CLOPIXOL TABLETS 10 MG

IL-604707

ˬϕέόΗϟ΍ϭˬϑϧϷ΍ϥϼϳγϭˬϡΎόρϟ΍ϥϣέϭϔϧϟ΍ϭˬϝΎϬγϹ΍ϭˬ΅ϳϘΗϟ΍ϭˬϥΎϳΛϐϟ΍ϝΛϣΊΟΎϔϣϝϛηΑ˯΍ϭΩϟ΍

Γέ΍έΣϟΎΑέϭόηϟ΍ϭˬΔΧϭΩϟ΍ˬΔϔΟέϟ΍ˬΔϳΑλόϟ΍ˬϕϠϘϟ΍ˬϕέϷ΍ˬΩϠΟϟ΍ίΧϭΔϛΣϟ΍ˬΕϼοόϟ΍ϲϓϡϻ΁ϭ

ΓΩϭέΑϟ΍ϭ΃

ϝϣόΗγ΍˯΍ϭΩϟ΍ϝϭΎϧΗΗΓέϣϝϛϲϓΔϋέΟϟ΍ϭΔϘλϼϟ΍ϥϣϕϘΣΗϟ΍ΏΟϳϭˬϡϼυϟ΍ϲϓΔϳϭΩϷ΍ϝϭΎϧΗΗϻ

ΎϬϳϟ·ΔΟΎΣϲϓΕϧϛ΍Ϋ·Ε΍έΎυϧϟ΍

ϲϟΩϳλϟ΍ϭ΃ϙΑϳΑρΑϝλΗ΍˯΍ϭΩϟ΍΍ΫϫϝΎϣόΗγ΍ϝϭΣΔϳϓΎο·ΔϠ΋γ΃ϱ΃ϙϳΩϟϥΎϛ΍Ϋ·

ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍˽

νόΑϟΔϳΑϧΎΟν΍έϋ΃ϲϓΏΑγΗϳΩϗϝϭγϛϳΑϭϠϛϟ΍˯΍ϭΩϝΎϣόΗγ·ϥΈϓˬ˯΍ϭΩϱ΃ϊϣϝΎΣϟ΍ϭϫΎϣϛ

ΎϬϧϣϱ΃ϥϣϲϧΎόΗϻΩϗΔϳΑϧΎΟϟ΍ν΍έϋϻ΍ΔΣ΋ϻΓ˯΍έϗΩϧϋωίϔΗϻϰοέϣϟ΍

ΔϳϟΎΗϟ΍ν΍έϋϷ΍ϥϣϱ΃ϪΟ΍ϭΗΕϧϛ΍Ϋ·έϭϔϟ΍ϰϠϋϰϔηΗγϣϟ΍ϰϟ·ϪΟϭΗϟ΍ϭ΃ϙΑϳΑρΑϝΎλΗϻ΍ϙϳϠϋΏΟϳ

ιΧη˺˹˹ϥϣ˺˹˺ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍έΎΛϵ΍Ϫό΋Ύηϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

ϪόϳέγΏϠϗΕΎϗΩ

Ύοϳέϣ˺˺˹˹˹ϰΗΣ˺˺˹˹ϥϣΔό΋ΎηέϳϏΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

έΧ΄Ηϣϟ΍ΔϛέΣϟ΍ϝϠΧϥϣΓέϛΑϣΔϣϼϋϥϭϛΗϥ΃ϥϛϣϳϩΫϫϥΎγϠϟ΍ϭϡϔϟ΍ϲϓΔϳΩ΍έ·ϻΕΎϛέΣ

ΕΎΟϧηΗ

ιΧη˺˹˹˹˹ϝλ΃ϥϣ˺˹˺ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍έΎΛϵ΍ΓέΩΎϧΔϳΑϧΎΟν΍έϋ΃

