Drugs List

Therapeutic Indications

Uses

Pain - moderate to severe

Contraindications

Acute alcohol intoxication
Children under 18 years
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute respiratory depression
Galactosaemia
Head trauma
Labour
Long QT syndrome
Obstructive pulmonary disease
Raised intracranial pressure
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Severe illness
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Drug misuse
Electrolyte imbalance
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of drug misuse
History of torsade de pointes
Hypotension
Hypothyroidism
Lactose intolerance
Pregnancy
Psychiatric disorder
Reduced respiratory reserve
Renal impairment
Seizures

Correct electrolyte disorders before treatment
May exacerbate asthma
Reduce dose in hypothyroidism
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Contains lactose
Perform ECG before and during treatment
If adrenal insufficiency occurs, consider corticosteroid cover
May cause respiratory depression
Monitor blood glucose periodically
Monitor serum electrolytes
Monitor serum prolactin during long-term use
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Reassess need for continued treatment at regular intervals
Tolerance and dependence may occur
Consider dose reduction or change in opioid if evidence of hyperalgesia
May induce or worsen existing constipation
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
Reduce dose in elderly
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

Before commencing treatment with methadone, a strategy should be constructed with the patient for ending treatment in order to reduce the risk of addiction and drug withdrawal syndrome.

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.

Long-term use of opioid analgesics may be associated with decreased sex hormone levels and increased prolactin.

Pregnancy and Lactation

Pregnancy

Use methadone with caution during pregnancy.

The manufacturer advises caution if methadone is used during pregnancy. 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.

Animals studies have shown reproductive toxicity. Detoxification of the mother from methadone should be avoided, especially after the 20th week of pregnancy. The manufacturer recommends administering maintenance treatment with methadone.

Lactation

Use methadone with caution during breastfeeding.

The manufacturer advises caution if methadone is used when breastfeeding. Methadone is known to be excreted into breastmilk 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
Asthenia
Bile duct dyskinesia
Blurred vision
Bradycardia
Constipation
Dependence
Disorientation
Dizziness
Dysmenorrhoea
Dysphoria
Euphoria
Facial flushing
Fatigue
Fluid retention
Galactorrhoea
Glossitis
Hallucinations
Headache
Hyperprolactinaemia
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hypotension
Insomnia
Miosis
Nausea
Oedema
Palpitations
Prolongation of QT interval
Pruritus
Pulmonary oedema
Raised intracranial pressure
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Sedation
Sweating
Syncope
Thrombocytopenia
Torsades de pointes
Urinary retention
Urticaria
Vertigo
Vomiting
Weight gain
Xerostomia

Presentation

Tablets containing methadone.

Drugs List

Therapeutic Indications

Uses

Pain - moderate to severe

Dosage

Use caution with repeated doses in elderly and ill patients due to its long plasma half-life.

Adults

Patients with Renal Impairment

Contraindications

Acute alcohol intoxication
Children under 18 years
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute respiratory depression
Galactosaemia
Head trauma
Labour
Long QT syndrome
Obstructive pulmonary disease
Raised intracranial pressure
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Severe illness
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Drug misuse
Electrolyte imbalance
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of drug misuse
History of torsade de pointes
Hypotension
Hypothyroidism
Lactose intolerance
Pregnancy
Psychiatric disorder
Reduced respiratory reserve
Renal impairment
Seizures

Correct electrolyte disorders before treatment
May exacerbate asthma
Reduce dose in hypothyroidism
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Contains lactose
Perform ECG before and during treatment
If adrenal insufficiency occurs, consider corticosteroid cover
May cause respiratory depression
Monitor blood glucose periodically
Monitor serum electrolytes
Monitor serum prolactin during long-term use
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Reassess need for continued treatment at regular intervals
Tolerance and dependence may occur
Consider dose reduction or change in opioid if evidence of hyperalgesia
May induce or worsen existing constipation
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
Reduce dose in elderly
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

Before commencing treatment with methadone, a strategy should be constructed with the patient for ending treatment in order to reduce the risk of addiction and drug withdrawal syndrome.

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.

Long-term use of opioid analgesics may be associated with decreased sex hormone levels and increased prolactin.

Pregnancy and Lactation

Pregnancy

Use methadone with caution during pregnancy.

The manufacturer advises caution if methadone is used during pregnancy. 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.

Animals studies have shown reproductive toxicity. Detoxification of the mother from methadone should be avoided, especially after the 20th week of pregnancy. The manufacturer recommends administering maintenance treatment with methadone.

Lactation

Use methadone with caution during breastfeeding.

The manufacturer advises caution if methadone is used when breastfeeding. Methadone is known to be excreted into breastmilk 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
Asthenia
Bile duct dyskinesia
Blurred vision
Bradycardia
Constipation
Dependence
Disorientation
Dizziness
Dysmenorrhoea
Dysphoria
Euphoria
Facial flushing
Fatigue
Fluid retention
Galactorrhoea
Glossitis
Hallucinations
Headache
Hyperprolactinaemia
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hypotension
Insomnia
Miosis
Nausea
Oedema
Palpitations
Prolongation of QT interval
Pruritus
Pulmonary oedema
Raised intracranial pressure
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Sedation
Sweating
Syncope
Thrombocytopenia
Torsades de pointes
Urinary retention
Urticaria
Vertigo
Vomiting
Weight gain
Xerostomia

Effects on Laboratory Tests

Opioid analgesics delay gastric emptying, thereby affecting test results. Delivery of technetium Tc 99m disofenin to the small bowel may be prevented and plasma amylase and plasma lipase activity may increase because opioid analgesics may cause constriction of the sphincter of Oddi and increased biliary tract pressure; in consequence delayed visualisation and thus resemble obstruction of the common bile duct is observed.

The diagnostic utility of determinations of these enzymes may be compromised for up to 24 hours after the medication has been administered.

Withdrawal Symptoms and Signs

Some or all of the methadone 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: September 2021

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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 tablets. Martindale Pharma. Revised May 2020.

The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.

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: 11 April 2019

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 September 2021

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Methadone. Last revised: 21 June 2021
Last accessed: 17 September 2021