Adverse drug reaction monitoring in a secondary care hospital in South India

Aims

To ascertain the current burden of ADRs at a Government hospital in Ooty and to assess the severity of reported ADRs and the additional financial burden associated with ADRs.

Methods

A prospective, spontaneous reporting study was conducted over a period of 9 months of inpatient admissions to the medical wards, co-ordinated by clinical pharmacists. The WHO definition of an ADR was adopted. The Naranjo algorithm scale was used for causality assessment. Confirmed ADRs were classified according to the Wills & Brown [7] method and assessed for severity and patient outcomes. The average cost incurred in treating the ADRs was calculated.

Results

Of the total of 187 adverse drug events (ADEs) reported, 164 reports from 121 patients were confirmed as ADRs, giving an overall incidence of 9.8%. This included 58 (3.4%) ADR related admissions and 63 (3.7%) ADRs occurring during the hospital stay. About two thirds of the reactions (102, 62.2%) were classified as probable. The majority of the reactions (88, 53.7%) were mild. Most patients (119, 72.6%) recovered from the incidence. The majority of the reactions were of type H (100, 61%) which indicates that they were not predictable and not potentially preventable. An average cost of 481 rupees (£6) was spent on each patient to manage ADRs.

Conclusions

The incidence and severity of ADRs documented in our study are lower than those reported in comparable populations in Western studies but more than those reported in India.

What is already known about this subject

• The benefits of adverse drug reaction (ADR) monitoring are well-known.
• Poor awareness and nonavailability of a central co-ordinating body resulted in lack of ADR monitoring in India.
• The National Pharmacovigilance Programme was recently initiated, encouraging ADR monitoring in selected centres, including our centre.

What this study adds

• This is the first study of its kind at GHQH, Ootacamund that has provided insight into the burden of ADRs here.
• The incidence and severity of ADRs documented in our study is lower than those reported in comparable populations in Western studies but more than those reported in India.

     

Information about adverse drug reactions reported in children: a qualitative review of empirical studies

AIM

To review the literature on adverse drug reactions (ADRs) in children with respect to occurrence, seriousness, type, therapeutic group, age and gender of the child and category of reporter.

METHODS

Medline and Embase databases were searched from origin and updated until February 2010. We included empirically based articles on ADRs in populations aged 0 to 17 years. Studies monitoring ADRs in patients with particular conditions or drug exposure were excluded. We extracted information about types and seriousness of ADRs, therapeutic groups, age and gender of the child and category of reporter. ADR occurrence was calculated as incidence rate and prevalence.

RESULTS

We included 33 studies monitoring ADRs in general paediatric populations. The highest numbers of ADRs were reported in national ADR databases where data were collected over a longer period than in studies monitoring inpatients and outpatients. However, prevalence and incidence were much lower in the national databases. Types of reported ADRs, seriousness of ADRs and types of medicines differed substantially between studies due to differences in time periods and patient populations. Information about ADRs was mainly provided by health care professionals, although parents also contributed reports.

CONCLUSIONS

We found a higher incidence rate of ADRs in hospitalized children and outpatients than in national databases. There seems to be considerable potential for increasing the knowledge of ADRs by advocating the submission of reports to the spontaneous reporting systems. Our study underscores that ADRs in children constitute a significant public health problem.     

Reported paediatric adverse drug reactions in the UK 2000-2009

AIMS

The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card Scheme) to collect ‘suspected’ adverse drug reaction (ADR) data. MHRA advice is to report all suspected ADRs in paediatric (<17 years) patients.

METHODS

Data on all ADRs reported to the MHRA in patients <17 years from the years 2000–9 were supplied in two datasets, inclusive and exclusive of vaccines.

RESULTS

Of 222 755 ADR reports received by the MHRA from 2000–9, 31 726 (14.2%) were in children <17 years. The number of reports in 2000 was greater than in subsequent years (12 035) due to a national vaccination programme (Meningococcal Serogroup C conjugate vaccine). The median number of ADR reports per annum (2001–2009) for children was 2146 (95% CI 1801, 2575). Vaccines were included in 22 102 (66.5%) paediatric ADR reports, with Meningococcal Serogroup C conjugate vaccine reported most frequently (12 106 reports) and headache the commonest symptom (3163). Excluding vaccines, methylphenidate (653 reports) and atomoxetine (491) were the most commonly reported medications, and the most commonly reported symptom was vomiting (374). Reporting by nurses increased from 396 in 2001 to 1295 in 2009 (41.8% of all reports); reporting by doctors stayed constant. Reports from patients, parents or carers more than doubled but remained infrequent (1.5% in 2005, 4.0% in 2009).