ΏϠϗΕΎϗΩˬ

ϊρϘϣΩϳΩϣΗΔϳΑϠϘϟ΍ΔΗϛγϟ΍ϰϟ·ϱΩ΅Ηϥ΃ϥϛϣϳϲΗϟ΍ΏϠϘϟ΍ΕΎΑέοϡΎυΗϧ΍ϡΩϋ

ϪϣυΗϧϣέϳϏ

ϥϳΗϔηϟ΍ϭϪΟϭϟ΍ϲϓϡέϭΗˬαϔϧΗϟ΍ϲϓΔΑϭόλΑ

ΔϳϠΟΗϣˬΔϳγΎγΣϟ΍ΔϣΩλΩϳΩηϲγγΣΗαΎϛΗέ΍

ϰϠϋϪΧϔΗϧϣΩΩϏϊϣΓΩϳΩηΔϛΣˬϊϠΑϟ΍ϭ΃αϔϧΗϟ΍ϲϓΔΑϭόλΏΑγϳΎϣϣˬϕϠΣϟ΍ϭ΃ϥΎγϠϟ΍ϭ

ϱΩϠΟϟ΍΢ϔρϟ΍ϭˬΩϠΟϟ΍

ϡΩϟ΍΢΋ΎϔλΩΩϋνΎϔΧϧ΍ΏΑγΑΕΎϣΩϛϭˬΔϳρΎΧϣϟ΍ΔϳηϏϷ΍ϭΩϠΟϟ΍ϥϣϑϳίϧ

ϲϓΩΎΣιϘϧΏΑγΑϰϣΣϟ΍ϥϳΗίϭϠϟ΍ΏΎϬΗϟ΍ΔλΎΧϭˬΕΎΑΎϬΗϟϻ΍ϭϯϭΩόϠϟΔοέϋˬϡΎϋϑόο

˯ΎοϳΑϟ΍ϡΩϟ΍ΎϳϼΧ

˺˹˹˹˹ϲϓΩΣ΍ϭιΧηϥϣϝϗ΃έϬυΗˬ΍ΩΟΓέΩΎϧϪϳΑϧΎΟν΍έϋ΍

ΎλϭλΧϭˬϲϋϭϟ΍ϲϓΕ΍έϳϐΗˬΔϳΩΎϋέϳϏΕϼοόϟ΍ΏϠλΗˬϡγΟϟ΍Γέ΍έΣΔΟέΩϲϓωΎϔΗέ΍

ϰϋΩΗΓέΩΎϧΔϟΎΣϟν΍έϋ΃ϥϭϛΗΩϗν΍έϋϻ΍ϩΫϫΔόϳέγΏϠϗΕΎοΑϧϭϕέόΗϟΎΑϥέΗϘϳΎϣΩϧϋ

ΔϔϠΗΧϣϥΎϫΫϟ΍Ε΍ΩΎοϣϝΎϣόΗγ΍ΩϧϋΕέϛΫϲΗϟ΍ϭˬ

ΔΛϳΑΧϟ΍ϥΎϫΫϟ΍ΔϣίϼΗϣ

ΩΑϛϟ΍ϥΎϗέϳϟ΍ϰϠϋΔϣϼϋϥϭϛϳϥ΃ϥϛϣϳϥϳόϟ΍νΎϳΑϭΩϠΟϟ΍έ΍έϔλ΍

ϝϭίΗν΍έϋϻ΍ϩΫϫϡυόϣΏϟΎϐϟ΍ϲϓϭΝϼόϟ΍Δϳ΍ΩΑϲϓϡΎΗΡϭοϭΑέϬυΗΔϳϟΎΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

Νϼόϟ΍έ΍έϣΗγ΍ϝϼΧ

Γέηϋϝλ΃ϥϣΩΣ΍ϭϥϣέΛϛ΃ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋ΃΍ΩΟΔό΋Ύηϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

ιΎΧη΃

ΔϳΩ΍έ·ϻΕΎϛέΣˬΎϳίϳΗΎϛϻ΍ϙ΍έΣϼΑ˯ΎϘΑϟ΍ϭ΃αϭϠΟϟ΍ϰϠϋΓέΩϘϟ΍ϡΩϋϭˬαΎόϧϟ΍

ΎϳίϳϧϛϭΑϳϫϡγΟϟ΍ΕΎϛέΣ΄ρΎΑΗˬΎϳίϳϧϛέΑϳϫ

ϡϔϟ΍ϑΎϔΟ

ιΧη˺˹˹ϥϣ˺˹˺ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍Ϫό΋Ύηϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

ΏΑγΑϪϳΩΎϋέϳϏϡγΟϟ΍ϲϓϪΗΑΎΛϭ΃ΓέέϛΗϣΕΎϛέΣˬϪϔΟέˬϥΎϘϔΧϟ΍ϭ΃ΏϠϘϟ΍ΕΎΑέοϝΩόϣΑΓΩΎϳί

ˬΓέϛ΍Ϋϟ΍ϥ΍ΩϘϓˬίϳϛέΗϟΎΑΕΎΑ΍έρο΍ˬΩϠΟϟ΍ϲϓίΧϭϭ΃έΩΧˬω΍Ωλϟ΍ˬΔΧϭΩϟ΍ˬΕϼοόϟ΍ΕΎΟϧηΗ

ϥΎϘΗΣ΍ˬέ΍ϭΩϟΎΑέϭόηΔΧϭΩϟ΍ˬϱέλΑϟ΍ίϳϛέΗϟΎΑϭ΃ΔϳέλΑΕΎΑ΍έρο·ΔϳόϳΑρέϳϏΔϳηϣϭ

έϭόηϟ΍ϭ΃ϡοϬϟ΍έγϋϭ˯ϲϘϟ΍ϭϙΎγϣϹ΍ˬΏΎόϠϟ΍ΝΎΗϧ·ϲϓΓΩΎϳίˬαϔϧΗϟ΍ϲϓϲϓϡϟ΃ϭ΃ΔΑϭόλˬϑϧϻ΍

ϲϓϡϻ΁ˬΔϛΣϟ΍ˬρέϔϣϟ΍ϕέόΗϟ΍ϝϭΑϟ΍ΕΎΑ΍έρο΍ˬϝΎϬγϹ΍ˬϥρΑϟ΍ϥϣϱϭϠόϟ΍˯ίΟϟ΍ϲϓΔΣ΍έϟ΍ϡΩόΑ

ˬϡϟϷ΍ˬνέϣϟ΍ϭ΃ΔΣ΍έϟ΍ϡΩόΑϡΎόϟ΍έϭόηϟ΍ˬέΗϭΗϟ΍ΏόΗϟ΍ˬϥίϭϟ΍ΓΩΎϳίˬΔϳϬηϟ΍ϲϓΓΩΎϳίˬΕϼοόϟ΍

ΔϳγϧΟϟ΍ΔΑϏέϟ΍νΎϔΧϧ΍ϭϪΑϳέϏϡϼΣ΍ΔϳΑλόϟ΍ϕϠϘϟ΍ˬΏΎ΋Ηϛϻ΍ϭϕέϷ΍

ιΧη˺˹˹˹ϥϣ˺˹˺ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍Δό΋ΎηέϳϏΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

