Managing delayed or missed pregabalin doses in patients with focal epilepsy: A Monte Carlo simulation study

Purpose Medication adherence is essential for effective seizure control. However, delayed or missed doses are inevitable in epilepsy pharmacotherapy. The current remedial measures recommended by the Food and Drug Administration (FDA) for missed or delayed pregabalin doses are generic and lack supporting clinical evidence. The present study used a Monte Carlo simulation to explore remedial strategies for delayed or missed pregabalin doses in patients with epilepsy. Methods A Monte Carlo simulation was performed using a published population pharmacokinetic (pop PK) model. The applicability of the FDA recommendations compared to five proposed remedial regimens (Strategies A–E) was assessed based on the total deviation time outside the on-therapy range. Results All proposed remedial strategies were associated with renal function and the duration of dosing delay. The total deviation times for Strategies C–E were shorter than those for Strategy A (skip the dose and take the next regular dose as scheduled) when pregabalin was taken near the next scheduled time. An alternative recommendation is to take 1.2-, 1.3-, or 1.5-fold the regular dose at the next scheduled time if a single dose is missed. In the case of two missed doses, it is advisable to administer 1.2-, 1.3-, or 1.7-fold the regular dose. Conclusion Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses. The proposed remedial strategies can help in supplementing or correcting FDA instructions and mitigating the risk of out-of-range treatment.