Does naltrexone (opioid receptor antagonist) affect folate levels?

Naltrexone Does Not Affect Folate Levels

Based on the available evidence, naltrexone does not appear to affect folate levels. While naltrexone is an opioid receptor antagonist with various clinical applications, there is no evidence in the provided guidelines or research suggesting it impacts folate metabolism.

Mechanism of Action of Naltrexone

• Naltrexone is a pure opioid receptor antagonist that competitively binds to opioid receptors in the central nervous system, blocking the effect of endogenous and exogenous opioids 1
• It is well absorbed orally but undergoes significant first-pass metabolism, with oral bioavailability ranging from 5-40%, leading to greater activity in the gastrointestinal tract than systemically 1
• When combined with bupropion (as in weight management applications), naltrexone antagonizes an inhibitory feedback loop that would otherwise limit bupropion's anorectic properties 1
• The combination activates pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, promoting release of α-melanocyte-stimulating hormone, an anorectic neuropeptide 1

Clinical Applications of Naltrexone

• FDA-approved for the treatment of alcohol and opioid dependence 2
• Used in combination with bupropion for obesity management 1
• Can be administered on daily, twice weekly, or three times weekly regimens depending on clinical needs 3
• May be used to manage opioid-induced constipation when combined with opioid therapy 1

Medications Known to Affect Folate Metabolism

• Several medications are known to affect folate levels, but naltrexone is not among them 4, 5
• Folate antagonists include aminopterin, methotrexate, pyrimethamine, trimethoprim, and triamterene, which inhibit dihydrofolate reductase 4
• Other drugs associated with reduced folate levels include:
  • Anticonvulsants (particularly enzyme-inducing agents like phenobarbital and carbamazepine) 4, 5, 6
  • Antituberculosis drugs 4, 5
  • Alcohol 4
  • Oral contraceptives 4, 5
  • Cholestyramine 5

Important Clinical Considerations

• When prescribing naltrexone, clinicians should be aware of its primary side effects, which include:
  • When used alone: no significant impact on nutritional parameters has been reported 3, 2
  • When used in combination with bupropion: nausea, constipation, headache, dizziness, insomnia, and dry mouth 1
• Naltrexone is contraindicated in patients currently taking opioid medications, as it will precipitate withdrawal 1
• For patients with hepatic impairment, caution is advised as adequate studies have not been conducted in this population 1

Monitoring Recommendations

• While specific folate monitoring is not necessary when using naltrexone, patients on medications known to affect folate levels (anticonvulsants, methotrexate, etc.) should have folate levels checked periodically 4, 5
• For patients on naltrexone, monitoring should focus on:
  • Efficacy for the intended indication (alcohol/opioid dependence, weight management)
  • Adherence to therapy
  • Side effects, particularly gastrointestinal symptoms when used in combination with bupropion 1

In conclusion, while naltrexone has various effects on the central nervous system and gastrointestinal tract, there is no evidence to suggest it impacts folate metabolism or levels. Clinicians should remain vigilant about other medications that do affect folate status.