ΔϳϠοόϟ΍ΕΎϛέΣϟ΍ϕϳγϧΗϰϠϋΓέΩϘϟ΍ϡΩϋϭˬ˯ΎϣϏϻ΍ϭˬεΎϋέϟ΍ˬΓΩΎΣΕΎϛέΣϭˬϝόϔϟ΍ΩϭΩέΓΩΎϳί

ϲϓΔϳέ΋΍ΩΕΎϛέΣϟ΍ˬϲϔλϧϟ΍ω΍Ωλϟ΍ˬΕΎΟϧηΗϟ΍ϭˬΕϼοόϟ΍ΓϭϗνΎϔΧϧ΍ˬϡϼϛϟ΍Ώ΍έρο΍ˬϕϳγϧΗϟ΍

ϰϠϋΓέΩϘϟ΍ϡΩϋϭ΃ΔϳΗϭλϟ΍Ε΍ΩΩέΗϟ΍νόΑϟϊϣγϟ΍ΔγΎΣϲϓϩΩϳΩηϪϳγΎγΣˬϥϳόϟ΍ΔϗΩΣωΎγΗ΍ˬϥϭϳόϟ΍

ˬϱΩϠΟϟ΍΢ϔρϟ΍ˬϥρΑϟ΍ΥΎϔΗϧ΍ˬϥΎϳΛϐϟ΍ˬϥρΑϟ΍ϲϓϡϻ΁ˬϥϳϧΫϷ΍ϲϓϥϳϧέϥϳϧρˬϲϣϭϳϟ΍˯Ύοϭοϟ΍ϝϣΣΗ

ΓΩΎϳίΏΑγΑϲϧϫΩΩϠΟΩϠΟϟ΍ϥΎόϣϟˬϩέ΍έϔλ΍ϭ΍ΩϠΟϟ΍ώΑλˬ˯ϭοϠϟΔϳγΎγΣϟ΍ΏΑγΑΩϠΟϟ΍ϝόϓΩέ

ϥϭϠϟ΍Δϳϧ΍ϭΟέ΍˯΍έϣΣϊϘΑέϭϬυϭΩϠΟϟ΍ΕΣΗϑϳίϧˬΩϠΟϟ΍ΏΎϬΗϟ΍ϭ΃ΎϣϳίϛϷ΍ˬϡϫίϟ΍ϥϭϫΩϟ΍ί΍έϓ·

ϪϳόοϭϭΔΑϗέϟ΍ϲϓΏϠλΗϭ΃˯΍ϭΗϟ΍ˬΩΎΗόϣϟΎϛϡϔϟ΍΢ΗϓϰϠϋΓέΩϘϟ΍ϡΩϋˬΕϼοόϟ΍ΏϠλΗˬΩϠΟϟ΍ϰϠϋ

ˬα΃έϟ΍ϲϓϪϳΩΎϳΗϋ΍έϳϏ

ϥϣϝϗ΃ϡγΟϟ΍Γέ΍έΣΔΟέΩˬερόϟ΍ˬΔϧΧΎγΕΎΑϫˬϡΩϟ΍ρϐονΎϔΧϧ΍ˬϥίϭϟ΍ϥ΍ΩϘϓˬΔϳϬηϟ΍ΔϠϗ

ˬΏΎλΗϧϻ΍ϑόοˬϑΫϘϟ΍έϳΧ΄ΗϲγϧΟϟ΍ίΟόϟ΍ˬΩΑϛϟ΍ϑ΋ΎυϭϥϣΔϳόϳΑρέϳϏΞ΋ΎΗϧˬϰϣΣϟ΍ˬΩΎΗόϣϟ΍

ΓΩΎϳίˬαϳΑ΍ϭϛϟ΍ˬΓϻΎΑϣϼϟ΍ˬ˯Ύγϧϟ΍ϲϓϝΑϬϣϟ΍ϑΎϔΟϭˬ˯Ύγϧϟ΍ΩϧϋΔϳγϧΟϟ΍Γϭηϧϟ΍ϰϟ·ϝϭλϭϟ΍ΔΑϭόλϭ

