Naltrexone
Opioid antagonist for the treatment of opioid and alcohol dependence
Naltrexone is a prescription opioid antagonist medication used as part of comprehensive treatment programs for opioid and alcohol dependence. It works by blocking opioid receptors in the brain, which eliminates the euphoric effects of opioids and reduces cravings for alcohol. Naltrexone does not cause dependence and has no addictive potential. This article covers uses, dosage, side effects, drug interactions, and important safety information based on international clinical guidelines from the WHO, EMA, FDA, and NICE.
Quick Facts: Naltrexone
Key Takeaways
- Naltrexone blocks opioid receptors in the brain, preventing the euphoric effects of opioids and reducing alcohol cravings.
- You must be opioid-free for at least 7–10 days before starting naltrexone to avoid precipitating severe withdrawal symptoms.
- Naltrexone does not cause addiction or dependence — it is a pure antagonist with no reinforcing or euphoric properties.
- Regular liver function monitoring is recommended as hepatotoxicity has been reported, particularly at higher doses.
- Treatment typically lasts at least 3 months and should always be combined with psychosocial support or a comprehensive rehabilitation program.
What Is Naltrexone and What Is It Used For?
Naltrexone hydrochloride belongs to a class of medications known as opioid antagonists — drugs that work on the central nervous system to treat substance use disorders. The active substance competitively binds to opioid receptors, primarily the mu-opioid receptor, in the brain and throughout the body. This binding effectively blocks the receptor without activating it, which means naltrexone prevents opioids from producing their characteristic effects without producing any euphoria or psychoactive effects of its own.
Opioid Dependence Treatment
In the treatment of opioid dependence, naltrexone is used as part of a comprehensive rehabilitation program to help individuals maintain abstinence after they have completed detoxification. When a person taking naltrexone uses an opioid such as heroin, morphine, or oxycodone, the drug's euphoric and reinforcing effects are blocked. The person will not experience the "high" they previously felt, which helps to break the cycle of addiction. This pharmacological blockade significantly reduces the motivation to use opioids, as the rewarding experience is eliminated.
It is critical to understand that naltrexone should only be started after the patient has been fully detoxified from opioids. The patient must be opioid-free for a minimum of 7–10 days before initiating treatment. Starting naltrexone while opioids are still present in the body will precipitate acute and potentially severe withdrawal symptoms, which can be extremely distressing and medically dangerous.
Alcohol Dependence Treatment
For alcohol dependence, naltrexone works through a different but related mechanism. Alcohol consumption stimulates the release of endogenous opioids (endorphins) in the brain, which contribute to the pleasurable and reinforcing effects of drinking. By blocking opioid receptors, naltrexone reduces the rewarding sensation associated with alcohol consumption, thereby decreasing cravings and helping patients maintain abstinence or reduce their drinking.
Clinical trials and systematic reviews, including Cochrane Reviews, have demonstrated that naltrexone significantly reduces the rate of heavy drinking days and the overall amount of alcohol consumed. According to NICE guidelines (CG115), naltrexone is recommended as a pharmacological treatment option for patients with moderate to severe alcohol dependence who are motivated to achieve abstinence or significantly reduce their alcohol intake. The medication is most effective when combined with psychosocial interventions such as cognitive behavioral therapy (CBT), motivational interviewing, or 12-step facilitation programs.
Important: Naltrexone Does Not Cause Dependence
Unlike some other medications used in addiction treatment, such as methadone (a full opioid agonist) or buprenorphine (a partial agonist), naltrexone is a pure antagonist. This means it produces no opioid-like effects, has no abuse potential, and does not lead to physical dependence. Stopping naltrexone does not cause withdrawal symptoms. This fundamental characteristic makes naltrexone a distinct pharmacological approach to managing substance use disorders.
Naltrexone is available under several brand names internationally, including Naltrexone POA Pharma, Naltrexone Accord, Naltrexon Molteni, ReVia, and Depade (oral tablets). An extended-release injectable formulation is marketed as Vivitrol. Generic formulations are widely available.