CONCLUSIONS

Although under-reporting is probably common, the Yellow Card Scheme in the UK receives more than 2000 reports per year on patients <17 years. Nurses now report more suspected ADRs in children than any other healthcare professional.     

Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol)

AIMS

Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P).

METHODS

All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference.

RESULTS

The reporting rate of ADRs was calculated as 24.9/100 000 person-years for DXP+P, 44.5/100 000 person-years for TRM+P and 12.5/100 000 person-years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P.

CONCLUSIONS

Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P.     

Pharmacist’s knowledge,practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process

Background

Adverse drug reactions (ADRs) are a major cause of drug related morbidity and mortality. Pharmacovigilance is the science that plays an essential role in the reduction of ADRs, thus the evolution and growth of this science are critical for effective and safe clinical practice.

Objectives

This study is considered the first study in the region to evaluate pharmacist’s knowledge, practice and attitudes toward ADRs reporting after establishing the national ADRs reporting center in Jordan.

Method

A cross sectional study was used to evaluate pharmacist knowledge and attitude toward ADRs reporting. A structured validated questionnaire was developed for this purpose and a total of 208 pharmacists were recruited to participate in this study.

Results

The majority of pharmacists have insufficient awareness and lack of knowledge about pharmacovigilance and ADRs reporting. Also the rate of reporting of ADRs was extremely poor. Several factors were found to discourage pharmacists from reporting ADRs, which include inadequate information available from the patient, unavailability of pharmacist ADRs form when needed, unawareness of the existence of the national ADRs reporting system. Also pharmacists think that ADRs are unimportant or they did not know how to report them.

Conclusion

The results of this study suggest that pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting. On the other hand, pharmacists had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting. Educational programs are needed to increase pharmacist’s role in the reporting process, and thus to have a positive impact on the overall patient caring process.     

Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review

Aims

A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children.

Methods

MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed.

Results

From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants.

Conclusions

Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base.     

Interpreting adverse drug reaction (ADR) reports as hospital patient safety incidents

AIM

In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications.

METHODS

ADRs identified in a 6-month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA.

RESULTS

Seven hundred and thirty-three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as ‘low’ (minor treatment), 181 (24.7%) as ‘moderate’ (moderate increase in treatment, no permanent harm), 14 (1.91%) as ‘severe’ (permanent harm) and 1 (0.14%) was categorized as ‘catastrophic’ (direct cause of death). In terms of impact on the organization, none was categorized as ‘no harm/ no risk’, 508 (69.3%) as ‘insignificant’, 188 (25.6%) as ‘minor’, 25 (3.4%) as ‘moderate’, 12 (1.6%) as ‘major’ and none was classed as ‘catastrophic’. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection.

CONCLUSIONS

Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card System. A consistent message needs to be sent to prospective reporters of ADRs; the availability of more than one system is likely to confuse reporters and does not aid patient safety.     

Comparing patients' and healthcare professionals' ADR reports after media attention: the broadcast of a Dutch television programme about the benefits and risks of statins as an example

AIMS

To compare adverse drug reaction (ADR) reports from patients and health professionals after the broadcast of a Dutch television consumer programme about the benefits and risks of statins.

METHODS

We performed a quantitative and qualitative analysis on patients'' and health professionals'' reports of ADRs to statins. These reports were received by the Netherlands Pharmacovigilance Centre Lareb between March 2007 and August 2007. Quantitative data consisted of patient age and gender, number of received reports and characteristics of the report (most frequently reported ADRs, seriousness, drug discontinuation and outcome of the reported reaction). Open text fields in the ADR reporting form were categorized and a content analysis was carried out.

