ABSTRACT
Title
Antiepileptic drugs: prescribing patterns and interaction risk in general practice.
Authors
M.S. Gagliostro1, R. Ferrara1, C. Sirianni1, C. Pagliaro2, I. Lombardi2, S. Moretti2, M. Tari2, A. Capuano3, E. Spina1, V. Arcoraci1.
1Department of Clinical and Experimental Medicine and Pharmacology, Pharmacology Unit, University of Messina, Italy; 2”Caserta-1” Local Health Unit, 3Pharmacovigilance and Pharmacoepidemiology Centre of Campania Region, Dept. of Experimental Medicine, Pharmacology Section, Second University of Napoli, Italy.
1Department of Clinical and Experimental Medicine and Pharmacology, Pharmacology Unit, University of Messina, Italy; 2”Caserta-1” Local Health Unit, 3Pharmacovigilance and Pharmacoepidemiology Centre of Campania Region, Dept. of Experimental Medicine, Pharmacology Section, Second University of Napoli, Italy.
Abstract
An increasingly use of antiepileptic drugs (AEDs) was observed in the last years particularly due to newer AEDs. Co-administration of drugs in clinical practice increases the risk of drug interactions. Aims of the study: To explore the trend of use of older and newer AEDs, to assess the exposure to potential interactions between AEDs and other drugs in a general practice setting of Southern Italy.
Methods: Data were extracted from the Arianna database that currently contains information about a population of almost 150,000 individuals living in Caserta and registered in 118 general practitioners’ (GPs) lists. Patients aged over 14 who received at least one AED prescription during 2004-2009 were identified. The use of newer and older AEDs was calculated as one-year prevalence and incidence; AEDs consumption was evaluated as DDD 1000/inh day. Clinically relevant interacting drugs were identified and the risk of drugs interactions was calculated as overlapping days between the exposition days of AEDs and interacting drugs. Sub-analyses by gender, age and indication of use were performed.
Results: Most of patients treated with older AED were affected by epilepsy (50,9%) while newer AED users were mainly treated because of pain (73.1%). Prevalence of older AED use slightly increased during the observational period (from 10.0/1000 in 2004 to 12.6 in 2009). Conversely, a strong increase of newer AED use was observed until 2006 followed by a deep fall in 2007 (from 13.0 in 2004 to 23.3 in 2006, to 12.3 in 2007). Concerning the incidence of use, a similar trend was observed. Gabapentin and pregabalin were the most used new AEDs: incidence of gabapentin use decreased from 69,3/10.000 inh in 2004 to 7,1/10.000 inhin 2008, while pregabalin, marketed in the last quarter of 2004, rose from 31,1/10.000 inhin 2005 to 105,2/10.000 inhin 2006 but decreased to 23,5/10.000 inhin 2007.Phenobarbitalwas the most widely used drug as DDD 1000/inh. Despite the newer AEDs consumption was lower than the older one, it was shown a significant increase in their use during the study period. Phenobarbital and carbamazepine show respectively 57.2 and 50.2 days/year at interaction risk, involving 68.8% and 71.9% of treated patients. Among newer AEDs, lamotrigine, topiramate and oxcarbazepine have the highest annual rate of co-prescription atinteraction risk. Concerning co-prescriptions at major interaction risk (level 1-2), lamotrigine is the drug with the highest annual rate (40.7day/year-47.2%pz), followed by carbamazepine, valproic acid and phenobarbital. Salicilate is the most co-prescribe drug at interaction risk (14.7% of the total days of interaction) followed by nifedipine, escitalopram, sertraline and warfarin.
