Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences.

BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

Drug Utilization Study of Gastroprotective Agents in Medicine and Surgery Wards of a Tertiary Care Teaching Hospital.

Introduction Drug utilization research (DUR) is "the marketing, distribution, prescription, and use of drugs in a society, with special emphasis on the resulting medical, social, and economic consequences" as per the definition of the World Health Organization (WHO). The ultimate goal of DUR is to evaluate whether the drug treatment is rational or not. Various gastroprotective agents are available today, such as proton pump inhibitors, antacids, and histamine 2A receptor antagonists (H2RAs). Proton pump inhibitors block the gastric H+/K+-adenosine triphosphatase (ATPase) via covalent binding to cysteine residues of the proton pump to inhibit gastric acid secretion. Antacids are compounds containing different combinations, such as calcium carbonate, sodium bicarbonate, aluminum, and magnesium hydroxide. Histamine 2A receptor antagonists (H2RAs) decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and action of the endogenous ligand histamine. A recent literature review has shown that inappropriate use of gastroprotective agents has increased the risk for adverse drug reactions (ADRs) and drug interactions. Methods A total of 200 inpatient prescriptions were analyzed. The extent of prescribing, dosing information given, and cost incurred on the use of gastroprotective agents in both surgery and medicine inpatient departments was assessed. Prescriptions were also analyzed using WHO core indicators and for drug-drug interactions. Results Proton pump inhibitors were prescribed to 112 male patients and 88 female patients. The most common diagnosis was diseases of the digestive system with 54 (27.5%) cases, followed by diseases of the respiratory tract with 48 (24%) cases. Out of 200 patients, 51 comorbidities were reported from 40 patients. Among all prescriptions, injection of pantoprazole was the most common route of administration (181 (90.5%)), followed by tablets of pantoprazole (19 (9.5%)). The most common dose prescribed of pantoprazole was 40 mg in 191 (95.5%) patients in both departments. The frequency of therapy was also most commonly prescribed twice daily (BD) in 146 (73%) patients. Potential drug interaction was most commonly found with aspirin in 32 (16%) patients. The total cost incurred on proton pump inhibitor therapy of the medicine and surgery departments was 20,637.4 Indian Rupees (INR). Of this, the cost for patients admitted in the medicine ward was 11,656.12 INR and in the surgery department was 8,981.28 INR. Conclusion Gastroprotective agents are a group of drugs that are used to protect the stomach and the gastrointestinal tract (GIT) from acid-related injury. Our study found that proton pump inhibitors were the most commonly prescribed gastroprotective agents among inpatient prescriptions, with pantoprazole being the most frequently used. The most common diagnosis among patients was diseases of the digestive system, and most of the prescriptions were for injection administration at a dose of 40 mg twice daily. These findings suggest that there may be opportunities for improvement in the rational use of gastroprotective agents to reduce the risk of adverse drug reactions and interactions and lower healthcare costs. Overall, the study highlights the need for healthcare providers to be aware of the appropriate use of gastroprotective agents to minimize irrational prescriptions and reduce polypharmacy.

Treatment outcome of different antiretroviral drug regimens in HIV-positive pregnant women.