RESULTS

Media attention led to a peak in patient reporting of ADRs but not in reporting by health professionals. There were no differences between patient and health professional reports in seriousness of the ADRs and drug cessation. Patients reported nonrecovery more often than health professionals. The TV programme is mentioned as a reason for drug discontinuation in almost 30 reports. Patients often felt that they did not receive sufficient information and that their concerns were not adequately addressed by healthcare professionals.

CONCLUSIONS

Media attention affects drug use and ADR reporting by patients. Patient reports can provide additional information, making them a useful source of information next to health professional reports. Content analysis provides vital insights into the impact of statins on daily life, and patients'' concerns about adverse reactions should be recognized in reports to national pharmacovigilance centres.     

Safety profile of enantiomers vs. racemic mixtures: it's the same?

AIMS

The objective was to investigate the safety profile of four drugs marketed as racemic and enantiomeric forms in France.

METHODS

Data from the French PharmacoVigilance Data Base (January 2005 to June 2010) were analysed for four pairs of racemic/isomeric drugs. A case–noncase approach was used to measure the disproportionality of combination between adverse drug reaction (ADR) and exposure to drug.

RESULTS

No significant difference in the number of ADRs was observed between Rac-cetirizine/(R)-cetirizine or Rac-citalopram/(S)-citalopram pairs. (S)-Omeprazole induced more haematological effects than Rac-omeprazole. Rac-Ofloxacin induced more haematological, renal and neuropsychiatric ADRs than (S)-ofloxacin, whereas levofloxacin was associated with more reports of musculoskeletal ADRs.

CONCLUSIONS

The profile of ADRs could differ for some drugs marketed as racemic and enantiomeric forms. Further studies would be necessary to confirm these data.     

Knowledge creation about ADRs – turning the perspective from the rear mirror to the projector?

Aims

Spontaneous reports of adverse drug reactions (ADRs) are often the only documentation used to justify the recall of drugs from the market. The purpose of this study was to investigate whether it would have been possible to foresee serious ADR cases based on available information on ADRs reported in Phase II and III clinical trials before marketing.

Methods

We conducted a retrospective analysis of reported ADR data in Phase II/III clinical trials in the registration material for three different ADR scenarios: (i) trovafloxacin/alatrofloxacin and hepatotoxicity; (ii) tolcapone and hepatotoxicity and neuroleptic malignant syndrome; and (iii) rituximab and cytokine release syndrome. We chose the scenarios because they were of serious character and caused great damage to the patients and because of different outcomes of the scientific discussions in the regulatory agencies.

Results

In all three cases, the registration material contained observations of ADRs, but there had been no follow-up on these observations. ADRs were mentioned in the summary of product information (SPC) purely as information, to some extent accompanied by recommendations. The information was not converted into new knowledge and remained tacit knowledge embedded in the SPCs disseminated to health professionals/prescribers.

Conclusions

The registration material analysed contained information about ADRs that were reported later, meaning that it would have been possible to foresee the occurrence of the ADRs at the time of licensing. More active utilization of the information from Phase II/III clinical trials is recommended to prevent the appearance of unexpected ADRs and further emphasis in SPC warnings to doctors about possible serious ADRs.

What is already known about this subject?

• Serious and unexpected adverse drug reactions (ADRs) have been reported shortly after marketing of a number of drugs.
• Review of ADR cases by the regulatory authorities has resulted in suspension of drugs or restrictions in product information.

What this study adds?

• Information about serious and unexpected ADRs of three drugs with reported serious ADRs was already present in the registration files.
• Observations of these ADRs were not investigated further before marketing.
• A more active utilization of the ADR information in premarketing studies could probably prevent the appearance of unexpected and serious ADR cases after marketing.

     

Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey

Aims

Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status.

Methods

We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was ‘possible’, ‘probable’ or ‘certain’ using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria.

Results

ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7).

Conclusions

In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support.     

Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase

AIM

To identify which drugs are associated with reports of suspected hepatic injury in children and adolescents.

METHODS

Using a worldwide pharmacovigilance database, VigiBase, we conducted a case/non-case study on suspected adverse drug reactions (ADRs) occurring in the population <18 years old. Cases were all the records with hepatic ADRs and non-cases were all the other ADR records. Records regarding topically administered drugs were excluded from both groups. The association between drug and suspected hepatic ADRs was calculated using the reporting odds ratio (ROR) as a measure of disproportionality while adjusting for gender, country, reporter and calendar year. Sub-analyses were performed within therapeutic class and by excluding vaccination-related reports to reduce confounding.

