- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Sugar free concentrated oral solution containing 10mg/ml methadone hydrochloride
Sugar free concentrated oral solution containing 20mg/ml methadone hydrochloride
For use in the treatment of opioid drug addictions (as a narcotic abstinence syndrome suppressant)
Dilute product before use
Initial dose of 10mg to 20mg a day.
Increase by 10mg to 20mg a day until there are no signs of withdrawal or intoxication. Adjust dose based on each individual patient, with the aim for gradual reduction.
The usual maintenance dose is between 40mg to 60mg a day.
The following alternate dosing schedule may be suitable:
Initial dose up to 40mg a day if tolerance high and under expert supervision.
Increase as necessary by 5mg to 10mg a day based on each individual patient response, until no signs of withdrawal nor evidence of intoxication. Maximum dose increase should not exceed 30mg a week.
The usual maintenance dose is between 60mg to 120mg a day.
Patients with Renal Impairment
Consider dose reduction or avoid as there may be an increased and prolonged effect, and increased cerebral sensitivity.
The Renal Drug Handbook offers the following dosages in renal impairment:
GFR 20 ml/minute to 50 ml/minute - Dose as in normal renal function
GFR 10 ml/minute to 20ml/minute - Dose as in normal renal function
GFR less than 10 ml/minute - 50% of normal dose, and titrate according to response
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.
As with other opioids, methadone may cause troublesome constipation, which is particularly dangerous in patients with severe hepatic impairment.
Additional Dosage Information
In severely ill patients, repeated doses should only be given with extreme caution because of the long half-life.
Patients who miss three days or more of their regular prescribed dose of opioid maintenance therapy are at risk of overdose because of loss of tolerance. Consider reducing the dose in these patients.
For oral administration
Concentrated oral solutions are intended to be used with a diluent
Acute respiratory depression
Acute alcohol intoxication
Raised intracranial pressure
Susceptibility to paralytic ileus
Obstructive airways disease
Within 2 weeks of discontinuing MAOIs
Children under 18 years of age
Use during an acute asthma attack
Torsade de pointes
Long QT syndrome
Precautions and Warnings
Methadone may cause tolerance and dependence.
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.
Methadone can produce drowsiness and reduce consciousness, although tolerance to these effects can occur after repeated use.
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.
Methadone has the potential to increase intracranial pressure, especially where it is already raised.
Asthma may be exacerbated due to histamine release. Use with caution in patients with asthma or decreased respiratory reserve.
Due to the slow accumulation of methadone in the tissues, respiratory depression may not be fully apparent for a week or two.
Pregnancy ( see Pregnancy)
Monitor infants for respiratory depression if born to mothers treated during pregnancy.
Infants born to mothers receiving methadone may suffer withdrawal symptoms.
Breastfeeding (see Lactation)
Methadone should be used with great caution in patients with acute alcoholism or convulsive disorders.
Tobacco smoke induces the cytochrome P450 isoenzyme CYP1A2, by which methadone is metabolised. This may result in reduced methadone plasma level. Dosage adjustment may be required if a patient starts or stops smoking during methadone therapy.
The risk benefit should be assessed, and methadone used with caution in the patients with:
biliary tract disorders
inflammatory or obstructive bowel disorders
Use with caution in patients at risk for QT prolongation, including:
history of cardiac conduction abnormalities
advanced heart disease or ischaemic heart disease
family history of sudden death
In patients with predisposition for QT prolongation or on concurrent drugs known to prolong the QT interval, monitor ECG before prior to treatment and again once dose is stabilised. Counsel patient on symptoms of arrhythmias.
In patients without recognised risk factors for QT prolongation, monitor ECG before dose titration above 100mg/day and at seven days after titration.
Electrolyte imbalance. Monitor serum electrolytes. Correct electrolyte disorders before treatment.
Family History of long QT syndrome.
History of torsade de pointes.
Methadone is a special hazard to children if ingested accidentally, even at low doses.
Elderly (see Dosage - Elderly )
Renal impairment (see Dosage - Renal impairment )
Hepatic impairment (see Dosage - Hepatic impairment )
As with other opioids, methadone may cause troublesome constipation, which is particularly dangerous in patients with severe hepatic impairment. Measures to avoid constipation should be initiated early.
Patients should not drive or use machines while taking methadone as it may cause drowsiness and reduce alertness. The ability to drive or use machines may be severely affected during and for some time after administration of methadone.
Alcohol may enhance the sedative and hypotensive effects of methadone and increase respiratory depression.
St John's Wort may lower plasma concentrations of methadone.
Some 'over the counter' medications may affect methadone serum levels.
Methadone may interfere with urine testing for pregnancy.
The product contains hydroxybenzoates which may cause a (delayed) allergic reaction.
