Opioid-induced constipation with advanced illness: SubQ: Dosing is according to body weight: Administer 1 dose every other day as needed; maximum: 1 dose/24 hours.
<38 kg: 0.15 mg/kg (round dose up to nearest 0.1 mL of volume).
38 to <62 kg: 8 mg.
62 to 114 kg: 12 mg.
>114 kg: 0.15 mg/kg (round dose up to nearest 0.1 mL of volume).
Opioid-induced constipation with chronic non-cancer pain: Note: Discontinue all maintenance laxatives prior to initiation of therapy; if response is not optimal after 3 days, laxative therapy may be reinitiated.
Oral: 450 mg once daily.
SubQ: 12 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl <60 mL/minute:
Opioid-induced constipation with advanced illness: SubQ:
<38 kg: 0.075 mg/kg every other day (round dose up to nearest 0.1 mL of volume)
38 to <62 kg: 4 mg every other day
62 to 114 kg: 6 mg every other day
>114 kg: 0.075 mg/kg every other day (round dose up to nearest 0.1 mL of volume)
Opioid-induced constipation with chronic non-cancer pain:
Oral: 150 mg once daily
SubQ: 6 mg once daily
End-stage renal impairment (dialysis-dependent): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Opioid-induced constipation with advanced illness: There are no dosage adjustments provided in the manufacturer's labeling. For the injection, consider following the subcutaneous dosing recommendations for opioid-induced constipation with chronic non-cancer pain in patients with severe impairment (Child-Pugh class C).
Opioid-induced constipation with chronic non-cancer pain:
Oral:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B and C): 150 mg once daily
SubQ:
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child Pugh class C):
<38 kg: 0.075 mg/kg once daily (round dose up to nearest 0.1 mL of volume)
38 to <62 kg: 4 mg once daily
62 to 114 kg: 6 mg once daily
>114 kg: 0.075 mg/kg once daily (round dose up to nearest 0.1 mL of volume)
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Relistor: 8 mg/0.4 mL (0.4 mL); 12 mg/0.6 mL (0.6 mL) [contains edetate (edta) calcium disodium]
Tablet, Oral, as bromide:
Relistor: 150 mg [contains edetate (edta) calcium disodium]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Subcutaneous:
Relistor: 12 mg/0.6 mL [contains edetate (edta) calcium disodium]
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Relistor: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021964s018,208271s002lbl.pdf#page=27
SubQ: Administer by subcutaneous injection into the upper arm, abdomen, or thigh. Rotate injection sites with each dose.
Tablet: Oral: Administer with water on an empty stomach at least 30 minutes before the first meal of the day.
Opioid-induced constipation with advanced illness (injection only): Treatment of opioid-induced constipation in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.
Opioid-induced constipation with chronic non-cancer pain (tablets and injection): Treatment of opioid-induced constipation in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (eg, weekly) opioid dosage escalation.
Methylnaltrexone may be confused with naltrexone
Relistor may be confused with Restoril
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Abdominal pain (14% to 29%), flatulence (13%), nausea (9% to 12%)
1% to 10%:
Central nervous system: Dizziness (7%), headache (4%), anxiety (2%), chills (1%)
Dermatologic: Hyperhidrosis (3% to 6%)
Endocrine & metabolic: Hot flash (3%)
Gastrointestinal: Diarrhea (5% to 6%), abdominal distention (4%), vomiting (2%)
Neuromuscular & skeletal: Muscle spasm (2%), tremor (1%)
Respiratory: Rhinorrhea (2%)
<1%, postmarketing, and/or case reports: Abdominal cramps, diaphoresis, flushing, gastrointestinal perforation, increased body temperature (Thomas 2008), malaise, opioid withdrawal syndrome, pain, syncope (Portenoy 2008)
GI obstruction (known or suspected); patients at increased risk of recurrent GI obstruction.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to methylnaltrexone or any component of the formulation
Concerns related to adverse effects:
• Diarrhea: Discontinue treatment for severe or persistent diarrhea.