ϙΎΑΗέϻ΍ϭˬΔϳγϧΟϟ΍ΔΑϏέϟ΍

ΎλΎΧΎϣΎϣΗϫ΍ΏϠρΗΗϲΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍

ιΧη˺˹˹˹˹ϥϣ˺˹˺ϲϓέϬυΗϲΗϟ΍ΔϳΑϧΎΟϟ΍ν΍έϋϷ΍ΓέΩΎϧΔϳΑϧΎΟν΍έϋϷ΍

ΎϳϼΧΩΩϋνΎϔΧϧ΍˯ΎοϳΑϟ΍ϡΩϟ΍΢΋ΎϔλΩΩϋνΎϔΧϧ΍ˬΕΎΣϳϔλϟ΍ϡΩϟ΍΢΋ΎϔλΩΩϋνΎϔΧϧ΍

ϥϳΗϛϻϭέΑϟ΍ϯϭΗγϣΓΩΎϳίˬΕΎΑΑΣϣϟ΍ΓέΩϧϲϣΎυόϟ΍ωΎΧϧϡϣγΗˬνϳΑϟ΍ΕΎϳέϛϟ΍˯ΎοϳΑϟ΍ϡΩϟ΍

ΕΎϳϧϫΩϟ΍ΔΑγϧωΎϔΗέ΍ˬίϭϛϭϠΟϟ΍ϝϣΣΗϡΩϋˬϡΩϟ΍έϛγρέϓϡΩϟ΍ϲϓέϛγϟ΍ΔΑγϧωΎϔΗέ΍ˬϡΩϟ΍ϲϓ

ΩΎΣϟ΍ϲγγΣΗϟ΍ϝόϔϟ΍ΩέˬΔϳγΎγΣϟ΍ρέϓϪρέϔϣϟ΍ΔϳγΎγΣϟ΍ˬϡΩϟ΍ϲϓ

έΛρέϔϣϟ΍ΏϳϠΣϟ΍ΝΎΗϧ·ˬϱΩΛΗϝΎΟέϟ΍ϯΩϟϱΩΛϟ΍έΑϛϲγγΣΗϝόϓΩέϡγΟϟ΍˯ΎΣϧ΍ϊϳϣΟΑ

ϕϠόΗϣέϳϏΔϠϳϭρΕ΍έΗϔϟϡϟ΅ϣϟ΍ΏΎλΗϧϻ΍ˬΙϣρϟ΍ωΎρϘϧ΍Ιϣρϟ΍Ε΍έΗϓΩϭΟϭϡΩϋˬϥΑϠϟ΍

ΔϳγϧΟϟ΍ΓϭϬηϟΎΑ

ϲϓϪϟΎόϔϟ΍ϩΩΎϣϟ΍ϝϭγϛϳΛϧΑϭϠϛίϟ΍˯΍ϭΩΔϠΛΎϣϣΔϘϳέρΑϝϣόΗϲΗϟ΍ϯέΧϷ΍ΔϳϭΩϷ΍ϊϣϝΎΣϟ΍ϭϫΎϣϛ

ΔϳϟΎΗϟ΍ΔϳΑϧΎΟϟ΍έΎΛϵ΍ϥϣΓέΩΎϧΕϻΎΣϥϋύϼΑϹ΍ϡΗˬϝϭγϛϳΑϭϠϛ

ΏϠϘϟ΍ρϳρΧΗϲϓΕ΍έϳϐΗϭΏϠϘϟ΍ΕΎϗΩοϝΩόϣ˯ρΑ

ΩϳΩϣΗ

ΕΎϗΩϡΎυΗϧ΍ϡΩϋˬϲϧϳρΑϟ΍ϥΎϔΟέϟ΍ˬϲϧϳρΑϟ΍ΏϠϘϟ΍ΕΎΑέοϡΎυΗϧ΍ϡΩϋϪϣυΗϧϣέϳϏΏϠϗΕΎϗΩ

ϲϧϳρΑϟ΍ΏϠϘϟ΍

ΏϠϘϟ΍ΕΎϗΩϡΎυΗϧ΍ϡΩϋϥϣιΎΧωϭϧ

Εϭϣϟ΍ϰϟ΍ΏϠϘϟ΍ΕΎΑέοϡΎυΗϧ΍ϡΩϋΏϠϘϟ΍ΕΎΑέοϝΩόϣϲϓΕΎΑ΍έρο΍ΕΩ΃ˬΓέΩΎϧΕϻΎΣϲϓ

ΊΟΎϔϣϟ΍

ϲϓέ΍έϣΣ΍ϭϡϟ΃ϭϡέϭΗν΍έϋϻ΍ϝϣηΗϭϥϳϗΎγϟ΍ϲϓΎλϭλΧϭΓΩέϭϷ΍ϲϓϡΩϟ΍ΕΎρϠΟΙϭΩΣ

αϔϧΗϟ΍ϲϓΔΑϭόλϭέΩλϟ΍ϲϓϡϟ΃ΏΑγϳΎϣϣϥϳΗ΋έϟ΍ϰϟ·ΔϳϭϣΩϟ΍ΔϳϋϭϷ΍έΑϋϝϘΗϧΗΩϗϲΗϟ΍ϭˬϕΎγϟ΍

έϭϔϟ΍ϰϠϋΔϳΑρϟ΍Γέϭηϣϟ΍ΏϠρ΃ˬν΍έϋϷ΍ϩΫϫϥϣϱ΃ΕυΣϻ΍Ϋ·

ϥϳΫϟ΍ϰοέϣϠϟΕΎϳϓϭϟ΍ΩΩϋϲϓΔϔϳϔρΓΩΎϳίϥϋύϼΑϹ΍ϡΗˬϑέΧϟ΍ϥϣϥϭϧΎόϳϥϳΫϟ΍ϥϳϧγϣϟ΍Ωϧϋ

Ε΍ΩΎοϣϟ΍ϩΫϫϥϭϣΩΧΗγϳϻϥϳΫϠϟ΍ϊϣΔϧέΎϘϣϥΎϫΫϟ΍Ε΍ΩΎοϣϥϭϟϭΎϧΗϳ

ϱ΃ΕυΣϻ΍Ϋ·ϭ΃ˬν΍έϋϷ΍ϩΫϫϥϣΔϳ΄ΑϡϗΎϔΗϙΎϧϫϥΎϛ΍Ϋ·ϭˬΔϳΑϧΎΟϟ΍ν΍έϋϷ΍ϩΫϫϯΩΣ·ΕέϬυ΍Ϋ·

ΏϳΑρϟ΍ΓέΎηΗγ΍ϰΟέϳˬΓέηϧϟ΍ϩΫϫϲϓΓέϭϛΫϣϟ΍έϳϏΔϳΑϧΎΟν΍έϋ΃

˯΍ϭΩϟ΍΍ΫϫϥϳίΧΗΔϳϔϳϛ˾

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ודי לע רשואו קדבנ ונכותו תואירבה דרשמ ידי לע עבקנ הז ןולע טמרופ

71.2.9.71

Physician Prescribing Information - Clopixol

®

Tablets 2 10 25 mg

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Clopixol 2 mg film-coated tablets

Clopixol 10 mg film-coated tablets

Clopixol 25 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Clopixol 2 mg: Each tablet contains 2 mg zuclopenthixol (as 2.364 mg zuclopenthixol

dihydrochloride)

Clopixol 10 mg: Each tablet contains 10 mg zuclopenthixol (as 11.82 mg zuclopenthixol

dihydrochloride)

Clopixol 25 mg: Each tablet contains 25 mg zuclopenthixol (as 29.55 mg zuclopenthixol

dihydrochloride)

Excipient with known effect:

Lactose monohydrate

Hydrogenated castor oil

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

2 mg: Round, biconvex, pale red, film-coated tablet.

10 mg: Round, biconvex, light red-brown film-coated tablet.

25 mg: Round, biconvex, red-brown, film-coated tablet.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Acute schizophrenia, other acute psychoses.

4.2 Posology and method of administration

Posology

Adults

Dosage should be individually adjusted according to the condition of the patient. In general,

small doses should be used initially and increased to the optimal effective level as rapidly as

possible based on the therapeutic response. The maintenance dose can usually be given as a

