Methylnaltrexone bromide for the treatment of opioid-induced constipation

Abstract

The extensive and alarming use of opioids for pain management in patients with chronic pain receiving palliative care is associated with non-tolerable gastrointestinal (GI) adverse effects. Opioid-induced constipation (OIC) is the most common adverse effect impairing patient quality of life (QOL). In addition, OIC is one of the treatment limiting consequences of opioid analgesics. Management of OIC is becoming a challenge since traditional laxatives have limited efficiency. Peripherally acting mu-opioid receptor antagonists (PAMORA) have been developed for the treatment of OIC with methylnaltrexone bromide being the first approved to treat OIC in adults with advanced illness undergoing palliative care. Areas covered: The authors systematically review the clinical evidence for methylnaltrexone bromide including a review of the pharmacokinetic and pharmacodynamic data along with clinical effectiveness and cost-effectiveness. Though there is a need for further long-term clinical investigation, there is a large body of evidence for both its efficacy and safety in the treatment of OIC. Expert opinion: Methylnaltrexone has both subcutaneous injection and oral dosage forms available in the market. The lack of more evidence in specific populations such as pregnant women, pediatrics and elderly still remains. The global consumption of methylnaltrexone shows a projection of increased use since its approval worldwide in 2008.

Improved Bowel Function With Oral Methylnaltrexone Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis

“…These results are similar to those found in studies of subcutaneous methylnaltrexone in adult populations with chronic OIC and pediatric oncology patients. [6][7][8][9]16 Our results support the postoperative use of methylnaltrexone in pediatric populations with acute OIC after PSF with no appreciable side effects.…”

“…Evidence in adult studies has shown methylnaltrexone to be significantly more effective than placebo in treating OIC in patients with cancer and chronic noncancer pain. 6,7 A small randomized placebo-controlled phase 2 study showed promise in the use of subcutaneous methylnaltrexone for the treatment of acute OIC after orthopaedic surgery. 14 In a study of adults with chronic noncancer pain, the efficacy of methylnaltrexone for the treatment of OIC was demonstrated with a comparable safety profile to placebo administration with no evidence of cardiac toxicity or opioid withdrawal symptoms.…”

“…Opiate activation of mu-opioid receptors in the GI tract can result in decreased peristalsis and delayed transit, which can lead to constipation after just a single dose. [5][6][7] Unfortunately, stool softeners, traditional osmotic and stimulating laxatives have been shown to be ineffective in about 50% of patients with OIC. 5 OIC can lead to additional, more invasive, interventions such as enemas and suppositories which negatively impact a child's postoperative experience and prolong hospital length of stay.…”

<p>Naldemedine: A New Option for OIBD</p>

“…It is a quaternary ammonium compound with a positive charge, which restricts its ability to cross the BBB. 24 Naloxegol [Movantik ® (US), Moventig ® (EU), previously NKTR-118] was the first orally administered PAMORA. It is a polyethylene glycol (PEG) derivative of naloxone.…”

“…31 Another minor metabolite, naldemedine-(7R)-7-hydroxide, is formed after oxidation of naldemedine. In the GI tract, enterobacteria cleave the parent compound, starting by reducing its oxadiazole portion and hydrolyzing the remaining amide bond to form benzamidine and naldemedine carboxylic acid 22,24 which are excreted in both urine and feces.…”