The study was retrospectively conducted from the ADR database of the National Pharmacovigilance Programme of India, included 17 hospitals from South India. The data was analyzed for the period of January 2005 to August 2009. The patient experienced Steven-Johnson syndrome or toxic epidermal necrolysis were included in the study. The ADR reports were analyzed for patient characteristics and classes of drugs involved.
Results: A total of 115 reports were analyzed from the database within the study period. 7 patients were died (6 %). Anti epileptic (40 %) and anti biotics (34 %) were the most commonly associated groups and it was followed by anti inflammatory (5.2 %), anti viral (3.5 %) drugs. Phenytoin (17.4 %) and carbamazepine (16.5 %) were the most common drug to cause SJS and TEN and those were followed by ciprofloxacin (5.2 %), diclofenac (3.5 %). Drug induced SJS/TEN were assessed by WHO-causality assessment scale revealed that 74 % of ADRs were probable, 18.3 % were possible, 2.6 % were certain.
Conclusion: Anti epileptics and anti biotics were the most commonly implicated drugs. This study brings out the importance for exercising precaution while prescribing these drugs for the patients and to ensure safer drug usage.
Get your grade
or your money back
using our Essay Writing Service!
Keywords: Adverse Drug Reaction, Steven-Johnson syndrome and toxic epidermal necrolysis.
Adverse drug reaction (ADR) has been defined by the World Health Organization (WHO) as "any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function".(1)
Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe cutaneous adverse drug reactions, may results in serious morbidity and mortality. SJS and TEN are variants of the same process, presenting as severe mucosal erosions with widespread erythematous, cutaneous macules or atypical targets. The cutaneous lesions often become confluent and show a positive Nikolsky sign and epidermal detachment.(15) In SJS, epidermal detachment involves less than 10% of the total body skin area; transitional SJS-TEN is defined by an epidermal detachment between 10 and 30%; TEN is defined by a detachment greater than 30%. (2)
Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the etiology remains unknown.(15) Mortality rates are 5% with SJS, 30-35% with TEN. (2) Extensive epidermal detachment to the entire skin surface, loss of epidermis, spreading of flaccid blisters, electrolyte imbalance, and high fluid loss occur in TEN. Genitalia, anus, eyes, and oropharynx are usually affected, widespread painful erosions result in impaired alimentation, photophobia, and painful micturition.(16) Necrosis of gastrointestinal or tracheo-bronchial epithelium my results in severe diarrhea or respiratory distress causing high morbidity. Blood abnormalities are almost always present. Immunologic alteration increases the risk of serious infections like sepsis. Even after the recovery, altered pigmentation and corneal lesions are the main long-term complications. (2, 3, 6).
The incidences of Stevens-Johnson syndrome and toxic epidermal necrolysis range from 1.2 to 6 per million per year and 0.4 to 1.2 per million per year, respectively.(4) Incidence and drug associated with risk of causing SJS - TEN is not clearly understood in India. Thus we conducted a retrospective study to find the association of specific drugs involved in causing Stevens-Johnson syndrome and toxic epidermal necrolysis and to provide better information on these reactions should help in medical decision making.
In our study we have analyzed the adverse drug reaction reports that were reported to Regional Pharmacovigilance Centre, Department of Pharmacology, JIPMER from 17 different hospitals of South India between the time periods January 2005 to August 2009. Reports of drug induced SJS - TEN in patients of all age group were included for the analysis. Besides JIPMER hospital, reports were received from Rajah Muthiah Medical College & Hospital, Chidambaram; PSG hospital, Sri Ramakrishna hospital; Coimbatore, Government Hospital, Ootacamunt; Amrita Institute of Medical Sciences, Kochi; JSS hospital, Sundara Clinic, Asha Kirana hospital, Mysore; Kasturba Medical College, Shirdi Saibaba Cancer hospital and Research Centre, Manipal; St. Martha's hospital, Victoria hospital, Sagar Apollo hospital, Bangalore, Sri Devarajur Medical College hospital, Kolar; JJM Medical College, Davangore; General Hospital, Chennai.
The ADRs were reported in a Suspected Adverse Drug Reaction Reporting form, provided by Central Drugs Standard Control Organization (CDSCO), Ministry of Health & Family Welfare, Government of India. All the suspected ADR reports were entered in the pharmacovigilance database and the data was extracted based on drug induced SJS - TEN in all age group. Either gender was included for the analysis. The ADRs were analyzed for patient characteristic, drugs involved and causality of the ADR. Causality of the ADR was analyzed using WHO Causality Assessment Scale where the ADRs are categorized as certain, probable, possible, unlikely, unclassified and unclassifiable.(5)
Always on Time
Marked to Standard
In the study period total of 7784 ADRs were reported, among them 115 were SJS / TEN. Among 115 reports 7 deaths were reported, caused by drugs ceftriaxone sodium, ciprofloxacin, penicillin, carbamazepine, terbinafine, acyclovir, isoniazid. The median age of the patients were 33 years (range 1-80 years). 50 (43 %) of them were female and 65 (57 %) were male. 84 (73 %) patients were affected by SJS and 31 (27 %) patients were affected by TEN. Some patients had SJS/TEN associated with bradycardia, hepatitis, pancytopenia, photophobia, mouth ulcers, sepsis, edema of eye.