OBJECTIVE: The objective of the study was to compare the maternal and fetal outcomes of currently preferred tenofovir-based regimen with previous zidovudine-based regimen and also to determine whether the time of starting antiretroviral therapy (ART), whether it can affect the pregnancy and fetal outcome. MATERIALS AND METHODS: Pregnant patients prescribed any of the above regimens were followed up every month till delivery and newborns for initial 6 months. Maternal endpoints were body weight, hemoglobin, and CD4 count, whereas fetal endpoints were birth weight, Apgar score, body weight, and HIV status at 6 months. Data were analyzed using ANOVA and unpaired t-test. P <0.05 was considered statistically significant. RESULTS: A significant increase in CD4 count was observed in patients treated with both the regimens at 12 months as compared to baseline (P < 0.001 and 0.05). Moreover, a significant increase in CD4 count was observed at 12 months as compared to baseline, whether treatment was started before or after the diagnosis of pregnancy (P < 0.05 and 0.001). A significant difference in mean body weight at the end of 9 months was observed in patients wherein ART was started before or after the diagnosis of pregnancy (P < 0.005). Majority of patients had a favorable maternal outcome, while fetal birth weight, Apgar score, body weight, and HIV status were comparable at 6 months irrespective of treatment and time of starting ART. CONCLUSION: All ART regimens are equally effective in terms of increase in CD4 count, gestational gain in body weight, and pregnancy and fetal outcome. Furthermore, there is no significant difference in efficacy, pregnancy, and fetal outcome in women who were already on ART when diagnosed pregnancy or who were started ART later in antenatal period.

Analysis of Cutaneous Adverse Drug Reactions Reported at the Regional ADR Monitoring Center.

INTRODUCTION: Skin is one of the major target organ for adverse drug reactions (ADRs). The incidence of dermatological ADRs among indoor patients in developed countries ranges from 1-3%, whereas in developing countries such as India, it is 2-5%. AIMS: To analyze the clinical spectrum, seriousness, outcome, causality, severity, and preventability of the cutaneous ADRs. MATERIAL AND METHODS: All cutaneous ADRs reported at the Regional Adverse Drug Reaction Monitoring Center between January 2013 to May 2016 were identified and evaluated. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and the Naranjo'a reactions (ADRs) Severity (Hartwig and Seigel scale), and preventability (Schumock and Thornton criteria) of a said drug. RESULTS: Out of 2171 ADRs reported during study period, 538 were cutaneous ADRs (24.78%). The most common clinical presentation was maculopapular rash (58.92%) followed by itching (10.59%), and Stevens-Johnson syndrome (4.83%). The time relationship of cutaneous ADRs to drug therapy revealed that they can develop within 1 week to 1 year of treatment. Most common causal drug groups were antimicrobials (46%), non-steroidal anti-inflammatory drugs (NSAIDs) (18%), and antiepileptics (10%). Polypharmacy was observed in 7% of the cases. Most of the cutaneous ADRs were non-serious (91%), however, 10 were life-threatening and 1 was resulted in death due to the Stevens-Johnson syndrome. Causality category for majority of cutaneous ADRs was possible. Although majority of cutaneous ADRs were moderately severe (81%), however, not preventable (89%). CONCLUSION: The occurrence of cutaneous ADRs is common and they developed within 1 week of therapy. Antimicrobial agents and NSAIDs are the most common implicated drug class. Hence, physicians should closely monitor the patient in the first week while using such therapy for early detection and prevention of cutaneous ADRs.

An analysis of adverse drug reactions in extremes of age group at tertiary care teaching hospital.

OBJECTIVES: To analyze clinical spectrum, seriousness, outcome, causality, severity and preventability of ADRs in geriatrics and pediatric patients. MATERIALS AND METHODS: All ADRs reported in geriatrics (≥ 65 years) and pediatrics (≤ 12 years) indoor as well outdoor patients from January, 2010 to April, 2016 at ADR monitoring centre, Department of Pharmacology, B. J. Medical College and Civil Hospital were identified. A retrospective analysis was carried out for clinical presentation, causality (as per WHO-UMC scale and Naranjo's algorithm), severity (Hatwig and Seigel scale) and preventability (Schaumock and Thornton criteria). RESULTS: Out of 3690 ADRs, 160 were in geriatric patients (4.33%) while 231 in pediatric patients (6.26%). The most commonly affected body system was gastrointestinal (53, 33.13%) followed by neurological disorders (26, 16.25%) in geriatric patients. While in pediatric patients, the most commonly affected body system was skin and appendages (73, 31.60 %) followed by gastrointestinal disorders (58, 25.11%). The most common causal drugs in geriatric patients was cardiovascular (38, 23.75%) followed by antimicrobials (28, 13.25%). While in pediatric patients, the most common causal drug group was antimicrobials (85, 33.46%) followed by blood products (36, 14.12%). Total 17 ADRs reported following vaccination, 7 (41.17%) were injection site abscess and 11 (64.70%) were due to pentavalent vaccine. Polypharmacy was common in geriatrics (31, 19.37%). Causality assessment for majority of ADRs in geriatrics (83, 52.5%) and pediatrics (171, 67.32%) were probable. CONCLUSION: ADRs are common in geriatric and pediatric patients usually within four weeks of oral therapy. Active surveillance of drug safety monitoring in these vulnerable population is recommended.

