Drugs List

Therapeutic Indications

Uses

Opioid drug dependency - treatment
Pain - moderate to severe

Unlicensed Uses

Treatment of neonatal opioid withdrawal

Contraindications

Acute alcohol intoxication
Children 1 month to 18 years
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute respiratory depression
Biliary tract disorder
Coma
Head trauma
Labour
Long QT syndrome
Non-opioid drug dependence
Obstructive pulmonary disease
Phaeochromocytoma
Raised intracranial pressure
Renal tract spasm
Severe hepatic disorder
Torsade de pointes
Ulcerative colitis

Precautions and Warnings

Debilitation
Elderly
Family history of long QT syndrome
Family history of sudden death
Females of childbearing potential
Neonates
Shock
Tobacco smoking
Active liver disease
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Brain damage
Breastfeeding
Drug misuse
Electrolyte imbalance
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
History of torsade de pointes
Hypotension
Hypothyroidism
Inflammatory bowel disease
Ischaemic heart disease
Mild hepatic impairment
Myasthenia gravis
Pregnancy
Psychiatric disorder
Reduced respiratory reserve
Renal impairment
Seizures

Correct electrolyte disorders before treatment
May cause hepatic encephalopathy in patients with hepatic disease
May exacerbate asthma
Reduce dose in patients with hepatic impairment
Reduce dose in patients with 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
Not all available brands are licensed for all indications
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain Quinoline Yellow (E104) : May cause allergic reactions
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain benzoic acid
Some formulations contain hydroxybenzoate
Some formulations contain propylene glycol
Some formulations contain sucrose
Some formulations contain tartrazine
Some formulations may contain alcohol
Perform ECG before and during treatment
Perform liver function tests before commencing therapy and during therapy
Monitor blood glucose during dose escalation
Monitor for constipation; give laxatives as required
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with hepatic impairment
Monitor patients with renal impairment
Monitor serum electrolytes
Neonate exposed in utero: Monitor for respiratory depression
Tolerance and dependence may occur
Consider dose reduction or change in opioid if evidence of hyperalgesia
High addiction potential
Neonate exposed in utero: Risk of visual disorder
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Prolonged use at high doses may result in hyperalgesia
May affect results of some laboratory tests
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment

Methadone can produce drowsiness and reduce consciousness, although tolerance to these effects can occur after repeated use.

Before commencing treatment with methadone hydrochloride, a strategy should be constructed with the patient for ending treatment in order to reduce the risk of addiction and drug withdrawal syndrome. Maintaining an active opioid prescription should be an active decision agreed between the patient and clinician and reviewed a minimum of every 3 months.

A full patient history should be established to document concomitant medications and past and present medical and psychiatric conditions. The risk of developing tolerance to methadone should be explained to the patient prior to treatment. All patients should be closely observed for signs of misuse, abuse or addiction. Patients at risk of opioid misuse may require additional support and monitoring.

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.

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.

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

Some brands contain propylene glycol. Due to the associated adverse affects reported in patients like renal dysfunction, acute renal failure and liver dysfunction, patients with renal or hepatic impairment should be monitored throughout treatment.

Due to the risk of concomitant use of methadone and sedatives, patients should only take sedative medicines where alternative treatment options are not possible. In these patients, sedation levels and signs of respiratory depression should be closely monitored.

Pregnancy and Lactation

Pregnancy

Use methadone with caution during pregnancy.

The manufacturer advises caution if methadone is used during pregnancy. Methadone should only be used in pregnancy if the potential benefits outweigh the risks. Use of methadone throughout pregnancy often leads to drug dependence in the foetus. 60%-90% of infants exposed in utero to methadone experience withdrawal symptoms which becomes evident shortly after birth, usually within 48 hours but can be delayed up to 7-14 days (Briggs, 2015). In such cases, advise the mother of the risk of neonatal opioid withdrawal syndrome and ensure necessary treatment will be available.

The manufacturer recommends that a careful assessment should be carried out before administration of methadone due to the risks to the foetus including respiratory depression, low birth weight and neonatal withdrawal syndrome.

Lactation

Use methadone with caution during breastfeeding.

The manufacturer advises caution if methadone is used when breastfeeding. Methadone is known to be excreted into breast milk at low levels. When considering breastfeeding, clinical specialist advice should be taken into account. If breastfeeding is considered, the dose should be as low as possible. The breastfeeding mother should be advised to monitor the infant for sedation and difficulties breathing and to seek immediate medical care at the first instance.