What Should You Know Before Taking Naltrexone?
Before starting naltrexone, your healthcare provider will conduct a thorough evaluation to ensure the medication is safe and appropriate for you. This assessment typically includes a physical examination, a review of your medical history, laboratory tests (especially liver function tests), and confirmation that you are opioid-free. Understanding the contraindications, warnings, and precautions associated with naltrexone is essential for safe and effective use.
Contraindications
You should not take naltrexone if any of the following apply to you:
- Allergy to naltrexone — If you are allergic to naltrexone hydrochloride or any other ingredient in the formulation (including lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal anhydrous silica, or magnesium stearate).
- Severe kidney problems — Naltrexone and its metabolites are primarily eliminated through the kidneys. Severe renal impairment may lead to dangerous accumulation of the drug.
- Severe liver problems or acute liver infection — Since naltrexone is metabolized by the liver, severe hepatic impairment significantly increases the risk of hepatotoxicity.
- Current opioid dependence — If you are currently physically dependent on opioids, taking naltrexone will precipitate severe withdrawal symptoms.
- Positive opioid urine test — If opioids are detected in your urine, treatment must not be started.
- Withdrawal symptoms after naloxone challenge — If you experience withdrawal after a naloxone injection test, you are not yet ready for naltrexone therapy.
- Current use of opioid-containing medications — Including certain cough medicines, antidiarrheal agents (such as codeine-containing preparations), and opioid analgesics.
- Current methadone use — Methadone must be completely discontinued and cleared from the body before starting naltrexone.
Do not attempt to overcome the opioid-blocking effect of naltrexone by taking large doses of opioids. This is extremely dangerous. While naltrexone blocks the normal effects of opioids, taking very high doses to try to override this block can cause life-threatening respiratory depression and cardiovascular collapse. Additionally, after naltrexone treatment ends, your opioid tolerance will be significantly reduced. Even previously tolerated doses of opioids could cause fatal overdose.
Warnings and Precautions
Speak with your doctor or pharmacist before taking naltrexone. Several important precautions should be considered:
Liver function monitoring: Liver problems are relatively common among individuals with opioid dependence. Naltrexone is processed through the liver, and hepatotoxicity has been reported, particularly with doses exceeding the recommended 50 mg daily. Your doctor will perform liver function tests before treatment begins and at regular intervals during therapy. If you experience symptoms such as abdominal pain lasting more than a few days, white or pale stools, dark urine, or yellowing of the eyes or skin, stop taking naltrexone immediately and contact your doctor.
Emergency medical treatment: You must inform all healthcare providers treating you that you take naltrexone. In emergency situations requiring anesthesia or pain relief, non-opioid alternatives should be used whenever possible. If opioid-based anesthetics are absolutely necessary, higher doses than usual may be required, and you may be more susceptible to respiratory depression and circulatory problems. This requires careful monitoring in a clinical setting.
Medical identification: It is advisable to carry a medical alert card or bracelet stating that you are taking naltrexone, so that emergency medical personnel can make appropriate treatment decisions.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using naltrexone. The safety of naltrexone during pregnancy has not been fully established in humans, though animal studies have not shown clear teratogenic effects at therapeutic doses. The decision to use naltrexone during pregnancy should involve careful consideration of the potential benefits versus risks, weighing the dangers of untreated substance use disorder against the unknown risks of the medication.
It is not fully established whether naltrexone passes into human breast milk. Because the safety of naltrexone in newborns and infants has not been demonstrated, breastfeeding is generally not recommended during naltrexone treatment. Your doctor can help you weigh the benefits of breastfeeding against the potential risks of medication exposure.
Children and Adolescents
Naltrexone is not recommended for use in children and adolescents under 18 years of age due to insufficient clinical data regarding safety and efficacy in this age group. Safe use in pediatric patients has not been established.
