Akynzeo · 4.3 Contraindications · 2

HOS-096966 · has-adverse-reaction-information · PDF-Seite 41

Summary of the safety profile Common adverse reactions reported with Akynzeo were headache (3.6%), constipation (3.0%) and fatigue (1.2%). None of these events was serious. Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA body system organ class and frequency. The following convention has been used for classification of frequency: 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). 41 Table 1: Adverse reactions System organ class Common Uncommon Rare Infections and Cystitis infestations Blood and lymphatic Neutropenia Leukopenia system disorders Leucocytosis Lymphocytosis Metabolism and Decreased appetite Hypokalaemia nutrition disorders Psychiatric disorders Insomnia Acute psychosis Mood altered Sleep disorder Nervous system Headache Dizziness Hypoaesthesia disorders Somnolence Eye disorders Conjunctivitis Vision blurred Ear and labyrinth Vertigo Tinnitus disorders Cardiac disorders Atrioventricular block Arrhythmia first degree Cardiomyopathy Atrioventricular block second degree Conduction disorder Bundle branch block left Tachycardia Bundle branch block right Mitral valve incompetence Myocardial ischaemia Ventricular extrasystoles Vascular disorders Hypertension Flushing

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096960 · has-adverse-reaction-information · PDF-Seite 23

Summary of the safety profile Common adverse reactions reported with Akynzeo were headache (3.6%), constipation (3.0%) and fatigue (1.2%). None of these events was serious. Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA body system organ class and frequency. The following convention has been used for classification of frequency: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 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). 23 Table 1: Adverse reactions System organ class Common Uncommon Rare Infections and Cystitis infestations Blood and lymphatic Neutropenia Leukopenia system disorders Leucocytosis Lymphocytosis Metabolism and Decreased appetite Hypokalaemia nutrition disorders Psychiatric disorders Insomnia Acute psychosis Mood altered Sleep disorder Nervous system Headache Dizziness Hypoaesthesia disorders Somnolence Eye disorders Conjunctivitis Vision blurred Ear and labyrinth Vertigo Tinnitus disorders Cardiac disorders Atrioventricular block Arrhythmia first degree Cardiomyopathy Atrioventricular block second degree Conduction disorder Bundle branch block left Tachycardia Bundle branch block right Mitral valve incompetence Myocardial ischaemia Ventricular extrasystoles Vascular disorders Hypertension Flushing

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096972 · has-adverse-reaction-information · PDF-Seite 58

Summary of the safety profile Common adverse reactions reported with netupitant/palonosetron sachets were headache (3.6%), constipation (3.0%) and fatigue (1.2%). Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA body system organ class and frequency. The following convention has been used for classification of frequency: 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). 58 Table1: Adverse reactions System organ class Common Uncommon Rare Infections and Cystitis infestations Blood and lymphatic Neutropenia Leukopenia system disorders Leucocytosis Lymphocytosis Metabolism and Decreased appetite Hypokalaemia nutrition disorders Psychiatric disorders Insomnia Acute psychosis Mood altered Sleep disorder Nervous system Headache Dizziness Hypoaesthesia disorders Somnolence Eye disorders Conjunctivitis Vision blurred Ear and labyrinth Vertigo Tinnitus disorders Cardiac disorders Atrioventricular Arrhythmia block first degree Cardiomyopathy Atrioventricular block second degree Conduction disorder Bundle branch block left Tachycardia Bundle branch block right Mitral valve incompetence Myocardial ischaemia Ventricular extrasystoles Vascular disorders Hypertension Flushing

