Diacomit · 4.3 Contraindications · 2

HOS-094286 · has-adverse-reaction-information · PDF-Seite 29

Summary of the safety profile The most common side effects with stiripentol are anorexia, weight loss, insomnia, drowsiness, ataxia, hypotonia and dystonia. Tabulated list of adverse reactions Adverse reactions encountered most often are as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing severity. System Organ Very Common Uncommon Rare Not known Class common (MedDRA terminology) Blood and Neutropenia Thrombocytopenia lymphatic * system disorders Metabolism Anorexia, and nutrition loss of disorders appetite, weight loss 29 Psychiatric Insomnia Aggressiveness, disorders irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders Nervous system Drowsiness, Hyperkinesias disorders ataxia, hypotonia, dystonia Eye disorders Diplopia Gastrointestinal Nausea, disorders vomiting Skin and Photosensitivity, subcutaneous rash, cutaneous tissue disorders allergy, urticaria General Fatigue disorders and administration site conditions Investigations Raised γGT Liver function test abnormal Infections and Pneumonia, infestations aspiration

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HOS-094292 · has-adverse-reaction-information · PDF-Seite 40

Summary of the safety profile The most common side effects with stiripentol are anorexia, weight loss, insomnia, drowsiness, ataxia, hypotonia and dystonia. Tabulated list of adverse reactions Adverse reactions encountered most often are as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing severity. System Organ Very Common Uncommon Rare Not known Class common (MedDRA terminology) Blood and Neutropenia Thrombocytopenia lymphatic * system disorders Metabolism Anorexia, and nutrition loss of disorders appetite, weight loss 40 Psychiatric Insomnia Aggressiveness, disorders irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders Nervous system Drowsiness, Hyperkinesias disorders ataxia, hypotonia, dystonia Eye disorders Diplopia Gastrointestinal Nausea, disorders vomiting Skin and Photosensitivity, subcutaneous rash, cutaneous tissue disorders allergy, urticaria General Fatigue disorders and administration site conditions Investigations Raised γGT Liver function test abnormal Infections and Pneumonia, infestations aspiration

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HOS-094280 · has-adverse-reaction-information · PDF-Seite 18

Summary of the safety profile The most common side effects with stiripentol are anorexia, weight loss, insomnia, drowsiness, ataxia, hypotonia and dystonia. Tabulated list of adverse reaction Adverse reactions encountered most often are as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing severity. System Organ Very Common Uncommon Rare Not known Class common (MedDRA terminology) Blood and Neutropenia Thrombocytopenia lymphatic * system disorders Metabolism Anorexia, and nutrition loss of disorders appetite, weight loss 18 Psychiatric Insomnia Aggressiveness, disorders irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders Nervous system Drowsiness, Hyperkinesias disorders ataxia, hypotonia, dystonia Eye disorders Diplopia Gastrointestinal Nausea, disorders vomiting Skin and Photosensitivity, subcutaneous rash, cutaneous tissue disorders allergy, urticaria General Fatigue disorders and administration site conditions Investigations Raised γGT Liver function test abnormal Infections and Pneumonia, infestations aspiration

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HOS-094274 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most common side effects with stiripentol are anorexia, weight loss, insomnia, drowsiness, ataxia, hypotonia and dystonia. Tabulated list of adverse reactions Adverse reactions encountered most often are as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing severity. System Organ Very Common Uncommon Rare Not known Class common (MedDRA terminology) Blood and Neutropenia Thrombocytopenia lymphatic * system disorders Metabolism Anorexia, and nutrition loss of disorders appetite, weight loss 7 Psychiatric Insomnia Aggressiveness, disorders irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders Nervous system Drowsiness, Hyperkinesias disorders ataxia, hypotonia, dystonia Eye disorders Diplopia Gastrointestinal Nausea, disorders vomiting Skin and Photosensitivity, subcutaneous rash, cutaneous tissue disorders allergy, urticaria General Fatigue disorders and administration site conditions Investigations Raised γ-GT Liver function test abnormal Infections and Pneumonia, infestations aspiration

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HOS-094270 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. A past history of psychoses in the form of episodes of delirium.

HOS-094282 · has-contraindication-information · PDF-Seite 26

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. A past history of psychoses in the form of episodes of delirium.

HOS-094288 · has-contraindication-information · PDF-Seite 37

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. A past history of psychoses in the form of episodes of delirium.

HOS-094276 · has-contraindication-information · PDF-Seite 15

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. A past history of psychoses in the form of episodes of delirium.

HOS-094281 · has-indication-information · PDF-Seite 24

Diacomit is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (SMEI, Dravet’s syndrome) whose seizures are not adequately controlled with clobazam and valproate.