Elderly Patients
There is limited clinical data regarding the safety and efficacy of naltrexone in elderly patients. If prescribed for older adults, treatment should be initiated with caution, with careful monitoring of liver and kidney function.
Driving and Operating Machinery
Naltrexone may impair the mental and physical abilities required for potentially hazardous tasks such as driving vehicles or operating machinery. Side effects including dizziness, drowsiness, and impaired concentration have been reported. You should assess your own ability to perform these tasks safely and discuss any concerns with your doctor.
Naltrexone film-coated tablets contain lactose monohydrate as an excipient. If you have been told by your doctor that you have an intolerance to certain sugars, contact your healthcare provider before taking this medicine.
How Does Naltrexone Interact with Other Drugs?
Drug interactions are an important consideration when taking naltrexone. Because naltrexone is a potent opioid receptor antagonist, its primary interactions involve opioid-containing medications. However, other interactions should also be considered. Always inform your doctor or pharmacist about all medications you are currently taking, have recently taken, or plan to take, including over-the-counter products and herbal supplements.
Major Interactions
The most clinically significant interactions involve opioid-containing medications. Naltrexone will block the therapeutic effects of these drugs, potentially leaving pain untreated or causing withdrawal in opioid-dependent patients. The following table summarizes the most important drug interactions:
| Drug / Drug Class | Interaction Type | Clinical Effect | Recommendation |
|---|---|---|---|
| Opioid analgesics (morphine, codeine, oxycodone, fentanyl, tramadol) | Pharmacodynamic antagonism | Complete blockade of opioid analgesic effect; risk of precipitated withdrawal | Contraindicated. Use non-opioid alternatives |
| Methadone | Pharmacodynamic antagonism | Severe precipitated withdrawal; potentially life-threatening | Contraindicated. Must discontinue methadone and wait 10–14 days |
| Buprenorphine (Suboxone, Subutex) | Pharmacodynamic antagonism | Precipitated withdrawal; blocked analgesic/agonist effect | Contraindicated. Must discontinue and wait 7–10 days |
| Opioid-containing cough medicines (codeine, dextromethorphan at high doses) | Pharmacodynamic antagonism | Blocked antitussive effect | Avoid. Use non-opioid cough remedies |
| Opioid-containing antidiarrheals (diphenoxylate, loperamide at supratherapeutic doses) | Pharmacodynamic antagonism | Reduced antidiarrheal effect at high doses | Caution. Loperamide at standard doses generally acceptable |
Emergency Situations
In rare emergency situations where opioid analgesia is absolutely necessary despite naltrexone treatment, the management must be carried out in a clinical setting with continuous monitoring. The dose of opioid required for pain relief may be substantially higher than usual due to receptor blockade. This significantly increases the risk of respiratory depression, which may be more severe and prolonged than expected. A physician experienced in managing opioid overdose and respiratory support must oversee such treatment.
Non-Opioid Medications
Naltrexone does not block the effects of non-opioid pain medications. The following common analgesics can be used safely during naltrexone treatment:
- Paracetamol (acetaminophen) — safe to use for mild to moderate pain and fever
- Ibuprofen and other NSAIDs — effective for pain and inflammation
- Aspirin (acetylsalicylic acid) — safe for pain relief and cardiovascular prevention
- Local anesthetics — can be used normally for dental and minor surgical procedures
Food and Drink
The absorption and efficacy of naltrexone are not significantly affected by food or drink. The tablets can be taken with or without meals. However, since naltrexone is prescribed for alcohol dependence, patients should be counseled to avoid alcohol as part of their overall treatment plan.
What Is the Correct Dosage of Naltrexone?
Always take naltrexone exactly as your doctor or pharmacist has instructed. Do not change your dose without consulting your healthcare provider. The dosage information below represents standard clinical practice based on international guidelines, but individual dosing may vary based on your specific clinical situation.
Adults
Standard Oral Dosing
Starting dose: 25 mg (half a tablet) once daily for the first few days, to assess tolerability.
Maintenance dose: 50 mg (one tablet) once daily.
