Relistor · 4.8 Undesirable effects · 1

HOS-154294 · has-adverse-reaction-information · PDF-Seite 16

Summary of the safety profile The most common adverse reactions in all patients exposed to methylnaltrexone bromide during all phases of placebo-controlled studies were abdominal pain, nausea, diarrhoea and flatulence. Generally, these reactions were mild or moderate. Tabulated list of adverse reactions The adverse reactions are classified as: 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) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Nervous system disorders Common: Dizziness Common: opioid-withdrawal-like symptoms (like chills, tremor, rhinorrhea, piloerection, hot flush, palpitation, hyperhidrosis, vomiting, abdominal pain) 16 Gastrointestinal disorders Not known: Gastrointestinal perforation (see section 4.4) Common: Vomiting Very common: Abdominal pain, nausea, diarrhoea, flatulence Skin and subcutaneous tissue disorders Common: Injection site reactions (e.g. stinging, burning, pain , redness, oedema) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

HOS-154300 · has-adverse-reaction-information · PDF-Seite 27

Summary of the safety profile The most common adverse reactions in all patients exposed to methylnaltrexone bromide during all phases of placebo-controlled studies were abdominal pain, nausea, diarrhoea and flatulence. Generally, these reactions were mild or moderate. Tabulated list of adverse reactions The adverse reactions are classified as: 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) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Nervous system disorders Common: Dizziness Common: opioid-withdrawal-like symptoms ( like chills, tremor, rhinorrhea, piloerection, hot flush, palpitation, hyperhidrosis, vomiting, abdominal pain) Gastrointestinal disorders Not known: Gastrointestinal perforation (see section 4.4) 27 Common: Vomiting Very common: Abdominal pain, nausea, diarrhoea, flatulence Skin and subcutaneous tissue disorders Common: Injection site reactions (e.g. stinging, burning, pain , redness, oedema) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

HOS-154288 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The most common adverse reactions in all patients exposed to methylnaltrexone bromide during all phases of placebo-controlled studies were abdominal pain, nausea, diarrhoea and flatulence. Generally, these reactions were mild or moderate. Tabulated list of adverse reactions The adverse reactions are classified as: 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) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Nervous system disorders Common: Dizziness Common: opioid-withdrawal-like symptoms (like chills, tremor, rhinorrhea, piloerection, hot flush, palpitation, hyperhidrosis, vomiting, abdominal pain) Gastrointestinal disorders 5 Not known: Gastrointestinal perforation (see section 4.4), Common: Vomiting Very common: Abdominal pain, nausea, diarrhoea, flatulence Skin and subcutaneous tissue disorders Common: Injection site reactions (e.g. stinging, burning, pain , redness, oedema) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

HOS-154290 · has-contraindication-information · PDF-Seite 14

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Use of methylnaltrexone bromide in patients with known or suspected mechanical gastrointestinal obstruction, patients at increased risk for recurrent obstruction or in patients with acute surgical abdomen is contraindicated due to the potential for gastrointestinal perforation.

HOS-154284 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Use of methylnaltrexone bromide in patients with known or suspected mechanical gastrointestinal obstruction, patients at increased risk for recurrent obstruction or in patients with acute surgical abdomen is contraindicated due to the potential for gastrointestinal perforation.

HOS-154296 · has-contraindication-information · PDF-Seite 25

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Use of methylnaltrexone bromide in patients with known or suspected mechanical gastrointestinal obstruction, patients at increased risk for recurrent obstruction or in patients with acute surgical abdomen is contraindicated due to the potential for gastrointestinal perforation.

HOS-154295 · has-indication-information · PDF-Seite 24

Relistor is indicated for the treatment of opioid-induced constipation when response to laxative therapy has not been sufficient in adult patients, aged 18 years and older.

HOS-154289 · has-indication-information · PDF-Seite 13

Relistor is indicated for the treatment of opioid-induced constipation when response to laxative therapy has not been sufficient in adult patients, aged 18 years and older.