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096954 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Common adverse reactions reported with netupitant/palonosetron capsules were headache (3.6%), constipation (3.0%) and fatigue (1.2%). Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA body system organ class and frequency. The following convention has been used for classification of frequency: 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). 7 Table1: Adverse reactions System organ class Common Uncommon Rare Infections and Cystitis infestations Blood and lymphatic Neutropenia Leukopenia system disorders Leucocytosis Lymphocytosis Metabolism and Decreased appetite Hypokalaemia nutrition disorders Psychiatric disorders Insomnia Acute psychosis Mood altered Sleep disorder Nervous system Headache Dizziness Hypoaesthesia disorders Somnolence Eye disorders Conjunctivitis Vision blurred Ear and labyrinth Vertigo Tinnitus disorders Cardiac disorders Atrioventricular Arrhythmia block first degree Cardiomyopathy Atrioventricular block second degree Conduction disorder Bundle branch block left Tachycardia Bundle branch block right Mitral valve incompetence Myocardial ischaemia Ventricular extrasystoles Vascular disorders Hypertension Flushing

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096956 · has-contraindication-information · PDF-Seite 19

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Pregnancy (see section 4.6).

HOS-096968 · has-contraindication-information · PDF-Seite 54

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Pregnancy (see section 4.6).

HOS-096962 · has-contraindication-information · PDF-Seite 37

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Pregnancy (see section 4.6).

HOS-096950 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Pregnancy (see section 4.6).

HOS-096967 · has-indication-information · PDF-Seite 53

Akynzeo is indicated in adults for the: - Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy. - Prevention of acute and delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-096961 · has-indication-information · PDF-Seite 36

Akynzeo is indicated in adults for the: - Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy. - Prevention of acute and delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-096949 · has-indication-information · PDF-Seite 2

Akynzeo is indicated in adults for the: - Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy. - Prevention of acute and delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-096955 · has-indication-information · PDF-Seite 18

Akynzeo is indicated in adults for the: - Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy. - Prevention of acute and delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-096952 · has-interaction-information · PDF-Seite 4

When netupitant/palonosetron capsules are used concomitantly with another CYP3A4 inhibitor, netupitant plasma concentrations could be elevated. When this medicinal product is used concomitantly with medicinal products that induce CYP3A4 activity, netupitant plasma concentrations could be reduced and this may result in decreased efficacy. This medicinal product can increase plasma concentrations of concomitantly administered medicinal products that are metabolised via CYP3A4. In humans, netupitant is eliminated mainly by hepatic metabolism mediated by CYP3A4 with a marginal renal excretion. At a dose of 300 mg in humans, netupitant is a substrate and moderate inhibitor of CYP3A4. Palonosetron is eliminated from the body through both renal excretion and metabolic pathways, with the latter mediated via multiple CYP enzymes. Palonosetron is mainly 4 metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. Interaction between oral netupitant and oral palonosetron: No clinically relevant pharmacokinetic interactions have been observed between oral netupitant and oral palonosetron. Interaction with CYP3A4 substrates: Dexamethasone Co-administration of a single dose of 300 mg netupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner. The AUC0-24 (Day 1), the AUC24-36 (Day 2) and the AUC84-108 and AUC84-∞ (Day 4) of dexamethasone increased 2.4-fold, with co-administration of 300 mg netupitant. The pharmacokinetic profile of netupitant was unchanged when administered in combination with dexamethasone. As such, the oral dexamethasone dose should be reduced by approximately 50% when co-administered with netupitant/palonosetron capsules (see section 4.2). Chemotherapeutic medicinal products (docetaxel, etoposide, cyclophosphamide) Exposure to docetaxel and etoposide was increased 37% and 21%, respectively, when co-administered with netupitant/palonosetron capsules. No consistent effect was seen with cyclophosphamide after netupitant co-administration. Oral contraceptives Netupitant/palonosetron capsules, when given with a single oral dose of 60 mcg ethinylestradiol and 300 mcg levonorgestrel had no significant effect on the

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096964 · has-interaction-information · PDF-Seite 38