HOS-094275 · has-indication-information · PDF-Seite 13

Diacomit is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (SMEI, Dravet’s syndrome) whose seizures are not adequately controlled with clobazam and valproate.

HOS-094269 · has-indication-information · PDF-Seite 2

Diacomit is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (SMEI, Dravet’s syndrome) whose seizures are not adequately controlled with clobazam and valproate.

HOS-094287 · has-indication-information · PDF-Seite 35

Diacomit is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (SMEI, Dravet’s syndrome) whose seizures are not adequately controlled with clobazam and valproate.

HOS-094290 · has-interaction-information · PDF-Seite 38

Potential medicinal product interactions affecting stiripentol The influence of other antiepileptic medicinal products on stiripentol pharmacokinetics is not well established. The impact of macrolides and azole antifungal medicinal product on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known. Likewise, the effect of stiripentol on their metabolism is not known. In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Effect of stiripentol on cytochrome P450 enzymes Many of these interactions have been partially confirmed by in vitro studies and in clinical trials. The increase in steady state levels with the combined use of stiripentol, valproate, and clobazam is similar in adults and children, though inter-individual variability is marked. At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4. As a result, pharmacokinetic interactions of metabolic origin with other medicines may be expected. These interactions may result in increased systemic levels of these active substances that may lead to enhanced pharmacological effects and to an increase in adverse reactions. Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) or CYP3A4 (e.g. several HIV protease inhibitors, antihistamines such as astemizole and chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse reactions (see further in this section for antiepileptic medicines). Monitoring of plasma concentrations or adverse reactions is recommended. A dose adjustment may be necessary. Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse reactions. Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded because of increased plasma levels of theophylline and caffeine which may occur via inhibition of their hepatic metabolism, potentially leading to toxicity. Use in combination with stiripentol is not recommended. This warning is not only r

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HOS-094284 · has-interaction-information · PDF-Seite 27

Potential medicinal product interactions affecting stiripentol The influence of other antiepileptic medicinal products on stiripentol pharmacokinetics is not well established. The impact of macrolides and azole antifungal medicinal product on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known. Likewise, the effect of stiripentol on their metabolism is not known. In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Effect of stiripentol on cytochrome P450 enzymes Many of these interactions have been partially confirmed by in vitro studies and in clinical trials. The increase in steady state levels with the combined use of stiripentol, valproate, and clobazam is similar in adults and children, though inter-individual variability is marked. At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4. As a result, pharmacokinetic interactions of metabolic origin with other medicines may be expected. These interactions may result in increased systemic levels of these active substances that may lead to enhanced pharmacological effects and to an increase in adverse reactions. Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) or CYP3A4 (e.g. several HIV protease inhibitors, antihistamines such as astemizole and chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse reactions (see further in this section for antiepileptic medicines). Monitoring of plasma concentrations or adverse reactions is recommended. A dose adjustment may be necessary. Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse reactions. Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded because of increased plasma levels of theophylline and caffeine which may occur via inhibition of their hepatic metabolism, potentially leading to toxicity. Use in combination with stiripentol is not recommended. This warning is not only re

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HOS-094278 · has-interaction-information · PDF-Seite 16

Potential medicinal product interactions affecting stiripentol The influence of other antiepileptic medicinal products on stiripentol pharmacokinetics is not well established. The impact of macrolides and azole antifungal medicinal products on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known. Likewise, the effect of stiripentol on their metabolism is not known. In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Effect of stiripentol on cytochrome P450 enzymes Many of these interactions have been partially confirmed by in vitro studies and in clinical trials. The increase in steady state levels with the combined use of stiripentol, valproate, and clobazam is similar in adults and children, though inter-individual variability is marked. At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4. As a result, pharmacokinetic interactions of metabolic origin with other medicines may be expected. These interactions may result in increased systemic levels of these active substances that may lead to enhanced pharmacological effects and to an increase in adverse reactions. Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) or CYP3A4 (e.g. HIV protease inhibitors, antihistamines such as astemizole and chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse reactions (see further in this section for antiepileptic medicines). Monitoring of plasma concentrations or adverse reactions is recommended. A dose adjustment may be necessary. Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse reactions. Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded because of increased plasma levels of theophylline and caffeine which may occur via inhibition of their hepatic metabolism, potentially leading to toxicity. Use in combination with stiripentol is not recommended. This warning is not only restricte

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HOS-094272 · has-interaction-information · PDF-Seite 5