HOS-154283 · has-indication-information · PDF-Seite 2

Relistor is indicated for the treatment of opioid-induced constipation when response to laxative therapy has not been sufficient in adult patients, aged 18 years and older.

HOS-154292 · has-interaction-information · PDF-Seite 15

Methylnaltrexone bromide does not affect the pharmacokinetics of medicinal products metabolised by cytochrome P450 (CYP) isozymes. Methylnaltrexone bromide is minimally metabolised by CYP isozymes. In vitro metabolism studies suggest that methylnaltrexone bromide does not inhibit the activity of CYP1A2, CYP2E1, CYP2B6, CYP2A6, CYP2C9, CYP2C19 or CYP3A4, while it is a weak inhibitor of the metabolism of a model CYP2D6 substrate. In a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.3 mg/kg of methylnaltrexone bromide did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate. The organic cation transporter (OCT)-related drug-drug interaction potential between methylnaltrexone bromide and an OCT inhibitor was studied in 18 healthy subjects by comparing the 15 single-dose pharmacokinetic profiles of methylnaltrexone bromide before and after multiple 400 mg doses of cimetidine. The renal clearance of methylnaltrexone bromide was reduced following multiple-dose administration of cimetidine (from 31 L/h to 18 L/h). However, this resulted in a small reduction in total clearance (from 107 L/h to 95 L/h). Consequently, no meaningful change in AUC of methylnaltrexone bromide, in addition to Cmax, was observed before and after multiple-dose administration of cimetidine.

HOS-154298 · has-interaction-information · PDF-Seite 26

Methylnaltrexone bromide does not affect the pharmacokinetics of medicinal products metabolised by cytochrome P450 (CYP) isozymes. Methylnaltrexone bromide is minimally metabolised by CYP isozymes. In vitro metabolism studies suggest that methylnaltrexone bromide does not inhibit the activity of CYP1A2, CYP2E1, CYP2B6, CYP2A6, CYP2C9, CYP2C19 or CYP3A4, while it is a weak inhibitor of the metabolism of a model CYP2D6 substrate. In a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.3 mg/kg of methylnaltrexone bromide did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate. The organic cation transporter (OCT)-related drug-drug interaction potential between methylnaltrexone bromide and an OCT inhibitor was studied in 18 healthy subjects by comparing the single-dose pharmacokinetic profiles of methylnaltrexone bromide before and after multiple 400 mg doses of cimetidine. The renal clearance of methylnaltrexone bromide was reduced following multiple-dose administration of cimetidine (from 31 L/h to 18 L/h). However, this resulted in a small reduction in total clearance (from 107 L/h to 95 L/h). Consequently, no meaningful change in AUC of 26 methylnaltrexone bromide, in addition to Cmax, was observed before and after multiple-dose administration of cimetidine.

HOS-154286 · has-interaction-information · PDF-Seite 4

Methylnaltrexone bromide does not affect the pharmacokinetics of medicinal products metabolised by cytochrome P450 (CYP) isozymes. Methylnaltrexone bromide is minimally metabolised by CYP isozymes. In vitro metabolism studies suggest that methylnaltrexone bromide does not inhibit the activity of CYP1A2, CYP2E1, CYP2B6, CYP2A6, CYP2C9, CYP2C19 or CYP3A4, while it is a weak inhibitor of the metabolism of a model CYP2D6 substrate. In a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.3 mg/kg of methylnaltrexone bromide did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate. The organic cation transporter (OCT)-related drug-drug interaction potential between methylnaltrexone bromide and an OCT inhibitor was studied in 18 healthy subjects by comparing the single-dose pharmacokinetic profiles of methylnaltrexone bromide before and after multiple 400 mg doses of cimetidine. The renal clearance of methylnaltrexone bromide was reduced following 4 multiple-dose administration of cimetidine (from 31 L/h to 18 L/h). However, this resulted in a small reduction in total clearance (from 107 L/h to 95 L/h). Consequently, no meaningful change in AUC of methylnaltrexone bromide, in addition to Cmax, was observed before and after multiple-dose administration of cimetidine.