It has been noted that breastfeeding may reduce the withdrawal response of the infant from methadone during pregnancy. If discontinuing breastfeeding is necessary, it should be gradual to avoid increased withdrawal symptoms in the infant.

Side Effects

Agitation
Amenorrhoea
Anorexia
Anti-diuretic effect
Biliary spasm
Bradycardia
Cardiac arrest
Confusion
Constipation
Dependence
Difficulty in micturition
Diminution of potency
Disorientation
Dizziness
Drowsiness
Dry eyes
Dry mouth
Dryness of nose
Dysmenorrhoea
Dysphoria
Euphoria
Exacerbation of pre-existing asthma
Facial flushing
Fainting
Galactorrhoea
Glossitis
Haemorrhage
Hallucinations
Headache
Hypotension
Hypothermia
Increased prolactin
Insomnia
Miosis
Mood changes
Muscle rigidity
Nausea
Oedema
Palpitations
Postural hypotension
Prolongation of QT interval
Pruritus
Raised intracranial pressure
Rash
Reduced libido
Respiratory depression
Restlessness
Sedation
Sexual dysfunction
Shock
Sleep disturbances
Sweating
Tachycardia
Torsades de pointes
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Weakness
Weight gain
Xerostomia

Presentation

Oral liquid formulations of methadone hydrochloride.

Drugs List

Therapeutic Indications

Uses

Opioid drug dependency - treatment
Pain - moderate to severe

Unlicensed Uses

Treatment of neonatal opioid withdrawal

Dosage

Adults

Neonates

Patients with Renal Impairment

Contraindications

Acute alcohol intoxication
Children 1 month to 18 years
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute respiratory depression
Biliary tract disorder
Coma
Head trauma
Labour
Long QT syndrome
Non-opioid drug dependence
Obstructive pulmonary disease
Phaeochromocytoma
Raised intracranial pressure
Renal tract spasm
Severe hepatic disorder
Torsade de pointes
Ulcerative colitis

Precautions and Warnings

Debilitation
Elderly
Family history of long QT syndrome
Family history of sudden death
Females of childbearing potential
Neonates
Shock
Tobacco smoking
Active liver disease
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Brain damage
Breastfeeding
Drug misuse
Electrolyte imbalance
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
History of torsade de pointes
Hypotension
Hypothyroidism
Inflammatory bowel disease
Ischaemic heart disease
Mild hepatic impairment
Myasthenia gravis
Pregnancy
Psychiatric disorder
Reduced respiratory reserve
Renal impairment
Seizures

Correct electrolyte disorders before treatment
May cause hepatic encephalopathy in patients with hepatic disease
May exacerbate asthma
Reduce dose in patients with hepatic impairment
Reduce dose in patients with 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
Not all available brands are licensed for all indications
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain Quinoline Yellow (E104) : May cause allergic reactions
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain benzoic acid
Some formulations contain hydroxybenzoate
Some formulations contain propylene glycol
Some formulations contain sucrose
Some formulations contain tartrazine
Some formulations may contain alcohol
Perform ECG before and during treatment
Perform liver function tests before commencing therapy and during therapy
Monitor blood glucose during dose escalation
Monitor for constipation; give laxatives as required
Monitor patients with a history of alcoholism and drug abuse
Monitor patients with hepatic impairment
Monitor patients with renal impairment
Monitor serum electrolytes
Neonate exposed in utero: Monitor for respiratory depression
Tolerance and dependence may occur
Consider dose reduction or change in opioid if evidence of hyperalgesia
High addiction potential
Neonate exposed in utero: Risk of visual disorder
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Prolonged use at high doses may result in hyperalgesia
May affect results of some laboratory tests
Avoid abrupt withdrawal
To discontinue, reduce dose gradually
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment

Methadone can produce drowsiness and reduce consciousness, although tolerance to these effects can occur after repeated use.

Before commencing treatment with methadone hydrochloride, a strategy should be constructed with the patient for ending treatment in order to reduce the risk of addiction and drug withdrawal syndrome. Maintaining an active opioid prescription should be an active decision agreed between the patient and clinician and reviewed a minimum of every 3 months.

A full patient history should be established to document concomitant medications and past and present medical and psychiatric conditions. The risk of developing tolerance to methadone should be explained to the patient prior to treatment. All patients should be closely observed for signs of misuse, abuse or addiction. Patients at risk of opioid misuse may require additional support and monitoring.

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.

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.

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

Some brands contain propylene glycol. Due to the associated adverse affects reported in patients like renal dysfunction, acute renal failure and liver dysfunction, patients with renal or hepatic impairment should be monitored throughout treatment.

