Instanyl · 4.8 Undesirable effects · 2

HOS-095164 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile Typical opioid adverse reactions are to be expected with Instanyl. Frequently, most of these will cease or decrease in intensity with continued use of the medicinal product. The most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these. The adverse reactions considered to be at least possibly related to treatment in the clinical trials of Instanyl are included in the table below. 8 Tabulated list of adverse reactions The following categories are used to rank the undesirable effects by frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); and very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The following adverse reactions have been reported with Instanyl and/or other fentanyl-containing compounds during clinical studies and post marketing experience: System organ class Common Uncommon Not known Immune system disorders Anaphylactic shock, anaphylactic reaction, hypersensitivity Psychiatric disorders Insomnia Hallucination, delirium, drug dependence (addiction), drug abuse Nervous system disorders Somnolence, Sedation, Convulsions, loss of dizziness, headache myoclonus, consciousness paraesthesia, dysaesthesia,

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HOS-095170 · has-adverse-reaction-information · PDF-Seite 21

Summary of the safety profile Typical opioid adverse reactions are to be expected with Instanyl. Frequently, most of these will cease or decrease in intensity with continued use of the medicinal product. The most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these. The adverse reactions considered to be at least possibly related to treatment in the clinical trials of Instanyl are included in the table below. Tabulated list of adverse reactions The following categories are used to rank the undesirable effects by frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); and very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The following adverse reactions have been reported with Instanyl and/or other fentanyl-containing compounds during clinical studies and post marketing experience: 21  System organ class Common Uncommon Not known Immune system disorders Anaphylactic shock, anaphylactic reaction, hypersensitivity Psychiatric disorders Insomnia Hallucination, delirium, drug dependence (addiction), drug abuse Nervous system disorders Somnolence, Sedation, myoclonus, Convulsions, loss of dizziness, headache paraesthesia, consciousness dysaesthesia,

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HOS-095176 · has-adverse-reaction-information · PDF-Seite 34

Summary of the safety profile Typical opioid adverse reactions are to be expected with Instanyl. Frequently, most of these will cease or decrease in intensity with continued use of the medicinal product. The most serious adverse 34 reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these. The adverse reactions considered to be at least possibly related to treatment in the clinical trials of Instanyl are included in the table below. Tabulated list of adverse reactions The following categories are used to rank the undesirable effects by frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); and very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The following adverse reactions have been reported with Instanyl and/or other fentanyl-containing compounds during clinical studies and post marketing experience: System organ class Common Uncommon Not known Immune system disorders Anaphylactic shock, anaphylactic reaction, hypersensitivity Psychiatric disorders Insomnia Hallucination, delirium, drug dependence (addiction), drug abuse Nervous system disorders Somnolence, Sedation, Convulsions, loss of dizziness, headache myoclonus, consciousness paraesthesia,

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HOS-095166 · has-contraindication-information · PDF-Seite 17

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients without maintenance opioid therapy as there is an increased risk of respiratory depression. Treatment of acute pain other than breakthrough pain. Patients being treated with medicinal products containing sodium oxybate. Severe respiratory depression or severe obstructive lung conditions. Previous facial radiotherapy. Recurrent episodes of epistaxis (see section 4.4). 17

HOS-095172 · has-contraindication-information · PDF-Seite 31

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients without maintenance opioid therapy as there is an increased risk of respiratory depression. Treatment of acute pain other than breakthrough pain. Patients being treated with medicinal products containing sodium oxybate. Severe respiratory depression or severe obstructive lung conditions. Previous facial radiotherapy. Recurrent episodes of epistaxis (see section 4.4).

HOS-095160 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients without maintenance opioid therapy as there is an increased risk of respiratory depression. Treatment of acute pain other than breakthrough pain. Patients being treated with medicinal products containing sodium oxybate. Severe respiratory depression or severe obstructive lung conditions. Previous facial radiotherapy. Recurrent episodes of epistaxis (see section 4.4).

HOS-095159 · has-indication-information · PDF-Seite 2

Instanyl is indicated for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain. Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

HOS-095165 · has-indication-information · PDF-Seite 15

Instanyl is indicated for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain. Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

HOS-095171 · has-indication-information · PDF-Seite 28

Instanyl is indicated for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain. Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

