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RELISTOR (methylnaltrexone bromide) Subcutaneous Injection
Initial U.S. Approval: 2008
RELISTOR (methylnaltrexone bromide) Subcutaneous Injection, a peripherally-acting mu-opioid receptor antagonist, is a sterile, clear and colorless to pale yellow aqueous solution. The chemical name for methylnaltrexone bromide is (R)-N-(cyclopropylmethyl) noroxymorphone methobromide. The molecular formula is C21H26NO4Br, and the molecular weight is 436.36.
Each 3 mL vial contains 12 mg of methylnaltrexone bromide in 0.6 mL of water. The excipients are 3.9 mg sodium chloride USP, 0.24 mg edetate calcium disodium USP, and 0.18 mg glycine hydrochloride. During manufacture, the pH may have been adjusted with hydrochloric acid and/or sodium hydroxide.
Each 8 mg/0.4 mL pre-filled syringe (1 mL syringe) contains 8 mg of methylnaltrexone bromide in 0.4 mL of water. The excipients are 2.6 mg sodium chloride USP, 0.16 mg edetate calcium disodium USP, and 0.12 mg glycine hydrochloride.
Each 12 mg/0.6 mL pre-filled syringe (1 mL syringe) contains 12 mg of methylnaltrexone bromide in 0.6 mL of water. The excipients are 3.9 mg sodium chloride USP, 0.24 mg edetate calcium disodium USP, and 0.18 mg glycine hydrochloride.
Mechanism of Action
Methylnaltrexone bromide is a selective antagonist of opioid binding at the mu-opioid receptor. 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 receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system.
Use of opioids induces slowing of gastrointestinal motility and transit. Antagonism of gastrointestinal mu-opioid receptors by methylnaltrexone bromide inhibits opioid-induced delay of gastrointestinal transit time in a dose-dependent manner in rats. The effects of methylnaltrexone bromide on central mu-opioid receptors were evaluated in a pharmacodynamic study in which subjects received a dose of remifentanil, sufficient to produce pupiliary constriction, followed by placebo, naloxone, or methylnaltrexone. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.
INDICATIONS AND USAGE
RELISTOR® is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond four months has not been studied.
RELISTOR is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
WARNINGS AND PRECAUTIONS
The most common (> 5%) adverse reactions reported with RELISTOR are abdominal pain, flatulence, nausea, dizziness, diarrhea and hyperhidrosis.
DOSAGE AND ADMINISTRATION
General Dosing Information
FOR SUBCUTANEOUS INJECTION ONLY
RELISTOR should be injected in the upper arm, abdomen or thigh.
RELISTOR is administered as a subcutaneous injection. The usual schedule is one dose every other day, as needed, but no more frequently than one dose in a 24-hour period.
The recommended dose of RELISTOR is 8 mg for patients weighing 38 to less than 62 kg (84 to less than 136 lb) or 12 mg for patients weighing 62 to 114 kg (136 to 251 lb). Patients whose weight falls outside of these ranges should be dosed at 0.15 mg/kg. See the table below to determine the correct injection volume. The pre-filled syringe is designed to deliver a fixed dose; therefore, patients requiring dosing calculated on a mg/kg basis should not be prescribed pre-filled syringes.
Use in Patients with Severe Renal Impairment
In patients with severe renal impairment (creatinine clearance less than 30 mL/min), dose reduction of RELISTOR by one-half is recommended.
The pre-filled syringe is designed to deliver a fixed dose; therefore, patients with severe renal impairment should not be prescribed pre-filled syringes unless their body weight calculated dose is 8 mg or 12 mg.
Preparation for Injection
RELISTOR is a sterile, clear, and colorless to pale yellow aqueous solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If any of these are present, the vial should not be used.
Preparation of RELISTOR Using the Single-use Vial
Once drawn into the syringe, if immediate administration is not possible, store at ambient room temperature and administer within 24 hours.
Preparation of RELISTOR Using the Single-use Pre-filled Syringe
Do not remove the pre-filled syringe from the tray until ready to administer.
DOSAGE FORMS AND STRENGTHS
RELISTOR is available in the following dosage forms and strengths. Only patients requiring an 8 mg or 12 mg dose should be prescribed pre-filled syringes.
Single-use vial containing 12 mg/0.6 mL solution for subcutaneous injection.
Single-use pre-filled syringe containing 8 mg/0.4 mL solution for subcutaneous injection, with a 29-gauge x half-inch fixed needle and a needle guard.
Single-use pre-filled syringe containing 12 mg/0.6 mL solution for subcutaneous injection, with a 29-gauge x half-inch fixed needle and a needle guard.
RELISTOR® should be stored at 20-25ºC (68-77ºF); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light.
Package Insert data:
Salix Pharmaceuticals, Inc.
Raleigh, NC 27615
Under license from:
Progenics Pharmaceuticals, Inc.
Tarrytown, NY 10591
PACKAGE LABEL - PRINCIPAL DISPLAY PANEL - 12 mg/0.6 mL - VIAL
12 mg/0.6 mL per vial
For Subcutaneous Injection Only
Sterile Single Use Vial
Discard After Use
Manufactured for Salix Pharmaceuticals, Inc.
Under license from Progenics Pharmaceuticals