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Gaunfacin

Klassificering: C

Preparat: Guanfacine, Guanfacine Tablets, Intuniv, Intuniv XR, Tenex

ATC kod: C02AC02

Sammanfattning

Förekomsten av biverkningar generellt liksom biverkningar som ledde till studieavbrott var cirka tre gånger högre hos kvinnor i en studie på vuxna. Det saknas könsuppdelade data i kliniska effektstudier på barn och vuxna med ADHD.

Additional information

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 [5]. In women, hyperactivity/impulsivity and conduct problems were stronger predictors of clinical diagnosis and prescriptions of pharmacological treatment, compared to men [6]. 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].

Pharmacokinetics and dosing

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 [10]. 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 [11].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 [12].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 [13].

Effects

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 [21].

Adverse effects

In the above-mentioned Japanese post-hoc analysis [21], 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 [21].

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 [22].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler pojkar/män än flickor/kvinnor hämtade ut tabletter innehållande guanfacin (ATC-kod C02AC02) på recept i Sverige år 2020, totalt 7 166 pojkar/män och 3 170 flickor/kvinnor. Det motsvarar 1,4 respektive 0,6 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 10-19 år hos båda könen. I genomsnitt var tabletter innehållande guanfacin 1,6 gånger vanligare hos pojkar/män [23].

Uppdaterat: 2022-03-22

Litteratursökningsdatum: 2022-02-02

Referenser

  1. Nøvik TS, Hervas A, Ralston SJ, Dalsgaard S, Rodrigues Pereira R, Lorenzo MJ et al. Influence of gender on attention-deficit/hyperactivity disorder in Europe--ADORE. Eur Child Adolesc Psychiatry. 2006;15 Suppl 1:I15-24. PubMed
  2. Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry. 2010;49(3):217-28e1-3. PubMed
  3. Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490-9. PubMed
  4. Gaub M, Carlson CL. Gender differences in ADHD: a meta-analysis and critical review. J Am Acad Child Adolesc Psychiatry. 1997;36(8):1036-45. PubMed
  5. Biederman J, Faraone SV, Monuteaux MC, Bober M, Cadogen E. Gender effects on attention-deficit/hyperactivity disorder in adults, revisited. Biol Psychiatry. 2004;55(7):692-700. PubMed
  6. Mowlem FD, Rosenqvist MA, Martin J, Lichtenstein P, Asherson P, Larsson H. Sex differences in predicting ADHD clinical diagnosis and pharmacological treatment. Eur Child Adolesc Psychiatry. 2019;28(4):481-489. PubMed
  7. Socialstyrelsen. Stöd till barn, ungdomar och vuxna med adhd. Socialstyrelsen.
  8. Mowlem F, Agnew-Blais J, Taylor E, Asherson P. Do different factors influence whether girls versus boys meet ADHD diagnostic criteria? Sex differences among children with high ADHD symptoms. Psychiatry Res. 2019;272:765-773. PubMed
  9. Kok FM, Groen Y, Fuermaier ABM, Tucha O. The female side of pharmacotherapy for ADHD-A systematic literature review. PLoS One. 2020;15(9):e0239257. PubMed
  10. Intuniv (guanfacine). EPAR - Product information. European Medicines Agency (EMA) [updated 2021-11-25, cited 2022-02-02]
  11. Clinical Pharmacology and Biopharmaceutics Review - INTUNIV (guanfacine). Drugs@FDA [www]. Food and Drug Administration (FDA). [updated 2009-02-09, cited 2022-02-02]. länk
  12. Boellner SW, Pennick M, Fiske K, Lyne A, Shojaei A. Pharmacokinetics of a guanfacine extended-release formulation in children and adolescents with attention-deficit-hyperactivity disorder. Pharmacotherapy. 2007;27(9):1253-62. PubMed
  13. Knebel W, Corcoran M, Ermer J, Gastonguay MR. Population Pharmacokinetic Modeling of Guanfacine in Pediatric Patients. Clin Pharmacokinet. 2015;54(8):875-83. PubMed
  14. Hervas A, Huss M, Johnson M, McNicholas F, van Stralen J, Sreckovic S et al. Efficacy and safety of extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial. Eur Neuropsychopharmacol. 2014;24(12):1861-72. PubMed
  15. Wilens TE, Robertson B, Sikirica V, Harper L, Young JL, Bloomfield R et al. A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(11):916-25e2. PubMed
  16. Newcorn JH, Harpin V, Huss M, Lyne A, Sikirica V, Johnson M et al. Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study. J Child Psychol Psychiatry. 2016;57(6):717-28. PubMed
  17. Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A et al. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008;121(1):e73-84. PubMed
  18. Sallee FR, McGough J, Wigal T, Donahue J, Lyne A, Biederman J et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009;48(2):155-65. PubMed
  19. Newcorn JH, Stein MA, Childress AC, Youcha S, White C, Enright G et al. Randomized, double-blind trial of guanfacine extended release in children with attention-deficit/hyperactivity disorder: morning or evening administration. J Am Acad Child Adolesc Psychiatry. 2013;52(9):921-30. PubMed
  20. Stein MA, Sikirica V, Weiss MD, Robertson B, Lyne A, Newcorn JH. Does Guanfacine Extended Release Impact Functional Impairment in Children with Attention-Deficit/Hyperactivity Disorder? Results from a Randomized Controlled Trial. CNS Drugs. 2015;29(11):953-62. PubMed
  21. Naya N, Sakai C, Okutsu D, Kiguchi R, Fujiwara M, Tsuji T et al. Efficacy and safety of guanfacine extended-release in Japanese adults with attention-deficit/hyperactivity disorder: Exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study. Neuropsychopharmacol Rep. 2021;41(1):26-39. PubMed
  22. Knebel W, Ermer J, Purkayastha J, Martin P, Gastonguay MR. Population pharmacokinetic/pharmacodynamic modeling of guanfacine effects on QTc and heart rate in pediatric patients. AAPS J. 2014;16(6):1237-46. PubMed
  23. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Författare: Diana Rydberg

Faktagranskat av: Carl-Olav Stiller, Pauline Raaschou

Godkänt av: Karin Schenck-Gustafsson