 0, 7, 14, 30, 60, 90, 120, 150, and 180 or until resolution of pain, whichever was earlier, using the Wong Baker FACES Pain Rating Scale, Neuropathic Pain Scale, and Insomnia Severity Index for intensity of pain, quality of pain, and quality of sleep, respectively. A total of 78 patients (46.0 [16.3] years) completed the study. They received nonsteroidal anti-inflammatory drugs (65), gabapentin (30), amitriptyline (27), and amitriptyline + gabapentin (21) for mean durations of 7.7 (3.0), 89.2 (7.2), 107.6 (46.3), and 104.5 (46) days, respectively. Improvement in the Wong Baker FACES Pain Rating Scale and Neuropathic Pain Scale score was similar among treatment groups except for a greater fall in Wong Baker FACES Pain Rating Scale score at days 7 and 120 and that in deep pain score at day 7 in combination treatment group vs the amitriptyline group. Clinically significant insomnia was detected in 35 patients at baseline and demonstrated progressive and similar improvement among groups. Treatment modification was required in 20 patients. Zoster-associated pain resolved in 69 patients. Nine adverse drug reactions, mostly mild, nonserious, and nonpreventable, were reported. To conclude, drugs commonly used for zoster-associated pain are effective and well tolerated. These have a similar effect on pain and quality of sleep, except for a possible greater effect of combination treatment in the early phase of intense and deep pain.

Comparison of Effect of Antidepressants on Psychomotor Functions.

OBJECTIVE: The comparison of the effect of antidepressants on psychomotor functions in patients with endogenous depression. MATERIALS AND METHODS: This prospective interventional study was carried out at a tertiary care teaching hospital on 95 literate patients with newly diagnosed endogenous depression matching inclusion and exclusion criteria. Patients were prescribed either desvenlafaxine (50 mg) or fluoxetine (40 mg) or sertraline (50 mg). Psychomotor functions were assessed by digit letter substitution, six letter cancellation, choice reaction time, hand steadiness and flicker fusion test at the baseline 1st month and 3rd month. Efficacy of drugs was also measured by Hamilton rating scale for depression. Data were analyzed by using ANOVA and P < 0.05 was considered as statistically significant. RESULTS: A total of 95 patients were enrolled. Fluoxetine, desvenlafaxine, and sertraline were prescribed in 32, 32, and 31 patients, respectively. At the end of 3 months, a significant improvement in psychomotor functions was observed in patients treated with sertraline (P < 0.05), while desvenlafaxine-treated patients did not show any significant change in any of the tests. Surprisingly, fluoxetine-treated patients showed deterioration in all psychomotor tests (P < 0.05). Hamilton rating score improved at the end of 3 months treatment as compared to baseline. Most commonly observed adverse reactions in all three drug groups were nausea (n = 20), dizziness (n = 3), headache (n = 20), and diarrhea (n = 3). CONCLUSION: Sertraline significantly improves psychomotor function as compared to desvenlafaxine while fluoxetine impairs.

Transfusion-related adverse reactions in pediatric and surgical patients at a tertiary care teaching hospital in India.

BACKGROUND: Use of blood and its components is lifesaving. However, their use is often associated with adverse events. OBJECTIVE: To analyze the pattern of adverse reactions associated with transfusion of blood and its components in pediatric and surgical patients at a tertiary care teaching hospital. MATERIALS AND METHODS: Patients receiving transfusion of blood or its components in a randomly selected unit each from Departments of Pediatrics, including thalassemia OPD and surgery, were monitored intensively for a period of 6 months. Clinical course, management, outcome, causality, severity, seriousness, and preventability of observed transfusion reactions (TRs) were analyzed. RESULTS: A total of 411 pediatric and 433 surgical patients received 594 and 745 transfusions respectively during the study period. Of these, TRs were observed in 69 (11.6%) children and 63 (8.4%) surgical patients. Majority of reactions in children (48, 69.5%) and surgical patients (51, 80.9%) were acute, developing within 24 h of transfusion. TRs were observed with packed cells (13.2%), cryoprecipitate (10%), platelet concentrate (14.3%) and fresh frozen plasma (1.3%) in pediatric patients and with packed cells (7.2%), whole blood (25%) and platelet concentrate (62.5%) in surgical patients. Most common TRs included febrile nonhemolytic TRs (FNHTRs) and allergic reactions. Reactions were more frequent in patients with a previous history of transfusion or those receiving more than one transfusion and in children, when transfusion was initiated after 30 min of issue of blood component. Majority of reactions were managed with symptomatic treatment, were nonserious, moderately severe, probably preventable and probably associated with the suspect blood component in both populations. CONCLUSION: Transfusion reactions in children and surgical patients are commonly observed with cellular blood components. Majority of reactions are acute and nonserious. FNHTRs and allergic reactions are the most common transfusion reactions. Risk of transfusion reactions is more in patients receiving multiple transfusions.

An evaluation of drug promotional literatures published in scientific medical journals.

