New Drug Approvals 2014 - Pt. XII - Naloxegol (Movantik™)

ATC Code: A06AH03

Wikipedia: Naloxegol

ChEMBL: CHEMBL2219418

On September 16th FDA approved Movantik (naloxegol, AZ-13337019), as an oral treatment for patients with opioid-induced constipation and chronic non-cancer pain.

Naloxegol
Naloxegol is an opioid receptor antagonist. Due to its similarity to noroxymorphone, a main metabolite of oxycodone, naloxegol is classed as a controlled substance. However, the FDA analysed its abuse potential and concluded that there was no risk of dependency.

Mode of Action

Opioids are a class of drugs which are used to manage pain, but have a common side effect of reducing the motility of the gastrointestinal tract, making bowel movements difficult. Opioids work by binding to the mu-receptors (CHEMBL233, UniProt:P35372) in the central nervous system, thereby reducing pain. However, they are also able to bind to the mu-receptors in the gastrointestinal tract, hence causing opioid-induced constipation.
Movantik is a peripherally-acting opioid receptor antagonist, which is able to prevent constipation by reducing this specific side effect of the opioids without affecting the efficacy of the pain management.

Clinical Trials
The clinical trials for this drug were carried out on a KODIAC clinical programme, comprising of four studies. Tests showed that 44% and 41% of patients receiving 25mg and 12.5mg, respectively, experienced increased bowel movements, compared to just 29% who took the placebo. [Paper]

Indication and Warnings

This drug is for non-cancer related pain. Side effects have been abdominal pain, diarrhea, headache and excessive gas in the stomach and/or intestinal area.
When used in conjunction with another peripherally-acting opioid antagonist, there is the chance of gastrointestinal perforation.
There is also the chance of withdrawal symptoms.
This is contraindicated for anyone who is also taking CYP3A4 (CHEMBL5792, UniProt:Q9HB55) inhibitors, such as clarithromycin (CHEMBL1741), as this will increase the exposure to naloxegol and could precipitate opioid withdrawal symptoms. [FDA]

Trade Names
Naloxegol was developed by AstraZeneca and is marketed under the trade name of Movantik. It is due for release during the first quarter of 2015.

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