Drug products: Guanfacine, Guanfacine Tablets, Intuniv, Intuniv XR, Tenex
ATC code: C02AC02
Substances: guanfacine, guanfacine hydrochloride
The incidence of adverse events in general and adverse events leading to discontinuation was approximately three times higher in women than men in a study on adults. Sex-divided data are lacking in clinical efficacy studies in children and adults with ADHD.
In children and adolescents, Attention Deficit Hyperactivity Disorder (ADHD) is more commonly diagnosed in boys, 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, the diagnosis in 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].
According to the European product information from the manufacturer, the systemic exposure to guanfacine is similar for men and women given the same mg/kg dose . The FDA approval document states that the population pharmacokinetic model predicts that patient’s sex would not be expected to be clinically important due to the estimated precision of its effect and lack of effect on interindividual variability .The plasma concentrations and concentration-related pharmacokinetic parameters of guanfacine extended-release formulation in children and adolescents (19 boys, 9 girls) with ADHD were higher in children than in adolescents. Similarly, after multiple daily 4-mg doses, both the AUC and the Cmax values were almost 30% higher in girls compared to boys in the younger age group. Heavier body weights may be associated with pharmacokinetic variables in adolescents and young male subjects .In a study using population pharmacokinetic modeling of guanfacine in pediatric patients, age 6-17 years (109 boys, 51 girls), the additional effect of patient’s sex was considered to have little to no clinical relevance .
Sex-stratified data on guanfacine efficacy in children and adolescents are lacking [14-20]. In a post-hoc subgroup analysis of a phase III trial of guanfacine extended-release in Japanese adults (129 men, 71 women) with ADHD, the effect was similar in men and women .
In the above-mentioned Japanese post-hoc analysis , the incidence of significant treatment-emergent adverse events, TEAEs (34.3%, 10.6%) and TEAEs leading to discontinuation (34.3%, 12.1%) was approximately three times higher in women than men. Significant TEAEs were severe TEAEs or TEAEs resulting in study discontinuation that were not serious, e.g. postural dizziness, somnolence, blood pressure decreased, bradycardia, and thirst .
Guanfacine effects in pediatric patients (153 boys, 64 girls) were assessed using an exposure-response (ER) model to describe guanfacine plasma concentrations and changes in heart rate and the QT interval. In the final ER model for population-corrected QT (QTcP), a typical baseline QTcP estimate of 9 (5-13) ms higher for girls, was found. The authors conclude that this effect is consistent with known physiology and is not related to guanfacine effects on QTcP .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2022-02-02
Reviewed by: Carl-Olav Stiller, Pauline Raaschou
Approved by: Karin Schenck-Gustafsson