• Gastrointestinal perforation: Gastrointestinal perforations have been reported in patients with advanced illnesses associated with impaired structural integrity of the GI wall (eg, Ogilvie’s syndrome, peptic ulcer disease, diverticular disease, infiltrative GI tract malignancies, or peritoneal metastases). Use with caution in these patients or in patients with other conditions that may result in impaired integrity of the GI wall (eg, Crohn disease); Monitor for development of severe, persistent or worsening abdominal pain; discontinue therapy if this occurs. Use is contraindicated in patients with known or suspected GI obstruction or in patients at increased risk of recurrent GI obstruction.
• Opioid withdrawal: May precipitate symptoms of opioid withdrawal (eg, abdominal pain, anxiety, chills, diarrhea, hyperhidrosis, and yawning). Use with caution in patients with disruptions to the blood-brain barrier; may increase the risk for withdrawal and/or reduced analgesia. Monitor for symptoms of opioid withdrawal in such patients.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustments recommended for moderate to severe hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended for moderate to severe renal impairment (CrCl <60 mL/minute).
Other warnings/precautions:
• Appropriate use: Use of injection beyond 4 months has not been studied. Discontinue methylnaltrexone if opioids are discontinued.
• Opioid-induced constipation with chronic non-cancer pain: Appropriate use: Efficacy has been established in patients who have taken opioids for ≥4 weeks; sustained exposure to opioids prior to initiation of methylnaltrexone may increase sensitivity to effects. All laxative maintenance therapy should be discontinued prior to initiation of therapy; laxative therapy may be added if a suboptimal response to therapy is noted after 3 days. When the opioid regimen has been changed, the patient should be re-evaluated for the need to continue methylnaltrexone therapy.
Substrate of CYP2D6 (minor), OCT1, OCT2; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Opioid Antagonists: Methylnaltrexone may enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Adverse events have not been observed in animal reproduction studies. Maternal use of methylnaltrexone during pregnancy may precipitate opioid withdrawal effects in newborn.
It is not known if methylnaltrexone is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant breastfeeding is not recommended by the manufacturer.
Severe, persistent, or worsening abdominal pain; symptoms of opioid withdrawal; adequate analgesia.
An opioid receptor antagonist which blocks opioid binding at the mu receptor, methylnaltrexone is a quaternary derivative of naltrexone with restricted ability to cross the blood-brain barrier. It therefore functions as a peripheral acting opioid antagonist, including actions on the gastrointestinal tract to inhibit opioid-induced decreased gastrointestinal motility and delay in gastrointestinal transit time, thereby decreasing opioid-induced constipation. Does not affect opioid analgesic effects.
Distribution: Vdss: ~1.1 L/kg
Protein binding: 11% to 15%
Metabolism: Metabolized to methyl-6-naltrexol isomers, methylnaltrexone sulfate, and other minor metabolites
Half-life elimination: Terminal: ~15 hours (oral)
Time to peak, plasma: SubQ: 30 minutes; Oral: ~1.5 hours (delayed by 2 hours with high fat meal)
Excretion: Urine (~44% to 54%, primarily as unchanged drug); feces (~17%, primarily as unchanged drug)
Altered kidney function: A single SubQ dose in patients with varying degrees of renal impairment resulted in a 1.3- to 1.9-fold higher AUC0-∞ of methylnaltrexone.
Hepatic function impairment: A single oral dose in patients with mild, moderate, and severe hepatic impairment resulted in a 1.7-, 4.8-and 3.8-fold higher Cmax of methylnaltrexone, respectively. AUC0-∞, increased ~2.1-fold in moderate and severe hepatic impairment.
Older adult: In elderly subjects (mean age: 72 years), mean clearance was about 20% lower (56 L/h versus 70 L/h) and AUC∞ was 26% higher.
Solution (Relistor Subcutaneous)
8 mg/0.4 mL (per 0.4 mL): $174.17
12 mg/0.6 mL (per 0.6 mL): $174.17
Tablets (Relistor Oral)
150 mg (per each): $29.03
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