Levopidon (Levomethadone)
Opioid Agonist for Opioid Substitution Therapy
Quick Facts About Levopidon
Key Takeaways
- Levopidon (levomethadone) is used exclusively for opioid substitution therapy in adults and must only be taken by mouth – never injected.
- Levomethadone is approximately twice as potent as racemic methadone; doses must be carefully titrated under medical supervision.
- Common side effects include nausea, vomiting, constipation, sweating and drowsiness; cardiac rhythm monitoring may be needed at higher doses.
- Numerous dangerous drug interactions exist, particularly with benzodiazepines, MAO inhibitors and drugs that prolong the QT interval.
- Treatment must never be stopped abruptly – gradual dose reduction under medical guidance is essential to avoid severe withdrawal symptoms.
What Is Levopidon and What Is It Used For?
Quick Answer: Levopidon contains levomethadone hydrochloride, a full opioid agonist used in opioid substitution therapy (also called opioid agonist therapy or OAT). It is prescribed to adults who are dependent on opioids to reduce withdrawal symptoms, suppress cravings and support recovery within a structured treatment programme.
Levopidon belongs to a class of medications that act on the central nervous system by binding to mu-opioid receptors. Levomethadone is the pharmacologically active R-enantiomer of racemic methadone. While racemic methadone contains a 50:50 mixture of the R- and S-enantiomers, only the R-form (levomethadone) has significant activity at opioid receptors. This means that levomethadone achieves the same therapeutic effect at roughly half the dose of racemic methadone.
The primary indication for Levopidon is opioid substitution therapy in adults who have developed dependence on opioids such as heroin, morphine or prescription opioid analgesics. When taken at the correct maintenance dose, levomethadone occupies opioid receptors sufficiently to prevent withdrawal symptoms and reduce cravings, without producing the intense euphoria associated with illicit opioid use. This pharmacological stabilisation allows patients to engage more effectively with psychological counselling, social support and rehabilitation services.
Opioid agonist therapy is recognised by the World Health Organization (WHO) as one of the most effective treatments for opioid dependence. It is associated with significant reductions in illicit opioid use, criminal activity, risk of blood-borne infections (such as HIV and hepatitis C) and overdose mortality. Levomethadone has been widely used in several European countries, particularly Germany, where it has been a standard component of opioid substitution programmes for many years.
Levomethadone also possesses weak NMDA (N-methyl-D-aspartate) receptor antagonist activity, which may contribute to its analgesic properties and potentially reduce the development of opioid tolerance to a degree. Additionally, its long elimination half-life (15–60 hours) allows for once-daily dosing, which simplifies treatment adherence and reduces the peaks and troughs in blood levels that can drive continued craving for short-acting opioids.
What Should You Know Before Taking Levopidon?
Quick Answer: Before starting Levopidon, your prescriber must assess your medical history, current medications and substance use. There are several absolute contraindications and many precautions that must be considered. Levomethadone is more potent than racemic methadone, so accurate dosing is critical to avoid potentially fatal overdose.
Contraindications
You must not take Levopidon if any of the following apply to you:
- You are allergic to levomethadone or any of the other ingredients in Levopidon (methylparahydroxybenzoate E 218, betaine hydrochloride, glycerol E 422, or purified water).
- You are taking or have taken monoamine oxidase inhibitors (MAOIs) – medicines used for depression or Parkinson’s disease – within the past two weeks.
- You have severe respiratory problems or lung disease that significantly impairs breathing.
- You are dependent on substances other than opioids (e.g. alcohol, benzodiazepines) without concurrent opioid dependence.
- You are currently receiving other opioid substitution medications such as methadone, buprenorphine or naltrexone (except in an emergency overdose situation).
Warnings and Precautions
Speak to your prescriber before taking Levopidon if you have or have ever had any of the following conditions:
- Respiratory conditions: Asthma, chronic obstructive pulmonary disease (COPD), or any condition that reduces lung capacity. Levomethadone can cause respiratory depression, which may be life-threatening in patients with compromised breathing.
