Drug products: Elvanse, Elvanse Vuxen, Vyvanse
ATC code: N06BA12
Substances: lisdexamfetamine, lisdexamfetamine dimesilate
There is no existing data supporting dose adjustments according to a patient’s sex in the treatment of ADHD-patients with lisdexamfetamine. Even though, some studies have found sex differences in the pharmacokinetics of lisdexamfetamine, as well as differences both in certain clinical scores, and in adverse effects between boys/men and girls/women.
In children and adolescents, Attention Deficit Hyperactivity Disorder (ADHD) is more commonly diagnosed in men, with the sex ratio ranging from 2:1 to 10:1 [1-4], with higher male-to-female ratios found in clinical versus population-based samples. The male-to-female ratio is smaller in adult clinical samples than in childhood and adolescent samples . In women, hyperactivity/impulsivity and conduct problems were stronger predictors of clinical diagnosis and prescriptions of pharmacological treatment, compared to men . Girls more often than boys have ADHD with mainly attention deficit disorder and more rarely clear hyperactivity/impulsivity problems. Therefore girls/women may be more difficult to recognize and be less likely to receive pharmacological treatment, and males with ADHD are more likely to receive ADHD medication than females with ADHD [6-9].Lisdexamfetamine is a prodrug of dextroamphetamine and is indicated for the treatment of ADHD [10, 11] and in some countries also used for treating moderate to severe Binge Eating Disorder (BED) in adults .
No dosage adjustment of lisdexamfetamine is necessary based on a patient’s sex according to the FDA approved prescribing information for Vyvanse, even though Cmax and AUC are higher in women .
In a two-period crossover trial, healthy adults (24 men, 23 women), stratified by age and sex received randomized and double-blind single doses of lisdexamfetamine 50 mg or placebo. Intact lisdexamfetamine (LDX) pharmacokinetics and safety were assessed. Descriptive pharmacokinetic data (the median Tmax, mean t1/2, and the mean creatinine clearance) were similar in men and women, in all three age groups (55-64, 65-74, ≥75 years). Women aged 55-64 years and ≥75 years tended to have higher values for intact LDX Cmax and AUC than men in all age groups .
The efficacy and tolerability of lisdexamfetamine in children (98 boys, 31 girls) with ADHD, were assessed in open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled 2-way crossover phase. Interaction between sex or age (age groups: 6-9, 10-12 years) and treatment and assessed effect size for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and Permanent Product Measure of Performance (PERMP) scales and ADHD Rating Scale IV measures, were analyzed in a post-hoc manner. Both sexes showed improvement on all assessments at postdose time points, but girls had. improved scores for SKAMP, in both treatment and placebo groups at all time points. There were significant effects of sex at all time points for SKAMP-D (subscale evaluating deportment) scores. For SKAMP-D scores, the only significant treatment-by sex interaction was seen at the 7.5-hour time point. Results of the sex analysis for SKAMP total mirrored those of SKAMP-D with significant effects at all time points and a significant treatment-by-sex interaction at 7.5 and 10 hours postdose. For PERMP, girls receiving placebo had less impaired scores than did boys receiving placebo. Both boys and girls with LDX treatment improved and had similar scores on PERMP. Furthermore, significant treatment-by-sex interactions were seen at 10 hours postdose for PERMP .
The protective effects of stimulant treatment on important functional outcomes, and whether these effects are moderated by sex, was examined in children (130 boys, 135 girls) with ADHD. The study participants were 11 years old at baseline and with a 20-year follow up with subjects derived from three independent studies. No interactions between proband sex and treatment status was found for any of the lifetime psychiatric and educational study outcomes .
No difference between the sexes was seen in the effect of lisdexamfetamine on self-reported quality of life (QoL), in adults with ADHD (88 men, 54 women). In the subgroup analysis by sex and age groups, age at the time of clinician diagnosis, and ADHD subtype among men and women and among younger (aged 18–26 years) and older (aged 27–55 years) adults were generally consistent across subgroups .
In adults with BED (105 men, 640 women), a post-hoc analysis showed comparable clinical characteristics and treatment responses to dose-optimized lisdexamfetamine versus placebo between men and women .
From a pharmacokinetic study mentioned above, blood pressure and pulse changes (vital signs) were also measured and found to be similar between men and women .
In the dose-optimization phase study described above , the common (≥2%) TEAEs reported for boys were upper abdominal pain, headache, affect lability, initial insomnia and insomnia. For girls, the most common reported TEAEs were nausea and decreased weight. During the crossover phase for those taking LDX, a higher incidence (≥2% greater) of upper abdominal pain and insomnia was observed in boys, and a higher incidence of nausea and headache in girls . In the study on QoL-effects from LDX treatment also mentioned above , the TEAE (treatment-emergent adverse event) profile and frequencies for both age groups and between sexes were also in general similar .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).A retrospective observational study comparing treatment adherence of lisdexamfetamine for the treatment of ADHD in both children and adolescents (n=18,908) and adult patients (n=7153) found differences in the proportions of males-to-females between the two patient populations. A majority of males was found in children and adolescents while the adult population had an ~1:1 ratio of males-to-females .
The majority of participants who received LDX were male (58-84%) in a large European drug utilization study in children, adolescents and adults with ADHD .
Date of litterature search: 2020-05-08
Reviewed by: Carl-Olav Stiller, Mia von Euler
Approved by: Karin Schenck-Gustafsson