Vivek Mahajan

Under-reporting of adverse drug reactions: A challenge for pharmacovigilance in India

Aim: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. Materials and Methods: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. Results: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. Conclusion: UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.

Antihypertensive drug prescription patterns, rationality, and adherence to Joint National Committee-7 hypertension treatment guidelines among Indian postmenopausal women

Aim of Study: The aim of this study is to evaluate antihypertensive drug prescription patterns, rationality and adherence to Joint National Committee (JNC-7) hypertension (HT) treatment recommendations among Indian postmenopausal women (PMW). Materials and Methods: An observational and cross-sectional prospective prescription audit study was carried over a period of 1 year. A total of 500 prescriptions prescribed to PMW for diagnosed HT, were identified for one point analysis. Drug prescription patterns/trends, and their adherence to JNC-7 report as well as rationality using WHO guide to good prescribing was assessed. Results: In the monotherapy, category angiotensin receptor blockers (ARBs) accounted (24.8%), calcium channel blockers (CCBs) (19.4%), angiotensin converting enzyme inhibitors (ACEIs) (11%), beta blockers (BBs) (2.8%), and diuretics (2%) of the total prescription. Individually, amlodipine was maximally prescribed in 16.4%. 31.6% had double combination, whereas 2.2% and 1% had triple and four drug combinations, respectively. About 3.6% of the prescription contained antihypertensive combination along with other class of drug. ARBs + diuretic were observed in 11%, CCBs + BB 10% and ACEI + diuretic in 2.6% of the total prescriptions. Among the combination therapy amlodipine + atenolol (8.4%), telmisartan + hydrochlorothiazide (6%) and losartan + hydrochlorothiazide (4.4%) were maximally prescribed. 84.21% (P < 0.001) of the prescription showed nonadherence as per recommendations for pre-HT. 100% and 43.25% adherence rates were noticed for Stage 1 HT (P < 0.001) and Stage 2 HT (P > 0.05) patients. Conclusion: Antihypertensive prescription trends largely adhere to existing guidelines and are rational except polypharmacy, generic and fixed dose combinations prescribing, were some of the common pharmacologically considered irrationality noticed.

Cycloserine induced psychosis with hepatic dysfunction

With the increase in the cases of multidrug resistance tuberculosis, second line anti-tubercular drugs like the cycloserine are being prescribed frequently. Isoniazid and ethambutol are reported to cause psychosis like state; however, few reports of cycloserine induced psychosis are available. To the best of our knowledge, this is the first case of cycloserine induced psychosis with hepatic dysfunction.

Adverse drug reactions profile of antimicrobials: A 3-year experience, from a tertiary care teaching hospital of India

Aim of Study: To evaluate adverse drug reaction (ADR) profile of antimicrobials over 3-year period. Material and Methods: A retrospective cross-sectional study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India (PvPI). Results: A total of 2,586 ADR events were recorded in 3 years, out of which 392 (15.15%) were because of antimicrobials. Male: female was 1.02:1. Medicine department contributed maximally (98.97%). The intravenous (IV) route of drug administration accounted maximum ADRs (53.32%), followed by oral route (45.41%). Monotherapy was responsible for 80.87%, whereas combination therapy for 19.13%. Combinations therapy was irrational in 79.67%. The most common antibiotic resulting in ADRs was injection ceftriaxone (35.71%), followed by tab. azithromycin (7.39%), tab. ofloxacin + ornidazol (5.35%), ofloxacin (3.57%), ciprofloxacin (2.29%), amoxicillin (2.55%), tab. cefixime (2.29%), inj. linezolid (2.04%). Rash remained the most common ADR, followed by diarrhoea and gastritis. Most common organ system involved was dermatological (47.44%), followed by gastrointestinal (GI) (39.28%), central nervous system (CNS) (5.35%), cardiovascular system (CVS) (3.57%) and renal and genitourinary (1.78%). While 47.96% ADR′s were latent, 26.785% were acute and 25.26% were sub-acute. Moreover, 89.79% of ADRs were moderate in nature, whereas 26.88% were severe and 3.33% mild in nature. Furthermore, 92.86% were non-serious and 7.14% serious in nature. Also, 65.06% of antimicrobial caused ADRs were type A and 34.64% were type B reactions. As per World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) scale, 73.98% of ADRs were probable/likely and 26.02% as possible. However, 99.47% of ADRs required intervention. Conclusion: The current study suggest that ADRs due to antimicrobials is a significant health problem.