Anti epileptic (40 %) and anti biotics (34 %) were the most commonly associated drug groups to cause SJS/TEN. Phenytoin, carbamazepine were the most common drugs in anti epileptic group and ciprofloxacin, levofloxacin were the most common drugs in anti biotic group in causing SJS/TEN. The other drug groups involved in causing SJS/TEN are given in table2. Top 5 drugs involved in causing SJS/TEN were shown in table 3. Phenytoin was the most commonly implicated drug with 17.4% report. The other common drugs involved were carbamazepine, ciprofloxacin, diclofenac, paracetamol. Drug induced SJS/TEN were assessed by WHO-causality assessment scale revealed that 74 % of the reactions were probable, 18.3 % were possible, 2.6 % were certain (Fig 1).
SJS/TEN is a life threatening adverse drug reaction with high rate of mortality and morbidity. Prevalence or incidence of drug induced SJS/TEN is lack in India. There are few retrospective studies were conducted in India, mostly based on limited samples. To the best of our knowledge this study is the largest study in India was conducted with more number of SJS/TEN cases. We found 115 cases of drug induced SJS and TEN. We found that anti epileptic (40 %) and anti biotics (34 %) were the most commonly implicated in causing SJS and TEN. Phenytoin, carbamazepine, Phenobarbital are the most common drug in anti epileptic group and ciprofloxacin, cotrimoxazole, penicillin are the most common drug in anti biotic group. More over male patient was most commonly affected by SJS/TEN. 7 deaths were reported with the mortality rate of 6%. Comparison of mortality rates of drug induced SJS/TEN with some other studies are shown in table 4.
A 6 year study by Khoo et al found 23 cases of SJS and TEN and they found that carbamazepine and Chinese medicine were the leading drugs to cause SJS and TEN. Among 23 cases 17 were female. 2 patients were died (10%).(7) A 3 years study by Rzany et al found 353 cases of erythema exsudativum multiforme (EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). 58 deaths reported (16.4%), among them 41 were females. Incidence of SJS and TEN in Germany is 1.89 cases per million populations per year. (8)
A 10 year study by Abarna et al found 46 case of SJS/Ten. In theirs study they found that antimicrobial were most common drug group to cause SJS/TEN with 32.6%. Five of the SJS/TEN cases died giving a mortality rate of 10.86%. (9) A 4 year study by Yap et al found 24 cases of SJS/TEN. They found that anticonvulsants were most common drug group to cause SJS/TEN with 36%. There were only 3 deaths noted with a mortality rate of 12.5%. (10)
A 7 year study by Siew-Kiang et al found 26 cases of drug induced SJS/TEN and anticonvulsants (35.7%) were the most common implicated drugs followed by antibiotics (28.5%).1 death was reported with a mortality rate of 3%. (11) A 3 year multi centric study by Barvaliya et al found 32 cases of SJS/TEN and found that anti microbial drugs were the most common drug to cause SJS/TEN (50%). And reported 1 death in SJS group and 4 deaths in TEN group, overall the mortality rate was 15.62%. (12) A study by Vinod et al found 30 cases of SJS/TEN and found that anticonvulsant drugs were commonly implicated in causing SJS/TEN with 35%. Reported 5 deaths with mortality rate of 16.66%. (13)
Most of the studies described were single hospital study, but our study was multi centric study. We found one banned drug Gatifloxacin in the list. More over Nimesulide the drug was banned in some other countries, this drug is still available in India and it caused 2 SJS in our study. The incidence of all drug reactions in the HIV-infected population is higher than in the general population . (14) We found 2 cases of SJS in AIDS patients, caused by Zidovudine + Lamivudine + Nevirapine (VIROCOMB-N) and Nevirapine.
This study concludes that anti epileptic and antibiotics are the more common drug groups to cause SJS/TEN. Phenytoin, carbamazepine, ciprofloxacin, diclofenac and paracetamol are the most common drug implicated in SJS/TEN. Before prescribing such drugs, especially in high risk patients (i.e. HIV positive), the possibility of TEN development should be taken into account. As the field of pharmacogenetics develops, there may come a time when patients who are genetically predisposed to serious cutaneous adverse reactions can be identified. This will allow for individualized therapies and prevention of unnecessary suffering.
This Essay is
a Student's Work
This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.Examples of our work