- Approval Id
- 647b044da2a2ace8
- Drug Approval Emc Name
- Relistor 8 mg Solution for injection in pre-filled syringes
- Drug Name
- Relistor 8 mg Solution for injection in pre-filled syringes
- Company Address
- 3013 Lake Drive, Citywest Business Campus, Dublin 24, Ireland, D24PPT3
- Company Telephone
- +353 1 466 1966
- Company Medical Info Email
- [email protected]
- Atc Code
- A06AH01
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Bausch Health Ireland Limited 3013 Lake Drive Citywest Business Campus Dublin 24, D24PPT3 Ireland
- Authorisation Number
- 8. Marketing authorisation number(s) PLGB 52637/0005
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 02 July 2008 Date of latest renewal: 27 May 2013
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Bausch Health Ireland Limited 3013 Lake Drive Citywest Business Campus Dublin 24, D24PPT3 Ireland
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PLGB 52637/0005
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 02 July 2008 Date of latest renewal: 27 May 2013
- Instruction Composition
- 2. Qualitative and quantitative composition Each pre-filled syringe of 0.4 mL contains 8 mg of methylnaltrexone bromide. One mL of solution contains 20 mg of methylnaltrexone bromide. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Solution for injection (injection). Clear solution, colourless to pale-yellow, essentially free from visible particulates.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications 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. 4.2 Posology and method of administration Posology Opioid-induced constipation in adult patients with chronic pain (except palliative care patients with advanced illness) The recommended dose of methylnaltrexone bromide is 12 mg (0.6 mL of solution) subcutaneously, as needed, given as at least 4 doses weekly, up to once daily (7 doses weekly). In these patients, the treatment with usual laxatives should be stopped when commencing treatment with Relistor (see section
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Laxatives, Peripheral opioid receptor antagonists, ATC code: A06AH01 Mechanism of action Methylnaltrexone bromide is a selective antagonist of opioid binding at the mu-receptor. In vitro studies have shown methylnaltrexone bromide to be a mu-opioid receptor antagonist (inhibition constant [Ki] = 28 nM), with 8-fold less potency for kappa opioid receptors (Ki = 230 nM) and much reduced affinity for delta opioid receptors. As a quaternary amine, the ability of methylnaltrexone bromide to cross the blood-brain barrier is restricted. This allows methylnaltrexone bromide to function as a peripherally acting mu-opioid antagonist in tissues such as the gastrointestinal tract, without impacting opioid-mediated analgesic effects on the central nervous system. Clinical efficacy and safety Opioid-induced constipation in adult patients with chronic non-cancer pain (12 mg dose) The efficacy and safety of methylnaltrexone bromide in the treatment of opioid-induced constipation in patients with chronic non-cancer pain were demonstrated in a randomized, double‑blind, placebo‑controlled study (Study 3356). In this study, the median patient age was 49 years (range 23‑83); 60% were females. The majority of patients had a primary diagnosis of back pain. Study 3356 compared 4-week treatment regimens of methylnaltrexone bromide 12 mg once daily and methylnaltrexone bromide 12 mg every other day with placebo. The 4-week, double-blind period was followed by an 8‑week, open-label period during which methylnaltrexone bromide was to be used as needed, but no more frequently than once daily. A total of 460 patients (methylnaltrexone bromide 12 mg once daily, n = 150, methylnaltrexone bromide 12 mg every other day, n = 148, placebo, n = 162) were treated in the double-blind period. Patients had a history of chronic non-cancer pain and were taking opioids with stable doses of at least 50 mg of oral morphine equivalents per day. Patients had opioid‑induced constipation (< 3 rescue medication-free bowel movements per week during the screening period). Patients were required to discontinue all previous laxative therapy. The first co-primary endpoint was the proportion of patients having a rescue free bowel movements (RFBMs) within 4 hours of the first dose administration and the second the percentage of active injections resulting in any RFBM within 4 hours during the double-blind phase. A RFBM was defined as a bowel movement that occurred without laxative use during the previous 24 hours. The proportion of patients having an RFBM within 4 hours of the first dose was 34.2% in the combined methylnaltrexone bromide group versus 9.9% in the placebo group (p<0.001). The mean percentage of methylnaltrexone bromide resulting in any RFBM within 4 hours were 28.9% and 30.2% respectively for the once daily and every other day dose groups compared with 9.4% and 9.3% respectively for the corresponding placebo regimen for daily and every other day dosing (p <0.001) during the double blind phase. The key secondary endpoint of adjusted mean change from baseline in weekly RFBMs was 3.1 in the methylnaltrexone bromide 12 mg once daily treatment group, 2.1 in the methylnaltrexone bromide 12 mg every other day treatment group, and 1.5 in the placebo treatment group during the 4-week double-blind period. The difference between methylnaltrexone bromide 12 mg once daily and placebo of 1.6 RFBMs per week is statistically significant (p < 0.001) and clinically meaningful. Another secondary endpoint evaluated the proportion of patients with ≥3 RFBMs per week during the 4‑week double-blind phase. This was achieved in 59% of the patients in the group receiving daily methylnaltrexone 12 mg (p<0.001 vs. placebo), in 61% of those receiving it every other day (p<0.001 vs. placebo), and in 38% of the placebo treated patients. A supplementary analysis evaluated a hard endpoint of the percentage of patients achieving ≥3 complete RFBMs per week and an increase of ≥1 complete RFBMs per week in at least 3 of the 4 treatment weeks. This was achieved in 28.7% of the patients in the group receiving daily methylnaltrexone 12 mg (p<0.001 vs. placebo), in 14.9% of those receiving it every other day (p=0.012 vs. placebo), and in