Pregabalin-induced self-harm behavior

Antiepileptic Drugs (AEDs) such as lamotrigine, gabapentin, and oxcarbazepine may have the potential to increase the risk of self-harm or suicidal behavior. We report a case of pregabalin-induced self-inflicted multiple injuries on forearm after its continuous use. This is an interesting adverse drug reaction (ADR) that is rare, unusual, and potentially serious.

Amisulpride Augmentation in Acute Catatonia

Benzodiazepines are the first-line treatment of catatonia, but a substantial number of patients do not respond to them. Amisulpride is one of the atypical antipsychotic that has been effective for negative symptoms of schizophrenia. We examined the effect of augmentation of oral low doses of amisulpride with lorazepam on resolution of catatonic symptoms. Fifteen patients with catatonia were treated with a combination of oral lorazepam (2–4 mg) with amisulpride (100 mg). Catatonic symptoms were rated using the Bush Francis Catatonia Rating Scale at the baseline and daily thereafter. There was complete resolution of catatonic symptoms on the third day in all patients. There was significant reduction of the total Bush Francis Catatonia Rating Scale score over time (F = 181.38, P < 0.001) with a strong effect size (partial &eegr;2 = 0.96). Augmentation of lorazepam with low-dose amisulpride can be a reliable strategy for management of catatonia.

Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India.

Background & objectives: Drug-induced diseases (DIDs) are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR) data collected form Pharmacovigilance Programme of India (PvPI) to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. Methods: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. Results: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99%) accounted for maximum DIDs followed by adult (37.79%) and paediatric (8.21%). Maximum events were probable (93.98%) followed by possible (6.04%). All DIDs required intervention. Gastritis (7.43%), diarrhoea (5.92%), anaemia (4.79%), hypotension (2.77%), hepatic dysfunction (2.69%), hypertension (1.51%), myalgia (1.05%), and renal dysfunction (1.01%) were some of the DIDs. Anti tubercular treatment (ATT), anti retroviral treatment (ART), ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. Interpretation & conclusions: Our findings show that DIDs are a significant health problem in our country, which need more attention.

Bleomycin Containing Chemotherapeutic Regimen Induced Acquired Partial Lipodystrophy.

Bleomycin toxicity predominantly affects the skin and lungs. Cutaneous toxicity classically known to present with bleomycin are flagellate erythema and drug rash. We hereby report an isolated case of (bleomyicn)-induced acquired partial (lipodytrophy) having potential cosmetic implications in a young women prescribed postoperatively following a case of germ cell carcinoma of ovary (endodermal sinus tumor).

Cilnidipine induced ankle edema.

Cilnidipine is a 4th generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema.

Fatal adverse drug reactions: Experience of adverse drug reactions in a tertiary care teaching hospital of North India - A case series

Medical burden of fatal adverse drug reactions (FADRs) is significant. The epidemiological data on FADR do exist from the western world, but there is scanty from India. We hereby report a case series of FADRs recorded in a 2 years period. Point prevalence of FADRs was 0.223%. Point prevalence of all cause death in the hospital was 1.20%. The drugs causing FADRs were injection bupivacaine, amphotericin B, directly observed treatment short-course Category-1, injection streptokinase, and tablet ferrous sulfate. All these FADR were labeled as possible expect one case as probable. All FADR were labeled as type A. In three out of five the central nervous system was involved, while the hepatic system and multiorgan failure accounted for one case each. Two cases each were acute and subacute, while one was latent in nature. Reporting of FADRs shall go a long way in patient safety.