From the Guidelines
Naltrexone can cause several side effects, including constipation, nausea, headache, xerostomia, and insomnia, as well as more serious but less common side effects such as suicidal thoughts and behaviors, especially in individuals younger than 24 years. According to the most recent and highest quality study 1, the recommended titration schedule for naltrexone-bupropion ER begins with 1 tablet daily in the morning, followed by weekly escalation to 1 tablet twice per day, then 2 tablets in the morning and 1 in the afternoon, until the maintenance dose of 2 tablets twice per day is reached.
Common Side Effects
- Constipation
- Nausea
- Headache
- Xerostomia
- Insomnia
Serious Side Effects
- Suicidal thoughts and behaviors, especially in individuals younger than 24 years
- Liver problems (indicated by yellowing of the skin or eyes, dark urine, or unusual fatigue)
- Severe abdominal pain
- Depression The medication works by blocking opioid receptors in the brain, which explains why it can cause withdrawal symptoms in people who have recently used opioids. Most side effects are mild to moderate and often diminish over time as the body adjusts to the medication. Patients should be opioid-free for 7-10 days before starting naltrexone to avoid precipitating withdrawal symptoms. Vital signs should be monitored in patients treated with naltrexone-bupropion ER and should be avoided in patients with uncontrolled hypertension 1.
From the FDA Drug Label
While extensive clinical studies evaluating the use of naltrexone hydrochloride in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone hydrochloride use, placebo-controlled studies employing up to five-fold higher doses of naltrexone hydrochloride (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that naltrexone hydrochloride causes hepatocellular injury in a substantial proportion of patients exposed at higher doses Reported Adverse Events Naltrexone hydrochloride has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be free of opioids for more than 7 to 10 days A number of alternative dosing patterns have been recommended to try to reduce the frequency of these complaints In an open label safety study with approximately 570 individuals with alcoholism receiving naltrexone hydrochloride, the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%) The following adverse reactions have been reported both at baseline and during the naltrexone hydrochloride clinical trials in opioid addiction at an incidence rate of more than 10%: Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache
The side effects of naltrexone include:
- Hepatocellular injury at higher doses
- Nausea (10%)
- Headache (7%)
- Dizziness (4%)
- Nervousness (4%)
- Fatigue (4%)
- Insomnia (3%)
- Vomiting (3%)
- Anxiety (2%)
- Somnolence (2%)
- Difficulty sleeping
- Abdominal pain/cramps
- Low energy
- Joint and muscle pain 2
From the Research
Naltrexone Side Effects
The side effects of naltrexone can vary depending on the individual and the condition being treated. Some common side effects include:
- Nausea 3, 4
- Headache 3
- Agitation 5
- Altered level of consciousness 5
- Vomiting 5
- Abdominal pain 5
- Diarrhea 5
- Bone and muscle pain 5
- Tachycardia 5
- Dilated pupils 5
Factors Influencing Side Effects
Certain factors can influence the likelihood and severity of naltrexone side effects, such as:
- Dose of naltrexone 5
- Duration of abstinence from alcohol or opioids 4
- Intensity of alcohol or opioid use 4
- Age and gender 4
- Presence of comorbid medical or psychiatric conditions 3
Management of Side Effects
While naltrexone is generally well-tolerated, some side effects can be managed with appropriate care. For example:
- Nausea can be a significant side effect, particularly in the first week of treatment 4
- Agitation can be a challenging aspect of withdrawal to manage, especially in opioid-dependent patients 5
- Low-dose naltrexone may have a paradoxical effect, increasing endogenous opioids and potentially reducing inflammation and discomfort 6