HOS-154299 · has-pregnancy-information · PDF-Seite 27

Pregnancy There are no adequate data with the use of methylnaltrexone bromide in pregnant women. Studies in animals have shown reproductive toxicity at high doses (see section 5.3). The potential risk for humans is unknown. Methylnaltrexone bromide should not be used during pregnancy unless clearly necessary. Breast-feeding It is unknown whether methylnaltrexone bromide is excreted in human breast milk. Animal studies have shown excretion of methylnaltrexone bromide in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with methylnaltrexone bromide should be made, taking into account the benefit of breast-feeding to the child and the benefit of methylnaltrexone bromide therapy to the woman. Fertility Subcutaneous injections of Relistor at 150 mg/kg/day decreased fertility in rats. Doses up to 25 mg/kg/day (18 times the exposure [AUC] in humans at a subcutaneous dose of 0.3 mg/kg) did not affect fertility or general reproductive performance.

HOS-154287 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no adequate data with the use of methylnaltrexone bromide in pregnant women. Studies in animals have shown reproductive toxicity at high doses (see section 5.3). The potential risk for humans is unknown. Methylnaltrexone bromide should not be used during pregnancy unless clearly necessary. Breast-feeding It is unknown whether methylnaltrexone bromide is excreted in human breast milk. Animal studies have shown excretion of methylnaltrexone bromide in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with methylnaltrexone bromide should be made, taking into account the benefit of breast-feeding to the child and the benefit of methylnaltrexone bromide therapy to the woman. Fertility Subcutaneous injections of Relistor at 150 mg/kg/day decreased fertility in rats. Doses up to 25 mg/kg/day (18 times the exposure [AUC] in humans at a subcutaneous dose of 0.3 mg/kg) did not affect fertility or general reproductive performance.

HOS-154293 · has-pregnancy-information · PDF-Seite 16

Pregnancy There are no adequate data with the use of methylnaltrexone bromide in pregnant women. Studies in animals have shown reproductive toxicity at high doses (see section 5.3). The potential risk for humans is unknown. Methylnaltrexone should not be used during pregnancy unless clearly necessary. Breast-feeding It is unknown whether methylnaltrexone bromide is excreted in human breast milk. Animal studies have shown excretion of methylnaltrexone bromide in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with methylnaltrexone bromide should be made, taking into account the benefit of breast-feeding to the child and the benefit of methylnaltrexone bromide therapy to the woman. Fertility Subcutaneous injections of Relistor at 150 mg/kg/day decreased fertility in rats. Doses up to 25 mg/kg/day (18 times the exposure [AUC] in humans at a subcutaneous dose of 0.3 mg/kg) did not affect fertility or general reproductive performance.

HOS-154285 · has-warning-information · PDF-Seite 3

Severity and worsening symptoms Patients should be advised to promptly report severe, persistent, and/or worsening symptoms. If severe or persistent diarrhoea occurs during treatment, patients should be advised not to continue therapy with methylnaltrexone bromide and consult their physician. Constipation not related to opioid use The activity of methylnaltrexone bromide has been studied in patients with constipation induced by opioids. Therefore, Relistor should not be used for treatment of patients with constipation not related to opioid use. Rapid onset of bowel movements 3 Data from clinical trials suggest treatment with methylnaltrexone bromide can result in the rapid onset (within 30 to 60 minutes on average) of a bowel movement. Duration of treatment Opioid-induced constipation in adult patients with advanced illness Methylnaltrexone bromide treatment has not been studied in adult patients with advanced illness in clinical trials for longer than 4 months, and should therefore only be used for a limited period (see section 5.1). Hepatic and renal impairment Methylnaltrexone bromide is not recommended in patients with severe hepatic impairment or with end-stage renal impairment requiring dialysis (see section 4.2). Gastrointestinal (GI) conditions and GI perforation Methylnaltrexone bromide should be used with caution in patients with known or suspected lesions of the GI tract. Use of methylnaltrexone bromide in patients with colostomy, peritoneal catheter, active diverticular disease or fecal impaction has not been studied. Therefore, Relistor should only be administered with caution in these patients. Cases of GI perforation have been reported in the postauthorisation period after use of methylnaltrexone bromide in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, pseudo obstruction (Ogilvie’s syndrome), diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). The overall risk-benefit profile should be taken into account when using methylnaltrexone bromide in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Patients should be monitored for severe, persistent, or worsening abdominal pain; methylnaltrexone bromide should

Auszug; vollständigen Abschnitt im Original lesen.

