Metadon DnE (Methadone Hydrochloride)
Oral solution for opioid dependence treatment
Quick facts about Metadon DnE
Key Takeaways
- Supervised treatment only: Metadon DnE must be prescribed and monitored by physicians experienced in opioid dependence treatment as part of a comprehensive program
- Respiratory depression risk: Methadone can cause life-threatening breathing problems, especially during initiation and dose increases — dose must be carefully titrated
- Cardiac effects: Methadone can prolong the QT interval and cause dangerous heart rhythm disturbances, particularly at higher doses
- Dangerous drug interactions: Benzodiazepines, alcohol, and other CNS depressants combined with methadone significantly increase the risk of fatal respiratory depression
- Keep away from children: Even small doses of methadone can be fatal for children — store in a secure location out of reach at all times
What Is Metadon DnE and What Is It Used For?
Metadon DnE is an oral solution containing methadone hydrochloride, a synthetic opioid used in opioid agonist therapy (OAT) for patients who have become dependent on opioids. Methadone works by acting on the same brain receptors as heroin and other opioids, preventing withdrawal symptoms and reducing drug cravings without producing intense euphoria at stable therapeutic doses.
Methadone is classified as a synthetic opioid agonist, meaning it is a laboratory-produced substance that mimics the effects of naturally occurring opioids. It was first synthesized in Germany in 1937 and has been used medically since the 1960s for the treatment of opioid dependence. Today, methadone is included on the World Health Organization (WHO) Model List of Essential Medicines, reflecting its critical role in addiction treatment globally.
Opioid agonist therapy with methadone is considered one of the most effective evidence-based treatments for opioid use disorder. Numerous systematic reviews and meta-analyses have demonstrated that methadone maintenance treatment significantly reduces illicit opioid use, criminal activity, risk of HIV and hepatitis C transmission, and all-cause mortality. According to Cochrane reviews, patients receiving methadone maintenance are approximately 33% more likely to remain in treatment compared to non-pharmacological approaches.
The key pharmacological advantage of methadone lies in its long half-life of 15 to 60 hours. This extended duration of action allows for once-daily oral dosing, providing stable blood levels throughout the day. Unlike short-acting opioids such as heroin (which has a half-life of only 2-6 minutes for its active metabolite), methadone prevents the cycle of intoxication and withdrawal that drives compulsive opioid use.
Treatment with Metadon DnE is not intended to simply replace one opioid with another. Rather, it is always prescribed as part of a comprehensive treatment program that includes medical monitoring, psychological counseling, and social support. The goal is to stabilize patients so they can engage in rehabilitation, address the underlying causes of addiction, improve their health, and rebuild their lives.
Your doctor may prescribe this medicine for uses or at doses different from those described in this information. Always follow your doctor's instructions. Methadone hydrochloride may also be approved for the treatment of severe pain in some countries, but Metadon DnE is specifically formulated for opioid dependence treatment.
What Should You Know Before Taking Metadon DnE?
Before starting Metadon DnE, your doctor must evaluate your complete medical history, current medications, and overall health. There are several conditions that may prevent you from using methadone or require special monitoring. Always inform your doctor about all medicines you take, including over-the-counter products and herbal supplements.
Contraindications
You must not use Metadon DnE in the following situations:
- Allergy to methadone hydrochloride or any of the other ingredients in the formulation (listed in the composition section below)
- Severe respiratory problems or respiratory diseases (such as acute asthma) that cause difficulty breathing — methadone further depresses respiratory function and could be fatal
- Current or recent use of MAO inhibitors (monoamine oxidase inhibitors) within the last two weeks — these are medications used for depression and Parkinson's disease; the combination can cause serotonin syndrome or severe respiratory depression
- Children: Metadon DnE must NOT be given to children due to serious risk of poisoning — even very small doses can be fatal in pediatric patients
Warnings and Precautions
Talk to your doctor before using Metadon DnE if any of the following apply to you:
- Acute asthma attacks or impaired lung capacity due to lung disease
- Kidney problems (including kidney stones or gallstones)
- Liver problems — methadone is extensively metabolized by the liver, and impaired liver function can lead to drug accumulation
- Underactive thyroid gland (hypothyroidism)
- Enlarged prostate or urethral stricture (difficulty urinating)
- Head injury or increased intracranial pressure — methadone can mask symptoms and worsen the condition
- Abdominal pain, diarrhea, or constipation
- Heart rhythm changes (QT prolongation) or other serious heart conditions
- Current use of other opioid medications such as morphine or pentazocine
- Current use of sedatives such as barbiturates or benzodiazepines
Metadon DnE can affect the electrical signals that control heartbeat contractions, particularly at higher doses. This effect, known as QT prolongation, can lead to potentially fatal cardiac arrhythmias including torsades de pointes. Tell your doctor if you have ever had heart problems. Your doctor may decide to monitor your heart with an ECG (electrocardiogram) at the start of treatment and during dose adjustments.