Pharmacokinetic interactions When administered intravenously fosnetupitant is rapidly converted to netupitant. Interactions with other medicinal products following administration of intravenous fosnetupitant are likely to occur with active substances that interact with oral netupitant. The following information was derived from studies conducted with oral netupitant and studies conducted with intravenous fosnetupitant. 38 In humans, netupitant is eliminated mainly by hepatic metabolism mediated by CYP3A4 with a marginal renal excretion. At a dose of 300 mg in humans, netupitant is a substrate and moderate inhibitor of CYP3A4. Palonosetron is eliminated from the body through both renal excretion and metabolic pathways, with the latter mediated via multiple CYP enzymes. Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. Interaction between oral netupitant and oral palonosetron No clinically relevant pharmacokinetic interactions have been observed between oral netupitant and oral palonosetron. Interaction with CYP3A4 substrates Dexamethasone Co-administration of a single oral dose of 300 mg netupitant or a single intravenous dose of 235 mg fosnetupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner. The AUC84-∞ (Day 4) of dexamethasone increased 2.4-fold with co-administration of 300 mg netupitant or 235 mg fosnetupitant. The pharmacokinetic profile of netupitant was unchanged when administered in combination with dexamethasone. As such, the oral dexamethasone dose should be reduced by approximately 50% when co-administered with fosnetupitant and palonosetron hydrochloride combination (see section 4.2). Chemotherapeutic medicinal products (docetaxel, etoposide, cyclophosphamide) Exposure to docetaxel and etoposide was increased 37% and 21%, respectively, when co-administered with netupitant/palonosetron capsules. No consistent effect was seen with cyclophosphamide after netupitant co-administration. Oral contraceptives Netupitant/palonosetron capsules, when given with a single oral dose of 60 mcg ethinylestradiol and 300 mcg levonorgestrel had no significant effect on the AUC of et

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096970 · has-interaction-information · PDF-Seite 55

When netupitant/palonosetron sachets are used concomitantly with another CYP3A4 inhibitor, netupitant plasma concentrations could be elevated. When this medicinal product is used concomitantly with medicinal products that induce CYP3A4 activity, netupitant plasma concentrations could be reduced and this may result in decreased efficacy. This medicinal product can increase plasma concentrations of concomitantly administered medicinal products that are metabolised via CYP3A4. In humans, netupitant is eliminated mainly by hepatic metabolism mediated by CYP3A4 with a marginal renal excretion. At a dose of 300 mg in humans, netupitant is a substrate and moderate inhibitor of CYP3A4. Palonosetron is eliminated from the body through both renal excretion and metabolic pathways, with the latter mediated via multiple CYP enzymes. Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. 55 Interaction between oral netupitant and oral palonosetron No clinically relevant pharmacokinetic interactions have been observed between oral netupitant and oral palonosetron. Interaction with CYP3A4 substrates Dexamethasone Co-administration of a single dose of 300 mg netupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner. The AUC0-24 (Day 1), the AUC24-36 (Day 2) and the AUC84-108 and AUC84-∞ (Day 4) of dexamethasone increased 2.4-fold, with co-administration of 300 mg netupitant. The pharmacokinetic profile of netupitant was unchanged when administered in combination with dexamethasone. As such, the oral dexamethasone dose should be reduced by approximately 50% when co-administered with netupitant/palonosetron sachets (see section 4.2). Chemotherapeutic medicinal products (docetaxel, etoposide, cyclophosphamide) Exposure to docetaxel and etoposide was increased 37% and 21%, respectively, when co-administered with netupitant/palonosetron sachets. No consistent effect was seen with cyclophosphamide after netupitant co-administration. Oral contraceptives Netupitant/palonosetron sachets, when given with a single oral dose of 60 mcg ethinylestradiol and 300 mcg levonorgestrel had no significant effect on the AUC o

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096958 · has-interaction-information · PDF-Seite 20