single dose at bedtime.

Acute schizophrenia and other acute psychoses:

Usually 10-50 mg/day. In moderate to severe cases initially 20 mg/day increased, if

necessary, by 10-20 mg every 2 to 3 days to 75 mg or more daily. Maximum dosage per

single dose is 40 mg and a total of 150 mg/day.

Older patients

Older patients should receive dosages in the lower end of the dosage range.

Children

Clopixol is not recommended for use in children due to lack of clinical experience.

Reduced renal function

Clopixol can be given in usual doses to patients with reduced renal function.

Reduced liver function

Careful dosing and, if possible, a serum level determination is advisable.

Method of administration

The tablets are swallowed with water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients, (see section 6.1).

Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with

alcohol, barbiturates or opiates), coma.

4.4 Special warnings and precautions for use

The possibility of development of neuroleptic malignant syndrome (hyperthermia, muscle

rigidity, fluctuating consciousness, instability of the autonomous nervous system) exists with

any neuroleptic.

The risk is possibly greater with the more potent agents. Patients with pre-existing organic

brain syndrome, mental retardation and opiate and alcohol abuse are over-represented among

fatal cases.

Treatment: Discontinuation of the neuroleptic. Symptomatic treatment and use of general

supportive measures. Dantrolene and bromocriptine may be helpful.

Symptoms may persist for more than a week after oral neuroleptics are discontinued and

somewhat longer when associated with the depot forms of the drugs.

Like other neuroleptics zuclopenthixol should be used with caution in patients with organic

brain syndrome, convulsion and advanced hepatic disease.

As described for other psychotropics zuclopenthixol may modify insulin and glucose

responses calling for adjustment of the antidiabetic therapy in diabetic patients.

Patients on long-term therapy, particularly on high doses, should be monitored carefully and

evaluated periodically to decide whether the maintenance dosage can be lowered.

As with other drugs belonging to the therapeutic class of antipsychotics, zuclopenthixol may

cause QT prolongation. Persistently prolonged QT intervals may increase the risk of

malignant arrhythmias.

Therefore, zuclopenthixol should be used with caution in susceptible individuals (with

hypokalemia, hypomagnesia or genetic predisposition) and in patients with a history of

cardiovascular disorders, e.g. QT prolongation, significant bradycardia (<50 beats per

minute), a recent acute myocardial infarction, uncompensated heart failure, or cardiac

arrhythmia. Concomitant treatment with other antipsychotics should be avoided (see section

4.5).