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Sodium chloride Sodium calcium edetate Glycine hydrochloride Water for injections Hydrochloric acid (to adjust pH) Sodium hydroxide (to adjust pH) 6.2 Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life 18 months 6.4 Special precautions for storage Store below 30°C. Keep the pre-filled syringe in the outer carton in order to protect from light. 6.5 Nature and contents of container Each pre-filled syringe contains 0.4 mL of solution for injection. Pre-filled syringe of clear type I glass with stainless-steel needle, plastic plunger, and polypropylene rigid needle cover. Pack sizes of 4, 7, 8 and 10 pre-filled syringes. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Each pre-filled syringe of 0.4 mL contains 8 mg of methylnaltrexone bromide. One mL of solution contains 20 mg of methylnaltrexone bromide. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Solution for injection (injection). Clear solution, colourless to pale-yellow, essentially free from visible particulates.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications 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. 4.2 Posology and method of administration Posology Opioid-induced constipation in adult patients with chronic pain (except palliative care patients with advanced illness) The recommended dose of methylnaltrexone bromide is 12 mg (0.6 mL of solution) subcutaneously, as needed, given as at least 4 doses weekly, up to once daily (7 doses weekly). In these patients, the treatment with usual laxatives should be stopped when commencing treatment with Relistor (see section
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Laxatives, Peripheral opioid receptor antagonists, ATC code: A06AH01 Mechanism of action Methylnaltrexone bromide is a selective antagonist of opioid binding at the mu-receptor. In vitro studies have shown methylnaltrexone bromide to be a mu-opioid receptor antagonist (inhibition constant [Ki] = 28 nM), with 8-fold less potency for kappa opioid receptors (Ki = 230 nM) and much reduced affinity for delta opioid receptors. As a quaternary amine, the ability of methylnaltrexone bromide to cross the blood-brain barrier is restricted. This allows methylnaltrexone bromide to function as a peripherally acting mu-opioid antagonist in tissues such as the gastrointestinal tract, without impacting opioid-mediated analgesic effects on the central nervous system. Clinical efficacy and safety Opioid-induced constipation in adult patients with chronic non-cancer pain (12 mg dose) The efficacy and safety of methylnaltrexone bromide in the treatment of opioid-induced constipation in patients with chronic non-cancer pain were demonstrated in a randomized, double‑blind, placebo‑controlled study (Study 3356). In this study, the median patient age was 49 years (range 23‑83); 60% were females. The majority of patients had a primary diagnosis of back pain. Study 3356 compared 4-week treatment regimens of methylnaltrexone bromide 12 mg once daily and methylnaltrexone bromide 12 mg every other day with placebo. The 4-week, double-blind period was followed by an 8‑week, open-label period during which methylnaltrexone bromide was to be used as needed, but no more frequently than once daily. A total of 460 patients (methylnaltrexone bromide 12 mg once daily, n = 150, methylnaltrexone bromide 12 mg every other day, n = 148, placebo, n = 162) were treated in the double-blind period. Patients had a history of chronic non-cancer pain and were taking opioids with stable doses of at least 50 mg of oral morphine equivalents per day. Patients had opioid‑induced constipation (< 3 rescue medication-free bowel movements per week during the screening period). Patients were required to discontinue all previous laxative therapy. The first co-primary endpoint was the proportion of patients having a rescue free bowel movements (RFBMs) within 4 hours of the first dose administration and the second the percentage of active injections resulting in any RFBM within 4 hours during the double-blind phase. A RFBM was defined as a bowel movement that occurred without laxative use during the previous 24 hours. The proportion of patients having an RFBM within 4 hours of the first dose was 34.2% in the combined methylnaltrexone bromide group versus 9.9% in the placebo group (p<0.001). The mean percentage of methylnaltrexone bromide resulting in any RFBM within 4 hours were 28.9% and 30.2% respectively for the once daily and every other day dose groups compared with 9.4% and 9.3% respectively for the corresponding placebo regimen for daily and every other day dosing (p <0.001) during the double blind phase. The key secondary endpoint of adjusted mean change from baseline in weekly RFBMs was 3.1 in the methylnaltrexone bromide 12 mg once daily treatment group, 2.1 in the methylnaltrexone bromide 12 mg every other day treatment group, and 1.5 in the placebo treatment group during the 4-week double-blind period. The difference between methylnaltrexone bromide 12 mg once daily and placebo of 1.6 RFBMs per week is statistically significant (p < 0.001) and clinically meaningful. Another secondary endpoint evaluated the proportion of patients with ≥3 RFBMs per week during the 4‑week double-blind phase. This was achieved in 59% of the patients in the group receiving daily methylnaltrexone 12 mg (p<0.001 vs. placebo), in 61% of those receiving it every other day (p<0.001 vs. placebo), and in 38% of the placebo treated patients. A supplementary analysis evaluated a hard endpoint of the percentage of patients achieving ≥3 complete RFBMs per week and an increase of ≥1 complete RFBMs per week in at least 3 of the 4 treatment weeks. This was achieved in 28.7% of the patients in the group receiving daily methylnaltrexone 12 mg (p<0.001 vs. placebo), in 14.9% of those receiving it every other day (p=0.012 vs. placebo), and in
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Sodium chloride Sodium calcium edetate Glycine hydrochloride Water for injections Hydrochloric acid (to adjust pH) Sodium hydroxide (to adjust pH) 6.2 Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life 18 months 6.4 Special precautions for storage Store below 30°C. Keep the pre-filled syringe in the outer carton in order to protect from light. 6.5 Nature and contents of container Each pre-filled syringe contains 0.4 mL of solution for injection. Pre-filled syringe of clear type I glass with stainless-steel needle, plastic plunger, and polypropylene rigid needle cover. Pack sizes of 4, 7, 8 and 10 pre-filled syringes. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Company Detail Path
- /organization/bausch-health-ireland-limited