Pharmacokinetic interactions When administered intravenously fosnetupitant is rapidly converted to netupitant. Interactions with other medicinal products following administration of intravenous fosnetupitant are likely to occur with active substances that interact with oral netupitant. The following information was derived from studies conducted with oral netupitant and studies conducted with intravenous fosnetupitant. 20 In humans, netupitant is eliminated mainly by hepatic metabolism mediated by CYP3A4 with a marginal renal excretion. At a dose of 300 mg in humans, netupitant is a substrate and moderate inhibitor of CYP3A4. Palonosetron is eliminated from the body through both renal excretion and metabolic pathways, with the latter mediated via multiple CYP enzymes. Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. Interaction between oral netupitant and oral palonosetron No clinically relevant pharmacokinetic interactions have been observed between oral netupitant and oral palonosetron. Interaction with CYP3A4 substrates Dexamethasone Co-administration of a single oral dose of 300 mg netupitant or a single intravenous dose of 235 mg fosnetupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner. The AUC84-∞ (Day 4) of dexamethasone increased 2.4-fold with co-administration of 300 mg netupitant or 235 mg fosnetupitant. The pharmacokinetic profile of netupitant was unchanged when administered in combination with dexamethasone. As such, the oral dexamethasone dose should be reduced by approximately 50% when co-administered with fosnetupitant and palonosetron hydrochloride combination (see section 4.2). Chemotherapeutic medicinal products (docetaxel, etoposide, cyclophosphamide) Exposure to docetaxel and etoposide was increased 37% and 21%, respectively, when co-administered with netupitant/palonosetron capsules. No consistent effect was seen with cyclophosphamide after netupitant co-administration. Oral contraceptives Netupitant/palonosetron capsules, when given with a single oral dose of 60 mcg ethinylestradiol and 300 mcg levonorgestrel had no significant effect on the AUC of eth

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096965 · has-pregnancy-information · PDF-Seite 40

Women of childbearing potential/contraception in females Women of childbearing potential should not be pregnant or become pregnant while on treatment with fosnetupitant/ palonosetron concentrate for solution for infusion. A pregnancy test should be performed on all pre-menopausal women prior to treatment. Women of childbearing potential must 40 use effective contraception during therapy and up to one month after treatment with this medicinal product. Pregnancy Fosnetupitant There are no data about the use of fosnetupitant or netupitant in pregnant women. Studies in animals have shown reproductive toxicity including teratogenic effects in rabbit without safety margin (see section 5.3). Palonosetron There are no data about the use of palonosetron in pregnant women. Animal data do not indicate direct or indirect harmful effects of palonosetron with the respect to reproductive toxicity (see section 5.3). Akynzeo is contraindicated during pregnancy (see section 4.3). Breast-feeding It is unknown whether palonosetron or netupitant are excreted in human milk. A risk to the newborns/infants cannot be excluded. Akynzeo should not be used during breast-feeding. Breast- feeding should be discontinued during treatment with this medicinal product and for 1 month after the last dose. Fertility Fosnetupitant No effect on fertility has been observed in animal studies. Palonosetron Degeneration of seminiferous epithelium has been observed in rat study (see section 5.3).

HOS-096953 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential/ contraception in females Women of childbearing potential should not be pregnant or become pregnant while on treatment with netupitant/palonosetron capsules. A pregnancy test should be performed on all pre-menopausal women prior to treatment. Women of childbearing potential must use effective contraception during therapy and up to one month after treatment with this medicinal product. Pregnancy Netupitant There are no data about the use of netupitant in pregnant women. Studies in animals have shown reproductive toxicity including teratogenic effects in rabbit without safety margin (see section 5.3). Palonosetron There are no data about the use of palonosetron in pregnant women. Animal data do not indicate direct or indirect harmful effects of palonosetron with the respect to reproductive toxicity (see section 5.3). Netupitant/palonosetron capsules are contraindicated during pregnancy (see section 4.3). Breast-feeding 6 It is unknown whether palonosetron or netupitant are excreted in human milk. A risk to the suckling child cannot be excluded. Netupitant/palonosetron capsules should not be used during breast-feeding. Breast-feeding should be discontinued during treatment with this medicinal product and for 1 month after the last dose. Fertility Netupitant No effect on fertility has been observed in animal studies. Palonosetron Degeneration of seminiferous epithelium has been observed in rat study (see section 5.3).