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since

patients treated with antipsychotics often present with acquired risk factors for VTE, all

possible risk factors for VTE should be identified before and during treatment with

zuclopenthixol and preventive measures undertaken

Older people

Cerebrovascular

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in

randomised placebo controlled clinical trials in the dementia population with some atypical

antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot

be excluded for other antipsychotics or other patient populations. Zuclopenthixol should be

used with caution in patients with risk factors for stroke.

Increased Mortality in Older people with Dementia

Data from two large observational studies showed that older people with dementia who are

treated with antipsychotics are at a small increased risk of death compared with those who are

not treated. There are insufficient data to give a firm estimate of the precise magnitude of the

risk and the cause of the increased risk is not known.

Zuclopenthixol is not licensed for the treatment of dementia-related behavioural disturbances.

Excipients

The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not

receive this medicine.

The tablets contain hydrogenated castor oil, may cause stomach upset and diarrhoea.

4.5 Interaction with other medicinal products and other forms of interaction

Combinations requiring precautions for use

Zuclopenthixol may enhance the sedative effect of alcohol and the effects of barbiturates and

other CNS depressants.

Neuroleptics may increase or reduce the effect of antihypertensive drugs; the antihypertensive

effect of guanethidine and similar acting compounds is reduced.

Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.

Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of each other.

Zuclopenthixol may reduce the effect of levodopa and the effect of adrenergic drugs.

Concomitant use of metoclopramide and piperazine increases the risk of extrapyramidal

disorder.

Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to

inhibit this enzyme may lead to decreased clearance of zuclopenthixol.

Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co-

administration of other drugs known to significantly increase the QT interval. Co-

administration of such drugs should be avoided. Relevant classes include:

class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)

some antipsychotics (e.g. thioridazine)

some macrolides (e.g. erythromycin)

some antihistamines (e.g. terfenadine, astemizole)

some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

The above list is not exhaustive and other individual drugs known to significantly increase

QT interval (e.g. cisapride, lithium) should be avoided.

Drugs known to cause electrolyte disturbances such as thiazidediuretica (hypokalemia) and

drugs known to increase the plasma concentration of zuclopenthixol should also be used with

caution as they may increase the risk of QT prolongation and malignant arrhythmias (see

section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

Zuclopenthixol should not be administered during pregnancy unless the expected benefit to

the patient outweighs the theoretical risk to the foetus.

Neonates exposed to antipsychotics (including zuclopenthizol) during the third trimester of

pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal

symptoms that may vary in severity and duration following delivery. There have been reports

of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding

disorder. Consequently, newborns should be monitored carefully.

Animal studies have shown reproductive toxicity (see section 5.3)

Breast-feeding

As zuclopenthixol is found in breast milk in low concentrations it is not likely to affect the

infant when therapeutic doses are used. The dose ingested by the infant is less than 1% of the

weight related maternal dose (in mg/kg). Breast-feeding can be continued during

zuclopenthixol therapy if considered of clinical importance but observation of the infant is

recommended, particularly in the first 4 weeks after giving birth.

Fertility

In humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile

dysfunction and ejaculation failure have been reported (see section 4.8). These events may

have a negative impact on female and/or male sexual function and fertility.

If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual dysfunctions

occur, a dose reduction (if possible) or discontinuation should be considered. The effects are

reversible on discontinuation.

Administration of zuclopenthixol to male and female rats was associated with a slight delay in

mating. In an experiment where zuclopenthixol was administered via the diet, impaired

mating performance and reduced conception rate was noted.

4.7 Effects on ability to drive and use machines

Clopixol is a sedative drug. Patients who are prescribed psychotropic medication may be

expected to have some impairment in general attention and concentration and should be

cautioned about their ability to drive or operate machinery.

4.8 Undesirable effects

Undesirable effects are for the majority dose dependent. The frequency and severity are most

pronounced in the early phase of treatment and decline during continued treatment.

Extrapyramidal reactions may occur, especially in the early phase of treatment. In most cases

these side effects can be satisfactorily controlled by reduction of dosage and/or use of

antiparkinsonian drugs. The routine prophylactic use of antiparkinsonian drugs is not

recommended. Antiparkinsonian drugs do not alleviate tardive dyskinesia and may aggravate

them. Reduction in dosage or, if possible, discontinuation of zuclopenthixol therapy is

recommended. In persistent akathisia a benzodiazepine or propranolol may be useful.

Frequencies are taken from the literature and spontaneous reporting. Frequencies are defined

Very common (

1/10), common (

1/100 to <1/10), uncommon (

1/1000 to <1/100), rare

1/10000 to<1/1000), very rare (<1/10000), or not known (can not be estimated from the

available data).

Cardiac disorders

Common

Tachycardia, palpitations

Rare

Electrocardiogram QT prolonged

Blood and lymphatic system

disorders

Rare

Thrombocytopenia, neutropenia,

leukopenia, agranulocytosis.