- Heart conditions: History of QT prolongation, arrhythmias, heart failure or other cardiac disease. Levomethadone can affect the electrical signals controlling heartbeat, particularly at higher doses. Your prescriber may order an ECG before and during treatment.
- Liver disease: Levomethadone is extensively metabolised by the liver, so impaired liver function may result in higher-than-expected blood levels and require dose adjustments.
- Kidney disease: Including kidney stones or gallstones. Renal impairment may affect drug elimination.
- Low potassium or magnesium levels: Electrolyte imbalances increase the risk of dangerous heart rhythm disturbances.
- Underactive thyroid (hypothyroidism): May increase sensitivity to opioid effects.
- Enlarged prostate or urethral narrowing: Opioids can worsen urinary retention.
- Head injury or raised intracranial pressure: Opioids can mask neurological symptoms and increase intracranial pressure.
- Abdominal conditions: Opioids affect gut motility and can worsen constipation, or mask symptoms of acute abdominal conditions.
- Adrenal insufficiency: Long-term opioid use may suppress adrenal function. Symptoms include weakness, fatigue, loss of appetite, nausea, vomiting and low blood pressure. Contact your prescriber if you experience these symptoms.
Tolerance, dependence and risk of misuse: Levomethadone is itself an opioid and carries risks of tolerance (reduced response over time), physical dependence and potential for misuse. These risks are managed through the structured framework of opioid agonist therapy, with supervised dosing, regular clinical review and psychosocial support. Factors that may increase the risk of problematic use include a personal or family history of substance use disorder, co-occurring mental health conditions (depression, anxiety, personality disorders), and smoking.
Sleep-related breathing disorders: Levomethadone can cause sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low blood oxygen during sleep). If you or others notice symptoms such as breathing pauses during sleep, nocturnal awakenings with shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness, inform your prescriber. A dose reduction may be considered.
Hormonal effects: Prolonged use of opioid medications can lead to decreased sex hormone levels and increased prolactin. This may manifest as reduced libido, erectile dysfunction, or absent menstruation. Contact your prescriber if you experience these symptoms.
Children and Adolescents
Levopidon must not be used in children or adolescents under 18 years of age. Children are particularly sensitive to the effects of levomethadone, and even very small doses can cause fatal poisoning. The medication must be stored securely and kept out of sight and reach of children at all times.
Pregnancy and Breastfeeding
Pregnancy: Levomethadone can affect the developing foetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, discuss this with your prescriber before using this medication. In some situations, opioid agonist therapy may be continued during pregnancy following a careful risk-benefit assessment by a specialist, ideally with monitoring at a specialised unit. Abrupt discontinuation of opioid agonist therapy during pregnancy is generally not recommended due to the risk of relapse and foetal distress.
Breastfeeding: Levomethadone passes into breast milk. Speak to your prescriber if you are breastfeeding or planning to breastfeed. If breastfeeding is considered appropriate, monitor your infant for signs of excessive drowsiness, breathing difficulties or poor muscle tone. Contact your prescriber immediately if you notice any of these symptoms.
Driving and Operating Machinery
Do not drive or operate machinery while taking Levopidon. The medication can cause drowsiness, impaired alertness, blurred vision and reduced reaction times. These effects may persist for some time after treatment has been stabilised or after discontinuation. Your prescriber will advise you when it is safe to drive.
Alcohol and Grapefruit Juice
Do not drink alcohol while taking Levopidon. The combination can cause severe respiratory depression and may be life-threatening. You should also avoid grapefruit juice, as it can inhibit the CYP3A4 enzyme that metabolises levomethadone, potentially increasing blood levels and the risk of side effects.
How Does Levopidon Interact with Other Drugs?
Quick Answer: Levopidon has numerous clinically significant drug interactions. Some combinations are absolutely contraindicated (MAO inhibitors, other opioid substitution therapies), while many others require dose adjustments or enhanced monitoring. Always inform your prescriber of all medications, supplements and herbal products you are taking.