HOS-096971 · has-pregnancy-information · PDF-Seite 57

Women of childbearing potential/ contraception in females Women of childbearing potential should not be pregnant or become pregnant while on treatment with netupitant/palonosetron sachets. A pregnancy test should be performed on all pre-menopausal women prior to treatment. Women of childbearing potential must use effective contraception during therapy and up to one month after treatment with this medicinal product. Pregnancy Netupitant There are no data about the use of netupitant in pregnant women. Studies in animals have shown reproductive toxicity including teratogenic effects in rabbit without safety margin (see section 5.3). Palonosetron There are no data about the use of palonosetron in pregnant women. Animal data do not indicate direct or indirect harmful effects of palonosetron with the respect to reproductive toxicity (see section 5.3). Netupitant/palonosetron sachets are contraindicated during pregnancy (see section 4.3). 57 Breast-feeding It is unknown whether palonosetron or netupitant are excreted in human milk. A risk to the suckling child cannot be excluded. Netupitant/palonosetron sachets should not be used during breast-feeding. Breast-feeding should be discontinued during treatment with this medicinal product and for 1 month after the last dose. Fertility Netupitant No effect on fertility has been observed in animal studies. Palonosetron Degeneration of seminiferous epithelium has been observed in rat study (see section 5.3).

HOS-096959 · has-pregnancy-information · PDF-Seite 22

Women of childbearing potential/contraception in females Women of childbearing potential should not be pregnant or become pregnant while on treatment with fosnetupitant/ palonosetron powder for concentrate for solution for infusion. A pregnancy test should be performed on all pre-menopausal women prior to treatment. Women of childbearing potential must 22 use effective contraception during therapy and up to one month after treatment with this medicinal product. Pregnancy Fosnetupitant There are no data about the use of fosnetupitant or netupitant in pregnant women. Studies in animals have shown reproductive toxicity including teratogenic effects in rabbit without safety margin (see section 5.3). Palonosetron There are no data about the use of palonosetron in pregnant women. Animal data do not indicate direct or indirect harmful effects of palonosetron with the respect to reproductive toxicity (see section 5.3). Akynzeo is contraindicated during pregnancy (see section 4.3). Breast-feeding It is unknown whether palonosetron or netupitant are excreted in human milk. A risk to the newborns/infants cannot be excluded. Akynzeo should not be used during breast-feeding. Breast- feeding should be discontinued during treatment with this medicinal product and for 1 month after the last dose. Fertility Fosnetupitant No effect on fertility has been observed in animal studies. Palonosetron Degeneration of seminiferous epithelium has been observed in rat study (see section 5.3).

HOS-096963 · has-warning-information · PDF-Seite 37

Constipation As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration (see section 4.8). Serotonin syndrome There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised (see section 4.8). QT Prolongation 37 An ECG study was conducted in adult male and female healthy volunteers with oral netupitant either 200 mg or 600 mg administered in combination with oral palonosetron 0.5 mg or 1.5 mg, respectively. The study demonstrated no clinically important effects on ECG parameters: the largest point estimate of the placebo and baseline corrected QTc interval was 7.0 ms (one-sided upper 95% confidence limit 8.8 ms), observed 16 hours after the administration of supratherapeutic doses (600 mg netupitant and 1.5 mg palonosetron). The upper 95% confidence limit of the point estimates of placebo and baseline corrected QTcI was constantly within 10 ms at all time points over 2 days after study administration of the medicinal product. However, since netupitant and palonosetron hydrochloride combination contains a 5-HT3 receptor antagonist, caution should be exercised in concomitant use with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and in patients taking anti-arrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesaemia should be corrected prior to administration. This medicinal product should not be used to prevent nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration. It should not be used to treat nausea and vomiting following chemotherapy. Caution should be exercised in patients with severe hepatic impairment since limited data are available in these patients. This medicinal produ