Nervous system disorders

Very

common

Somnolence, akathisia, hyperkinesia,

hypokinesia.

Common

Tremor, dystonia, hypertonia, dizziness,

headache, paraesthesia, disturbance in

attention, amnesia, gait abnormal.

Uncommon

Tardive dyskinesia, hyperreflexia, dyskinesia,

parkinsonism, syncope, ataxia, speech

disorder, hypotonia, convulsion, migraine.

Very rare

Neuroleptic malignant syndrome

Eye disorders

Common

Accommodation disorder, vision abnormal.

Uncommon

Oculogyration, mydriasis

Ear and labyrinth disorders

Common

Vertigo.

Uncommon

Hyperacusis, tinnitus

Respiratory, thoracic and

medistianal disorders

Common

Nasal congestion, dyspnoea

Gastrointestinal disorders

Very

common

Dry mouth

Common

Salivary hypersecretion, constipation,

vomiting, dyspepsia, diarrhoea.

Uncommon

Abdominal pain, nausea, flatulence.

Renal and urinary disorders

Common

Micturition disorder, urinary retention,

polyuria.

Skin and subcutaneous tissue

disorders

Common

Hyperhidrosis, pruritus

Uncommon

Rash, photosensitivity reaction, pigmentation

disorder, seborrhoea, dermatitis, purpura.

Musculoskeletal and

connective tissue disorder

Common

Myalgia

Uncommon

Muscle rigidity, trismus, torticollis

Endocrine disorders

Rare

Hyperprolactinaemia

Metabolism and nutrition

disorders

Common

Increased appetite, weight increased

Uncommon

Decreased appetite, weight decreased

Rare

Hyperglycaemia, glucose tolerance impaired,

hyperlipidaemia.

Vascular disorders

Uncommon

Hypotension, hot flush

Very rare

Venous thromboembolism

General disorders and

administration site conditions

Common

Asthenia, fatigue, malaise, pain

Uncommon

Thirst, hypothermia, pyrexia

Immune system disorders

Rare

Hypersensitivity, anaphylactic reaction

Hepato-biliary disorders

Uncommon

Liver function test abnormal

Very rare

Cholestatic hepatitis, jaundice

Pregnancy, puerperium

and perinatal conditions

Not known

Drug withdrawal syndrome neonatal (see

4.6)

Reproductive system and

breast

disorders

Uncommon

Ejaculation failure, erectile dysfunction,

female orgasmic disorder, vulvovaginal

dryness.

Rare

Gynaecomastia, galactorrhoea, amenorrhoea,

priapism.

Psychiatric disorders

Common

Insomnia, depression, anxiety, nervousness,

abnormal dreams, agitation, libido decreased.

Uncommon

Apathy, nightmare, libido increased,

confusional state.

As with other drugs belonging to the therapeutic class of antipsychotics, rare cases of QT

prolongation, ventricular arrhythmias - ventricular fibrillation, ventricular tachycardia,

Torsade dePointes and sudden unexplained death have been reported for zuclopenthixol (see

section 4.4).

Abrupt discontinuation of zuclopenthixol may be accompanied by withdrawal symptoms. The

most common symptoms are nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating,

myalgias, paraesthesias, insomnia, restlessness, anxiety, and agitation. Patients may also

experience vertigo, alternate feelings of warmth and coldness, and tremor. Symptoms

generally begin within 1 to 4 days of withdrawal and abate within 7 to 14 days.

4.9 Overdose

Symptoms

Somnolence, coma, movement disorders, convulsions, shock, hyperthermia/hypothermia.

ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular

arrhythmias have been reported when zuclopenthixol has been taken in overdose together

with drugs known to affect the heart.

The highest orally administered dose of zuclopenthixol in clinical trials was 450 mg daily.

Treatment

Treatment is symptomatic and supportive. Measures to support the respiratory and

cardiovascular systems should be instituted. Epinephrine (adrenaline) should not be used as

further lowering of blood pressure may result. Convulsions may be treated with diazepam and

movement disorders symptoms with biperiden.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group

Antipsychotics - Thioxanthene derivative.

ATC-code: N 05 AF 05

Mechanism of action

Zuclopenthixol is a neuroleptic of the thioxanthene group.

The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking effect

but possibly also 5-HT (5-hydroxytryptamine) receptor blockade contributes. In vitro

zuclopenthixol has high affinity for both dopamine D

and D

receptors, for α

-adrenoceptors

and 5-HT

receptors but no affinity for cholinergic muscarine receptors. It has weak histamine

) receptor affinity and no α

-adrenoceptor blocking activity.

In vivo the affinity for D

binding sites dominates over the affinity for D

receptors.

Zuclopenthixol has proven to be a potent neuroleptic in all the behavioural studies for

neuroleptic (dopamine receptor blocking) activity. Correlation is found in the in vivo test

models, the affinity for dopamine D

binding sites in vitro and the average, daily oral

antipsychotic doses.

Inhibition of locomotor activity and prolongation of alcohol- and barbiturate-induced sleeping

time indicate a sedative action of zuclopenthixol.

Like most other neuroleptics zuclopenthixol increases the serum prolactin level.