HOS-095162 · has-interaction-information · PDF-Seite 7

Concomitant use of medicinal products containing sodium oxybate and fentanyl is contraindicated (see section 4.3). Coadministration of fentanyl with a serotoninergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition. Instanyl is not recommended for use in patients who have received Monoamine Oxidase Inhibitors (MAOIs) within 14 days because severe and unpredictable potentiation by MAOIs inhibitors has been reported with opioid analgesics. Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when Instanyl is given concurrently with medicinal products that affect CYP3A4 activity. Coadministration with medicinal products that induce 3A4 activity may reduce the efficacy of Instanyl. The concomitant use of Instanyl with strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression. Patients receiving Instanyl concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. Dose increase should be done with caution. In a pharmacokinetic interaction study it was found that the maximum plasma concentration of nasally applied fentanyl was reduced about 50% by the concomitant use of oxymetazoline, while the time to reach Cmax (Tmax) was doubled. This may reduce the efficacy of Instanyl. It is recommended that concomitant use of nasal decongestants is avoided (see section 5.2). The concomitant use of Instanyl with other central nervous system depressants (including opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquillisers, sedating antihistamines and alcohol), skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin) may produce additive depressant effects: hypoventilation, hypotension, profound sedation, respiratory depression, coma or death may occur. Therefore, the use of any of these medicinal products concomitantly with Instanyl requires special patient care and obs

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HOS-095168 · has-interaction-information · PDF-Seite 20

Concomitant use of medicinal products containing sodium oxybate and fentanyl is contraindicated (see section 4.3). Coadministration of fentanyl with a serotoninergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition. Instanyl is not recommended for use in patients who have received Monoamine Oxidase Inhibitors (MAOIs) within 14 days because severe and unpredictable potentiation by MAOIs inhibitors has been reported with opioid analgesics. Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when Instanyl is given concurrently with medicinal products that affect CYP3A4 activity. Coadministration with medicinal products that induce 3A4 activity may reduce the efficacy of Instanyl. The concomitant use of Instanyl with strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression. Patients receiving Instanyl concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. Dose increase should be done with caution. In a pharmacokinetic interaction study it was found that the maximum plasma concentration of nasally applied fentanyl was reduced about 50% by the concomitant use of oxymetazoline, while the time to reach Cmax (Tmax) was doubled. This may reduce the efficacy of Instanyl. It is recommended that concomitant use of nasal decongestants is avoided (see section 5.2). The concomitant use of Instanyl with other central nervous system depressants (including opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquillisers, sedating antihistamines and alcohol), skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin) may produce additive depressant effects: hypoventilation, hypotension, profound sedation, respiratory depression, coma or death may occur. Therefore, the use of any of these medicinal products concomitantly with Instanyl requires special patient care and obs

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095174 · has-interaction-information · PDF-Seite 33

Concomitant use of medicinal products containing sodium oxybate and fentanyl is contraindicated (see section 4.3). Coadministration of fentanyl with a serotoninergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition. Instanyl is not recommended for use in patients who have received Monoamine Oxidase Inhibitors (MAOIs) within 14 days because severe and unpredictable potentiation by MAOIs inhibitors has been reported with opioid analgesics. Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when Instanyl is given concurrently with medicinal products that affect CYP3A4 activity. Coadministration with medicinal products that induce 3A4 activity may reduce the efficacy of Instanyl. The concomitant use of Instanyl with strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression. Patients receiving Instanyl concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. Dose increase should be done with caution. In a pharmacokinetic interaction study it was found that the maximum plasma concentration of nasally applied fentanyl was reduced about 50% by the concomitant use of oxymetazoline, while the time to reach Cmax (Tmax) was doubled. This may reduce the efficacy of Instanyl. It is recommended that concomitant use of nasal decongestants is avoided (see section 5.2). The concomitant use of Instanyl with other central nervous system depressants, (including opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquillisers, sedating antihistamines and 33 alcohol), skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin) may produce additive depressant effects: hypoventilation, hypotension, profound sedation, respiratory depression, coma or death may occur. Therefore, the use of any of these medicinal products concomit

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HOS-095175 · has-pregnancy-information · PDF-Seite 34

Pregnancy There are no adequate data from the use of fentanyl in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Instanyl should not be used in pregnancy unless clearly necessary and if the benefits outweigh the risks. Following long-term treatment, fentanyl may cause withdrawal in the new-born infant. It is advised not to use fentanyl during labour and delivery (including caesarean section) because fentanyl passes through the placenta and may cause respiratory depression in the newborn (neonate). If Instanyl has been administered, an antidote for the child should be readily available. Breast-feeding Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed child. Fentanyl should not be used by breastfeeding women and breastfeeding should not be restarted until at least 5 days after the last administration of fentanyl. Fertility There are no human data on fertility available. In animal studies, male and female fertility was impaired at sedative doses (see section 5.3).

HOS-095163 · has-pregnancy-information · PDF-Seite 8

Pregnancy There are no adequate data from the use of fentanyl in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Instanyl should not be used in pregnancy unless clearly necessary and if the benefits outweigh the risks. Following long-term treatment, fentanyl may cause withdrawal in the new-born infant. It is advised not to use fentanyl during labour and delivery (including caesarean section) because fentanyl passes through the placenta and may cause respiratory depression in the newborn (neonate). If Instanyl has been administered, an antidote for the child should be readily available. Breast-feeding Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed child. Fentanyl should not be used by breastfeeding women and breastfeeding should not be restarted until at least 5 days after the last administration of fentanyl. Fertility There are no human data on fertility available. In animal studies, male and female fertility was impaired at sedative doses (see section 5.3).