RESULTS

Overall, 6595 (1%) out of 624 673 ADR records in children and adolescents concerned hepatic injury. Most of the reported hepatic injuries concerned children 12–17 years of age. Drugs that were most frequently reported as suspected cause and were associated with hepatic injury comprised paracetamol, valproic acid, carbamazepine, methotrexate, minocycline, zidovudine, pemoline, ceftriaxone, bosentan, ciclosporin, atomoxetine, olanzapine, basiliximab, erythromycin and voriconazole. The association between hepatotoxicity and all these drugs, except for basiliximab, is already known.

CONCLUSIONS

Drug-induced hepatic injury is infrequently reported (only 1% of total) as a suspected ADR in children and adolescents. The drugs associated with reported hepatotoxicity (paracetamol, antiepileptic and anti-tuberculosis agents) are known to be hepatotoxic in adults as well, but age related changes in associations were observed. VigiBase is useful as a start to plan further drug safety studies in children.     

A computerized system for detecting signals due to drug–drug interactions in spontaneous reporting systems

AIMS

In spontaneous reporting systems (SRS), there is a growing need for the automated detection of adverse drug reactions (ADRs) resulting from drug–drug interactions. In addition, special attention is also needed for systems facilitating automated data preprocessing. In our study, we set up a computerized system to signal possible drug–drug interactions by which data acquisition and signal detection could be carried out automatically and the process of data preprocessing could also be facilitated.

METHODS

This system was developed with Microsoft Visual Basic 6.0 and Microsoft Access was used as the database. Crude ADR reports submitted to Shanghai SRS from January 2007 to December 2008 were included in this study. The logistic regression method, the Ω shrinkage measure method, an additive model and a multiplicative model were used for automatic detection of drug–drug interactions where two drugs were used concomitantly.

RESULTS

A total of 33 897 crude ADR reports were acquired from the SRS automatically. The 10 drug combinations most frequently reported were found and the 10 most suspicious drug–drug ADR combinations for each method were detected automatically after the performance of the system.

CONCLUSIONS

Since the detection of drug–drug interaction depends upon the skills and memory of the professionals involved, is time consuming and the number of reports is increasing, this system might be a promising tool for the automated detection of possible drug–drug interactions in SRS.     

Perceived adverse drug reactions among non-institutionalized children and adolescents in Germany

AIMS

Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non-institutionalized children in Germany.

METHODS

All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0–17 years who participated in the 2003–06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children''s parents and confirmed by trained medical professionals during the medical interview.

RESULTS

One hundred and fifty-seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders. Perceived ADRs were most frequently reported in relation to drugs acting on the nervous system (25.8%), followed by systemic anti-infectives (18.7%) and drugs acting on the respiratory system (16.2%). Risk factors for perceived ADRs included older age groups, polypharmacy (≥2) and a poor health status.

CONCLUSION

Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems.     

Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational study

Aims

To describe the frequency, nature and preventability of community-acquired and hospital-acquired adverse drug reactions (ADRs) in a South African hospital serving a community with a high prevalence of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome.

Methods

A 3-month prospective observational study of 665 adults admitted to two medical wards.

Results

Forty-one (6.3%) patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in hospital. Many of the ADRs (46.2%) were considered preventable, although less likely to be preventable in HIV-infected patients than in those with negative or unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital-acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but 60% of community-acquired ADRs at hospital admission were in patients <60 years old. Among patients <60 years old, those HIV infected were more likely to be admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17, 4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral therapy (ART) were more likely to be admitted with an ADR than those not receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs were fatal. Antibiotics and drugs used for opportunistic infections were implicated in two-thirds of hospital-acquired ADRs.

Conclusions

ADRs are an important, often preventable cause of hospitalizations and inpatient morbidity in South Africa, particularly among the elderly and HIV-infected. Although ART-related injury contributed to hospital admissions, many HIV-related admissions were among patients not receiving ART, and many ADRs were associated with medicines used for managing opportunistic infections.