Administration: Swallow the tablet whole with a small amount of water. May be taken with or without food.
Duration: Typically at least 3 months, though treatment may continue longer as determined by your physician. Naltrexone should always be used as part of a comprehensive treatment program that includes psychosocial support.
| Patient Group | Starting Dose | Maintenance Dose | Notes |
|---|---|---|---|
| Adults (opioid dependence) | 25 mg/day | 50 mg/day | Must be opioid-free 7–10 days. Naloxone challenge test recommended. |
| Adults (alcohol dependence) | 25 mg/day | 50 mg/day | Combine with psychosocial support. Minimum 3 months. |
| Elderly | 25 mg/day (with caution) | 50 mg/day | Limited data. Monitor liver and kidney function closely. |
| Children & adolescents (<18 years) | Not recommended | Not recommended | Insufficient safety and efficacy data in pediatric patients. |
| Renal impairment (mild–moderate) | 25 mg/day | 50 mg/day (with monitoring) | Dose adjustment may not be needed. Monitor for accumulation. |
| Hepatic impairment (mild–moderate) | 25 mg/day | As tolerated (with monitoring) | Regular liver function tests required. Contraindicated in severe impairment. |
Pre-Treatment Requirements
Before starting naltrexone for opioid dependence, several important steps must be completed:
- Opioid-free period: You must not have taken any opioids for at least 7–10 days. This includes street drugs, prescription pain medications, and opioid substitution therapies.
- Urine drug screening: Your doctor may test your urine to confirm the absence of opioids.
- Naloxone challenge test: In some cases, your doctor may administer a small dose of naloxone (another opioid antagonist with a shorter duration of action) to check for precipitated withdrawal before starting naltrexone.
- Liver function assessment: Baseline liver function tests should be performed.
Missed Dose
If you forget to take a dose of naltrexone, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten one. Missing occasional doses may temporarily reduce the protective blocking effect, so consistent daily dosing is important for optimal treatment outcomes.
Overdose
If you take more naltrexone than prescribed, or if a child accidentally ingests the medication, contact your doctor, emergency department, or poison control center immediately for assessment and advice. While naltrexone has a relatively wide safety margin, overdose may cause nausea, abdominal pain, drowsiness, and dizziness. Supportive care and symptomatic treatment should be provided under medical supervision.
Stopping Treatment
If you are considering stopping naltrexone before the agreed treatment period has ended, always discuss this with your doctor first. Premature discontinuation may increase the risk of relapse. It is also crucial to understand that after stopping naltrexone, your tolerance to opioids will be significantly reduced. This means that doses of opioids that you could previously tolerate may now cause life-threatening overdose.
What Are the Side Effects of Naltrexone?
Like all medications, naltrexone can cause side effects, although not everyone experiences them. The side effects are categorized below by their frequency of occurrence, based on clinical trial data and post-marketing surveillance. Most side effects are mild to moderate in severity and tend to diminish after the first few weeks of treatment as your body adjusts to the medication.
- Abdominal pain lasting more than a few days
- White or clay-colored stools
- Dark urine
- Yellowing of the eyes or skin (jaundice)
These may be signs that your liver is not functioning properly.