Levomethadone is primarily metabolised by the cytochrome P450 enzymes CYP3A4 and CYP2B6, with additional involvement of CYP2D6 and CYP1A2. Drugs that inhibit or induce these enzymes can significantly alter levomethadone blood levels. Additionally, levomethadone can prolong the QT interval, so combining it with other QT-prolonging drugs increases the risk of potentially fatal cardiac arrhythmias (torsades de pointes). The concomitant use of other central nervous system depressants amplifies the risk of respiratory depression, sedation and death.
Contraindicated Combinations
| Drug / Class | Risk | Recommendation |
|---|---|---|
| MAO inhibitors (e.g. phenelzine, tranylcypromine, selegiline) | Risk of serotonin syndrome, severe hypertension, respiratory depression | Contraindicated. Wait at least 14 days after stopping MAOIs. |
| Methadone (racemic) | Overlapping opioid agonism, unpredictable dose equivalence, overdose risk | Do not use concurrently. Careful cross-titration under specialist supervision only. |
| Buprenorphine, naltrexone, naloxone (except emergency) | Buprenorphine: partial agonist can precipitate withdrawal. Naltrexone/naloxon: antagonists block opioid effects. | Do not combine. Naloxone is only used in emergency overdose situations. |
Major Interactions Requiring Close Monitoring
| Drug / Class | Category | Effect | Recommendation |
|---|---|---|---|
| Benzodiazepines (e.g. diazepam, alprazolam) | CNS depressant | Increased risk of sedation, respiratory depression, coma and death | Avoid if possible. If prescribed, use lowest effective dose and monitor closely. |
| Gabapentin, pregabalin | CNS depressant | Increased risk of opioid overdose, respiratory depression; potentially fatal | Use with extreme caution. Monitor for sedation and breathing difficulties. |
| Alcohol (ethanol) | CNS depressant | Severe respiratory depression, enhanced sedation, risk of death | Contraindicated. Patients must abstain from alcohol. |
| Rifampicin | CYP3A4 inducer | Significantly reduced levomethadone levels; may precipitate withdrawal | Dose increase likely needed. Monitor closely for withdrawal symptoms. |
| Carbamazepine, phenytoin, phenobarbital | CYP enzyme inducers | Reduced levomethadone levels; risk of withdrawal symptoms | Dose adjustment required. Monitor plasma levels if possible. |
| St. John’s Wort | CYP3A4 inducer | Reduced levomethadone levels; may cause withdrawal | Avoid concurrent use. |
| Fluconazole, ketoconazole, itraconazole | CYP3A4 inhibitors | Increased levomethadone levels; risk of toxicity and QT prolongation | Monitor for over-sedation and cardiac effects. Dose reduction may be needed. |
| Ritonavir, lopinavir, efavirenz, nevirapine | Antiretrovirals (mixed effects) | Some increase, some decrease levomethadone levels; variable effects | Close monitoring required. Dose adjustments based on clinical response. |
| Amiodarone, sotalol, quinidine | QT-prolonging antiarrhythmics | Additive QT prolongation; risk of torsades de pointes | Avoid if possible. ECG monitoring essential if combined. |
| Fluoxetine, paroxetine, sertraline, fluvoxamine | SSRIs / CYP inhibitors | Increased levomethadone levels; risk of serotonin syndrome | Monitor for serotonin syndrome symptoms: agitation, hallucinations, rapid heart rate, fever, muscle rigidity. |
| Erythromycin, clarithromycin, telithromycin | CYP3A4 inhibitors / QT-prolonging | Increased levomethadone levels and additive QT prolongation | Use alternative antibiotic where possible. Monitor ECG. |
| Haloperidol, risperidone, sertindole, thioridazine | Antipsychotics / QT-prolonging | CNS depression, QT prolongation | Use with caution. ECG monitoring recommended. |
This is not a complete list of all possible drug interactions. Cannabis-containing products, anticholinergics, loperamide, dexamethasone, ciclosporin, tamoxifen and many other medications may also interact with levomethadone. Always inform your prescriber and pharmacist of every medication, over-the-counter product and herbal supplement you are taking.
What Is the Correct Dosage of Levopidon?