Due to the risk of concomitant use of methadone and sedatives, patients should only take sedative medicines where alternative treatment options are not possible. In these patients, sedation levels and signs of respiratory depression should be closely monitored.

Pregnancy and Lactation

Pregnancy

Use methadone with caution during pregnancy.

The manufacturer advises caution if methadone is used during pregnancy. Methadone should only be used in pregnancy if the potential benefits outweigh the risks. Use of methadone throughout pregnancy often leads to drug dependence in the foetus. 60%-90% of infants exposed in utero to methadone experience withdrawal symptoms which becomes evident shortly after birth, usually within 48 hours but can be delayed up to 7-14 days (Briggs, 2015). In such cases, advise the mother of the risk of neonatal opioid withdrawal syndrome and ensure necessary treatment will be available.

The manufacturer recommends that a careful assessment should be carried out before administration of methadone due to the risks to the foetus including respiratory depression, low birth weight and neonatal withdrawal syndrome.

Lactation

Use methadone with caution during breastfeeding.

The manufacturer advises caution if methadone is used when breastfeeding. Methadone is known to be excreted into breast milk at low levels. When considering breastfeeding, clinical specialist advice should be taken into account. If breastfeeding is considered, the dose should be as low as possible. The breastfeeding mother should be advised to monitor the infant for sedation and difficulties breathing and to seek immediate medical care at the first instance.

It has been noted that breastfeeding may reduce the withdrawal response of the infant from methadone during pregnancy. If discontinuing breastfeeding is necessary, it should be gradual to avoid increased withdrawal symptoms in the infant.

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

Side Effects

Agitation
Amenorrhoea
Anorexia
Anti-diuretic effect
Biliary spasm
Bradycardia
Cardiac arrest
Confusion
Constipation
Dependence
Difficulty in micturition
Diminution of potency
Disorientation
Dizziness
Drowsiness
Dry eyes
Dry mouth
Dryness of nose
Dysmenorrhoea
Dysphoria
Euphoria
Exacerbation of pre-existing asthma
Facial flushing
Fainting
Galactorrhoea
Glossitis
Haemorrhage
Hallucinations
Headache
Hypotension
Hypothermia
Increased prolactin
Insomnia
Miosis
Mood changes
Muscle rigidity
Nausea
Oedema
Palpitations
Postural hypotension
Prolongation of QT interval
Pruritus
Raised intracranial pressure
Rash
Reduced libido
Respiratory depression
Restlessness
Sedation
Sexual dysfunction
Shock
Sleep disturbances
Sweating
Tachycardia
Torsades de pointes
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Weakness
Weight gain
Xerostomia

Effects on Laboratory Tests

Elevated levels of globulins and blood albumin have been noted in patients taking methadone.

Methadone may result in false results during urine testing for pregnancy.

Withdrawal Symptoms and Signs

Some or all of the opioid drug withdrawal syndrome side effects are: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

When a patient no longer requires treatment, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

Overdosage

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 ).

Further Information

Last Full Review Date: February 2022

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Methadone 1 mg/ml Oral solution BP-Sugar Free. Thornton & Ross Ltd. Revised April 2015.
Summary of Product Characteristics: Methadone Mixture 1 mg/ml. Thornton & Ross Ltd. Revised March 2015.

Summary of Product Characteristics: Methadone 1 mg/ml Oral solution Sugar Free. Martindale Pharmaceuticals Ltd. Revised October 2021.
Summary of Product Characteristics: Methadone Mixture DTF 1 mg/ml Physeptone Mixture. Martindale Pharmaceuticals Ltd. Revised May 2020.

Summary of Product Characteristics: Methadone Hydrochloride DTF 1 mg/ml Oral solution. Rosemont Pharmaceuticals Ltd. February 2022.
Summary of Product Characteristics: Methadone Hydrochloride Sugar Free 1 mg/ml Oral solution. Rosemont Pharmaceuticals Ltd. Revised December 2021.
Summary of Product Characteristics: Metharose Sugar Free 1 mg/ml Oral solution. Rosemont Pharmaceuticals Ltd. Revised December 2021.

Summary of Product Characteristics: Physeptone Mixture 1mg/ml. Martindale Pharmaceuticals Ltd. Revised May 2020.
Summary of Product Characteristics: Physeptone 1mg/ml Oral solution sugar-free. Martindale Pharmaceuticals Ltd. Revised October 2021.

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: 18 February 2022

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 February 2022

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