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Naldemedin – Uses, Dosage & Side Effects

Naldemedin is a medication used to treat opioid-induced constipation in adults. It blocks opioid receptors in the gut without reversing the pain-relieving effects of opioids.

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Things worth knowing about "Naldemedin"

Naldemedin is a medication used to treat opioid-induced constipation in adults. It blocks opioid receptors in the gut without reversing the pain-relieving effects of opioids.

What is Naldemedin?

Naldemedin is a prescription medication used to treat opioid-induced constipation (OIC). It belongs to a drug class known as peripherally acting mu-opioid receptor antagonists (PAMORAs). In the European Union, it is approved under the brand name Rizmoic for use in adults who have previously received a laxative. In other markets, including the United States, it is marketed under the name Symproic.

Indication

Naldemedin is indicated for adult patients suffering from constipation caused by opioid pain medications such as morphine, oxycodone, or fentanyl. Opioids bind to receptors throughout the gastrointestinal tract, slowing bowel movements and leading to constipation. Naldemedin is specifically intended for patients who have had an inadequate response to conventional laxatives.

Mechanism of Action

Naldemedin acts as an antagonist at mu-, delta-, and kappa-opioid receptors located in the gastrointestinal tract. Its molecular structure is specifically designed so that it does not readily cross the blood-brain barrier. As a result, it blocks the effects of opioids in the gut – restoring normal bowel motility – without interfering with the central pain-relieving effects of opioid therapy in the brain.

Dosage and Administration

The recommended dose of naldemedin is 0.2 mg once daily, taken orally as a tablet. It can be taken with or without food. Treatment should be discontinued if opioid therapy is stopped. Patients should always follow the dosing instructions provided by their healthcare provider.

Side Effects

Like all medications, naldemedin may cause side effects. The most commonly reported side effects involve the gastrointestinal system:

  • Abdominal pain (very common)
  • Diarrhea
  • Nausea and vomiting
  • Gastrointestinal discomfort such as flatulence

In rare cases, opioid withdrawal symptoms may occur, particularly in patients with physical dependence on opioids. Patients should seek immediate medical attention if they experience severe abdominal pain or signs of bowel obstruction.

Contraindications and Drug Interactions

Naldemedin should not be used in patients with:

  • Known hypersensitivity to the active substance
  • Known or suspected mechanical bowel obstruction
  • An increased risk of recurrent bowel obstruction

Important drug interactions include:

  • Strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin): may increase naldemedin plasma levels
  • Strong CYP3A4 inducers (e.g., rifampicin, phenytoin): may reduce naldemedin levels and decrease efficacy
  • Other opioid antagonists: concurrent use should be avoided

Treatment Context

Naldemedin is part of the PAMORA drug class, which also includes methylnaltrexone and naloxegol. These agents were developed to address one of the most common and burdensome side effects of long-term opioid therapy. Opioid-induced constipation affects an estimated 40–80% of patients receiving chronic opioid treatment and can significantly impair quality of life. Clinical trials have demonstrated that naldemedin significantly increases the frequency of spontaneous bowel movements and is generally well tolerated.

References

  1. European Medicines Agency (EMA): Rizmoic (Naldemedin) – Summary of Product Characteristics (SmPC), 2019. Available at: www.ema.europa.eu
  2. Katakami N. et al.: Randomized Phase III and Extension Studies of Naldemedine in Patients with Opioid-Induced Constipation and Cancer. Journal of Clinical Oncology, 2017; 35(34):3859–3866.
  3. Hale M. et al.: Efficacy and Safety of Naldemedine in Patients with Opioid-Induced Constipation and Chronic Noncancer Pain. Pain, 2017; 158(2):268–278.

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