Clinical efficacy and safety

In clinical use zuclopenthixol is intended for the treatment of acute psychoses.

Besides causing a significant reduction or complete elimination of the nuclear symptoms of

schizophrenia such as hallucinations, delusions and thought disturbances zuclopenthixol also

has a marked effect on accompanying symptoms like hostility, suspiciousness, agitation and

aggressiveness.

Zuclopenthixol induces a transient dose-dependent sedation. However, such an initial

sedation is usually advantageous in the acute phase of the illness. Tolerance to the unspecific

sedative effect develops rapidly.

5.2 Pharmacokinetic properties

Absorption

Oral administration results in maximum serum levels in about 4 hours. Zuclopenthixol can be

taken without regard to food intake. Oral bioavailability is about 44 %.

Distribution

The apparent volume of distribution (V

is about 20 l/kg.

The plasma protein binding is about 98-99 %.

Biotransformation

The metabolism of zuclopenthixol proceeds along three main routes - sulphoxidation, side

chain Ndealkylation and glucuronic acid conjugation. The metabolites are devoid of

psychopharmacological activity. Zuclopenthixol dominates over metabolites in brain and

other tissues.

Elimination

The elimination half-life (T

½ β

) is about 20 hours and the mean systemic clearance (Cl

) is

about 0.86 L/min.

Zuclopenthixol is excreted mainly with faeces, but also to some degree (about 10 %) with the

urine.

Only about 0.1 % of the dose is excreted unchanged with the urine, meaning that the drug

load on the kidneys is negligible.

In nursing mothers zuclopenthixol is excreted in small amounts with the breast milk. In steady

state the pre-dose mean ratio milk conc./serum conc. in women treated orally or with the

decanoate was about 0.29.

Linearity

The kinetics is linear. Steady state plasma levels are achieved in about 3-5 days. The mean

minimum steady state level corresponding to 20 mg zuclopenthixol orally once a day was

about 25 nmol/l.

Older patients

The pharmacokinetic parameters are widely independent of the age of the patients.

Reduced renal function

Based on the above characteristics for elimination it is reasonable to assume that reduced

kidney function is likely not to have much influence on the serum levels of parent drug.

Reduced hepatic function

No data available.

Polymorphism

An in vivo investigation has shown that some part of the metabolic pathways is subject to

genetic polymorphism of the sparteine/debrisoquine oxidation (CYP2D6).

Pharmacokinetic / Pharmacodynamic relationship

A minimum (i.e. concentration measured just before administration of a dose) serum

concentration of 2.8-12 ng/ml (7-30 nmol/l) is suggested as guideline for maintenance

treatment of schizophrenic patients with low-moderate degree of illness.

5.3 Preclinical safety data

Acute toxicity

Zuclopenthixol has low acute toxicity.

Chronic toxicity

In chronic toxicity studies there were no findings of concern for the therapeutic use of

zuclopenthixol.

Reproduction toxicity

In a three-generation study in rats a delay in mating was noted. Once mated there was no

effect on fertility. In an experiment where zuclopenthixol was administered via the diet,

impaired mating performance and reduced conception rate was noted.

Animal reproduction studies have not shown evidence of embryotoxic or teratogenic effects.

In a peri/postnatal study in rats, dosages of 5 and 15 mg/kg/day resulted in an increase of

stillbirths, reduced pup survival and delayed development of pups The clinical significance of

these findings is unclear and it is possible that the effect on pups was due to neglect from the

dams that were exposed to doses of zuclopenthixol producing maternal toxicity.

Mutagenicity and carcinogenicity

Zuclopenthixol has no mutagenic or carcinogenic potential.

In a rat oncogenecity study 30 mg/kg/day for two years (top dosage) resulted in slight non-

statistical increases in the incidence of mammary adenocarcinomas, pancreatic islet cell

adenomas, carcinomas in females, and thyroid parafollicular carcinomas. The slight increase

in the incidence of these tumors is a common finding for D

antagonists, which increase

prolactin secretion when administered to rats.

The physiological differences between rats and humans with regard to prolactin make the

clinical significance of these findings unclear, but it is accepted as not predicting an

oncogenic risk in patients.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Potato starch,

Lactose monohydrate,

Microcrystalline cellulose,

Copovidone,

Glycerol 85%,

Talc,

Hydrogenated castor oil,

Magnesium stearate.

Coating:

Hypromellose5,

Macrogol 6000

Colours:

Titanium dioxide (E 171),

Red iron oxide (E 172),

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

6.4 Special precautions for storage

Do not store above 25ºC.

6.5 Nature and contents of container

2 mg: 50, 100 and 250 in plastic container.

10 mg: 30, 50, 60, 100 and 250 in plastic container, 30 in blister packs.

25 mg: 30, 50, 60, 100 and 250 in plastic container, 20 in blister packs.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with

local requirements.

7. MARKETING AUTHORISATION HOLDER AND MANUFACTURER

H. Lundbeck A/S

Ottiliavej 9

DK-2500 Valby, Copenhagen

Denmark

8. LICENSE HOLDER:

LUNDBECK ISRAEL LTD

4 derech Hashalom st, Tel Aviv

17.9.2014