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.

Treatment Outcome of Ovulation-inducing Agents in Patients with Anovulatory Infertility: A Prospective, Observational Study.

OBJECTIVE: To compare different treatment regimens on pregnancy rate and outcome in patients with anovulatory infertility. PATIENTS AND METHODS: A prospective observational study was conducted on patients with infertility due to anovulation. Patients treated with clomiphene citrate (CC) 50/100 mg/day from 2nd to 6th day of menstrual cycle (MC) (n = 38), short gonadotropin-releasing hormone (GnRH) agonist regimen (leuprolide [0.5 mg subcutaneous] + recombinant follicle-stimulating hormone [rFSH] [225 IU intramuscular [IM] from 2nd to 10th day of MC [n = 32]), long GnRH agonist regimen (leuprolide from 21st day followed by leuprolide + rFSH from 2nd to 10th day of MC [n = 19]), and antagonist regimen (human menopausal gonadotropin [hMG] [150 IU IM] from 2nd day followed by hMG + cetrorelix from 7th to 10th day of MC) (n = 6) were recruited and followed up for follicular size, endometrial thickness, and pregnancy test. Data were analyzed using appropriate statistical test andP < 0.05 was considered statistically significant. RESULTS: A significant increase in follicular diameter and endometrial thickness was observed in patients treated with gonadotropin regimens as compared to CC alone (P < 0.0001). The highest number of positive pregnancy test with ultrasonographic evidence of gestational sac was observed with leuprolide + rFSH (long regimen) (10/19, 52.6%) followed by leuprolide + rFSH (short regimen) (13/32, 40.6%) while least in antagonist regimen (2/6, 33.3%) and CC (1/38, 2.63%). All regimens were well tolerated. CONCLUSION: Treatment outcome was better with long agonist regimen.

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.

An analysis of serious adverse drug reactions at a tertiary care teaching hospital.

OBJECTIVE: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. MATERIALS AND METHODS: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria). RESULTS: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. CONCLUSION: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.

Critical Analysis of Cardiovascular and Central Nervous System Fixed Dose Combinations Available in Indian Market.

INTRODUCTION: Fixed Dose Combinations (FDCs) are being increasingly used to improve compliance and achieve greater benefits of the two or more active ingredients given together than the corresponding individual drug components given separately. AIM: To analyse the rationality of Cardiovascular (CV) and Central Nervous System (CNS) FDCs available in Indian market. MATERIALS AND METHODS: CVS and CNS FDCs, enlisted in Indian Drug Review, 2014, were analysed by a pretested validated eight point criteria tool. Each FDC was assessed for number of active pharmacological ingredients, approval by regulatory authority, listing in WHO Essential Medicine List. While efficacy, safety, pharmacokinetic, pharmacodynamic interactions and advantages of each FDC were analysed by literature search. The total score of the tool was 12 and score ≥7 was considered rational. FDCs were divided in four groups as per rationality and DCGI approval. ANOVA was used for statistical analysis and p<0.05 was considering statistically significant. RESULTS: Out of 152 FDCs, 107 were CV and 45 belonged to CNS group and 40 had documented evidence of efficacy and safety. Majority of FDCs showed advantage of being convenient by reducing pill count and only 32 showed reducing adverse drug reactions. Out of 107 CV FDCs, 46 were rational and 61 were irrational with a mean rationality score of 6.72±2.82 (CI- 95 %, 3.90 - 9.54). While out of 45 CNS FDCs, 8 were rational and 37 were irrational with a mean rationality score of 6.22±2.08 (CI - 95 %, 4.14 - 8.30). A significant difference in mean rationality score of group A (DCGI approved + rational) was observed as compared to group B (DCGI approved + irrational) and group C (DCGI unapproved + rational) as compared to group D (DCGI unapproved + irrational) (p<0.05). CONCLUSION: The absence of watertight pre-requisite, critical analysis of the scientific validity of the formulations and 'convenience' category has resulted into proliferation of irrational FDCs. This calls for strict regulatory approval process to avoid miserable FDC scenario in the country.

