Blanka Koristkova

Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma concentrations were used as an indicator of the quality of treatment. PDDs were compared with the defined daily doses (DDDs) suggested by WHO in the ATC/DDD index 2005. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of mean PDDs. The study included 2,824 adult out- and in-patients in Huddinge treated from 1995 to 1999 and 1,268 out-patients treated in Ostrava from 1993 to 2004. The differences in PDD were tested by Student's t-test. Mean values of PDD were used when patients were examined more than once. Doses given in mono- and polytherapy were compared. Mean PDDs (in mg) in mono-/polytherapy in Huddinge and Ostrava were as follows (DDDs in parenthesis): carbamazepine 588/842 and 618/770 (1,000), clonazepam 3.0/2.5 and 3.4/2.4 (8), phenytoin 278/314 and 291/288 (300), gabapentin -/1,533 and -/921 (1,800), lamotrigine 228/228 and 216/195 (300), phenobarbital 90/75 and 183/117 (100), vigabatrin -/1,794 and -/1,259 (2,000), valproic acid 1,139/1,476 and 814/950 (1,500). The PDDs of most of the AEDs were lower than the DDDs with the exceptions for valproic acid (Huddinge, in polytherapy only), phenytoin, for which PDDs and DDDs were very close, and phenobarbital for which they were similar in Huddinge but higher in Ostrava. PDDs in monotherapy were only slightly lower than in combination therapy. Patients with plasma concentrations within the therapeutic range were usually treated with slightly higher doses than the remainder. In general, plasma concentrations tended to be in the low therapeutic range. The differences in PDDs between hospitals were significant in the case of valproic acid (P < 0.001), phenobarbital (except monotherapy within), vigabatrin, and gabapentin (P < 0.01), and carbamazepine (in monotherapy P < 0.05, polytherapy P < 0.01). Our data suggest that the DDDs of AEDs should be reconsidered as, in the majority of cases, they appear to be too high.

Prescribed daily doses (PDDs) of antiepileptics (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospital in Ostrava, Czechia. Plasma levels were used as an indicator of the quality of treatment. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of PDDs and plasma levels. The study included 1,144 in-patients examined in the period 1993 - 2004. The differences in PDD were tested by Mann-Whitney-U-test. ATC/DDD index 2005 was used. Doses given in mono- and polytherapy were compared. Median PDDs in samples within the therapeutic range (in mg) in mono-/polytherapy were as follows (DDDs in parenthesis): carbamazepine 600/800 (1,000), clonazepam 2.0/2.0 (8), phenytoin 300/300 (300), ethosuximide -/1000 (1,250), lamotrigine 250/200 (300), phenobarbital -/200 (100), primidone 500/625 (1,250), topiramate -/300 (300), valproic acid 750/1,000 (1,500). Median PDDs in polytherapy with antiepileptics not analyzed for TDM were: gabapentin 900 (1,800), levetiracetam 1,500 (1,500), vigabatrin 1,500 (2,000). PDDs in monotherapy were similar or slightly lower than in combination therapy with an exception for lamotrigine, NS. The differences were significant in carbamazepine, p < 0.0001, and valproic acid, p < 0.001. Patients with plasma levels within the therapeutic range were usually treated with similar or slightly higher doses than the remainder. In polytherapy the PDDs were similar to DDDs in carbamazepine, ethosuximide, phenytoin, and topiramate in samples within the therapeutic range when difference +/- 20 per cent was considered as acceptable PDD of levetiracetam was also similar to actual DDD. In general plasma levels tended to be below the therapeutic range. The differences between PDD and DDD of antiepileptics have to be taken into account especially when utilization of different drugs is compared.

Drug utilization expresses the exposition of a drug in the relationship with determined population, certain time period, and specific socioeconomic background. The aim of this study was to compare the antiepileptic drug utilization (N03A) in the Czech Republic (CR) and in Ostrava University Hospital (FNsP). The sources of the data were I) wholesale data (SUKL, CR), II) prescriptions (UZIS, CR), III) request forms (FNsP), IV) request forms for therapeutic drug monitoring (FNsP). The utilization was expressed in DDD/TID (I, II), or in DDD/100 BD in neurological departments (III) on 5th or 4th level, resp. ATC/DDD index 2001, for levetiracetam 2004. Carbamazepine had the highest utilization that was increasing in the CR, while remaining high and constant in FNsP. The utilization of valproic acid is increasing. The number of patients shows greater prescription than utilization in DDD. The utilization of phenytoin was high in the CR, but diminished in FNsP. The number of patients was lower than expected. The utilization of barbiturates was considerable in the CR, but below the average in FNsP. The utilization of clonazepam and N03AX was increasing. The most important substance there was lamotrigin. The outcomes are in agreement with current recommendations. The utilization in FNsP and CR follows the same trend with a faster shift to newer drugs in FNsP.

Long-term trends in utilization of antiepileptic drugs expressed in DDD/TID according to the 4th ATC level were studied. Wholesale data recorded from statistical yearbooks and the database of the State Institute for Drug Control (SUKL) were the source of data. The correlation between trends in the Czech Republic (CR) and the other countries was studied. The utilization was expressed in DDD/1000 inhabitants and day (DDD/TID). The lowest utilization of antiepileptics was in the Czech Republic, while highest in Norway (until 1994) and Finland (from 1995). The utilization of barbiturates is decreasing. The highest one was in Norway and CR. Hydantoins were the most widely utilized group in Australia, Sweden, and CR. Even though their utilization was lower in Finland and Norway, they were one of the most widely utilized groups there. The utilization of succnimide derivatives was very low and still decreases. Benzodiazepins were the most widely utilized group in Finland, until 1995 also in Australia, from 1996 in Norway. Their utilization increases. Even though the utilization of carboxamide derivatives was lower in CR and Australia, they belong to the second most widely utilized group there. Fatty acid derivatives were most widely utilized in Australia and Finland. Their utilization is lower, but increasing in CR. The utilization of N03AX has been increasing in the recent period in all countries. The utilization of antiepileptics in CR follows the trends in other countries, but on a lower level of DDD/TID.