Quick Answer: Levopidon dosage is highly individualised and must be determined by a specialist prescriber experienced in addiction medicine. Treatment begins with a low starting dose that is gradually increased over several weeks (induction phase) until a stable maintenance dose is achieved. Levomethadone is approximately twice as potent as racemic methadone, so dose conversion requires careful calculation.
The dose of levomethadone is determined by your prescriber based on several factors, including the severity of your opioid dependence, the timing and severity of withdrawal symptoms, your tolerance to opioids, your weight and overall health. It is critically important that you take Levopidon exactly as prescribed. Do not take more, less, or at different intervals than instructed.
Adults
Induction Phase (First Weeks)
Treatment starts with a low dose, typically determined by your prescriber based on your individual circumstances. The dose is then gradually increased over a period of several weeks until withdrawal symptoms are adequately controlled and cravings are managed. This careful titration is essential because levomethadone is more potent than racemic methadone and overdose can be fatal.
Maintenance Phase
Once stabilised, the maintenance dose is taken once daily. The optimal dose varies considerably between individuals, typically ranging from 10 mg to 60 mg of levomethadone daily, though some patients may require higher doses. The aim is to find the dose that eliminates withdrawal symptoms and cravings throughout the full 24-hour dosing interval without causing excessive sedation.
Dose Conversion from Racemic Methadone
If switching from racemic methadone to levomethadone, the approximate conversion ratio is 2:1. For example, a patient receiving 80 mg of racemic methadone would be expected to require approximately 40 mg of levomethadone. However, this conversion must always be performed under close medical supervision as individual variation can be significant.
Elderly Patients
Patients over 65 years of age or those who are in very poor general health may require lower doses. The prescriber will typically start with a lower dose and titrate more slowly, with closer monitoring for adverse effects including excessive sedation, respiratory depression and cardiovascular effects.
Patients with Liver or Kidney Impairment
Dose reductions may be necessary for patients with kidney problems or severe, chronic liver disease. Levomethadone is extensively metabolised by the liver, so hepatic impairment can lead to accumulation and increased risk of toxicity. Your prescriber will monitor you more closely if you have liver or kidney problems.
How to Take Levopidon
The oral solution is supplied in ready-to-use unit-dose containers (30 ml brown plastic bottles with child-resistant caps). Simply open the container and swallow the solution. Do not dilute or mix with other liquids unless specifically instructed by your prescriber. During the initial phase of treatment, dosing may take place under direct observation at a clinic or pharmacy.
Missed Dose
If you forget a dose during a course of treatment, take it as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose and take the next one at the usual time. Do not take a double dose to make up for a forgotten one. Missing doses can lead to the re-emergence of withdrawal symptoms. If you frequently forget doses, speak to your prescriber about strategies to improve adherence.
Overdose
Stopping Levopidon
Do not stop taking Levopidon without first consulting your prescriber. Abrupt discontinuation can cause severe withdrawal symptoms and carries a high risk of relapse. If you and your prescriber decide to end treatment, the dose will be reduced gradually over a period of weeks to months. The rate of dose reduction will be guided by your individual response and adjusted if withdrawal symptoms become difficult to manage.
What Are the Side Effects of Levopidon?
Quick Answer: Like all opioid medications, Levopidon can cause side effects. The most common are nausea and vomiting (affecting more than 1 in 10 people). Many side effects may improve as your body adjusts to the medication, although constipation and excessive sweating tend to persist. Some side effects, such as respiratory depression and cardiac rhythm disturbances, can be serious.
The following side effects have been reported with Levopidon. Not everyone will experience them. Some side effects are dose-related and may be more likely at higher doses. If any side effects become severe or persistent, or if you notice any effects not listed here, contact your prescriber or pharmacist.
Very Common
Affects more than 1 in 10 people
- Nausea
- Vomiting
Common
Affects up to 1 in 10 people
- Fluid retention (oedema)
- Euphoria (feeling of elation)
- Hallucinations (seeing or hearing things that are not real)
- Drowsiness
- Blurred vision
- Constricted pupils (miosis)
- Constipation
- Skin rash
- Excessive sweating
- Fatigue
- Weight gain
Uncommon
Affects up to 1 in 100 people
- Loss of appetite
- Low mood (depression)
- Anxiety and restlessness
- Sleep difficulties (insomnia)
- Confusion regarding time and place
- Decreased sex drive (libido)
- Headache
- Fainting (syncope)
- Facial flushing
- Low blood pressure (hypotension)
- Fluid in the lungs (pulmonary oedema)
- Difficulty breathing (including with cough)
- Dry mouth
- Inflammation of the tongue (glossitis)
- Biliary spasm (causing abdominal pain)
- Itching (pruritus)
- Hives (urticaria)
- Severe fluid retention
- Difficulty urinating (urinary retention)
- Erectile dysfunction
- Menstrual disturbances
- Swollen legs
- Weakness
Rare
Affects up to 1 in 1,000 people
- Slowed heart rate (bradycardia)
- Palpitations (feeling the heart beating)
- Heart problems, particularly at high doses (QT prolongation, arrhythmias)
Not Known
Frequency cannot be estimated from available data
- Low potassium or magnesium levels in the blood
- Decreased platelet count (thrombocytopenia)
- Low blood sugar (hypoglycaemia)
- Development of dependence on levomethadone
- Sleep apnoea (breathing pauses during sleep)
Some side effects may become less severe over time as your body adjusts. However, constipation and increased sweating are unlikely to improve on their own. Your prescriber or pharmacist can advise on treatments to help manage these persistent effects, such as laxatives for constipation.
How Should You Store Levopidon?
Quick Answer: Store Levopidon out of the sight and reach of children in a secure location where others cannot access it. This medication can cause serious harm or death in people for whom it was not prescribed, especially children.
Proper storage of Levopidon is critically important given the extreme danger this medication poses to anyone other than the intended patient. Follow these storage guidelines:
- Keep out of sight and reach of children: Children are particularly sensitive to levomethadone. Even very small amounts can cause fatal poisoning in a child. Store in a locked cabinet or container if possible.
- Secure storage: Keep the medication in a place where other people cannot access it. Accidental or intentional ingestion by someone without opioid tolerance can be fatal.
- Check the expiry date: Do not use Levopidon after the expiry date printed on the label and carton (after EXP). The expiry date refers to the last day of that month.
- Disposal: Do not dispose of medications via the drain or with household waste. Return unused or expired medication to your pharmacy for safe disposal. This protects the environment and prevents accidental exposure.
What Does Levopidon Contain?
Quick Answer: The active ingredient is levomethadone hydrochloride, available in unit-dose oral solutions ranging from 5 mg to 75 mg. Inactive ingredients include methylparahydroxybenzoate (E 218), betaine hydrochloride, glycerol (E 422) and purified water.
Active Ingredient
Each unit-dose container of Levopidon contains levomethadone hydrochloride. Available strengths are: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg and 75 mg.
Inactive Ingredients (Excipients)
- Methylparahydroxybenzoate (E 218) – preservative; may cause allergic reactions (possibly delayed)
- Betaine hydrochloride – buffering agent
- Glycerol (E 422) – solvent and humectant
- Purified water – vehicle
Appearance and Packaging
Levopidon is a clear, colourless oral solution provided in unit-dose containers. Each container is a 30 ml brown plastic bottle with a tamper-evident seal and a blue, child-resistant screw cap. Pack sizes available are 1, 3 or 7 bottles. Not all pack sizes may be marketed in all countries.
The marketing authorisation holder is dne pharma as (Karihaugveien 22, NO-1086 Oslo, Norway) and the manufacturer is Pharma Production AS (same address).
Frequently Asked Questions About Levopidon
Racemic methadone is a 50:50 mixture of two mirror-image molecules (enantiomers): R-methadone (levomethadone) and S-methadone. Only the R-enantiomer (levomethadone) has significant activity at opioid receptors and is responsible for essentially all the desired therapeutic effects. The S-enantiomer contributes little to opioid activity but may contribute to side effects, including cardiac QT prolongation. By using the purified R-enantiomer (levomethadone), the therapeutic dose is approximately halved while potentially reducing some cardiac side effects associated with the S-enantiomer.