What is already known about this subject

• Studies conducted primarily in developed countries have shown that adverse drug reactions (ADRs) are a significant cause of hospital admission, prolong hospital stay and consequently increase the cost of disease management in patients.
• Cardiovascular medicines, hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are the most frequently implicated medicines in these studies.
• A large proportion of these ADRs have been shown to be preventable through improved drug prescribing, administration and monitoring for adverse effects.

What this paper adds

• This is the first Sub-Saharan African study in the HIV/AIDS era that describes the contribution of ADRs to patient morbidity, hospitalisation and mortality.
• Cardiovascular medicines and antiretroviral therapy contributed the most to community-acquired ADRs at the time of hospital admission while medicines used for opportunistic infections (such as antifungals, antibiotics and antituberculosis medicines were most frequently implicated in hospital acquired ADRs.
• ADRs in HIV-infected patients were less likely to be preventable.

     

Detection of adverse drug reactions by medication antidote signals and comparison of their sensitivity with common methods of ADR detection

Objective

To determine the PPVs of selected ten medication antidote signals in recognizing potential ADRs and comparison of their sensitivity with manual chart analysis, and voluntary reporting recognizing the same ADRs.

Method

The inpatient EMR database of internal medicine department was utilized for a period of one year, adult patients prescribed at least one of the ten signals, were included in the study, recipient patients of antidote signals were assessed for the occurrence of an ADR by Naranjo’s tool of ADR evaluation. PPVs of each antidote signal were verified.

Result

PPV of Methylprednisolone and Phytonadione was 0.28, Metoclopramide and Potassium Chloride – 0.29, Dextrose 50%, Promethazine, Sodium Polystyrene and Loperamide – 0.30, Protamine and Acetylcysteine – 0.33. In comparison of confirmed ADRs of antidote signals with other methods, Dextrose 50%, Metoclopramide, Sodium Polystyrene, Potassium Chloride, Methylprednisolone and Promethazine seem to be extremely significant (P value > 0.0001), while ADRs of Phytonadione, Protamine, Acetylcysteine and Loperamide were insignificant.

Conclusion

Antidote medication signals have definitive discerning evaluation value of ADRs over routine methods of ADR detection with a high detection rate with a minimum cost; Their integration with hospital EMR database and routine patient safety surveillance enhances transparency, time-saving and facilitates ADR detection.     

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.     

Post-Marketing Surveillance of Levofloxacin 0.5% Ophthalmic Solution for External Ocular Infections

Background

Levofloxacin 0.5% ophthalmic solution is an antibacterial formulation, which was approved and marketed for the treatment of ocular infections in Japan in 2000.

Objective

This study was designed to investigate the safety and efficacy of levofloxacin 0.5% ophthalmic solution in patients who received treatment for external ocular bacterial infections in regular clinical practice.

Methods

Patients were recruited from more than 800 medical facilities in Japan, in accordance with Japanese Ministry of Health, Labour and Welfare ordinance guidelines. They were followed during three distinct time periods: April 2000 to December 2001, January 2002 to June 2003, and July 2003 to December 2004.

Results

Information from 6760 patients receiving levofloxacin for the treatment of a variety of ocular infections was collected. Levofloxacin was well tolerated: adverse drug reactions (ADRs) were reported in 42 of 6686 patients (0.63%), with no serious ADRs reported. The most commonly reported ADRs were ocular disorders such as blepharitis, eye irritation, and punctate keratitis. The incidence of ADRs did not differ significantly with age, but it was significantly higher in females (0.82%) than in males (0.36%; p = 0.028). A clinical response was observed in 95.5% of patients receiving levofloxacin, with no difference in response between the three time periods. The rate of response to levofloxacin by bacterial disease ranged from 97.4% in keratitis to 88.3% in dacryocystitis. The rate was lower in patients with dacryocystitis, elderly patients, patients with a long duration of illness, and relapsing cases (all p < 0.001).

Conclusion

This post-marketing surveillance of levofloxacin, conducted over 4 years, confirms the safety and efficacy of levofloxacin in regular clinical use and highlights that levofloxacin is a promising treatment for a variety of external ocular bacterial infections.