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Methadone parenteral


Solution for injection containing methadone hydrochloride

Drugs List

  • methadone 10mg/1ml injection
  • methadone 20mg/2ml injection
  • methadone 50mg/1ml injection
  • PHYSEPTONE 10mg/1ml injection
  • PHYSEPTONE 50mg/1ml injection
  • SYNASTONE 20mg/2ml injection
  • Therapeutic Indications


    Opioid drug dependency - treatment
    Pain - moderate to severe


    Opioid dependence

    The use of injectable methadone must be initiated by physicians with adequate experience and expertise in addiction therapy.

    Treatment must be part of a broader treatment programme, including regular treatment reviews, and must be supervised by specialist services.

    The dose of methadone should only be given once or twice a day at most, this is to avoid the risk of accumulation and overdosage.


    Management of opioid dependence

    Initially 10 to 20 mg per day, increasing by 10 to 20 mg per day (the maximum recommended weekly increase is 30 mg) until there are no signs of withdrawal or intoxication. The usual dose is 10 to 60 mg per day. After stabilisation, the dose is gradually decreased until total withdrawal is achieved.

    The dose should be adjusted according to the individual needs of the patient with the aim of gradual reduction. Providing a dosage schedule is difficult as it is largely subjective based on the drug misuser's reported drug use and a clinical assessment of their dependence. A cautious approach is usually adopted starting at a low dose and following with incremental increases as determined to be appropriate keeping in mind the general health of the patient.

    Treatment of moderate to severe pain
    Usually 5 to 10 mg every 6 to 8 hours as required although doses should be adjusted according to response. In prolonged use it should be given twice a day or less.


    Reduce dose in elderly and debilitated patients. If repeated doses are required, use with extreme caution due to the long plasma half life. There may be a greater risk of respiratory depression, with or without any associated renal or hepatic impairment in this age group.

    Patients with Renal Impairment

    Consider dose reduction in moderate or severe renal impairment as there may be an increased and prolonged effect, and increased cerebral sensitivity.

    The Renal drug handbook recommends using 50% of normal dose in patients with a GFR of less than 10 ml/minute and titrating according to response. They comment that it is probably not appropriate as an analgesic for patients with severe renal impairment.

    Patients with Hepatic Impairment

    In patients with severe liver damage, the dose of methadone should be reduced and carefully controlled as there is a risk that methadone might precipitate porto-systemic encephalopathy and coma.


    Give by intramuscular, subcutaneous or intravenous injection only if using high strength preparation.

    The intramuscular route is preferred when repeated administration is required. Volumes greater than 2 ml may need to be given in divided doses at different sites. To avoid injection of large volumes, consider higher strengths for patients requiring treatment with larger doses of methadone.


    Children under 16 years
    Risk of paralytic ileus
    Within 2 weeks of discontinuing MAOIs
    Acute asthma
    Acute respiratory depression
    Head trauma
    Obstetric use
    Obstructive pulmonary disease
    Raised intracranial pressure

    Precautions and Warnings

    Acute alcohol intoxication
    Family history of long QT syndrome
    Tobacco smoking
    Adrenal insufficiency
    Benign prostatic hyperplasia
    Biliary tract disorder
    Circulatory failure
    Gastrointestinal obstruction
    History of torsade de pointes
    Inflammatory bowel disease
    Long QT syndrome
    Myasthenia gravis
    Reduced respiratory reserve
    Renal impairment
    Severe hepatic impairment

    May exacerbate asthma
    Reduce dose in patients with moderate renal impairment
    Advise patient ability to drive or operate machinery may be impaired
    Advise patient not to drive until they know how the medicine affects them
    Advise patient this medicine is subject to driving restrictions
    Gradual titration must precede use of high concentration product
    Not all available brands are licensed for all routes of administration
    Not all available strengths are licensed for all indications
    Reduced plasma level and efficacy in smokers
    Treatment to be initiated and supervised by a specialist
    Monitor ECG in patients at risk of QT prolongation
    Monitor patient for signs and symptoms of respiratory depression
    Neonate exposed in utero: Monitor for respiratory depression
    Tolerance and dependence may occur
    Neonate exposed in labour: Risk of respiratory depression
    Avoid abrupt withdrawal
    Dose adjustment required if patient starts/stops smoking during therapy
    Alcohol may enhance side effects

    Methadone can produce drowsiness and reduce consciousness although tolerance to these effects can occur after repeated use. Alcohol may enhance the sedative and hypotensive effects of methadone and increase respiratory depression.

    Due to the slow accumulation of methadone in the tissues, respiratory depression may not be fully apparent for a week or two due to accumulation in the tissues.

    Accumulation is possible due to its long half life, particularly in the elderly and debilitated. A single dose to relieve symptoms may lead to accumulation and possible death if repeated on a daily basis.

    Injection site reactions may occur, inspect these sites regularly. Injections may be painful.

    In patients without recognised risk factors for QT prolongation, monitor ECG before dose titration above 100 mg/day and at seven days after titration.

    Pregnancy and Lactation


    In pregnancy methadone should only be used with caution and with monitoring of the infant.

    Due to its long half-life, methadone is the first choice for substitution therapy for heroin dependency. It has been used safely for many years and is the preferred option for ensuring continuity of care during pregnancy and afterwards. It is recommended the mother should be under the care of an obstetrician and/or a midwife specializing in drug misuse and also supported by the local drug dependency service.

    The main problems associated with methadone use by the mother include neonatal narcotic withdrawal syndrome and low birth weight. There is also a reported increased incidence of prematurity, jaundice, thrombocytosis, stillbirths, mortality and Sudden Infant Death Syndrome (SIDS). However methadone has not been associated with congenital malformations.

