Targeted Treatment of OIC

Agents that directly address opioids’ interaction with peripheral opioid receptors have the most utility in treating OIC.

Oxycodone hydrochloride/naloxone hydrochloride extended-release is an orally administered opioid analgesic combined with an opioid antagonist that acts at µ, κ, and δ opioid receptors by displacing opioid agonists.7 It consists of prolonged-release (PR) oxycodone with PR naloxone in a single tablet, and is an abuse-deterrent formulation. Oxycodone provides analgesia, while naloxone addresses constipation.8,9 It is FDA-approved for severe pain, when alternative treatment options are inadequate.10 However, it is not specifically approved for OIC.

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Methylnaltrexone is a peripherally acting µ-opioid receptor antagonist  (PAMORA), which is indicated for OIC in patients receiving palliative care who do not respond sufficiently to laxative therapy.4 It blocks opioid binding at the µ-opioid receptor and does not cross the blood brain barrier, so its effects remain localized within the intestine.3 Currently, it is available only as a subcutaneous injection, which limits its utility.11

Methylnaltrexone has been shown to be significantly more effective than placebo in relieving OIC without reducing analgesia or causing opioid withdrawal symptoms.12,13 However, it is effective only in about 50% of patients. Its effectiveness may be connected with the particular opioid the patient is taking.3 A study currently underway is evaluating the efficacy of methylnaltrexone in alleviating OIC in three common opioid subtypes: morphine, oxycodone, and fentanyl.3 (NCT01955213)

Alvimopan is a PAMORA that does not cross the blood-brain barrier, thereby allowing it to block the peripheral effects of opioids on the GI tract, without reversing centrally mediated analgesia.2,5 However it is approved only for shortening the course of postoperative ileus, and is contraindicated in OIC.5,14