6/10/2023

Janusmed kön och genus

Janusmed kön och genus – Ziprasidon

Janusmed kön och genus är ett kunskapsstöd som tillhandahåller information om köns- och genusaspekter på läkemedelsbehandling. Kunskapsstödet är avsedd främst för hälso- och sjukvårdspersonal. Texterna är generella och ska inte ses som behandlingsriktlinjer. Det är alltid behandlande läkare som ansvarar för patientens medicinering.

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Ziprasidon

Ziprasidon

Klass: A

Produkter

Zeldox, Ziprasidon 2care4, Ziprasidon Abacus Medicine, ......

Zeldox, Ziprasidon 2care4, Ziprasidon Abacus Medicine, Ziprasidon Actavis, Ziprasidon Ebb, Ziprasidon Krka, Ziprasidon Paranova, Ziprasidon STADA, Ziprasidone Sandoz
ATC-koder

N05AE04

N05AE04
Substanser

ziprasidon, ziprasidonhydroklorid (vattenfri), ziprasid......

ziprasidon, ziprasidonhydroklorid (vattenfri), ziprasidonhydrokloridmonohydrat, ziprasidonmesilattrihydrat, ziprasidonvätesulfatdihydrat
Sammanfattning

Publicerade data visar likvärdig effekt och biverkningsprofil hos män och kvinnor. Inga kliniskt relevanta könsskillnader i farmakokinetik har rapporterats.
Ziprasidon är associerat med QT-förlängning och därmed risk för allvarlig rytmrubbning av typen Torsade de Pointes kammartakykardi. Könsskillnad har inte påvisats för just ziprasidon, men allmänt är det vanligare med Torsade de Pointes hos kvinnor än hos män.

Publicerade data visar likvärdig effekt och biverkningsprofil hos män och kvinnor. Inga kliniskt relevanta könsskillnader i farmakokinetik har rapporterats. Ziprasidon är associerat med QT-förlängning och därmed risk för allvarlig rytmrubbning av typen Torsade de Pointes kammartakykardi. Könsskillnad har inte påvisats för just ziprasidon, men allmänt är det vanligare med Torsade de Pointes hos kvinnor än hos män.
Background

Ziprasidone is a second-generation antipsychotic which is used in schizophrenia and manic episodes in bipolar disease [1]. A higher risk of all psychotic disorders and schizophrenia in men compared to women has been reported in a meta-analysis with male-to-female incidence rate ratio of 1.4 and 1.7 [2]. The onset of schizophrenia in men is 3-5 years earlier than in women with a peak onset 21-25 vs 25-30 years. Women also have a second peak of onset after the age of 45. The course of schizophrenia is generally more severe in men. Furthermore, men present more often with more negative symptoms and women with more mood disturbance and depressive symptoms [3, 4]. The incidence of bipolar disease is approximately equal in men and women [5].

Pharmacokinetics and dosing
In a multiple-dose study in young healthy individuals (18-45 years, 8 men, 11 women) and elderly individuals (>65 years, 8 men, 8 women) steady state pharmacokinetics day 8 showed no clinically or statistically significant sex differences in Cmax or AUC (0-12 h) [6]. In a plasma concentration study (53 men, 68 women), no d......

