Methylnaltrexone

Dosage Forms & Strengths

injectable solution

• 8mg/0.4mL vial
• 12mg/0.6mL vial

tablet

• 150mg

Opioid-Induced Constipation (Advanced Illness Receiving Palliative Care)

Indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has been insufficient

38-62 kg: 8 mg/dose SC every other day 

62-114 kg: 12 mg/dose SC every other day

<38 kg or >114 kg: 0.15 mg/kg/dose SC every other day

Dosing considerations

• Usual dose is every other day; not to exceed 1 dose/24 hr
• Use beyond 4 months has not been studied in the advanced illness population

Opioid-Induced Constipation (Chronic Noncancer Pain)

Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain

12 mg SC qDay, OR

450 mg PO qDay in morning

Also see Administration

Dosage Modifications

Renal impairment

• Mild: No dose adjustment recommended
• Moderate-to-severe (CrCl <60 mL/min): Modified dosage shown by indication below according to indication and dosage form
• OIC with chronic noncancer pain
  • Tablets: 150 mg PO qDay in morning
  • SC injection: 6 mg SC qDay
• OIC with advanced illness receiving palliative care
  • Every other day SC injection based on weight
  • <38 kg: 0.075 mg/kg
  • 38 to <62 kg: 4 mg
  • 62-114 kg: 6 mg
  • >114 kg: 0.075 mg/kg

Hepatic impairment

• Tablets
  • Mild (Child-Pugh A): No dose adjustment recommended
  • Moderate-to-severe (Child-Pugh B or C): 150 mg PO qDay in morning
• SC injection
  • Every other day SC injection based on weight for severe hepatic impairment
  • <38 kg: 0.075 mg/kg
  • 38 to <62 kg: 4 mg
  • 62-114 kg: 6 mg
  • >114 kg: 0.075 mg/kg

Safety and efficacy not established

>10%

Abdominal pain (28.5%)

Flatulence (13.5%)

Nausea (11.5%)

1-10%

Dizziness (7.3%)

Hyperhidrosis (6.7%)

Diarrhea (5.5%)

Postmarketing Reports

Gastrointestinal: Cramping, perforation, vomiting

General disorders and administrative site disorders: Diaphoresis, flushing, malaise, pain

General Information

Be within close proximity to toilet facilities when administered

Shown to be efficacious in patients who have taken opioids for at least 4 weeks

Discontinue all maintenance laxative therapy prior to initiation; laxatives can be used prn if there is suboptimal response to methylnaltrexone after 3 days

Reevaluate the continued need for methylnaltrexone when the opioid regimen is changed to avoid adverse reactions

Discontinue if the opioid pain medication is also discontinued

SC Administration

Administer in upper arm, abdomen, or thigh (rotate injection site)

Oral Administration

Take with water on an empty stomach at least 30 minutes before the first meal of the day

Storage

Tablets or injection: Store at controlled room temperature up to 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

Injection: Do not freeze and protect from light

Serious side effects have been reported with methylnaltrexone. See the “Methylnaltrexone Precautions” section.

Common side effects of methylnaltrexone include:

• abdominal (stomach) pain
• gas
• headache
• swelling or a feeling of fullness or pressure in your abdomen
• anxiety
• muscle spasms
• runny nose
• chills
• nausea
• dizziness
• diarrhea
• sweating
• hot flush
• tremor

If you get diarrhea that is severe or does not stop while taking methylnaltrexone, stop taking it and call your healthcare provider.

If you get stomach pain that is severe or will not go away, or nausea or vomiting that is new or worse, stop taking methylnaltrexone and call your healthcare provider.

These are not all of the possible side effects of methylnaltrexone. Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1‑800‑FDA‑1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take other opioid antagonists. This is because when taken together they increase the risk of opioid withdrawal.

This is not a complete list of methylnaltrexone drug interactions. Ask your doctor or pharmacist for more information.

Tablets:

• Store methylnaltrexone tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• The bottle of methylnaltrexone tablets contains 2 desiccant canisters to help keep your medicine dry. Do not remove the desiccant canisters from the bottle.

Injection:

• Store methylnaltrexone vials or pre-filled syringes at 68 to 77°F (20 to 25°C).
• Do not freeze methylnaltrexone.
• Keep methylnaltrexone away from light until you are ready to use it.
• If methylnaltrexone has been drawn into a syringe and you are unable to use the medicine right away, keep the syringe at room temperature for up to 24 hours. The syringe does not need to be kept away from light during the 24-hour period.

Keep methylnaltrexone and all medicines, needles and syringes out of the reach of children.

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.

Injection: Store intact vials and prefilled syringes between 20°C and 25°C (68°F and 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Do not freeze. Protect from light. Solution withdrawn from the single use vial is stable in a syringe for 24 hours at room temperature. Do not remove the prefilled syringe from the tray until ready to administer.

Tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

>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% (Limited to important or life-threatening): Abdominal cramps, diaphoresis, flushing, gastrointestinal perforation, increased body temperature (Thomas 2008), malaise, opioid withdrawal syndrome, pain, syncope (Portenoy 2008)

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).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.