Abstracts

Compulsory generic substitution may lead to adverse effects in epilepsy patients because of the consequences linked with a single seizure recurrence. This concern is magnified by the widespread use of narrow therapeutic index (NTI) drugs for epilepsy. The objectives of the study are (1) quantify the switch-back rates from generic to brand-name AEDs compared to other drugs, and (2) assess the clinical impact of switching from branded Lamictal[reg] (BL) to generic lamotrigine (GL)., We used a public payer database from Ontario, Canada, comprising pharmacy claims from 01/2002 to 03/2006. The Ontario Drug Benefit formulary adopted compulsory conversion to GL in 01/2003, and a steep hurdle was imposed that prevented patients from switching back to BL without documented medical necessity from their doctor. We first calculated the switch-back rates from generic to brand AEDs (Lamictal[reg], Frisium[reg], Depakene[reg]) using a Kaplan-Meier approach, compared to other chronically used drugs (Zocor[reg], Prozac[reg]). Secondly, two cohorts of lamotrigine patients were compared with respect to their clinical outcomes: (1) those switching back to BL after being converted to GL (switch-back group), and (2) those staying on GL after generic entry (generic group). A stratified analysis was conducted on BL patients receiving monotherapy vs polytherapy of AED. The clinical endpoints were proxy for seizure control and tolerability, and included dosages of BL, of GL and number of concomitant AEDs and non-AED use before and after generic entry., 1452 BL patients (437 monotherapy, 1015 polytherapy) were converted to GL, of which 12.9% switched back to BL (11.7% monotherapy, 13.4% polytherapy). Switch-back rates of other AEDs were about 20% for Frisium[reg] and Depakene[reg], both of which were significantly higher than Zocor[reg] (1.5%) or Prozac[reg] (2.9%). In the switch-back group, the average BL daily dose increased from 229.5 mg at baseline to 279.9 mg GL (p=0.039) after the generic entry. In the generic group, a similar dose increase was observed from baseline to generic periods (BL 242.8 mg/day versus GL 266.1 mg/day, p[lt]0.0001). The average number of drug entities dispensed increased for non-AED co-dispensings after generic entry compared to baseline (switch-back group: +12.2%, p=0.004; generic group: +7.4%, p=0.03)., Switch-back rates were considerably and significantly higher for Lamictal[reg] and other AEDs than for other chronic disease drugs. Higher generic doses and utilization of other drugs were also found. The extent of switchback differences compared with non AEDs raises concerns. This may be due to loss of seizure control or refusal of epilepsy patients to substitute, despite high cost penalties. Studies to investigate the clinical reasons or resistance to generic switching are required., (Supported by GlaxoSmithKline, RTP, NC, USA.)