Ziprasidone is a second-generation antipsychotic which is used in schizophrenia and manic episodes in bipolar disease [1]. A higher risk of all psychotic disorders and schizophrenia in men compared to women has been reported in a meta-analysis with male-to-female incidence rate ratio of 1.4 and 1.7 [2]. The onset of schizophrenia in men is 3-5 years earlier than in women with a peak onset 21-25 vs 25-30 years. Women also have a second peak of onset after the age of 45. The course of schizophrenia is generally more severe in men. Furthermore, men present more often with more negative symptoms and women with more mood disturbance and depressive symptoms [3, 4]. The incidence of bipolar disease is approximately equal in men and women [5]. # Pharmacokinetics and dosing In a multiple-dose study in young healthy individuals (18-45 years, 8 men, 11 women) and elderly individuals (>65 years, 8 men, 8 women) steady state pharmacokinetics day 8 showed no clinically or statistically significant sex differences in Cmax or AUC (0-12 h) [6]. In a plasma concentration study (53 men, 68 women), no difference between concentration/dose ratio in men or women was observed for ziprasidone nor for its active metabolite S-methyl-dihydroziprasidone [7]_._ No significant age- and sex differences in the pharmacokinetics of intramuscular or oral ziprasidone were observed in a population pharmacokinetic model based on phase I, II and III studies [8]. According to the pharmaceutical company, no dose adjustment is necessary for age or patient´s sex [1,9]. # Effects **Specific for ziprasidone** In the EUFEST randomized trial (European First Episode Schizophrenia Trial, there was no sex difference in the positive and negative syndrome scale (PANSS) after 12 months in the ziprasidone group (24 men, 28 women) [10]. In a 9-year Swedish national registry study of patients with bipolar disease treated with ziprasidone (103 men, 351 women) ziprasidone was found to reduce the rate of bipolar rehospitalizations in men but not in women (hazard ratio 0.35 (0.21–0.59) vs. 0.96 (0.62–1.47) [11]. **Antipsychotics in general** Four studies show similar effect in men and women [12-15] and one study shows better results in men [16] and one in women [17]. A meta-analysis of 32 randomized studies of treatment with risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole in acute schizophrenia (5200 men, 2064 women, 12% participating in ziprasidone studies) showed that men and women improved in a similar way [12]. # Adverse effects **Hyperprolactinemia** In an open label randomized trial of endocrine changes during ziprasidone treatment (20 men, 27 women), prolactin increased significantly in both men and women, 17.1 nmol/mL in men and 25.3 nmol/mL in women [18]. Ziprasidone have minimal effects on prolactin levels [19]. Hyperprolactinemia can cause hypogonadism with infertility, menstrual disturbances and sometimes galactorrhea in premenopausal women. Postmenopausal women don’t usually get symptoms from hyperprolactinemia. Hyperprolactinemia in men can cause hypogonadism with decreased libido, impotence, infertility, gynecomastia or galactorrhea. However, the degree of hyperprolactinemia does not always correlate with severity of symptoms [20-24]. **Metabolic changes** Ziprasidone, compared to other antipsychotics, has minimal weight gain effect [19]. Leptin, a hormone secreted from adipose tissue that has been associated with weight gain was not significantly increased neither in men nor women treated with ziprasidone (11 men, 24 women) [18]. Specific data on ziprasidone and sex differences in weight gain is lacking. A review article on second generation antipsychotics found women to have a higher risk for weight gain during treatment in five studies, while men had a higher risk in two studies [25]. **Other adverse effects** Ziprasidone is associated with acquired QT-prolongation on ECG and risk for Torsade de Pointes ventricular arrythmia [1]. No studies on sex differences in the potential of QT-prolongation by ziprasidone have been found. However, the QT-interval is generally longer in women, and female sex is a risk factor for acquired long QT-interval [26]. Prevalence of extrapyramidal symptoms was similar in men and women according to a cross-sectional study of 129 men and 84 women aged 18-65 years that was treated with second-generation oral antipsychotics, including ziprasidone [27]. Specific data on ziprasidone is lacking. # Reproductive health issues Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Försäljning på recept

