Preparat: Zeldox, Zeldox®, Ziprasidon 2care4, Ziprasidon Actavis, Ziprasidon Ebb, Ziprasidon Krka, Ziprasidon Paranova, Ziprasidon STADA, Ziprasidone Sandoz
ATC kod: N05AE04
Substanser: ziprasidon, ziprasidonhydroklorid (vattenfri), ziprasidonhydrokloridmonohydrat, ziprasidonmesilattrihydrat, ziprasidonvätesulfatdihydrat
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.
Ziprasidone is a second-generation antipsychotic which is used in schizophrenia and manic episodes in bipolar disease . 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 . 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 .
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) . 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 .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 .According to the pharmaceutical company, no dose adjustment is necessary for age or patient´s sex [1,9].
Specific for ziprasidoneIn 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) . 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) .
Antipsychotics in generalFour studies show similar effect in men and women [12-15] and one study shows better results in men  and one in women . 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 .
HyperprolactinemiaIn 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 .Ziprasidone have minimal effects on prolactin levels . 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 changesZiprasidone, compared to other antipsychotics, has minimal weight gain effect . 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) . 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 .
Other adverse effectsZiprasidone is associated with acquired QT-prolongation on ECG and risk for Torsade de Pointes ventricular arrythmia . 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 .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 . Specific data on ziprasidone is lacking.
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Fler kvinnor än män hämtade ut ziprasidon (ATC-kod N05AE04) på recept i Sverige år 2021, totalt 610 män och 359 kvinnor .
Faktagranskat av: Carl-Olav Stiller, Pauline Raaschou
Godkänt av: Karin Schenck-Gustafsson