Hormonal effects: Long-term use of methadone can lead to decreased levels of sex hormones and increased levels of the hormone prolactin. Contact your doctor if you experience symptoms such as reduced sex drive, erectile dysfunction, or absence of menstrual periods.
Adrenal insufficiency: Talk to your doctor or pharmacist if you experience any of the following symptoms while taking Metadon DnE: weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. These may be symptoms of the adrenal glands producing too little of the hormone cortisol, and you may need hormone supplementation.
Sleep-related breathing disorders: Methadone can cause sleep-related breathing disorders such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, waking at night due to shortness of breath, difficulty maintaining sleep, or excessive daytime drowsiness. If you or another person observes these symptoms, contact your doctor, who may consider reducing the dose.
Tolerance, Dependence, and Misuse
Methadone is an opioid medication, and repeated use can lead to tolerance (diminished effect), physical dependence, and potential misuse that may result in life-threatening overdose. While opioid agonist therapy intentionally uses controlled dependence as a therapeutic tool, it is important to only take the dose agreed upon with your doctor.
You may be at greater risk of dependence or misuse of methadone if:
- You or a family member has a history of alcohol, prescription medicine, or illicit drug misuse
- You smoke tobacco
- You have a history of mood disorders (depression, anxiety, or personality disorder) or have been treated by a psychiatrist
Signs that may indicate problematic use include: needing to take the medication for longer than prescribed, needing higher doses than recommended, using it for reasons other than prescribed (e.g., to "keep calm" or "help sleep"), repeated failed attempts to stop or control use, and experiencing withdrawal symptoms when stopping.
Pregnancy and Breastfeeding
If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before taking this medicine. Methadone can affect the fetus. However, the WHO and major medical guidelines recommend continuing opioid agonist therapy during pregnancy rather than attempting abrupt discontinuation, which carries significant risks including miscarriage and fetal distress.
If you are breastfeeding or planning to breastfeed while taking methadone, talk to your doctor. Methadone passes into breast milk. Monitor your infant for unusual signs and symptoms such as increased drowsiness, breathing difficulties, or muscle limpness. Contact your doctor immediately if you notice any of these symptoms. Your doctor will advise whether breastfeeding is appropriate based on your dose and individual circumstances.
Driving and Operating Machinery
Methadone affects coordination between the brain and body until treatment has been stabilized at an appropriate level. Do not drive a car or operate tools or machinery until you have been stable on treatment and dose for at least 6 months. Your prescribing doctor will advise you when it is safe to begin driving. You should not drive or perform hazardous work until you are certain it is safe to do so.
The oral solution contains 2.3% ethanol (alcohol), equivalent to the alcohol content of a light beer. The solution also contains the preservative methylparahydroxybenzoate (E 218), which may cause an allergic reaction (possibly delayed).
How Does Metadon DnE Interact with Other Drugs?
Metadon DnE has numerous significant drug interactions that can be dangerous or life-threatening. The most critical interactions involve benzodiazepines, MAO inhibitors, and other CNS depressants, which can cause fatal respiratory depression. Always inform your doctor and pharmacist about all medications you are taking.
Methadone is metabolized primarily by the cytochrome P450 enzyme system in the liver (CYP3A4, CYP2B6, CYP2D6), making it susceptible to interactions with many medications that either induce or inhibit these enzymes. Some drugs can increase methadone blood levels (increasing the risk of toxicity), while others can decrease methadone levels (potentially causing withdrawal symptoms).
Major Interactions
Concurrent use of Metadon DnE with benzodiazepines (such as diazepam, alprazolam) or similar sedatives increases the risk of drowsiness, respiratory depression (difficulty breathing), coma, and death. This combination should only be considered when no other treatment options are possible. If your doctor prescribes Metadon DnE together with sedative medications, the dose and duration of treatment should be limited.
| Drug / Drug Class | Effect on Methadone | Clinical Consequence |
|---|---|---|
| Benzodiazepines (diazepam, alprazolam, etc.) | Additive CNS depression | Fatal respiratory depression, coma, death |
| MAO inhibitors | Contraindicated combination | Serotonin syndrome, severe respiratory depression |
| Rifampicin (tuberculosis treatment) | Strongly decreases methadone levels (CYP3A4 induction) | Withdrawal symptoms, treatment failure |
| Anticonvulsants (phenytoin, carbamazepine, phenobarbital) | Decreases methadone levels (enzyme induction) | Withdrawal symptoms, dose adjustment needed |
| Naltrexone / Naloxone | Blocks opioid receptors | Precipitated withdrawal, treatment reversal |
| Gabapentin / Pregabalin | Additive CNS/respiratory depression | Increased risk of opioid overdose, breathing difficulties, may be life-threatening |
| St. John's Wort | Decreases methadone levels (CYP3A4 induction) | Withdrawal symptoms |
| QT-prolonging drugs (sotalol, amiodarone) | Additive QT prolongation | Risk of fatal cardiac arrhythmias (torsades de pointes) |
Other Important Interactions
The following medications can also interact with methadone and require monitoring or dose adjustment:
| Drug / Drug Class | Effect | Action Required |
|---|---|---|
| Antidepressants (SSRIs: fluoxetine, sertraline, paroxetine) | May increase methadone levels; risk of serotonin syndrome | Monitor for serotonin syndrome symptoms |
| Antipsychotics (risperidone, haloperidol) | Additive CNS depression; may affect heart rhythm | ECG monitoring may be needed |
| Azole antifungals (fluconazole, ketoconazole) | May increase methadone levels (CYP3A4 inhibition) | Monitor for signs of toxicity |
| Macrolide antibiotics (clarithromycin, erythromycin) | May increase methadone levels | Monitor for increased side effects |
| Antiretrovirals (HIV) (efavirenz, nevirapine, ritonavir) | Variable; some decrease, some increase methadone levels | Close monitoring; dose adjustment likely needed |
| Cimetidine (acid reflux) | May increase methadone levels | Monitor for side effects |
| Cannabidiol (seizure medication) | May alter methadone metabolism | Monitor sedation and breathing |
Grapefruit juice: Do not drink grapefruit juice during methadone treatment, as it can alter the effect of the medication by inhibiting CYP3A4 enzymes, potentially increasing methadone blood levels. Alcohol: Be very cautious with alcohol while on Metadon DnE — the combination increases the risk of dangerous respiratory depression and can be life-threatening.
What Is the Correct Dosage of Metadon DnE?
The dose of Metadon DnE is always determined and individually tailored by your doctor. There is no standard dose that applies to all patients. It is critically important that you do not take more than the dose you and your doctor have agreed upon, as even a small excess can be dangerous.
Metadon DnE is an oral solution that should be swallowed. Under no circumstances should you inject this medicine, as an injection can cause severe, permanent damage to the body and may be fatal. The solution contains particulate matter and excipients not intended for intravenous use.
Adults
Dosing of methadone for opioid dependence treatment is highly individualized. Your doctor will determine the starting dose based on your level of opioid tolerance, the severity of your dependence, and your overall health status. The dose is then gradually adjusted (titrated) over days and weeks until a stable maintenance dose is reached that prevents withdrawal symptoms and cravings without causing excessive sedation.
According to international guidelines (WHO, NICE, and the Cochrane Collaboration), effective maintenance doses typically range from 60 to 120 mg/day, although some patients may require higher or lower doses. The dose adjustment period is the most dangerous phase of treatment, as the risk of fatal overdose is highest during the first two weeks.
Children
Metadon DnE must NOT be given to children. There is a serious risk of poisoning. Children are more sensitive to methadone than adults, and poisoning can occur at very low doses. Always store the medicine in a secure place, out of reach of children. Even a small amount ingested accidentally can be fatal to a child.
Elderly and Patients with Liver or Kidney Problems
Extra caution is required if you are elderly, have liver or kidney problems, or are ill. These patients may metabolize methadone more slowly, leading to drug accumulation and increased risk of toxicity. Your doctor will typically start with lower doses and adjust more gradually. Regular monitoring of liver and kidney function may be necessary.
Missed Dose
If you miss a dose during treatment, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only the next dose at the regular time. Do NOT take a double dose to make up for a missed dose, as this significantly increases the risk of overdose.
Overdose
If you take too much Metadon DnE, you may experience the following symptoms:
- Breathing difficulties (slow, shallow breathing or cessation of breathing)
- Extreme drowsiness, fainting, or coma
- Pinpoint pupils (very small pupils)
- Muscle weakness
- Cool and clammy skin
- Slow heart rate, low blood pressure, cardiac arrest, or shock
- Low blood sugar
- Toxic leukoencephalopathy (a brain condition)
In severe cases, a methadone overdose can lead to death from respiratory arrest. If you suspect an overdose — whether in yourself, another adult, or a child who has accidentally ingested the medication — contact emergency services immediately. Naloxone (an opioid reversal agent) can reverse methadone overdose, but because methadone's half-life is much longer than naloxone's, repeated doses or continuous infusion may be necessary.
What Are the Side Effects of Metadon DnE?
Like all medicines, Metadon DnE can cause side effects, although not everybody gets them. The most common side effects are nausea and vomiting. Many side effects are dose-related and may improve as your body adjusts to the medication or when the dose is reduced. Always report any new or worsening symptoms to your doctor.
Side effects of methadone are classified by frequency based on clinical trial data and post-marketing surveillance. Understanding the likelihood of different side effects can help you and your healthcare team monitor your treatment effectively.
Very Common
May affect more than 1 in 10 people
- Nausea
- Vomiting
Common
May affect up to 1 in 10 people
- Weight gain
- Fluid retention (edema)
- Constipation
- Euphoria
- Hallucinations (seeing or hearing things that are not real)
- Dizziness or vertigo
- Blurred vision
- Pinpoint pupils (miosis)
- Drowsiness
- Skin rash
- Excessive sweating
- Fatigue
Uncommon
May affect up to 1 in 100 people
- Loss of appetite
- Breathing difficulties (including cough)
- Dry mouth
- Inflammation of the tongue
- Dysphoria (feeling of unease or dissatisfaction)
- Restlessness or anxiety
- Sleep difficulties (insomnia)
- Confusion
- Decreased sex drive
- Headache
- Fainting
- Low blood pressure (hypotension)
- Itching, hives (urticaria)
- Swollen legs
- Weakness
- Biliary spasm (gallbladder pain)
- Facial flushing
- Difficulty urinating (urinary retention)
- Erectile dysfunction
- Menstrual irregularities
Rare
May affect up to 1 in 1,000 people
- Heart problems (cardiac arrhythmias)
- Slower heart rate (bradycardia)
- Palpitations (awareness of heartbeat)
Frequency Not Known
Reported cases, frequency cannot be estimated
- Low potassium or magnesium levels in the blood
- Decreased platelet count (thrombocytopenia)
- Low blood sugar (hypoglycemia)
- Dependence on methadone (see Warnings section)
- Sleep apnea (breathing pauses during sleep)
If any side effects become severe or if you notice any side effects not listed here, contact your doctor or pharmacist. Reporting suspected side effects after the medicine has been approved is important to allow continuous monitoring of its benefit-risk balance.
How Should You Store Metadon DnE?
Store Metadon DnE out of the sight and reach of children in a secure location where others cannot access it. Methadone can cause serious harm and death in people for whom it has not been prescribed. No special storage conditions are required beyond keeping it secure.
Keep the medication in a secure place. Methadone is a controlled substance and must be stored where unauthorized individuals, especially children, cannot reach it. A locked cabinet or medicine safe is recommended.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month. Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines that are no longer needed. These measures help protect the environment and prevent accidental exposure.
What Does Metadon DnE Contain?
The active substance in Metadon DnE is methadone hydrochloride at a concentration of 1 mg/ml. The solution also contains several inactive ingredients including ethanol (2.3%), sodium citrate, citric acid, saccharin sodium, and flavoring agents.
Active substance: Methadone hydrochloride 1 mg/ml
Other ingredients (excipients):
- Methylparahydroxybenzoate (E 218) — preservative (may cause allergic reactions, possibly delayed)
- Ethanol (96%) 24 mg/ml — approximately 2.3% alcohol content
- Sodium citrate
- Anhydrous citric acid
- Saccharin sodium — sweetener
- Masking flavor
- Flavoring agent (blackcurrant/apple)
- Purified water
Appearance and packaging: Metadon DnE is a clear oral solution (liquid) supplied in brown plastic bottles with child-resistant and tamper-evident screw caps. The 1 mg/ml strength is available in bottle sizes ranging from 15 ml to 150 ml. Individual bottles or packs of 3 or 7 bottles may be available. Not all pack sizes may be marketed.