There is no fixed duration for opioid agonist therapy with levomethadone. Treatment is highly individualised and depends on your recovery progress, psychosocial stability and overall goals. International guidelines, including those from the WHO and EMCDDA, support long-term or even indefinite maintenance therapy for many patients, as research consistently shows that longer durations of treatment are associated with better outcomes. Decisions about tapering or discontinuing treatment should be made collaboratively between you and your specialist prescriber.
Travelling with opioid substitution medication requires advance planning. Regulations vary significantly between countries. Within the EU/EEA, you typically need a certificate from your prescriber endorsed by a national health authority (under the Schengen agreement, up to 30 days of medication). For travel outside Europe, you should check the specific import regulations of your destination country, carry a letter from your prescriber confirming your treatment, and ensure you have sufficient supply. Some countries strictly prohibit the import of opioid medications. Consult your prescriber and the relevant embassy well in advance of travel.
Non-opioid pain medications such as paracetamol (acetaminophen) and ibuprofen can generally be used safely alongside levomethadone for mild-to-moderate pain. However, you should always consult your prescriber before taking any additional opioid pain medication, as the combination can cause dangerous respiratory depression. The management of moderate-to-severe pain in patients on opioid agonist therapy requires specialist expertise. Never take additional opioid medications without medical guidance.
This is a medical emergency. Call your local emergency number immediately (e.g. 911 in the US, 999 in the UK, 112 in the EU). Levomethadone can be fatal in people who do not have opioid tolerance, especially children. While waiting for emergency services, try to keep the person awake and breathing. If you have access to naloxone (an opioid reversal agent), administer it according to the instructions. Note that levomethadone has a long half-life, so the effects may outlast a single dose of naloxone, and repeated doses or continuous infusion may be necessary.
Yes, levomethadone will typically be detected on drug tests that screen for methadone. Standard immunoassay urine drug screens used in many settings include a panel for methadone/EDDP (a methadone metabolite). You should inform any healthcare provider or testing facility that you are receiving prescribed opioid agonist therapy with levomethadone. Your treatment provider can supply documentation confirming your prescribed medication.
Medical References
This article is based on the approved product information for Levopidon and supplemented with current evidence from the following peer-reviewed and institutional sources:
- World Health Organization (WHO). Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva: WHO; 2009.
- European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Best Practice Portal: Opioid Substitution Treatment. Lisbon: EMCDDA; 2023.
- American Society of Addiction Medicine (ASAM). The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. J Addict Med. 2020;14(2S):1-91.
- National Institute for Health and Care Excellence (NICE). Drug Misuse in Over 16s: Opioid Detoxification (CG52). London: NICE; 2007 (updated 2019).
- Mattick RP, Breen C, Kimber J, Davoli M. Methadone Maintenance Therapy Versus No Opioid Replacement Therapy for Opioid Dependence. Cochrane Database Syst Rev. 2009;(3):CD002209.
- Eap CB, Buclin T, Baumann P. Interindividual Variability of the Clinical Pharmacokinetics of Methadone: Implications for the Treatment of Opioid Dependence. Clin Pharmacokinet. 2002;41(14):1153-1193.
- Kreek MJ, Borg L, Ducat E, Ray B. Pharmacotherapy in the Treatment of Addiction: Methadone. J Addict Dis. 2010;29(2):200-216.
- European Medicines Agency (EMA). Levopidon – Summary of Product Characteristics. Accessed 2026.
- WHO Model List of Essential Medicines, 23rd List. Geneva: World Health Organization; 2023. Methadone included for opioid dependence treatment.
- Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of Methadone. J Pain Palliat Care Pharmacother. 2005;19(4):13-24.
Editorial Team
Medical Review
Content medically reviewed by the iMedic Medical Review Board – a panel of physicians specialising in addiction medicine, clinical pharmacology and psychiatry. All information follows the GRADE evidence framework and international guidelines from the WHO, EMCDDA and ASAM.
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