Discussion: An increasing use of AEDs has been observed in the last years, mostly due to newer compounds in diseases other than epilepsy. On January 2007 the Italian Drug Agency revised reimbursement criteria of newer AED drugs, as reported in “Nota 4”. This regulatory restriction could explain the reduction of newer AED use during 2007. On the contrary, the increased use of pregabalin since 2005 confirms the trend of new marketed drugs to be widely prescribed in general practice after their introduction in the drug market. The lower risk of adverse events could explain the increasing trend of newer AEDs consumption, generally used for epilepsy, like oxcarbazepine, levetiracetam and lamotrigine. Ahigh number of patients treated with AEDs receive co-prescription at clinically relevant interaction risk. Most of these prescriptions concerns older AEDs such as carbamazepine, phenobarbital or valproic acid. However, in our study, some newer AEDs, like lamotrigine and topiramate, show a high annual rate of possible interaction. As a consequence, the co-prescription should be evaluated with caution and avoided if possible. Furthermore, some drugs could be replaced with less interaction risk drugs having same indication of use.
Methods: Data were extracted from the Arianna database that currently contains information about a population of almost 150,000 individuals living in Caserta and registered in 118 general practitioners’ (GPs) lists. Patients aged over 14 who received at least one AED prescription during 2004-2009 were identified. The use of newer and older AEDs was calculated as one-year prevalence and incidence; AEDs consumption was evaluated as DDD 1000/inh day. Clinically relevant interacting drugs were identified and the risk of drugs interactions was calculated as overlapping days between the exposition days of AEDs and interacting drugs. Sub-analyses by gender, age and indication of use were performed.
Results: Most of patients treated with older AED were affected by epilepsy (50,9%) while newer AED users were mainly treated because of pain (73.1%). Prevalence of older AED use slightly increased during the observational period (from 10.0/1000 in 2004 to 12.6 in 2009). Conversely, a strong increase of newer AED use was observed until 2006 followed by a deep fall in 2007 (from 13.0 in 2004 to 23.3 in 2006, to 12.3 in 2007). Concerning the incidence of use, a similar trend was observed. Gabapentin and pregabalin were the most used new AEDs: incidence of gabapentin use decreased from 69,3/10.000 inh in 2004 to 7,1/10.000 inhin 2008, while pregabalin, marketed in the last quarter of 2004, rose from 31,1/10.000 inhin 2005 to 105,2/10.000 inhin 2006 but decreased to 23,5/10.000 inhin 2007.Phenobarbitalwas the most widely used drug as DDD 1000/inh. Despite the newer AEDs consumption was lower than the older one, it was shown a significant increase in their use during the study period. Phenobarbital and carbamazepine show respectively 57.2 and 50.2 days/year at interaction risk, involving 68.8% and 71.9% of treated patients. Among newer AEDs, lamotrigine, topiramate and oxcarbazepine have the highest annual rate of co-prescription atinteraction risk. Concerning co-prescriptions at major interaction risk (level 1-2), lamotrigine is the drug with the highest annual rate (40.7day/year-47.2%pz), followed by carbamazepine, valproic acid and phenobarbital. Salicilate is the most co-prescribe drug at interaction risk (14.7% of the total days of interaction) followed by nifedipine, escitalopram, sertraline and warfarin.
Discussion: An increasing use of AEDs has been observed in the last years, mostly due to newer compounds in diseases other than epilepsy. On January 2007 the Italian Drug Agency revised reimbursement criteria of newer AED drugs, as reported in “Nota 4”. This regulatory restriction could explain the reduction of newer AED use during 2007. On the contrary, the increased use of pregabalin since 2005 confirms the trend of new marketed drugs to be widely prescribed in general practice after their introduction in the drug market. The lower risk of adverse events could explain the increasing trend of newer AEDs consumption, generally used for epilepsy, like oxcarbazepine, levetiracetam and lamotrigine. Ahigh number of patients treated with AEDs receive co-prescription at clinically relevant interaction risk. Most of these prescriptions concerns older AEDs such as carbamazepine, phenobarbital or valproic acid. However, in our study, some newer AEDs, like lamotrigine and topiramate, show a high annual rate of possible interaction. As a consequence, the co-prescription should be evaluated with caution and avoided if possible. Furthermore, some drugs could be replaced with less interaction risk drugs having same indication of use.