Prospective observational evaluation of incidences and implications of drug-drug interactions induced adverse drug reactions in critically ill patients.

The primary aim of this study is to identify and analyze the importance of adverse drug reaction due to drug-drug interaction as a contributing factor towards drug safety. Patients more than 18 years of age admitted in multidisciplinary intensive care unit of a tertiary care hospital were included in this study. Patients who stayed less than 48 h and patients in whom all treatment modalities have been withdrawn and were on comfort measures only (no drugs were prescribed), were excluded. All the drugs that were given during intensive care unit stay were checked for presence of potential interactions which led to adverse drug reaction. Drug-drug interactions that were detected clinically or through investigations were recorded and also any therapeutic actions taken for drug-drug interactions were noted. From June 2006 to April 2007, 400 patients-prescriptions were analyzed. Adverse drug reactions due to drug-drug interactions were identified in 64% patients. Among those patients 38.67% had a single drug-drug interaction. Potential drug-drug interactions were 602. Clinically significant drug-drug interactions among the potential were 208 (34.55%). Clinically relevant drug-drug interactions were 103 (49.52% of 208 episodes). The adverse drug reactions due to drug-drug interactions in our sample were managed either by substituting another drug (50.48% of 103 episodes) or by adjusting the dose (1% of 103 episodes) or by omitting the drug (48.54% of 103 episodes). Among the 208 observed drug-drug interactions induced adverse drug reactions 21.63% was severe drug-drug interactions induced adverse drug reactions, 23.08% was moderate drug-drug interactions induced adverse drug reactions and 55.29% was minor drug-drug interactions induced adverse drug reactions. The interactions which were life threatening and/ or require medical intervention to minimize or prevent serious adverse effects were considered as severe drug-drug interactions and those interaction which resulted in an exacerbation of the patient's condition and/ or require an alteration in therapy were considered as moderate drug-drug interactions. The interactions which were limited clinical effects and manifestations may include an increase in the frequency or severity of side effects but generally would not require a major alteration in therapy were classified as minor drug-drug interactions. The correlation coefficient was 0.86 between the number of drugs given to the patient & number of average potential adverse drug reactions found among the patients. Increase in number of prescribed drug significantly (one way) increases number of potential adverse drug reaction due to drug-drug interaction (p<0.0001). Critically ill patients are more susceptible to drug-drug interactions due to the administration of multiple drugs and complex drug combinations. Several drug-drug interactions were clinically irrelevant.