Potential medicinal product interactions affecting stiripentol The influence of other antiepileptic medicinal products on stiripentol pharmacokinetics is not well established. The impact of macrolides and azole antifungal medicinal agents on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known. Likewise, the effect of stiripentol on their metabolism is not known. In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Effect of stiripentol on cytochrome P450 enzymes Many of these interactions have been partially confirmed by in vitro studies and in clinical trials. The increase in steady state levels with the combined use of stiripentol, valproate, and clobazam is similar in adults and children, though inter-individual variability is marked. At therapeutic concentrations, stiripentol significantly inhibits several CYP450 isoenzymes: for example, CYP2C19, CYP2D6 and CYP3A4. As a result, pharmacokinetic interactions of metabolic origin with other medicines may be expected. These interactions may result in increased systemic levels of these active substances that may lead to enhanced pharmacological effects and to an increase in adverse reactions. Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) or CYP3A4 (e.g. HIV protease inhibitors, antihistamines such as astemizole and chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse reactions (see further in this section for antiepileptic medicines). Monitoring of plasma concentrations or adverse reactions is recommended. A dose adjustment may be necessary. Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse reactions. Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded because of the increased plasma levels of theophylline and caffeine which may occur via inhibition of their hepatic metabolism, potentially leading to toxicity. Use in combination with stiripentol is not recommended. This warning is not only restri

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HOS-094285 · has-pregnancy-information · PDF-Seite 28

Pregnancy Risk related to epilepsy and antiepileptic medicinal products in general It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. Although other factors, e.g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment. In the treated population, an increase in malformations has been noted with polytherapy. However, effective anti-epileptic therapy should not be interrupted during pregnancy, since the aggravation of the illness may be detrimental to both the mother and the foetus. 28 Risk related to stiripentol No data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (see section 5.3). In view of the indication, administration of stiripentol during pregnancy and in women of childbearing potential would not be expected. The clinical decision for use of stiripentol in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks. Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable. Breastfeeding In the absence of human studies on excretion in breast milk, and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment. In case stiripentol therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects. Fertility No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, potential risk for human is unknown.

HOS-094279 · has-pregnancy-information · PDF-Seite 17

Pregnancy Risk related to epilepsy and antiepileptic medicinal products in general It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. Although other factors, e.g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment. In the treated population, an increase in malformations has been noted with polytherapy. However, effective anti-epileptic therapy should not be interrupted during pregnancy, since the aggravation of the illness may be detrimental to both the mother and the foetus. 17 Risk related to stiripentol No data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (see section 5.3). In view of the indication, administration of stiripentol during pregnancy and in women of childbearing potential would not be expected. The clinical decision for use of stiripentol in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks. Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable. Breastfeeding In the absence of human studies on excretion in breast milk and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment. In case stiripentol therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects. Fertility No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, potential risk for human is unknown.

HOS-094273 · has-pregnancy-information · PDF-Seite 6

Pregnancy Risk related to epilepsy and antiepileptic medicinal products in general It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. Although other factors, e.g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment. In the treated population, an increase in malformations has been noted with polytherapy. However, effective anti-epileptic therapy should not be interrupted during pregnancy, since the aggravation of the illness may be detrimental to both the mother and the foetus. 6 Risk related to stiripentol No data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (see section 5.3). In view of the indication, administration of stiripentol during pregnancy and in women of childbearing potential would not be expected. The clinical decision for use of stiripentol in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks. Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable. Breastfeeding In the absence of human studies on excretion in breast milk, and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment. In case stiripentol therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects. Fertility No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, potential risk for human is unknown.

HOS-094291 · has-pregnancy-information · PDF-Seite 39

Pregnancy Risk related to epilepsy and antiepileptic medicinal products in general It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. Although other factors, e.g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment. In the treated population, an increase in malformations has been noted with polytherapy. However, effective anti-epileptic therapy should not be interrupted during pregnancy, since the aggravation of the illness may be detrimental to both the mother and the foetus. 39 Risk related to stiripentol No data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (see section 5.3). In view of the indication, administration of stiripentol during pregnancy and in women of childbearing potential would not be expected. The clinical decision for use of stiripentol in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks. Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable. Breastfeeding In the absence of human studies on excretion in breast milk, and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment. In case stiripentol therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects. Fertility No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, potential risk for human is unknown.

