Clinical assessment of pediatric pharmacotherapy and its predictors at tertiary care hospitals of Peshawar, Pakistan

Abstract

Pediatric pharmacotherapy aims to ensure safe and effective use of drugs in various population of children. However, due to varied pediatric pharmacokinetic drug profile and lack of pediatric drug data as compared to adults, it is difficult to achieve the optimal drug therapy in pediatrics. Studies regarding dosage errors, drug interactions, unlicensed and off label drug use in pediatric population will help the health care professionals in identification and management of drug interactions as well as unlicensed and off label drug use. Patient drug profiles of 4240 patients were evaluated using Micromedex Drug-Dex and Drug-Reax at pediatric department in four tertiary care hospitals of Pakistan (3 public and 1 private). The association between studied risk factors was analyzed using logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). In pediatric surgical units, total of 895 patients drug profiles were analyzed which described mean number of drug was 3.51 ± 1.50. Of all the patients, 351 (39.21%) had sub-therapeutic doses and 67 (7.48%) had overdoses, while 148 (16.54%) patients were exposed to DDIs. A total of 11 drug combinations were observed that led to 160 DDIs. Overall, 3168 drugs were prescribed of which 1931 (64.89%) were unlicensed and 1542 (48.67%) were off labeled. Indication (38.71%) and dose (34.82%) were the most frequent off label categories in all the therapeutics classes. Chi square value revealed that unlicensed drug use was significantly associated with the type of hospital (p<0.0001). A significant association was also found between unlicensed (p<0.0001) and off label (p<0.031) drug prescribing with age groups. Multivariate binary logistic regression analysis revealed that infants (OR 4.092, 95%CI 2.272-7.370) and children (OR 2.691, 95%CL 1.581-4.581) age groups were 4 times and 2.6 times respectively more likely to receive unlicensed medicines, while they were significantly less likely, Abstract v (OR 0.270, 95%CI 0.109-0.667) and (OR 0.320, 95%CL 0.133-0.769), to receive off label medicines than adolescent group. Pediatric patients receiving less than 5 medications were significantly less likely to receive unlicensed drug (OR 0.105, 95%CL 0.051-0.213) and off-label drugs (OR 0.117, 95%CL 0.42-0.323) as compared to pediatric patients that received 5 or more medications. Male patients were 2.1 times more likely to receive unlicensed medicines (OR 2.103, 95%CL 1.507-2.937), while they received substantially less amount of off-label medicines (OR 0.685, 95%CL 0.458-1.024) as compared to females. Hospital stay of less than 5 days (OR 0.397, 95%CL 0.228-0.629) carried significantly less risk of off label prescription as compared to patients staying at hospital for more than 5 days. In the pediatric medical wards of all the hospitals 1375 patients were analyzed. The mean number of prescribed drugs per patient was 3.93 ± 1.85. Analysis of 1375 cases revealed sub-therapeutic doses in 571 (41.2%) cases while overdoses was observed in 136 (9.89%) cases. In 1375 medical ward patients, 239 (17.38%) had at least one DDI regardless of type of severity. A total of 101 interacting drug pairs were identified causing 417 drug-drug interactions, while 100 drugs were prescribed 5708 times, of which 65.66% prescriptions were unlicensed by FDA. The percentage of off label prescriptions were 52.99%. Evaluating off label drug categories showed that dose (35.7%) and age (19.4%) were the highest reason observed for off label prescriptions. Significant association was found between unlicensed drug use with type of hospitals (p<0.001). A significant association was also found between unlicensed (p<0.002) and off label (p<0.0001) use of drugs with age groups. Multivariate binary logistic regression revealed that pediatric patients receiving drugs 5 or less drugs were significantly less likely to receive unlicensed prescriptions (OR 0.112, CL95% 0.027- Abstract vi 0.461) and off label drugs (OR 0.180, CL95% 0.073-447) as compared to patients who received 5 or more drugs. Analysis of 250 patients in the cardiology ward of HMC revealed the mean number of prescribed drugs to be 4.67±2.07. Of all the patients, 59.69% had sub-therapeutic doses and 5.52% had overdoses while132 (52.8%) had at least one DDI regardless of type of severity. Out of total drug prescriptions (1231), 43.05% were unlicensed and 44.59% were off labeled. In multivariate analysis, occurrence of unlicensed prescriptions were significantly more likely associated with infants (OR 10.288, CL 1.839-57.547) and children (OR 12.822, CL 2.004-62.025) age group as compared to adolescent group, while infant (OR 5.850, CL 1.131-30.246) age group was significantly 5.8 times more likely to receive off label prescription as compared to adolescent group. Among 1300 neonatal patients, 192 (14.76%) were premature in all nurseries of four tertiary care hospitals. Mean number of prescribed drugs were 2.85±1.35, while 358 (27.5%) had sub-therapeutic doses and 50 (3.8%) had overdoses. At least one DDI was present in 7.38% patients and a total of 21 drug combinations attributed to 112 DDIs. A total of 52 drugs were prescribed 3448 times, of which 1150 (33.35%) were unlicensed and 1798 (52.14%) were off labeled. Dose (61.29%) and indication (13.68%) were the most frequent off label categories in all the therapeutics classes. Chi square value determine that unlicensed drug use was significantly associated with the type of hospital (p<0.0001) and age groups (p<0.0001). Off label drug prescribing was also significantly associated with age groups (p<0.001). Multivariate binary logistic regression analysis showed that neonatal patients of age 0 to 7 days (OR 1.355, 95% 1.021-1.799), were significantly less likely to receive off unlicensed prescriptions as compare to reference age group. Male patients (OR 1.355, 95%CL 1.021-1.799) were significantly 1.3 times more exposed to receive unlicensed medicines compared to Abstract vii females. Neonatal patients of age 0 to 7 days (OR 1.631 (1.048-2.536) were also significantly 1.6 times more likely to receive off label medication as compared to patients of age 22 and above days. Of 420 patients admitted in pediatric intensive care units, the mean number of prescription per child was 4.13 ± 2.19, while 175 (41.66%) had sub-therapeutic doses and 54 (12.85%) had overdoses. Moreover, 74 (17.61%) patients had at least one DDI regardless of type of severity which were due to 41 interacting drug combinations leading to 156 DDIs. A total of 96 different drugs were prescribed 2453 times. Of these, 29.8% prescriptions were unlicensed from FDA and 42.27% were off label prescriptions. Dose (340, 32.79%) and indication (26.13%) was the highest reason for off label prescriptions. Multivariate regression analysis showed that patients receiving medications less than 5 (OR 0.280, 95%CL 0.137-0.570) were significantly less likely to receive off label prescriptions as compared to patients received 6 or more medications. In conclusion, prevalence of dosage errors and drug interactions was found to be higher in pediatric cardiology unit. A high prevalence of unlicensed and off label prescriptions was also observed in the present study which showed poor pediatric pharmacotherapy of our region. Increased number of prescribed drugs and infant age group were found to be significant predictors for unlicensed as well as for off label drug use. Unlicensed and off label drug use can also lead to adverse drug events. Therefore, to avoid exposing pediatrics to unnecessary risks, activities of health regularity agencies and perhaps, extra incentives are required to encourage the proper evidence based pediatric prescribing.