Methylnaltrexone bromide

Methylnaltrexone bromide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Methylnaltrexone bromide is an opioid antagonist that is FDA approved for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non‑cancer pain and with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Common adverse reactions include abdominal pain, nausea, diarrhea, hyperhidrosis, hot flush, tremor, chills,flatulence, and dizziness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

• RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with chronic non‑cancer pain.

Opioid-Induced Constipation in Adult Patients with Advanced Illness

• RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient.

Limitation of Use

• Use of RELISTOR beyond four months has not been studied in the advanced illness population.

Dosage

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

• The recommended dosage of RELISTOR is 12 mg subcutaneously once daily.

Opioid-Induced Constipation in Adult Patients with Advanced Illness

• The recommended dose of RELISTOR administered subcutaneously is 8 mg for adult patients weighing 38 kg to less than 62 kg and 12 mg for patients weighing 62 kg to 114 kg. Adult patients whose weight falls outside of these ranges should be dosed at 0.15 mg/kg. The recommended dosage regimen is one dose every other day, as needed.

• See Table 1 to determine the correct dose by patient weight and injection volume to be administered. The pre-filled syringe is designed to deliver a fixed dose; therefore, adult patients requiring dosing calculated on a mg/kg basis should not be prescribed pre-filled syringes.

This image is provided by the National Library of Medicine.

Use in Patients with Severe Renal Impairment

• In adult patients with severe renal impairment (creatinine clearance less than 30 mL/min as estimated by Cockcroft-Gault), dose reduction of RELISTOR by one-half is recommended [see Use in Specific Populations (8.6)]. No dosage adjustment is recommended for adult patients with mild to moderate renal impairment.

• The pre-filled syringe is designed to deliver a fixed dose; therefore, adult patients with severe renal impairment should only be prescribed single-use vials to ensure correct dosing.

DOSAGE FORMS AND STRENGTHS

Single-use Vial:

• 12 mg/0.6 mL solution for subcutaneous injection, for use with a 27 gauge x ½-inch needle and 1 mL syringe

• 12 mg/0.6 mL solution for subcutaneous injection, with one 1 mL syringe with retractable 27 gauge x ½-inch needle, two alcohol swabs

Single-use Pre-filled Syringe:

• 8 mg/0.4 mL solution for subcutaneous injection, with a 29-gauge x ½-inch fixed needle and a needle guard

• 12 mg/0.6 mL solution for subcutaneous injection, with a 29-gauge x ½-inch fixed needle and a needle guard

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methylnaltrexone bromide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methylnaltrexone bromide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Methylnaltrexone bromide in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methylnaltrexone bromide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methylnaltrexone bromide in pediatric patients.

Contraindications

• RELISTOR is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation

Warnings

Gastrointestinal Perforation

• Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness 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, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

Severe or Persistent Diarrhea

• If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Opioid Withdrawal

• Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Adverse Reactions

Clinical Trials Experience

Serious and important adverse reactions described elsewhere in labeling include:

• Gastrointestinal perforation

• Severe or persistent diarrhea

• Opioid withdrawal

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

• The safety of RELISTOR was evaluated in a double-blind, placebo-controlled trial in adult patients with opioid-induced constipation and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 4-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR 12 mg once daily (150 patients) or placebo (162 patients). After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR 12 mg was administered less frequently than the recommended dosage regimen of 12 mg once daily.

• Adverse reactions in adult patients with opioid-induced constipation and chronic non-cancer pain receiving RELISTOR are shown in Table 2. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.

This image is provided by the National Library of Medicine.

• During the 4-week double-blind period, in patients with opioid-induced constipation and chronic non-cancer pain that received RELISTOR 12 mg every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily Relistor dosing. Use of RELISTOR 12 mg every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 1) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%).

• The safety of RELISTOR was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with opioid-induced constipation and chronic non-cancer pain (Study 2). Patients were allowed to administer RELISTOR 12 mg less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48‑week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 1. Additionally, in Study 2, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR.

Opioid-Induced Constipation in Adult Patients with Advanced Illness

• The safety of RELISTOR was evaluated in two, double-blind, placebo-controlled trials in adult patients with opioid-induced constipation and advanced illness receiving palliative care: Study 3 included a single‑dose, double‑blind, placebo-controlled period, whereas Study 4 included a 14-day multiple dose, double-blind, placebo-controlled period.

