Usage
Naltrexone is primarily prescribed for the treatment of alcohol dependence and opioid use disorder. It belongs to the pharmacological classification of opioid antagonists. It works by blocking opioid receptors in the brain, thereby reducing the pleasurable effects associated with alcohol and opioids, and diminishing cravings.
Alternate Names
Naltrexone is also known as Naltrexone Hydrochloride. Popular brand names include ReVia (oral formulation) and Vivitrol (injectable extended-release formulation).
How It Works
Pharmacodynamics: Naltrexone competitively binds to opioid receptors (mu, kappa, and delta), blocking the effects of both endogenous opioids and exogenous opioid drugs. This reduces the reinforcing effects of these substances, leading to decreased cravings and relapse potential. For alcohol dependence, this action is believed to work, in part, by affecting the endogenous opioid system related to alcohol consumption.
Pharmacokinetics:
- Absorption: Oral naltrexone is readily absorbed from the gastrointestinal tract, but undergoes significant first-pass metabolism in the liver, resulting in low bioavailability. The extended-release injectable formulation bypasses first-pass metabolism, providing sustained release of naltrexone.
- Metabolism: Naltrexone is primarily metabolized in the liver to its major active metabolite, 6-β-naltrexol, and other minor metabolites. The CYP450 enzyme system, particularly CYP2C9, plays a role.
- Elimination: Both naltrexone and its metabolites are primarily excreted in the urine, with a small amount eliminated in feces. The elimination half-life of oral naltrexone is approximately 4 hours, while the half-life of 6-β-naltrexol is around 13 hours. The extended-release formulation has an elimination half-life of 5-10 days.
Dosage
Standard Dosage
Adults:
- Alcohol Dependence: Oral: 50 mg once daily. Injectable: 380 mg intramuscularly once every 4 weeks.
- Opioid Use Disorder: Oral: Initial dose of 25 mg; if tolerated, increase to 50 mg once daily. Injectable: 380 mg intramuscularly once every 4 weeks.
Children:
The safety and efficacy of naltrexone in children younger than 18 years have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate carefully, monitoring for adverse effects.
- Patients with Renal Impairment: Dose adjustment may be necessary in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Naltrexone is contraindicated in patients with acute hepatitis or liver failure. Use with caution in patients with mild to moderate hepatic impairment. Dose reduction may be required.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease or seizure disorders.
Clinical Use Cases
Naltrexone is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. While injectable naltrexone has been used for anesthesia-assisted rapid opioid detoxification (AAROD), this procedure is associated with significant risks and is no longer generally recommended. Naloxone is typically used to reverse opioid overdose in these settings.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient response, tolerability, and the presence of renal or hepatic impairment. Therapeutic drug monitoring may be useful in optimizing dosage.
Side Effects
Common Side Effects
Nausea, headache, dizziness, insomnia, anxiety, abdominal pain/cramps, vomiting, decreased appetite, tiredness.
Rare but Serious Side Effects
Hepatotoxicity (especially with high doses), suicidal ideation, allergic reactions (including anaphylaxis), injection site reactions (with injectable formulation).
Long-Term Effects
Potential long-term effects include liver damage (with chronic high doses) and opioid dependence relapse if naltrexone is discontinued prematurely.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe hepatotoxicity, anaphylaxis, and precipitated opioid withdrawal (in patients with opioid dependence who have not adequately detoxified).
Contraindications
Absolute contraindications: Current or recent opioid use (within 7-10 days), acute hepatitis or liver failure, hypersensitivity to naltrexone.
Relative contraindications: Significant hepatic impairment, current opioid dependence (without detoxification).
Drug Interactions
- Opioids: Naltrexone blocks the effects of opioids. Concomitant use can precipitate opioid withdrawal in opioid-dependent individuals.
- Thioridazine: Concomitant use may cause increased drowsiness and sedation.
- Drugs metabolized by CYP2C9: Naltrexone may inhibit CYP2C9 activity, potentially affecting the metabolism of other drugs metabolized by this enzyme.
- Alcohol: While naltrexone is used to treat alcohol dependence, concurrent use of alcohol and naltrexone may increase the risk of liver damage.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C. Naltrexone should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: It is unknown if naltrexone is excreted in human milk. Caution is advised when administering naltrexone to breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: Opioid receptor antagonist.
- Side Effects: Nausea, headache, dizziness, hepatotoxicity (rare).
- Contraindications: Current opioid use, acute hepatitis/liver failure.
- Drug Interactions: Opioids, thioridazine.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: 50 mg/day orally or 380 mg/month IM.
- Monitoring Parameters: Liver function tests, signs of opioid withdrawal.
Popular Combinations
Naltrexone is sometimes used in combination with bupropion for weight management (brand name Contrave).
Precautions
- General Precautions: Assess for opioid use and liver function before starting naltrexone. Monitor for hepatotoxicity and precipitated withdrawal.
- Specific Populations: Pregnant women and breastfeeding mothers should use with caution. Use with caution in the elderly and those with renal impairment.
- Lifestyle Considerations: Patients should avoid opioid-containing medications (including cough syrups and antidiarrheal medications).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Naltrexone?
A: For adults with alcohol dependence or opioid use disorder, the typical oral dose is 50 mg once daily after a starting dose of 25 mg initially to check tolerance. The extended-release injectable formulation is 380 mg intramuscularly every 4 weeks.
Q2: How does Naltrexone differ from Naloxone?
A: Both are opioid antagonists, but naloxone is primarily used for the emergency treatment of opioid overdose, while naltrexone is used for long-term treatment of opioid use disorder and alcohol dependence.
Q3: Can Naltrexone be used in patients with liver disease?
A: Naltrexone is contraindicated in patients with acute hepatitis or liver failure. Caution and dose adjustments are required in patients with mild to moderate hepatic impairment.
Q4: What are the most common side effects of Naltrexone?
A: Nausea, headache, dizziness, insomnia, anxiety, and abdominal pain/cramps are among the most commonly reported side effects.
Q5: Can patients on Naltrexone take opioid medications for pain?
A: No, naltrexone blocks the effects of opioid pain medications. Patients needing analgesia may require higher doses of non-opioid analgesics or regional anesthesia.
Q6: How long should patients take Naltrexone?
A: The duration of treatment varies depending on the individual and the condition being treated. Many individuals benefit from long-term naltrexone therapy to maintain abstinence.
Q7: What should be done if a patient on naltrexone experiences precipitated opioid withdrawal?
A: Supportive care, including management of symptoms like nausea, vomiting, muscle aches, and anxiety, should be provided. Symptoms typically subside within a few days.
Q8: Are there any drug interactions I should be aware of with naltrexone?
A: Avoid concomitant use of opioids, and use caution with drugs that affect liver function or are metabolized by CYP2C9.
Q9: Can naltrexone be used in pregnant or breastfeeding women?
A: It should be used during pregnancy only if the potential benefit outweighs the risk. Caution is advised during breastfeeding due to the potential for drug excretion in breast milk.
Q10: How does naltrexone help with alcohol dependence?
A: It’s thought to reduce the pleasurable effects and craving associated with alcohol, potentially by modulating the endogenous opioid system involved in alcohol consumption.