OBJECTIVES: Evaluation and comparison of ethical standards of published drug promotional literatures (DPLs) between different Indian and non-Indian scientific medical journals regarding compliance to the World Health Organization (WHO) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMAs) guidelines. MATERIALS AND METHODS: A cross-sectional, observational study was carried out at pharmacology department. DPLs published in Indian and non-Indian scientific medical journals available at central library of medical college during the period of 6 months were collected according to selection criteria. DPLs were evaluated and compared for compliance to ethical standards of drug promotion laid by the WHO and IFPMA. Data were analyzed using Fisher's exact test. RESULTS: Out of total 178 DPLs, 103 DPLs were from Indian journals and 75 DPLs were from non-Indian journals. When compared regarding compliance to all the 11 ethical criteria of WHO, no significant difference was found between DPLs published in Indian and non-Indian journals. However, DPLs from indian journals contained significantly less information regarding dosage regimen (P = 0.0096), adverse drug reactions (P = 0.0028), warnings (P = 0.0104) and major drug interactions (P < 0.0001) as compared to non-Indian journals. Compliance to all the five IFPMA criteria was significantly higher in DPLs of non-Indian journals (88%) than Indian journals (39%) (P < 0.0001). CONCLUSION: Noncompliance to ethical standards of WHO and IFPMA guidelines is more common in DPLs of Indian journals as compared to non-Indian journals. Thus strict implementation of regulatory measures regarding DPLs published in Indian medical journals is recommended.

Evaluation of impact of teaching clinical pharmacology and rational therapeutics to medical undergraduates and interns.

OBJECTIVES: To find out the impact of teaching clinical pharmacology and rational therapeutics (CPT) to medical undergraduates (UGs) and interns. MATERIALS AND METHODS: This cross-sectional, prospective study was conducted on three UGs batches and interns using two pretested validated structured questionnaires, modified from the work of Tobaiqy et al. The study was approved by the Institutional Ethics Committee. ANOVA and Chi-square test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. RESULTS: A total of 379 UGs and 96 interns participated in this study. Mean knowledge score of interns was significantly reduced as compared to UGs (P < 0.0001). A significant increase in confidence for unsupervised prescribing of nonsteroidal anti-inflammatory drugs (99%), oral rehydration salt, iron salts was perceived among interns as compared to UGs (P < 0.05). However, 63.5% confessed problems in selection of drugs, drug-drug interactions, prescribing in special patient population. Although they were confident prescribing fixed dose combination for adult patients (89.5%), majority were hesitant to prescribe opioids (77%), steroids (76%), vaccines (75%), and antihypertensives (62%). CONCLUSION: The theoretical CPT teaching transfers knowledge to UGs; however, it is not retained in internship and does not adequately prepare interns to prescribe safe and rational drugs.

A Survey of Knowledge, Attitude, and Practice of Consumers at a Tertiary Care Hospital Regarding the Disposal of Unused Medicines.

OBJECTIVES: To evaluate the knowledge, attitude and practice of consumers in India about disposal of unused medicines. MATERIALS AND METHODS: A questionnaire comprising 11 questions evaluating the Knowledge (2), Attitude (3) and Practice (6) of unused medicines was prepared and pre validated before administering to 200 consumers of medicines attending the outpatient department of Civil Hospital Ahmedabad, a tertiary care teaching hospital in Western India. Requisite permissions from Institutional Ethics Committee and informed consent were obtained prior to recruiting them for the study. Responses were recorded, in Microsoft Excel® spreadsheet and evaluated for percentage response. RESULTS: Majority of the respondents (136, 68%) stored unused medicines at home. Analgesics (26.5%) were the most common unused medicine stored. Safe disposal of medicine was considered necessary by majority respondents (160, 80%) for different reasons like prevention of illegal/unintended use (84, 42%), prevention of environmental pollution (32, 16%) or possible ADR caused by old drugs (54, 27%). Only 78 (39%) respondents were aware of appropriate methods of disposal. Disposal in household trash (61, 30.5%) was the most common method used. Majority of respondents felt the need for a facility or programme to collect unused medicines (152, 76%) and an increased awareness among consumers regarding hazards and methods of disposal of unused medicines (154, 77%). CONCLUSION: Majority of consumers are aware about the need for safe disposal of unused medicines. But the right attitude for and practice of safe disposal of medicines is lacking. A need for increased awareness regarding safe disposal of medicines is acknowledged by majority of consumers.

Steroid-induced central serous retinopathy.

A-24 year-old male was prescribed prednisolone (60 mg/day) for left sided facial palsy. After three days of therapy, the patient complained of black spots in his vision in right eye. Fluorescein angiography of right eye showed evidence of central serous retinopathy (CSR). Prednisolone dose was withdrawn gradually and the patient improved within a week. There were no other systemic or ophthalmic diseases reported by the patient, which could have caused this condition. An improvement after dechallenge confirmed steroid-induced CSR. Recurrent CSR is known to cause permanent loss of vision. Hence, awareness regarding this adverse drug reaction (ADR) with steroids and its reporting can minimize this complication and help in better patient management.