- Swelling of the face, lips, or tongue
- Skin rash or hives
- Difficulty breathing
Very Common
- Difficulty sleeping (insomnia)
- Anxiety or nervousness
- Stomach cramps and abdominal pain
- Nausea and/or feeling unwell
- Lack of energy or weakness (asthenia)
- Joint and/or muscle pain
- Headache
- Rapid or irregular heartbeat
- Restlessness
Common
- Irritability and mood swings
- Increased energy or feeling depressed
- Dizziness and lightheadedness
- Chills and increased sweating
- Increased tearing (lacrimation)
- Rapid pulse or palpitations
- ECG changes and chest pain
- Diarrhea or constipation
- Skin rash
- Difficulty urinating (urinary retention)
- Delayed ejaculation or erectile difficulties
- Loss of appetite and thirst
Uncommon
- Hallucinations, confusion, or paranoia
- Depression or disorientation
- Nightmares and abnormal dreams
- Decreased sex drive
- Tremors and drowsiness
- Blurred vision and light sensitivity
- Ear pain, tinnitus (ringing in ears)
- Blood pressure fluctuations and hot flushes
- Nasal congestion, sneezing, coughing
- Shortness of breath and yawning
- Dry mouth and increased salivation
- Flatulence and hemorrhoids
- Liver problems (including hepatitis) and elevated liver enzymes
- Itching, acne, and hair loss
- Increased urination and bladder inflammation
- Changes in appetite, weight loss, or weight gain
- Fever, cold extremities, or feeling hot
Rare to Very Rare
- Suicidal thoughts or suicidal behavior
- Bleeding disorders
- Speech difficulties
- Euphoria (feeling of elation)
- Rhabdomyolysis (skeletal muscle damage)
- Severe skin reactions
Liver Function Monitoring
Naltrexone can affect liver function. Your doctor will typically perform blood tests to check your liver enzymes before starting treatment and at regular intervals during therapy. Hepatotoxicity appears to be dose-related, with a greater risk observed at doses exceeding the recommended 50 mg daily. Patients with pre-existing liver conditions, including hepatitis B or C (which are more prevalent among individuals with opioid use disorders), require particularly careful monitoring.
Mental Health Monitoring
Although rare, naltrexone has been associated with depressive symptoms and, in very rare cases, suicidal ideation. Patients with a history of depression or other mental health conditions should be monitored closely during treatment. If you experience worsening mood, persistent feelings of sadness, or any thoughts of self-harm, contact your healthcare provider immediately.
It is important to report suspected side effects after the medicine has been authorized. This allows continuous monitoring of the medication's benefit-risk balance. Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national pharmacovigilance authority (e.g., FDA MedWatch in the US, Yellow Card Scheme in the UK, or corresponding agencies in other countries).
How Should You Store Naltrexone?
Proper storage of naltrexone is important to maintain its effectiveness and safety. The following guidelines will help ensure your medication remains in optimal condition throughout the treatment period.
- Keep out of sight and reach of children — Store the medication in a secure location where children cannot access it.
- Expiration date — Do not use naltrexone after the expiration date stated on the carton and blister pack. The expiration date refers to the last day of that month.
- Storage conditions — No special storage conditions are required for this medicine. Store at room temperature away from excessive heat and moisture.
- Disposal — Do not dispose of medications via wastewater or household waste. Return unused or expired medication to a pharmacy for proper disposal. This helps protect the environment.
What Does Naltrexone Contain?
Active Ingredient
Each film-coated tablet contains 50 mg naltrexone hydrochloride as the active substance.
Inactive Ingredients (Excipients)
Tablet core: Lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal anhydrous silica, magnesium stearate.
Film coating: Hypromellose (E464), macrogol 400, polysorbate 80 (E433), yellow iron oxide (E172), red iron oxide (E172), titanium dioxide (E171).
Appearance and Pack Sizes
Naltrexone tablets are yellow, oval, biconvex, film-coated tablets with a score line on one side and flat on the other. The tablet can be divided into two equal doses of 25 mg each. They are available in blister packs containing 7, 14, 28, 30, 50, or 56 tablets. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About Naltrexone
Naltrexone is an opioid antagonist used to treat two primary conditions: opioid dependence (as part of a comprehensive treatment program to help individuals maintain abstinence after detoxification) and alcohol dependence (to reduce cravings and support abstinence from alcohol). It works by blocking opioid receptors in the brain, preventing the rewarding and euphoric effects of opioids and modulating the brain's response to alcohol. Naltrexone is always used alongside psychosocial support such as counseling or rehabilitation programs.