• The most common (≥ 5%) adverse reactions in adult patients with opioid-induced constipation and advanced illness receiving RELISTOR are shown in Table 3 below.

This image is provided by the National Library of Medicine.

• The rates of discontinuation due to adverse events during the double-blind placebo controlled clinical trials (Study 3 and Study 4) were comparable between RELISTOR (1%) and placebo (2%).

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

• The following adverse reactions have been identified during post-approval use of RELISTOR. Because they are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal

Perforation, cramping, vomiting

General Disorders and Administrative Site Disorders

Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported.

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methylnaltrexone bromide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methylnaltrexone bromide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Methylnaltrexone bromide with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Methylnaltrexone bromide with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Methylnaltrexone bromide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methylnaltrexone bromide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methylnaltrexone bromide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methylnaltrexone bromide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methylnaltrexone bromide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methylnaltrexone bromide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methylnaltrexone bromide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Subcutaneous

Important Administration Information

• RELISTOR is for subcutaneous use only.

• Inject RELISTOR subcutaneously in the upper arm, abdomen or thigh.Do not inject at the same spot each time (rotate injection sites).

• Be within close proximity to toilet facilities once RELISTOR is administered.

Discontinue RELISTOR if treatment with the opioid pain medication is also discontinued.

• In patients with chronic non-cancer pain and opioid-induced constipation:

• RELISTOR has been shown to be efficacious in patients who have taken opioids for at least 4 weeks. Sustained exposure to opioids prior to starting RELISTOR may increase the patient’s sensitivity to the effects of RELISTOR.

• Discontinue all maintenance laxative therapy prior to initiation of RELISTOR. Laxative(s) can be used as needed if there is a suboptimal response to RELISTOR after three days.

• Inject one dose every day.

• Re-evaluate the continued need for RELISTOR when the opioid regimen is changed to avoid adverse reactions.

• In patients with advanced illness and opioid-induced constipation:

• Inject one dose every other day, as needed, but no more frequently than one dose in a 24-hour period.

Administration and Storage

• RELISTOR is a sterile, clear, and colorless to pale yellow aqueous solution. Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use the vial if any of these are present.

Single-use Vials

• Once drawn into the 1 mL syringe with a 27-gauge x ½-inch needle, if immediate administration is not possible, store at ambient room temperature and administer within 24 hours. Discard any unused portion that remains in the vial. Advise patients concerning proper training in subcutaneous technique.

Single-use Pre-filled Syringes

• Only adult patients requiring an 8 mg or 12 mg dose should be prescribed pre-filled syringes. Do not remove the pre-filled syringe from the tray until ready to administer.

Monitoring

There is limited information regarding Monitoring of Methylnaltrexone bromide in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Methylnaltrexone bromide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Methylnaltrexone bromide in the drug label.

Pharmacology

There is limited information regarding Methylnaltrexone bromide Pharmacology in the drug label.

Mechanism of Action

Structure

File:Methylnaltrexone bromide01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Methylnaltrexone bromide in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Methylnaltrexone bromide in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Methylnaltrexone bromide in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Methylnaltrexone bromide in the drug label.

How Supplied

Storage

There is limited information regarding Methylnaltrexone bromide Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Methylnaltrexone bromide |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Methylnaltrexone bromide |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Methylnaltrexone bromide in the drug label.

Precautions with Alcohol

• Alcohol-Methylnaltrexone bromide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

{{#subobject:

 |Page Name=Methylnaltrexone bromide
 |Pill Name=No image.jpg
 |Drug Name=
 |Pill Ingred=|+sep=;
 |Pill Imprint=
 |Pill Dosage={{{dosageValue}}} {{{dosageUnit}}}
 |Pill Color=|+sep=;
 |Pill Shape=
 |Pill Size (mm)=
 |Pill Scoring=
 |Pill Image=
 |Drug Author=
 |NDC=

}}

{{#subobject:

 |Label Page=Methylnaltrexone bromide
 |Label Name=Methylnaltrexone bromide11.png

}}

{{#subobject:

 |Label Page=Methylnaltrexone bromide
 |Label Name=Methylnaltrexone bromide11.png

}}