Drug products: Lacosamide Accord, Lacosamide Krka, Lacosamide STADA, Lacosamide Teva, Lacosamide Zentiva, Vimpat
ATC code: N03AX18
The inter-individual variability in pharmacokinetics is large. Differences have been shown in some studies, with higher exposure and lower elimination in women in than men. However, most of the difference disappear if weight adjustment is performed. No larger analyses of sex differences regarding efficacy or safety have been found.
Pharmacokinetics and dosing
A study in healthy volunteers (24 men, 43 women) found women to have higher AUC and Cmax than men. Elderly men and women had higher exposure of lacosamide than their younger counterparts. Without correction for weight and lean body weight young women had 36% higher AUC and 42% higher Cmax than young men. After weight correction, only 3% difference remained in AUC and 13% in Cmax . In a study in patients with focal epilepsy (287 men, 278 women), clearance was higher in men (men 2.06 L/H and women 1.88 L/h) . A Norwegian study based on routine measures of lacosamide (165 men, 179 women) found a pronounced pharmacokinetic variability despite similar doses. Neither differences between men and women nor differences related to age were found . Clinical studies show that patient's sex does not have a clinically significant effect on the plasma concentrations of lacosamide and no sex differentiation in dosing has been recommended by the manufacturer .
The number of men and women included in the RCT of lacosamide as add-on treatment in epilepsy has been similar . A small retrospective study of the effect of lacosamide in children (14 boys, 8 girls) with a mean age of 12.9 years found the proportion of responders to be 75% in girls and 29% in boys. Responders were defined as having a lasting ≥50% reduction of seizures .
The number of men and women included in the RCT of lacosamide as add-on treatment in epilepsy has been similar . Analysis of adverse events and lacosamide concentrations have been published (33 men, 37 women) but no relevant sex analysis on adverse effect was presented .
Reproductive health issues
Lacosamide does not seem to interact with oral contraceptives . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
There is no published data on lacosamide during pregnancy [9, 10]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
An observational study in patients with focal epilepsy using lacosamide as an add-on (61 men, 67 women) found the maximal concentration to be higher in women (37±24 µmol/L) than in men (27±13 µmol/L) .
A Finnish study of antiepileptic drug utilization in focal refractory epilepsy in adults found 137 patients using lacosamide, 51% women and 49% men. The retention rate was high, 77% (95%CI 68-84%) and similar in men and women .
A small study in men (n=11) treated with levetiracetam and carbamazepine found that when the enzyme inducer carbamazepine was exchanged for lacosamide, the men showed favorable changes and more normalized levels in serum profiles of lipids, and reproductive and thyroid hormones . The clinical significance of this is unknown.
Date of litterature search: 2018-03-27
- Schiltmeyer B, Cawello W, Kropeit D, Hammes W, Horstmann R. Pharmacokinetics of the new antiepileptic drug SPM 927 in human subjects with different age and gender. Epilepsia. 2004;Suppl 7(45):31.
- Schaefer C, Cawello W, Waitzinger J, Elshoff JP. Effect of age and sex on lacosamide pharmacokinetics in healthy adult subjects and adults with focal epilepsy. Clin Drug Investig. 2015;35:255-65. PubMed
- Svendsen T, Brodtkorb E, Baftiu A, Burns ML, Johannessen SI, Johannessen Landmark C. Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability. Neurochem Res. 2017;42(7):2077-2083. PubMed
- VIMPAT (lakosamid). Summary of Product Characteristics. Medical Products Agency - Sweden; 2012.
- Paquette V, Culley C, Greanya ED, Ensom MH. Lacosamide as adjunctive therapy in refractory epilepsy in adults: a systematic review. Seizure. 2015;25:1-17. PubMed
- Toupin JF, Lortie A, Major P, Diadori P, Vanasse M, Rossignol E et al. Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study. Epileptic Disord. 2015;17(4):436-43. PubMed
- Hillenbrand B, Wisniewski I, Jürges U, Steinhoff BJ. Add-on lacosamide: a retrospective study on the relationship between serum concentration, dosage, and adverse events. Epilepsy Behav. 2011;22:548-51. PubMed
- Cawello W, Rosenkranz B, Schmid B, Wierich W. Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers. Epilepsia. 2013;54:530-6. PubMed
- Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013;54:405-14. PubMed
- Reimers A. New antiepileptic drugs and women. Seizure. 2014;23:585-91. PubMed
- Markoula S, Teotonio R, Ratnaraj N, Duncan JS, Sander JW, Patsalos PN. Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs. Ther Drug Monit. 2014;36:494-8. PubMed
- Mäkinen J, Peltola J, Raitanen J, Alapirtti T, Rainesalo S. Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market. J Neurol. 2017;264(7):1345-1353. PubMed
- Elger CE, Rademacher M, Brandt C, Elmoufti S, Dedeken P, Eckhardt K et al. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial. Epilepsy Behav. 2016;62:1-5. PubMed
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson