Naltrexone Does Not Directly Cause Dehydration
Naltrexone itself does not cause dehydration as a direct pharmacological effect. The FDA label and clinical guidelines do not list dehydration as a recognized adverse effect of naltrexone therapy 1.
Common Side Effects of Naltrexone
The most frequently reported adverse effects of naltrexone include 2:
- Nausea (most common gastrointestinal complaint)
- Constipation
- Headache
- Dizziness
- Insomnia
- Dry mouth
In a retrospective survey of 206 patients treated with low-dose naltrexone for gastrointestinal disorders, 61.2% experienced side effects, with neurological complaints (58 patients) and gastrointestinal symptoms (32 patients) being most common—but dehydration was not reported 3.
Safety in Patients with Renal Impairment
Caution is recommended when administering naltrexone to patients with renal impairment, but this relates to drug accumulation rather than dehydration risk 1:
- Naltrexone and its primary metabolite (6-β-naltrexol) are excreted primarily by the kidney (53-79% of the dose) 1
- In hemodialysis patients with end-stage renal disease, peak plasma concentrations (Cmax) are significantly higher (255±117 ng/mL) compared to healthy subjects (9-44 ng/mL) due to decreased hepatic first-pass metabolism and renal impairment 4
- However, hemodialysis has little effect on naltrexone blood levels, with only 1.27 mg removed during a 4-hour dialysis session, and dosage adjustment is generally not required 4
Safety in Patients with Liver Disease
Naltrexone can be safely used in patients with liver disease, including those with compensated and decompensated cirrhosis, without causing dehydration 5, 6:
- In a retrospective cohort of 160 patients with alcohol use disorder (100 with liver disease, 47 with cirrhosis), liver enzyme levels actually decreased after naltrexone prescription compared to before 5
- A large study of 3,285 patients with cirrhosis initiated on naltrexone found no drug-induced liver injury using RUCAM scoring, and no deaths or new decompensations were attributed to naltrexone 6
- Naltrexone bioavailability increases 5-fold in compensated cirrhosis and 10-fold in decompensated cirrhosis due to reduced first-pass metabolism, but this does not translate to dehydration risk 1, 7
Clinical Context: Dehydration in Special Populations
While naltrexone itself does not cause dehydration, clinicians should be aware of dehydration as a potential precipitating factor for other complications in vulnerable populations:
- In cancer patients with delirium, dehydration may be a precipitating factor, and clinically assisted hydration may be trialed on a case-by-case basis 2
- In patients with hepatocellular carcinoma and cirrhosis, NSAIDs (not naltrexone) are associated with decompensation of ascites and nephrotoxicity and should be avoided 2
Key Clinical Pitfall to Avoid
Do not confuse naltrexone with naloxone or assume opioid antagonists cause dehydration. The gastrointestinal side effects of naltrexone (nausea, constipation) do not include diarrhea or fluid loss mechanisms that would lead to dehydration 2, 3. If a patient on naltrexone develops dehydration, investigate alternative causes such as inadequate fluid intake, concurrent medications, or underlying medical conditions rather than attributing it to naltrexone therapy.