Naltrexone begins blocking opioid receptors within 1–2 hours of oral administration. For opioid dependence, the blocking effect is immediate once therapeutic levels are reached. For alcohol dependence, many patients report reduced cravings within the first week, but the full therapeutic benefit typically develops over several weeks of consistent use. Treatment is usually recommended for at least 3 months, though longer courses may be advised by your physician.
No, you must not take naltrexone while currently using opioids or opioid-containing medications. This includes prescription pain medications, some cough medicines, certain antidiarrheal agents, methadone, and buprenorphine. You must be completely opioid-free for at least 7–10 days before starting naltrexone. Taking naltrexone while opioid-dependent will trigger severe and potentially dangerous withdrawal symptoms. Your doctor may perform a naloxone challenge test or urine screening to confirm you are opioid-free before beginning treatment.
No, naltrexone does not cause addiction or physical dependence. Unlike some other medications used in addiction treatment (such as methadone or buprenorphine), naltrexone is a pure antagonist with no agonist activity at opioid receptors. It produces no euphoria, has no reinforcing properties, and stopping it does not cause withdrawal symptoms. This makes it a fundamentally different pharmacological approach to treating substance use disorders.
The most common side effects of naltrexone (affecting more than 1 in 10 people) include difficulty sleeping, anxiety or nervousness, stomach cramps and abdominal pain, nausea, lack of energy, joint and muscle pain, headache, and restlessness. These side effects are generally mild to moderate and often improve after the first few weeks of treatment. Serious but less common side effects include liver problems — signs include abdominal pain lasting more than a few days, dark urine, or yellowing of the eyes, which require immediate medical attention.
While naltrexone alone is not specifically approved for weight loss, a combination product containing naltrexone and bupropion (marketed as Contrave in the US and Mysimba in Europe) has been approved for weight management in some countries. Standard naltrexone (50 mg) is approved only for opioid and alcohol dependence. Any off-label use should only be considered under strict medical supervision. Low-dose naltrexone (LDN), typically 1.5–4.5 mg, is also being investigated for various conditions including autoimmune diseases, but this is not yet supported by sufficient clinical evidence for routine clinical use.
References & Sources
This article is based on the following peer-reviewed sources, international guidelines, and regulatory documents:
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2023.
- European Medicines Agency (EMA). Summary of Product Characteristics: Naltrexone Hydrochloride. EMA; 2024.
- U.S. Food and Drug Administration (FDA). FDA-Approved Labeling: Naltrexone Hydrochloride Tablets. FDA; 2024.
- Røsner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database of Systematic Reviews. 2010;(12):CD001867. Updated 2018. doi:10.1002/14651858.CD001867.pub4
- National Institute for Health and Care Excellence (NICE). Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk) and alcohol dependence. Clinical guideline CG115. NICE; 2011 (updated 2023).
- Joint Formulary Committee. British National Formulary (BNF). London: BMJ Group and Pharmaceutical Press; 2024. Naltrexone hydrochloride monograph.
- Substance Abuse and Mental Health Services Administration (SAMHSA). Medications for Opioid Use Disorder: Treatment Improvement Protocol (TIP) 63. Rockville, MD: SAMHSA; 2021.
- Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews. 2011;(4):CD001333. doi:10.1002/14651858.CD001333.pub4
- Anton RF, O'Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study. JAMA. 2006;295(17):2003-2017. doi:10.1001/jama.295.17.2003
- Krupitsky EM, Blokhina EA. Long-acting injectable naltrexone for the treatment of opioid dependence. Current Opinion in Psychiatry. 2010;23(3):210-214.
Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with expertise in clinical pharmacology and addiction medicine.
Medical Content
Written by licensed physicians specializing in clinical pharmacology, addiction medicine, and psychiatry.
Medical Review
Independently reviewed by the iMedic Medical Review Board according to WHO, EMA, FDA, and NICE guidelines.
Evidence Standard
Level 1A evidence from systematic reviews, meta-analyses, and randomized controlled trials. GRADE framework applied.
Editorial Independence
No pharmaceutical company funding or advertising. Complete editorial independence maintained.