Marketing authorization holder: dne pharma as, Karihaugveien 22, NO-1086 Oslo, Norway.
Manufacturer: Pharma Production AS, Karihaugveien 22, NO-1086 Oslo, Norway.
Frequently Asked Questions About Metadon DnE
Metadon DnE is an oral solution containing methadone hydrochloride, used as part of opioid agonist therapy (OAT) for patients who have become dependent on opioids such as heroin or prescription painkillers. It is always prescribed as part of a comprehensive treatment program that includes medical, psychological, and social support. The medication works by preventing withdrawal symptoms and reducing cravings, allowing patients to stabilize their lives and engage in rehabilitation.
Methadone is a long-acting synthetic opioid agonist that acts on the same mu-opioid receptors in the brain as heroin and other opioids. Its key advantage is its long half-life of 15 to 60 hours, which provides stable blood levels throughout the day with once-daily dosing. This prevents the cycle of intoxication and withdrawal that drives compulsive opioid use. At stable therapeutic doses, methadone reduces cravings and withdrawal symptoms without producing the intense euphoria associated with short-acting opioids.
The most common side effects, affecting more than 1 in 10 people, are nausea and vomiting. Common side effects (up to 1 in 10 people) include constipation, sweating, drowsiness, dizziness, weight gain, fluid retention, blurred vision, pinpoint pupils, skin rash, and fatigue. Many of these side effects improve over the first weeks of treatment as the body adjusts. If side effects persist or become bothersome, talk to your doctor about possible dose adjustments.
You should be very cautious with alcohol while taking methadone. Combining methadone with alcohol significantly increases the risk of dangerous respiratory depression, excessive sedation, and can be life-threatening. Both substances depress the central nervous system, and their combined effect is greater than either alone. You should also avoid grapefruit juice as it can alter how methadone is metabolized in the body, potentially increasing drug levels and side effects.
Methadone can affect the fetus and should only be used during pregnancy under close medical supervision. However, the World Health Organization (WHO) and most international guidelines recommend continuing opioid agonist therapy (methadone or buprenorphine) during pregnancy rather than attempting detoxification, as abrupt opioid withdrawal carries significant risks including miscarriage and fetal distress. Newborns exposed to methadone in utero may experience neonatal abstinence syndrome and will need monitoring after birth.
The duration of methadone maintenance treatment varies significantly between individuals. Some patients may be on treatment for months, while others may require years or indefinite treatment. Research consistently shows that longer treatment duration is associated with better outcomes, including lower rates of relapse and reduced mortality. Any dose reduction or discontinuation should be done very gradually and under medical supervision. Abrupt discontinuation can cause severe withdrawal symptoms and carries a high risk of relapse and overdose death.
References
This article is based on the following peer-reviewed sources and international medical guidelines:
- World Health Organization (WHO). Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva: WHO; 2009. Updated 2023.
- Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews. 2009;(3):CD002209. doi:10.1002/14651858.CD002209.pub2
- European Medicines Agency (EMA). Summary of Product Characteristics: Methadone Hydrochloride. EMA/CHMP guidelines.
- National Institute for Health and Care Excellence (NICE). Drug misuse in over 16s: opioid detoxification. Clinical guideline CG52. Updated 2022.
- U.S. Food and Drug Administration (FDA). Methadone Hydrochloride Prescribing Information. FDA labeling requirements and safety communications.
- Substance Abuse and Mental Health Services Administration (SAMHSA). Federal Guidelines for Opioid Treatment Programs. HHS Publication No. (SMA) 15-4154.
- Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. Methadone maintenance at different dosages for opioid dependence. Cochrane Database of Systematic Reviews. 2003;(3):CD002208.
- British National Formulary (BNF). Methadone hydrochloride monograph. NICE Evidence Services. 2024.
About the Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which consists of licensed physicians specializing in pharmacology, addiction medicine, and clinical toxicology. All content follows the GRADE evidence framework and is based on the highest available quality of evidence.
Every article undergoes multi-stage review: initial research by clinical pharmacists, medical writing by physician editors, fact-checking against primary sources, and final approval by the Medical Review Board.
We prioritize Level 1A evidence (systematic reviews of RCTs) and cite guidelines from WHO, EMA, FDA, NICE, and Cochrane. No commercial funding influences our content.