Fler kvinnor än män hämtade ut ziprasidon (ATC-kod N05AE04) på recept i Sverige år 2021, totalt 610 män och 359 kvinnor [28].
Referenser
  1. Zeldox (ziprasidone). Summary of Product Characteristics. Swedish Medical Products Agency (MPA) [updated 2021-08-19, cited 2022-08-01]
  2. Jongsma HE, Turner C, Kirkbride JB, Jones PB. International incidence of psychotic disorders, 2002-17: a systematic review and meta-analysis. Lancet Public Health. 2019;4(5):e229-e244.
  3. Li R, Ma X, Wang G, Yang J, Wang C. Why sex differences in schizophrenia?. J Transl Neurosci (Beijing). 2016;1(1):37-42.
  4. Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int Rev Psychiatry. 2010;22(5):417-28.
  5. Seedat S, Scott KM, Angermeyer MC, Berglund P, Bromet EJ, Brugha TS et al. Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys. Arch Gen Psychiatry. 2009;66(7):785-95.
  6. Wilner KD, Tensfeldt TG, Baris B, Smolarek TA, Turncliff RZ, Colburn WA et al. Single- and multiple-dose pharmacokinetics of ziprasidone in healthy young and elderly volunteers. Br J Clin Pharmacol. 2000;49 Suppl 1:15S-20S.
  7. Chermá MD, Reis M, Hägg S, Ahlner J, Bengtsson F. Therapeutic drug monitoring of ziprasidone in a clinical treatment setting. Ther Drug Monit. 2008;30(6):682-8.
  8. Preskorn SH. Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. Clin Pharmacokinet. 2005;44(11):1117-33.
  9. Food and Drug Administration (FDA). Medical Review - GEODON (ziprasidone). Drugs@FDA [www]. [updated 2001-02-05, cited 2022-08-02].
  10. Ceskova E, Prikryl R, Libiger J, Svancara J, Jarkovsky J. Gender differences in the treatment of first-episode schizophrenia: Results from the European First Episode Schizophrenia Trial. Schizophr Res. 2015;169(1):303-307.
  11. Ragazan DC, Eberhard J, Berge J. Sex-Specific Associations Between Bipolar Disorder Pharmacological Maintenance Therapies and Inpatient Rehospitalizations: A 9-Year Swedish National Registry Study. Front Psychiatry. 2020;11:598946.
  12. Woods SW, Gueorguieva RV, Baker CB, Makuch RW. Control group bias in randomized atypical antipsychotic medication trials for schizophrenia. Arch Gen Psychiatry. 2005;62:961-70.
  13. Rabinowitz J, Werbeloff N, Caers I, Mandel FS, Stauffer V, Ménard F et al. Determinants of antipsychotic response in schizophrenia: implications for practice and future clinical trials. J Clin Psychiatry. 2014;75(4):e308-16.
  14. Zhang ZJ, Yao ZJ, Liu W, Fang Q, Reynolds GP. Effects of antipsychotics on fat deposition and changes in leptin and insulin levels Magnetic resonance imaging study of previously untreated people with schizophrenia. Br J Psychiatry. 2004;184:58-62.
  15. Pelayo-Terán JM, Diaz FJ, Pérez-Iglesias R, Suárez-Pinilla P, Tabarés-Seisdedos R, de León J et al. Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis. Psychol Med. 2014;44:37-50.
  16. Walther S, Moggi F, Horn H, Moskvitin K, Abderhalden C, Maier N et al. Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized, controlled study with oral haloperidol, risperidone, and olanzapine. J Clin Psychopharmacol. 2014;34:124-8.
  17. Pérez-Iglesias R, Ortiz-Garcia de la Foz V, Martínez García O, Amado JA, Garcia-Unzueta MT, Ayesa-Arriola R et al. Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis. Schizophr Res. 2014;159(1):90-4.
  18. Zhang XY, Zhou DF, Qi LY, Chen S, Cao LY, Chen DC et al. Superoxide dismutase and cytokines in chronic patients with schizophrenia: association with psychopathology and response to antipsychotics. Psychopharmacology (Berl). 2009;204:177-84.
  19. Aichhorn W, Whitworth AB, Weiss EM, Marksteiner J. Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles?. Drug Saf. 2006;29(7):587-98.
  20. Eberhard J, Lindström E, Holstad M, Levander S. Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatr Scand. 2007;115:268-76.
  21. Kinon BJ, Gilmore JA, Liu H, Halbreich UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology. 2003;28 Suppl 2:55-68.
  22. Findling RL, Kusumakar V, Daneman D, Moshang T, De Smedt G, Binder C. Prolactin levels during long-term risperidone treatment in children and adolescents. J Clin Psychiatry. 2003;64:1362-9.
  23. Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol. 1999;19:57-61.
  24. Clinical manifestations and evaluation of hyperprolactinemia. UpToDate [www]. [updated 2022-02-09, cited 2022-04-12].
  25. Bou Khalil R. Atypical antipsychotic drugs, schizophrenia, and metabolic syndrome in non-Euro-American societies. Clin Neuropharmacol. 2012;35(3):141-7.
  26. Taylor D. Ziprasidone in the management of schizophrenia : the QT interval issue in context. CNS Drugs. 2003;17(6):423-30.
  27. Ribeiro SB, de Araújo AA, Medeiros CA, Chaves KM, Alves MD, Oliveira AG et al. Factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics. Eur J Clin Pharmacol. 2017;73(3):351-355.
  28. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.]
Uppdaterat

Litteratursökningsdatum 8/1/2022

Litteratursökningsdatum 8/1/2022