HOS-095169 · has-pregnancy-information · PDF-Seite 21

Pregnancy There are no adequate data from the use of fentanyl in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Instanyl should not be used in pregnancy unless clearly necessary and if the benefits outweigh the risks. Following long-term treatment, fentanyl may cause withdrawal in the new-born infant. It is advised not to use fentanyl during labour and delivery (including caesarean section) because fentanyl passes through the placenta and may cause respiratory depression in the newborn (neonate). If Instanyl has been administered, an antidote for the child should be readily available. Breast-feeding Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed child. Fentanyl should not be used by breastfeeding women and breastfeeding should not be restarted until at least 5 days after the last administration of fentanyl. Fertility There are no human data on fertility available. In animal studies, male and female fertility was impaired at sedative doses (see section 5.3).

HOS-095161 · has-warning-information · PDF-Seite 5

Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep Instanyl in a safe and secure place, not accessible by others. Respiratory depression Clinically significant respiratory depression may occur with fentanyl, and patients must be observed for these effects. Patients with pain who receive chronic opioid therapy develop tolerance to respiratory depression and hence the risk of respiratory depression in these patients may be reduced. The use of concomitant central nervous system depressants may increase the risk of respiratory depression (see section 4.5). Chronic pulmonary disease In patients with chronic obstructive pulmonary diseases, fentanyl may have more severe adverse reactions. In these patients, opioids may decrease respiratory drive. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Instanyl and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Instanyl concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5). Impaired renal or hepatic function Fentanyl should be administered with caution to patients with moderate to severe hepatic or renal impairment. The influence of hepatic and renal impairment on the pharmacokinetics of Instanyl have not been evaluated; however, when administered intravenously the clearance of fentanyl has shown to be altered due to hepatic and renal impairment caused by alterations in metabolic clearance and plasma proteins. Increased intracranial pressure Fentanyl should be used with caution in patients with evidence of increased intracranial pressure, impaired consciousness or coma. Instanyl should be used with caution in patients with cerebral tumour or head injury. 5 Cardiac disease Fentanyl use may be associated with

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HOS-095173 · has-warning-information · PDF-Seite 31

Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep Instanyl in a safe and secure place, not accessible by others. Respiratory depression Clinically significant respiratory depression may occur with fentanyl, and patients must be observed for these effects. Patients with pain who receive chronic opioid therapy develop tolerance to respiratory depression and hence the risk of respiratory depression in these patients may be reduced. The use of concomitant central nervous system depressants may increase the risk of respiratory depression (see section 4.5). Chronic pulmonary disease In patients with chronic obstructive pulmonary diseases, fentanyl may have more severe adverse reactions. In these patients, opioids may decrease respiratory drive. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Instanyl and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Instanyl concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5). Impaired renal or hepatic function Fentanyl should be administered with caution to patients with moderate to severe hepatic or renal impairment. The influence of hepatic and renal impairment on the pharmacokinetics of Instanyl have not been evaluated; however, when administered intravenously the clearance of fentanyl has shown to be altered due to hepatic and renal impairment caused by alterations in metabolic clearance and plasma proteins. 31 Increased intracranial pressure Fentanyl should be used with caution in patients with evidence of increased intracranial pressure, impaired consciousness or coma. Instanyl should be used with caution in patients with cerebral tumour or head injury. Cardiac disease Fentanyl use may be associated with

Auszug; vollständigen Abschnitt im Original lesen.

HOS-095167 · has-warning-information · PDF-Seite 18

Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep Instanyl in a safe and secure place, not accessible by others. Respiratory depression Clinically significant respiratory depression may occur with fentanyl, and patients must be observed for these effects. Patients with pain who receive chronic opioid therapy develop tolerance to respiratory depression and hence the risk of respiratory depression in these patients may be reduced. The use of concomitant central nervous system depressants may increase the risk of respiratory depression (see section 4.5). Chronic pulmonary disease In patients with chronic obstructive pulmonary diseases, fentanyl may have more severe adverse reactions. In these patients, opioids may decrease respiratory drive. Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Instanyl and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Instanyl concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5). Impaired renal or hepatic function Fentanyl should be administered with caution to patients with moderate to severe hepatic or renal impairment. The influence of hepatic and renal impairment on the pharmacokinetics of Instanyl have not been evaluated; however, when administered intravenously the clearance of fentanyl has shown to be altered due to hepatic and renal impairment caused by alterations in metabolic clearance and plasma proteins. Increased intracranial pressure Fentanyl should be used with caution in patients with evidence of increased intracranial pressure, impaired consciousness or coma. Instanyl should be used with caution in patients with cerebral tumour or head injury. Cardiac disease Fentanyl use may be associated with bradycardia. Fentanyl should therefore be used with cau

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