HOS-154291 · has-warning-information · PDF-Seite 14

Severity and worsening of symptoms Patients should be advised to promptly report severe, persistent, and/or worsening symptoms. If severe or persistent diarrhoea occurs during treatment, patients should be advised not to continue therapy with methylnaltrexone bromide and consult their physician. Constipation not related to opioid use The activity of methylnaltrexone bromide has been studied in patients with constipation induced by opioids. Therefore, Relistor should not be used for treatment of patients with constipation not related to opioid use. 14 Rapid onset of bowel movement Data from clinical trials suggest treatment with methylnaltrexone bromide can result in the rapid onset (within 30 to 60 minutes on average) of a bowel movement. Duration of treatment Opioid-induced constipation in adult patients with advanced illness Methylnaltrexone bromide treatment has not been studied in adult patients with advanced illness in clinical trials for longer than 4 months, and should therefore only be used for a limited period (see section 5.1). Hepatic or renal impairment Methylnaltrexone bromide is not recommended in patients with severe hepatic impairment or with end-stage renal impairment requiring dialysis (see section 4.2). Gastrointestinal (GI) conditions and GI perforation Methylnaltrexone bromide should be used with caution in patients with known or suspected lesions of the GI tract. Use of methylnaltrexone bromide in patients with colostomy, peritoneal catheter, active diverticular disease or fecal impaction has not been studied. Therefore, Relistor should only be administered with caution in these patients. Cases of GI perforation have been reported in the postauthorisation period after use of methylnaltrexone bromide in patientswith conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, pseudo obstruction (Ogilvie’s syndrome), diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). The overall risk-benefit profile should be taken into account when using methylnaltrexone bromide in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Patients should be monitored for severe, persistent, or worsening abdominal pain; methylnaltrexone bromide should

Auszug; vollständigen Abschnitt im Original lesen.

HOS-154297 · has-warning-information · PDF-Seite 25

Severity and worsening of symptoms Patients should be advised to promptly report severe, persistent, and/or worsening symptoms. If severe or persistent diarrhoea occurs during treatment, patients should be advised not to continue therapy with methylnaltrexone bromide and consult their physician. Constipation not related to opioid use The activity of methylnaltrexone bromide has been studied in patients with constipation induced by opioids. Therefore, Relistor should not be used for treatment of patients with constipation not related to opioid use. Rapid onset of bowel movements Data from clinical trials suggest treatment with methylnaltrexone bromide can result in the rapid onset (within 30 to 60 minutes on average) of a bowel movement. 25 Duration of treatment Opioid-induced constipation in adult patients with advanced illness Methylnaltrexone bromide treatment has not been studied in adult patients with advanced illness in clinical trials for longer than 4 months, and should therefore only be used for a limited period (see section 5.1). Hepatic or renal impairment Methylnaltrexone bromide is not recommended in patients with severe hepatic impairment or with end-stage renal impairment requiring dialysis (see section 4.2). Gastrointestinal (GI) conditions and GI perforation Methylnaltrexone bromide should be used with caution in patients with known or suspected lesions of the GI tract. Use of methylnaltrexone bromide in patients with colostomy, peritoneal catheter, active diverticular disease or fecal impaction has not been studied. Therefore, Relistor should only be administered with caution in these patients. Cases of GI perforation have been reported in the postauthorisation period after use of methylnaltrexone bromide in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, pseudo obstruction (Ogilvie’s syndrome), diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). The overall risk-benefit profile should be taken into account when using methylnaltrexone bromide in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Patients should be monitored for severe, persistent, or worsening abdominal pain; methylnaltrexone bromide shoul

Auszug; vollständigen Abschnitt im Original lesen.