Understanding MOVANTIK (Naloxegol) and OIC
MOVANTIK (naloxegol) is a prescription medication for opioid-induced constipation (OIC) in adults with chronic non-cancer pain. OIC is a common side effect of opioid use, resulting from opioids binding to receptors in the GI tract. MOVANTIK is designed to block these effects in the gut without impacting the pain relief provided by opioids in the brain.
The Core Question: Why Was MOVANTIK a Controlled Substance?
MOVANTIK was initially classified as a Schedule II controlled substance when it was approved by the FDA in September 2014. This category includes substances with a high potential for abuse. The reason for this initial scheduling was its structural resemblance to noroxymorphone, which is a controlled substance derived from opium. According to the Controlled Substances Act, a drug structurally related to a controlled substance may be placed in the same schedule.
The Science Behind its Mechanism: Why Abuse Potential is Low
MOVANTIK is a Peripherally Acting Mu-Opioid Receptor Antagonist (PAMORA). Its active ingredient, naloxegol, is related to naloxone, an opioid antagonist. Naloxegol is modified through PEGylation, attaching a polyethylene glycol (PEG) chain to the molecule. This modification makes the molecule larger, significantly reducing its ability to cross the blood-brain barrier (BBB). It is also actively pumped out of the brain by the P-glycoprotein (P-gp) transporter. Because it primarily acts outside the brain, naloxegol does not cause euphoria and has a low potential for abuse, while still blocking opioid effects in the GI tract.
The Path to De-scheduling: From Schedule II to Non-Controlled
Despite the initial Schedule II classification based on structure, the FDA-approved labeling noted no risk of abuse or dependency for MOVANTIK. AstraZeneca, the manufacturer, petitioned the DEA for de-scheduling. The DEA, in consultation with the HHS, reviewed the data, which confirmed naloxegol's minimal BBB penetration and low abuse potential. This led the HHS to recommend removing it from the controlled substances list. Consequently, the DEA issued a final rule, effective January 23, 2015, removing naloxegol from the Controlled Substances Act schedules. Thus, MOVANTIK is no longer a controlled substance.
Comparison of OIC Treatment Approaches
| Treatment | Mechanism of Action | Administration | Key Characteristic |
|---|---|---|---|
| MOVANTIK (naloxegol) | Peripherally Acting Mu-Opioid Receptor Antagonist (PAMORA) | Oral tablet | PEGylated structure limits entry into the central nervous system. |
| RELISTOR (methylnaltrexone) | Peripherally Acting Mu-Opioid Receptor Antagonist (PAMORA) | Oral tablet or injection | Does not cross the blood-brain barrier, preventing opioid withdrawal symptoms. |
| NALOXONE | Systemic Opioid Antagonist | Injection, nasal spray | Crosses the blood-brain barrier; used for overdose reversal, not routinely for OIC as it can reverse analgesia. |
| LUBIPROSTONE (Amitiza) | Chloride Channel Activator | Oral capsule | Increases intestinal fluid secretion to soften stool and improve transit; not an opioid antagonist. |
| OTC LAXATIVES (e.g., Senna, Miralax) | Stimulant or Osmotic | Varies (oral) | General-purpose constipation treatments; often used first but may be insufficient for OIC. |
Potential Side Effects and Risks of MOVANTIK
Common side effects of MOVANTIK include abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache. Severe abdominal pain and diarrhea have been reported, sometimes requiring hospitalization. Symptoms of opioid withdrawal may occur, particularly in patients with a compromised blood-brain barrier or those on methadone. Rare cases of gastrointestinal perforation have been reported with PAMORAs, making MOVANTIK unsuitable for patients with known or suspected GI obstruction.
Conclusion: A Unique Regulatory Journey
MOVANTIK's journey through drug scheduling is notable. It was initially deemed a Schedule II controlled substance due to its chemical heritage from an opium alkaloid. However, compelling evidence showed its design prevents central nervous system penetration, thus eliminating abuse potential. This led the DEA to de-schedule the drug in 2015, confirming its status as a non-controlled medication for OIC.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult with a healthcare professional for any medical concerns or before starting or stopping any medication.