HOS-094277 · has-warning-information · PDF-Seite 15

Carbamazepine, phenytoin and phenobarbital These substances should not be used in conjunction with stiripentol in the management of Dravet’s syndrome. The daily dosage of clobazam and/or valproate should be reduced according to the onset of side effects whilst on stiripentol therapy (see section 4.2). Growth rate of children Given the frequency of gastrointestinal adverse reactions to treatment with stiripentol and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored. Blood count Neutropenia may be associated with the administration of stiripentol, clobazam and valproate. Blood counts should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, blood counts should be checked every 6 months. Liver function It should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, liver function should be checked every 6 months. Hepatic or renal impairment In the absence of specific clinical data in patients with impaired hepatic or renal function, Stiripentol is not recommended for use in patients with impaired hepatic and/or renal function (see section 4.2). Substances interfering with CYP enzymes Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions (see section 4.5). In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Paediatric population The pivotal clinical studies did not include children below 3 years old. As a consequence, it is recommended that children between 6 months and 3 years of age are carefully monitored whilst on stiripentol therapy. This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’. 15

HOS-094289 · has-warning-information · PDF-Seite 37

Carbamazepine, phenytoin and phenobarbital These substances should not be used in conjunction with stiripentol in the management of Dravet’s syndrome. The daily dosage of clobazam and/or valproate should be reduced according to the onset of side effects whilst on stiripentol therapy (see section 4.2). Growth rate of children Given the frequency of gastrointestinal adverse reactions to treatment with stiripentol and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored. Blood count Neutropenia may be associated with the administration of stiripentol, clobazam and valproate. Blood counts should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, blood counts should be checked every 6 months. Liver function It should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, liver function should be checked every 6 months. Hepatic or renal impairment In the absence of specific clinical data in patients with impaired hepatic or renal function, stiripentol is not recommended for use in patients with impaired hepatic and/or renal function (see section 4.2). Substances interfering with CYP enzymes Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions (see section 4.5). In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Paediatric population The pivotal clinical studies did not include children below 3 years old. As a consequence, it is recommended that children between 6 months and 3 years of age are carefully monitored whilst on Diacomit therapy. Diacomit powder for oral suspension in sachet contains aspartame, a source of phenylalanine. Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age. Therefore it may be harmful for people with phenylketonuria. Patients with rare glucose-galactose malabsorption should not take this medicine, as the formulation contains glucose. As the flavouring component contains small amount of sorbitol, patients with hereditary problems of

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HOS-094271 · has-warning-information · PDF-Seite 4

Carbamazepine, phenytoin and phenobarbital These substances should not be used in conjunction with stiripentol in the management of Dravet’s syndrome. The daily dosage of clobazam and/or valproate should be reduced according to the onset of side effects whilst on stiripentol therapy (see section 4.2). Growth rate of children Given the frequency of gastrointestinal adverse reactions to treatment with stiripentol and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored. Blood count Neutropenia may be associated with the administration of stiripentol, clobazam and valproate. Blood counts should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, blood counts should be checked every 6 months. Liver function It should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, liver function should be checked every 6 months. Hepatic or renal impairment In the absence of specific clinical data in patients with impaired hepatic or renal function, stiripentol is not recommended for use in patients with impaired hepatic and/or renal function (see section 4.2). Substances interfering with CYP enzymes Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions (see section 4.5). In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Paediatric population The pivotal clinical studies did not include children below 3 years old. As a consequence, it is recommended that children between 6 months and 3 years of age are carefully monitored whilst on stiripentol therapy. This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’. 4

HOS-094283 · has-warning-information · PDF-Seite 26

Carbamazepine, phenytoin and phenobarbital These substances should not be used in conjunction with stiripentol in the management of Dravet’s syndrome. The daily dosage of clobazam and/or valproate should be reduced according to the onset of side effects whilst on stiripentol therapy (see section 4.2). Growth rate of children Given the frequency of gastrointestinal adverse reactions to treatment with stiripentol and valproate (anorexia, loss of appetite, nausea, vomiting), the growth rate of children under this combination of treatment should be carefully monitored. Blood count Neutropenia may be associated with the administration of stiripentol, clobazam and valproate. Blood counts should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, blood counts should be checked every 6 months. Liver function It should be assessed prior to starting treatment with stiripentol. Unless otherwise clinically indicated, liver function should be checked every 6 months. Hepatic or renal impairment In the absence of specific clinical data in patients with impaired hepatic or renal function, stiripentol is not recommended for use in patients with impaired hepatic and/or renal function (see section 4.2). Substances interfering with CYP enzymes Stiripentol is an inhibitor of the enzymes CYP2C19, CYP3A4 and CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions (see section 4.5). In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4 and possibly other enzymes. Caution is advised when combining stiripentol with other substances that inhibit or induce one or more of these enzymes. Paediatric population The pivotal clinical studies did not include children below 3 years old. As a consequence, it is recommended that children between 6 months and 3 years of age are carefully monitored whilst on stiripentol therapy. Stiripentol powder for oral suspension in sachet contains aspartame, a source of phenylalanine. Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age. Therefore it may be harmful for people with phenylketonuria. Patients with rare glucose- galactose malabsorption should not take this medicine, as the formulation contains glucose. As the flavouring component contains small amount of sorbitol, patients with hereditary probl

Auszug; vollständigen Abschnitt im Original lesen.