The product contains propylene glycol, monitor patients with renal or hepatic impairment for adverse effects such as acute tubular necrosis.
Prolonged use may lead to adrenal insufficiency or hypogonadism.
Pregnancy and Lactation
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, according to the Clinical Knowledge Summaries.
The main problems associated with methadone use in the mother include neonatal narcotic withdrawal syndrome and low birth weight. There is also a reported increased incidence of prematurity, jaundice, thrombocytosis, stillbirths and Sudden Infant Death Syndrome (SIDS).
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, as is miscarriage. It is therefore advisable to avoid attempts at detoxification at this time. Use for prolonged periods of time, or at high doses, especially at term should also be avoided.
Methadone should not be used during labour, due to the risk of gastric stasis and inhalation pneumonia in the mother, and foetal distress.
In some cases, neonates must be closely observed for many weeks to ensure that delayed severe withdrawal symptoms can be treated. Phenobarbital the drug of choice for this treatment. 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 14-17 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 ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Crosses placenta? - Yes.
Effects on foetus - Possibility of premature birth, IUGR, SIDS, stillbirth.
Other information - Methadone is the drug of choice for treating heroin dependency, but should be used with caution, especially during first and third trimesters, and avoided during labour.
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 breastfeeding, 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.
Studies suggest that methadone is well tolerated during breastfeeding (Schaefer 2007). The Clinical Knowledge Summaries state that 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 long term effects of opioids on breastfed children cannot easily be separated from the effects of prenatal opiate exposure, but breastfeeding infants who have been exposed to opioids in utero may decrease neonatal withdrawal symptoms. However, only small amounts are transferred in the milk, so the neonate may require further dosing to prevent withdrawal symptoms effectively. Propylene glycol, an excipient of this product, has been shown to be present in breast milk. Studies of breastfed infants exposed to propylene glycol have shown no teratogenic effects.
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 https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Drug excreted in breast milk? - Yes.
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 https://www.gov.uk
Advise patients that methadone treatment may severely effect their ability to drive and operate machinery.
Advise patients to avoid alcohol as concurrent use may cause serious respiratory depression and hypotension.
Advise patients to avoid products containing St John's Wort as it may lower plasma concentrations of methadone.
Advise patients to check with their pharmacist before taking over the counter preparations as some may affect serum levels of methadone.
Advise patients that methadone may interfere with urine testing for pregnancy.
Raised intracranial pressure
Difficulty in micturition
Prolongation of QT interval
Torsades de pointes
Exacerbation of pre-existing asthma
Dryness of nose
Diminution of potency
Effects on Laboratory Tests
Methadone may interfere with urine testing for pregnancy.
Withdrawal Symptoms and Signs
Symptoms and signs of acute opioid withdrawal include:
- Sweating, watering eyes, rhinorrhoea, yawning, feeling hot and cold, goosebumps, dilated pupils, cough.
- Anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased bowel sounds.
- Tremor, insomnia, restlessness, anxiety, irritability, tachycardia, hypertension.
- Generalized aches and pains.
Methadone withdrawal symptoms typically reach their peak 2-4 days after the last dose of methadone (4-6 days after stopping high doses). Symptoms do not substantially subside for 10-12 days.
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 ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Shelf Life and Storage
Store below 25 degrees C
Do not refrigerate
Discard contents 3 months after first opening container and/or diluting
Last Full Review Date: February 2011
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, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Methadose 20mg/1ml Oral Concentrate. Rosemont Pharmaceuticals Ltd. Revised March 2020.
Summary of Product Characteristics: Methadose 10mg/1ml Oral Concentrate. Rosemont Pharmaceuticals Ltd. Revised March 2020.
Therapeutics in Pregnancy and Lactation (2000) Lee, A., Inch, S. and Finnigan, D. Radcliffe Medical Press, Abingdon.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Clinical Knowledge Summaries - Opioid dependence
Available at: https://cks.library.nhs.uk/opioid_dependence/management/detailed_answers/managing_special_groups/pregnant_or_breastfeeding_women/pregnant_women
Last accessed: 11/08/08
Clinical Knowledge Summaries - Opioid dependence - Management
How should I manage someone who is breastfeeding?
Available at: https://cks.library.nhs.uk/opioid_dependence/management/detailed_answers/managing_special_groups/pregnant_or_breastfeeding_women/breastfeeding_women
Last accessed: 09/07/08
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed). Record 367 - Methadone
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: 01/04/08
Last accessed: 11/08/08
Gov.uk. 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: https://www.gov.uk Last accessed: 6 January 2015
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 September 2017
Specialist Pharmacy Service (SPS)
Available at: https://www.sps.nhs.uk/
What are the clinically significant drug interactions with tobacco smoking? Last revised: July 2020
Last accessed: 07 December 2020
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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