    Maternal withdrawal of methadone during pregnancy should be avoided, as this appears to increase the risk of premature birth, stillbirth and neonatal mortality. The risk of spontaneous abortion is greater during the first trimester. It is therefore advisable to avoid attempts at detoxification at this time. Attempts at opiate withdrawal in the third trimester have caused premature labour. Use for prolonged periods of time, or at high doses, especially at term should also be avoided.

    One study found a connection between the severity of neonatal withdrawal and SIDS. Maternal withdrawal during pregnancy has been observed to produce a significant response of the foetal adrenal glands and sympathetic nervous system. An increased stillborn and neonatal mortality rate has also been reported. The available evidence is against detoxification of the mother during gestation particularly in the first and third trimesters. Withdrawal of methadone in the first trimester may result in or be blamed for a miscarriage. Treatment should be stabilised in the first trimester. In the third trimester drug withdrawal should not normally be attempted either as evidence exists that even mild withdrawal can cause foetal stress, distress and stillbirth.

    It may be necessary to increase the dose of methadone in pregnancy if withdrawal symptoms develop, in pregnancy increased clearance and reduced plasma levels have been reported.

    Methadone should not be used during labour, due to the risk of gastric stasis and inhalation pneumonia in the mother, and foetal distress.

    In pregnancy morning sickness may result in the woman vomiting methadone soon after swallowing, and it is essential that the prescription is replaced and a safe antiemetic is given in such circumstances.

    In some cases, neonates must be closely observed for many weeks to ensure that delayed severe withdrawal symptoms can be treated. The long term effects of methadone exposure on the infant's behaviour and motor development are not known, but interuterine growth retardation can persist into childhood.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    In breastfeeding methadone should only be used with caution and with monitoring of the infant.

    Methadone, like all opioids, is excreted in breast milk. The infant should be monitored for drowsiness, adequate weight gain and developmental milestones, and medical advice should be sought immediately if the infant suffers from increased sleepiness, has difficulty feeding, breathing difficulties or limpness. Particular care should be taken with children with a tendency for apnoea, due to the risk of respiratory depression, and infants should be monitored for somnolence and respiratory problems in the case of repeated doses of methadone. Maternal doses above 100 mg are particularly associated with sedation and respiratory depression in the infant, especially if the infant wasn't exposed in utero.

    The studies referred to in Schaefer indicate that methadone is well tolerated during breastfeeding. Breastfeeding should be encouraged, and it is recommended that mothers should breastfeed immediately before a dose in order to avoid peak concentrations of opioid in the breast milk. The mother should be advised to monitor her infant for symptoms of both exposure to methadone and withdrawal symptoms. The evidence suggests breastfeeding infants who have been exposed in utero may decrease neonatal withdrawal symptoms. However, only small amounts are transferred in the milk, so further dosing may be required to prevent neonatal withdrawal symptoms effectively.

    A study conducted where eight women breastfed their baby whilst on methadone showed no effects of methadone exposure on the infant during the duration of breastfeeding (2.5 to 21 months) or within the dose range 25 to 180 mg. The estimated mean daily methadone dose in the newborn was 0.05 mg. Other studies consider the amount secreted in breast milk to be negligible.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Effects on Ability to Drive and Operate Machinery

    This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving. When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them. It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1.The medicine has been prescribed to treat a medical or dental problem and 2.The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine and 3.The medicine was not affecting the ability to drive safely. For further guidance see


    Abrupt cessation of treatment can lead to withdrawal symptoms which, although similar to those with morphine, are less intense but more prolonged. Withdrawal of treatment should therefore be gradual.

    Patients should be advised that alcohol may enhance the sedative and hypotensive effects of methadone, and increase respiratory depression.

    Advise patients to go to their doctor if they start or wish to stop smoking as dosage adjustment may be required. Patients should be told that they may experience a reduced effect and possible withdrawal symptoms if they start smoking or increased effects and possible side effects if they stop smoking without their doctor first modifying their dose.

    Advise patient that their ability to drive or operate machinery may be affected by side effects.

    Side Effects

    Biliary spasm
    Difficulty in micturition
    Dry eyes
    Dry mouth
    Dryness of nose
    Facial flushing
    Induration (injection site)
    Local pain (injection site)
    Local reaction at injection site
    Mood changes
    Muscle rigidity
    Orthostatic hypotension
    Prolongation of QT interval
    Raised intracranial pressure
    Reduced libido
    Respiratory depression
    Sexual dysfunction
    Sleep disturbances
    Torsades de pointes
    Ureteric spasm
    Urinary retention
    Visual disturbances


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: May 2014

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on March 24, 2014.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Summary of Product Characteristics: Methadone 10 mg/ml solution for injection. Wockhardt UK Ltd. Revised March 2007.

    Summary of Product Characteristics: Methadone Injection BP 1%. Martindale Pharmaceuticals. Revised March 2009.

    Summary of Product Characteristics: Methadone Injection B.P. 10 mg/ml, 1 ml, 2 ml, 5 ml & 10 ml. Mercury Pharma International Ltd. Revised August 2012.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon

    Therapeutics in Pregnancy and Lactation (2000) Lee, A., Inch, S. and Finnigan, D. Radcliffe Medical Press, Abingdon.

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Methadone Last revised: January 16, 2014.
    Last accessed: March 24, 2014. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: Last accessed: 6 January 2015

    Specialist Pharmacy Service (SPS)
    Available at:
    What are the clinically significant drug interactions with tobacco smoking? Last revised: July 2020
    Last accessed: 07 December 2020

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