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096969 · has-warning-information · PDF-Seite 54

Constipation As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration (see section 4.8). Serotonin syndrome There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised (see section 4.8). QT prolongation An ECG study was conducted in adult male and female healthy volunteers with oral netupitant either 200 or 600 mg administered in combination with oral palonosetron 0.5 or 1.5 mg, respectively. The study demonstrated no clinically important effects on ECG parameters: the largest point estimate of the placebo and baseline corrected QTc interval was 7.0 ms (one-sided upper 95% confidence 54 limit 8.8 ms), observed 16 hours after the administration of supratherapeutic doses (600 mg netupitant and 1.5 mg palonosetron). Upper 95% confidence limit of the point estimates of placebo and baseline corrected QTcI was constantly within 10 ms at all time points over 2 days after study substance administration. However, since netupitant/palonosetron sachets contain a 5-HT3 receptor antagonist, caution should be exercised in concomitant use with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and in patients taking anti-arrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesaemia should be corrected prior to administration. Caution should be exercised in patients with severe hepatic impairment since limited data are available in these patients. This medicinal product should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range (see section 4.5). Chemotherapeutic agents that are substrates for CYP3A4 Netupitant is a moderate inhibito

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096957 · has-warning-information · PDF-Seite 19

Constipation As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration (see section 4.8). Serotonin syndrome There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised (see section 4.8). QT Prolongation 19 An ECG study was conducted in adult male and female healthy volunteers with oral netupitant either 200 mg or 600 mg administered in combination with oral palonosetron 0.5 mg or 1.5 mg, respectively. The study demonstrated no clinically important effects on ECG parameters: the largest point estimate of the placebo and baseline corrected QTc interval was 7.0 ms (one-sided upper 95% confidence limit 8.8 ms), observed 16 hours after the administration of supratherapeutic doses (600 mg netupitant and 1.5 mg palonosetron). The upper 95% confidence limit of the point estimates of placebo and baseline corrected QTcI was constantly within 10 ms at all time points over 2 days after study administration of the medicinal product. However, since netupitant and palonosetron hydrochloride combination contains a 5-HT3 receptor antagonist, caution should be exercised in concomitant use with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and in patients taking anti-arrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesaemia should be corrected prior to administration. This medicinal product should not be used to prevent nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration. It should not be used to treat nausea and vomiting following chemotherapy. Caution should be exercised in patients with severe hepatic impairment since limited data are available in these patients. This medicinal produ

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096951 · has-warning-information · PDF-Seite 3

Constipation As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration (see section 4.8). Serotonin syndrome There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised (see section 4.8). QT Prolongation An ECG study was conducted in adult male and female healthy volunteers with oral netupitant either 200 or 600 mg administered in combination with oral palonosetron 0.5 or 1.5 mg, respectively. The study demonstrated no clinically important effects on ECG parameters: the largest point estimate of the placebo and baseline corrected QTc interval was 7.0 ms (one-sided upper 95% confidence limit 8.8 ms), observed 16 hours after the administration of supratherapeutic doses (600 mg netupitant and 1.5 mg palonosetron). Upper 95% confidence limit of the point estimates of placebo 3 and baseline corrected QTcI was constantly within 10 ms at all time points over 2 days after study substance administration. However, since netupitant/palonosetron capsules contains a 5-HT3 receptor antagonist, caution should be exercised in concomitant use with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and in patients taking anti-arrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesaemia should be corrected prior to administration. Caution should be exercised in patients with severe hepatic impairment since limited data are available in these patients. This medicinal product should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range (see section 4.5). Chemotherapeutic agents that are substrates for CYP3A4 Netupitant is a moderate inhibi

Auszug; vollständigen Abschnitt im Original lesen.