ABSTRACT
Title
Prescription of potential drug-drug interaction in two Italian Regions
Authors
E. Tragni1, M. Casula1, V. Pieri1, G. Favato1, A. Marcobelli2, M.G. Trotta3, AL Catapano1
1-Epidemiology and Preventive Pharmacology Centre (SEFAP), Dept of Pharmacological Sciences, University of Milan, Italy
2-Regional Health Authority (ASSR) Marche, Ancona, Italy
3-Regional Health Authority (ASSR) Basilicata, Potenza, Italy
1-Epidemiology and Preventive Pharmacology Centre (SEFAP), Dept of Pharmacological Sciences, University of Milan, Italy
2-Regional Health Authority (ASSR) Marche, Ancona, Italy
3-Regional Health Authority (ASSR) Basilicata, Potenza, Italy
Abstract
Background. Drug-drug interaction (DDI) are a concern for patients and providers, as multiple medication use is becoming more common to manage complex disease. The consequences of DDIs can range from no untoward effects to drug-related morbidity and mortality. Although DDIs are considered preventable medication-related events, studies have found that up to 11% of patients’ experience symptoms associated with DDIs, and DDIs are responsible for up to 2.8% of hospital admission.
Aim. The objective of this study was to estimate the prevalence of prescriptions of relevant "potentially interacting drugs" in two Italian Regions and to examine possible predictors of potential DDI (pDDI) exposure, such as age and sex of patients and number of prescribed drugs.
Methods. A retrospective follow-up study of outpatient prescription data was conducted. We analysed all drug prescriptions dispensed from 1 January 2004 to 31 August 2005 to all individual registered under the Regional Health Authorities of Basilicata and Marche, central and southern Italian Regions, respectively, with a population of almost 2,1 millions individuals. We identified 27 couples of drugs, potentially interacting, on the bases of clinical relevance, documentation and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected for analyses.We used DDDs from the ATC/DDD system to construct a proxy measure of days supply. We assumed days supply for a particular prescription to be equal to the total amount of drug with that prescription divided by DDD. Several patterns of co-medication can be defined. In this paper two patterns are evaluated: co-prescribing is defined as “the jointly prescribing of more than one drug by the physician in the same day”; concomitant medication is defined as the prescription of two drugs with coverage overlapping in time, according to information from the pharmaceutical database. These pattern cover co-medication resulting from the use of drugs as recommended by medical doctors. A logistic regression analysis was conducted to examine patients characteristics as predictors of pDDIs.
Results. The study population included 2,081,422 plan participants. 957.553 subjects (54.4% female) (46.0% of study population) were exposed at least to 1 of the 25 drugs/classes of the 27 pairs, that could be captured using the Basilicata and Marche databases. These pDDIs occurred 2,465,819 times (Sof the number of concomitant prescriptions of each patient) in the population in 2004-2005 period. Considering concomitant prescriptions, males/females ratio was >1 in 10/27 (37%) pairs of drugs, with the highest value for omeprazole+clopidogrel pair (0.74) and the smallest value for NSAIDs-ASA+SSRI pair (0.31). Considering concomitant prescriptions the lowest mean ages (59.1±15.7; 60.0±15.4) regarded methotrexate in both its pairs (omeprazole; NSAIDs-ASA). Only for one pair (digoxin+verapamil) the mean age of involved patients was ≥75 years. In 13/27 (48%) the mean ages were ≥70 years. All subjects involved in pDDI received several drugs during observation period; in 35/54 (68%) cohorts the number of drugs prescribed were ≥10.
The most commonly identified potentially interacting medication pair was warfarin and non-steroidal anti-inflammatory drugs (12,492 subjects with prescriptions of both drugs in the examined period; 7581 with concomitant prescription, and 2804 with co-prescriptions). Odds of exposure were generally highest among subjects aged 65 years or older, males, and those with more chronic conditions taking a higher number of drugs.
Conclusions. A substantial number of clinically important pDDIs were identified, particularly among warfarin users. Awareness of the most prevalent pDDIs can help practitioners in preventing concomitant use of these potentially dangerous medication combinations, thus ameliorating quality of drug prescription and potentially avoiding unwanted side effects.
Aim. The objective of this study was to estimate the prevalence of prescriptions of relevant "potentially interacting drugs" in two Italian Regions and to examine possible predictors of potential DDI (pDDI) exposure, such as age and sex of patients and number of prescribed drugs.
Methods. A retrospective follow-up study of outpatient prescription data was conducted. We analysed all drug prescriptions dispensed from 1 January 2004 to 31 August 2005 to all individual registered under the Regional Health Authorities of Basilicata and Marche, central and southern Italian Regions, respectively, with a population of almost 2,1 millions individuals. We identified 27 couples of drugs, potentially interacting, on the bases of clinical relevance, documentation and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected for analyses.We used DDDs from the ATC/DDD system to construct a proxy measure of days supply. We assumed days supply for a particular prescription to be equal to the total amount of drug with that prescription divided by DDD. Several patterns of co-medication can be defined. In this paper two patterns are evaluated: co-prescribing is defined as “the jointly prescribing of more than one drug by the physician in the same day”; concomitant medication is defined as the prescription of two drugs with coverage overlapping in time, according to information from the pharmaceutical database. These pattern cover co-medication resulting from the use of drugs as recommended by medical doctors. A logistic regression analysis was conducted to examine patients characteristics as predictors of pDDIs.
Results. The study population included 2,081,422 plan participants. 957.553 subjects (54.4% female) (46.0% of study population) were exposed at least to 1 of the 25 drugs/classes of the 27 pairs, that could be captured using the Basilicata and Marche databases. These pDDIs occurred 2,465,819 times (Sof the number of concomitant prescriptions of each patient) in the population in 2004-2005 period. Considering concomitant prescriptions, males/females ratio was >1 in 10/27 (37%) pairs of drugs, with the highest value for omeprazole+clopidogrel pair (0.74) and the smallest value for NSAIDs-ASA+SSRI pair (0.31). Considering concomitant prescriptions the lowest mean ages (59.1±15.7; 60.0±15.4) regarded methotrexate in both its pairs (omeprazole; NSAIDs-ASA). Only for one pair (digoxin+verapamil) the mean age of involved patients was ≥75 years. In 13/27 (48%) the mean ages were ≥70 years. All subjects involved in pDDI received several drugs during observation period; in 35/54 (68%) cohorts the number of drugs prescribed were ≥10.
The most commonly identified potentially interacting medication pair was warfarin and non-steroidal anti-inflammatory drugs (12,492 subjects with prescriptions of both drugs in the examined period; 7581 with concomitant prescription, and 2804 with co-prescriptions). Odds of exposure were generally highest among subjects aged 65 years or older, males, and those with more chronic conditions taking a higher number of drugs.
Conclusions. A substantial number of clinically important pDDIs were identified, particularly among warfarin users. Awareness of the most prevalent pDDIs can help practitioners in preventing concomitant use of these potentially dangerous medication combinations, thus ameliorating quality of drug prescription and potentially avoiding unwanted side effects.