Naloxegol (Movantik), developed by AstraZeneca, is a peripherally acting opioid (mu-receptors) antagonist. It is used in the treatment of constipation caused by opioids.

Naloxegol (Movantik) Uses:

• Opioid-induced constipation:

  • Used treatment of opioid-induced constipation (OIC) 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.

Naloxegol (Movantik) Dose in Adults

Note:

• Discontinue all maintenance laxative therapy prior to use
• may reintroduce laxatives as needed if a suboptimal response to naloxegol after 3 days.
• Alteration in the analgesic dosing regimen prior to initiating naloxegol is not required.

Naloxegol (Movantik) Dose in the treatment of Opioid-induced constipation:

P/O:

• 25 mg once a day.
• If not tolerated, reduce dose to 12.5 mg once a day.
• Discontinue treatment if opioid pain medication is discontinued.

• Naloxegol (Movantik) Dosing adjustment with concomitant medications:

  • Moderate CYP3A4 Inhibitors (eg, diltiazem, erythromycin, verapamil):

    • • Avoid concomitant use.
    • If concurrent use is unavoidable, reduce the dose of naloxegol to 12.5 mg once a day & monitor for adverse reactions.

  • Strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole):

    • contraindicated for concomitant use.

Naloxegol (Movantik) Dose in Childrens

Not indicated in children.

Naloxegol Pregnancy Risk Category: C

• In animal reproduction studies, adverse events were not seen.
• Exposure during pregnancy can lead to opioid withdrawal in the baby.

Naloxegol use during breastfeeding:

• It is unknown if naloxegol secretes in breast milk.
• The manufacturer does not recommend breastfeeding due to the possibility of serious adverse reactions, such as opioid withdrawal in the infant.

Naloxegol (Movantik) Dose in Kidney Disease:

CrCl ≥60 mL/minute:

• Dosage adjustment not necessary.

CrCl <60 mL/minute and end-stage renal disease (ESRD):

• An initial dose of 12.5 mg once daily
• if well tolerated but opioid-induced constipation symptoms continue, it may increase to 25 mg once daily, taking into consideration the potential for markedly increased exposures in some patients with renal impairment and the increased risk of adverse reactions with higher exposures.

Dialysis:

• Not readily dialyzed (ineffective).

Naloxegol (Movantik) Dose in Liver disease:

Mild to moderate impairment (Child-Pugh class A and B):

• No dosage adjustment necessary.

Severe impairment (Child-Pugh class C):

• Avoid use (has not been studied).

Side Effects of Naloxegol (Movantik):

• Gastrointestinal:

  • Abdominal pain
  • Diarrhea
  • Nausea
  • Flatulence
  • Vomiting

• Central Nervous System:

  • Headache
  • Opioid Withdrawal Syndrome

• Dermatologic:

  • Hyperhidrosis.

Contraindications to Naloxegol (Movantik):

• Severe or severe hypersensitivity reaction to any drug or component of the formulation
• GI obstruction (known, suspected or suspected) or at an increased risk for recurrent obstruction
• Use with strong CYP3A4 inhibitors (eg clarithromycin, ketoconazole)

Warnings and precautions

• Gastrointestinal effects:

  • Reports of severe abdominal pain or diarrhea were received
  • Hospitalization may be necessary.
  • The 25 mg dose was responsible for most cases of severe abdominal pain. These symptoms usually occurred within a few days.
  • Watch out for signs of diarrhea and abdominal pain.
  • If this happens, discontinue treatment.
  • You may want to try a lower dose.

• Perforation of the GI:

  • GI perforation has been reported with the use of another peripherally acting opioid antagonist (ie, methylnaltrexone) in patients with a localized or diffuse reduction of structural wall integrity of the GI tract (eg, peptic ulcer disease, Ogilvie syndrome, diverticular disease, infiltrative GI tract malignancies, peritoneal metastases).
  • These patients, or patients with Crohn disease, should be cautious.
  • If you feel severe, persistent or worsening abdominal pain, discontinue treatment immediately.
  • Patients with GI obstruction (known, suspected or suspected) or who are at greater risk of recurrent GI dysfunction should not use this product.

• Withdrawal of Opioid:

  • Some symptoms of opioid withdrawal include hyperhidrosis and diarrhea, nausea, vomiting, anxiety, irritability and yawning.
  • Patients at risk of opioid withdrawal or reduced pain relief should be treated with caution.
  • Check for signs and symptoms of opioid withdrawal in these patients.

• Hepatic impairment

  • Do not use if you have severe hepatic impairment.

• Renal impairment

  • Patients with CrCl >60 mL/minute should adjust their dosage.

Naloxegol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Symptoms of GI obstruction (eg, severe, persistent, or worsening abdominal pain)
• Symptoms of opioid withdrawal (eg, chills, diaphoresis, anxiety, irritability, changes in blood pressure, or heart rate).

How to administer Naloxegol (Movantik)?

• During treatment, avoid grapefruit and grapefruit juice.

Oral:​​​​​​​

• Take the medication on an empty stomach at the least one hour before or two hours after your first meal of the day.
• Take the tablets whole and do not chew.
• Patients who are unable to swallow the tablet whole may crush it into a powder, mix 120 mL of liquid, and then drink right away.

Nasogastric (NG), feeding tube:

• Use a 60 mL syringe to flush the NG tube.
• Mix the powder with 60 mL water to crush the tablet
• Mix the mixture with the 60 mL Syringe. Then, use the NG tube to administer it.
• Rinse the container that was used to prepare the dose. Use 60mL water.
• Use the same syringe to draw up the water.

Mechanism of action of Naloxegol (Mavantik):

• Naloxegol is an antagonist of mu-opioid receptors.
• It is made of naloxone and a polyethylene glycol-polymer combination, which restricts its ability to cross blood-brain barriers.
• Naloxegol is a peripheral drug that functions in tissues, such as the GI tract. This reduces constipation, which can be caused by opioids.

Absorption:

• Rapid. With a high-fat meal, C and AUC increased by 30% and 45%, respectively.

Protein binding:

• ~4.2%

Metabolism:

• Hepatic via CYP3A (primarily). Data suggests no major metabolites.
• Minor metabolites formed via N-dealkylation, O-demethylation, oxidation, and partial loss of the PEG chain.

Half-life elimination:

• 6 to 11 hours

Time to peak serum concentration:

• less than 2 hours

Excretion:

• Feces (68%; ~16% as unchanged drug);
• Urine (16%; <6% as unchanged drug)

International Brand Names of Naloxegol:

• Moventig
• Movantik

Naloxegol Brand Names in Pakistan:

No Brands Available in Pakistan.