Tenofovir induced Fanconi syndrome: a possible pharmacokinetic interaction.

Tenofovir was introduced as a second line drug for the treatment of human immunodeficiency virus (HIV) infection in India in December 2009. Although rare, renal toxicity is a recognized adverse drug reaction (ADR) of this drug, especially when administered with boosted lopinavir-ritonavir. In this case, an HIV positive patient receiving tenofovir based antiretroviral therapy (ART) for last 1 year developed albuminuria, glycosuria and hypophosphatemia. Renal function tests and random blood sugar were within normal limits. He was diagnosed as a case of tenofovir induced Fanconi syndrome. Tenofovir was discontinued and patient was prescribed an alternate regimen. Five months later clinical symptoms and renal functions returned to normal. A pharmacokinetic interaction between tenofovir and ritonavir may have resulted in the toxicity. A periodic monitoring of renal functions is desirable in patients on tenofovir based ART.

Intensive monitoring of adverse drug reactions in hospitalized patients of two medical units at a tertiary care teaching hospital.

OBJECTIVE: To detect incidence of adverse drug reactions (ADRs) in hospitalized patients and to assess their causality, seriousness, preventability, and the possible economic impact. MATERIALS AND METHODS: This was a prospective study carried out in two medical units at a tertiary care, teaching hospital, for about 18 months. All the admitted patients who developed an ADR after admission (group A) or who were admitted primarily for the treatment of an ADR (group B) were included. Descriptive statistics with 95% CI, χ(2), χ(2) for the trend and kappa test were used. RESULTS: Out of 6601 patients, 140 patients developed 154 ADRs with an incidence of 2.12%. Causality of the majority of the ADRs in group A was 'possible' while those in group B was 'probable'. Among 109 ADRs (34 serious) in group A, 38 were preventable. On the other hand, out of 45 serious ADRs in group B, 19 were preventable. The total cost of 154 ADRs in 140 patients was Rs. 1,49,803 with an average of Rs. 1070 per patient. The preventable cost for 57/154 ADR was Rs. 96,310. CONCLUSION: Around 2% of the hospital patients develop ADRs. A large number of these ADRs were preventable. A substantial saving can be made if adequate caution is exerted.

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital.

OBJECTIVES: Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. MATERIALS AND METHODS: A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. RESULTS: A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). CONCLUSION: The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.

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.

Atorvastatin-induced pancreatitis.

Drugs account for 1-2% of all cases of pancreatitis. A 58-year-old man was prescribed atorvastatin 10 mg for 6 months for hyperlipidemia. He developed acute abdominal pain and vomiting with epigastric tenderness. Serum lipase and CT scan of the patient suggested the presence of acute pancreatitis. The patient was hospitalized; atorvastatin was stopped and treated symptomatically. He recovered completely within 10 days of drug withdrawal. The causality of the adverse drug reaction according to Naranjo and WHO-UMC Scale was probable. The exact mechanism of pancreatitis due to atorvastatin is not known. It may be a class effect of HMG CoA reductase inhibitors as it had been reported with other statins too. The definite causal relationship is difficult to establish, as rechallenge with the suspected drug was not done due to ethical consideration.