Methadone

• Methadone is a type of medicine called an opioid. Opioids include painkillers such as codeine, morphine and diamorphine (heroin). They work by mimicking the action of naturally occurring pain-reducing chemicals called endorphins.

What is it used for?

• Treatment of addiction to opioids such as heroin.
• Relief of moderate to severe pain.
• Cough in terminal disease, eg lung cancer.

How does it work?

• Methadone is a type of medicine called an opioid. Opioids include painkillers such as codeine, morphine and diamorphine (heroin). They work by mimicking the action of naturally occurring pain-reducing chemicals called endorphins
• Endorphins are found in the brain and spinal cord and reduce pain by combining with opioid receptors. However, opioids also act in the brain to produce a 'high' (feelings of euphoria) and hallucinations. They can be both physically and psychologically addictive and people taking them long-term can become dependent on them.
• Methadone is an opioid that is used mainly to wean people off their addiction to stronger opioids such as diamorphine (heroin). It is prescribed as a substitute for such drugs. By acting on the same opioid receptors as other opioids, methadone prevents the physical withdrawal symptoms that occur when these drugs are stopped. This prevents physical cravings for the drug. Over time, the dose of methadone can be gradually reduced until it can be stopped completely.
• Methadone is itself physically addictive, but is less psychologically addictive than heroin because it does not produce the same 'high' or sense of euphoria. This makes it easier to gradually reduce the methadone dose until no physical dependence remains.
• Methadone substitution therapy for opioid addiction must be used in combination with other medical, social and psychological treatment.
• Methadone, being an opioid, is also sometimes prescribed for the relief of moderate to severe pain.
• Methadone can also be used to suppress dry cough in people with terminal illnesses such as lung cancer. Coughing is a reflex response to irritation of the airways. Methadone may be used to block the cough reflex in situations where the cough serves no purpose (eg dry persistent cough due to lung irritation in lung cancer). It suppresses coughs by decreasing nerve messages from the brain that cause coughing.

Key Points

• This medicine may cause drowsiness. If affected do not drive or operate machinery. Drowsiness will be made worse by alcohol, tranquilisers, sedatives and sleeping tablets, for example benzodiazepines such as temazepam. Taking these in combination with methadone can also cause potentially dangerous problems with breathing and so should be avoided while you are taking this medicine.
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• Methadone is physically addictive and, as a result, withdrawal symptoms can occur if the medicine is stopped suddenly after prolonged use. For this reason, when a person no longer needs this medicine it is usually necessary to reduce treatment gradually to avoid withdrawal symptoms.

Use with caution in

• Elderly people.
• Weak, ill or debilitated people.
• People with decreased kidney function.
• People with liver disease or decreased liver function.
• People with decreased lung function or breathing difficulties, for example asthma.
• People with a history of convulsions (fits), eg epilepsy.
• Inflammatory bowel disorders, eg Crohn's disease or ulcerative colitis.
• People with severe constipation or any obstruction in the bowel.
• People with diseases of the bile ducts.
• People who have difficulty passing urine, for example men with an enlarged prostate gland.
• People with an underactive thyroid gland (hypothyroidism).
• People with reduced production of natural steroid hormones from the adrenal glands (adrenocortical insufficiency).
• A condition called myasthenia gravis, which involves abnormal muscle weakness.
• People with low blood pressure (hypotension).
• People with reduced blood flow to vital internal organs (shock).
• Heart disease.
• People with a history of problems with the electrical signals in the heart or abnormal heart beats (arrhythmias).
• People with a personal or family history of an abnormal heart rhythm, seen on a heart monitoring trace (ECG) as a 'prolonged QT interval', and people taking other medicines that can could increase the risk of this (see end of factsheet for more details).
• People with a family history of sudden death.
• People with disturbances in the levels of electrolytes in their blood (eg low potassium or magnesium levels).

Not to be used in

• Children.
• People with very slow, shallow breathing (respiratory depression).
• People with chronic obstructive airways disease (COPD).
• People having an asthma attack.
• People with a head injury or raised pressure inside the skull.
• People with a type of tumour of the adrenal glands called a phaeochromocytoma.
• People dependent on non-opioid drugs.
• People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

• Methadone should be used with caution during pregnancy and only if the expected benefit to the mother outweighs any potential risk to the baby. If the mother is dependent on methadone during the third trimester of pregnancy, the baby may have withdrawal symptoms and breathing problems after birth and will need to be closely monitored.
• Methadone passes into breast milk. However, it is recommended that women who are dependent on methadone should breastfeed their babies, because the benefits of breastfeeding to the baby usually outweigh the risks.

Side effects

• Drowsiness. 
• Confusion.
• Nausea and vomiting.
• Dry mouth, eyes or nose.
• Contracted (pinpoint) pupils.
• Constipation.
• Difficulty passing urine.
• Slow, shallow breathing (respiratory depression).
• Low blood pressure (hypotension).
• Feeling of unease, restlessness, agitation or being unwell.
• Seeing or hearing things that are not really there (hallucinations).
• Mood changes.
• Decreased heart rate.
• Awareness of your heartbeat (palpitations).
• Rash or itching.
• Decreased sex drive.
• Painful periods or stopping of periods.
• Addiction to the medicine (dependence).
• Excessive sweating.
• Abnormal heartbeats (arrhythmias).
• Raised pressure inside the skull (intracranial pressure).
• Hypothermia.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

Methadone should not be taken by people who have taken a monoamine oxidase inhibitor (MAOI) in the last 14 days. MAOIs include the antidepressants phenelzine, isocarboxazid, tranylcypromine and moclobemide.

There may be an increased risk of side effects such as drowsiness, sedation, low blood pressure and slow, shallow breathing that can potentially be fatal, if this medicine is used with other medicines that have a sedative effect on the central nervous system. These include the following and they should be avoided while taking this medicine:

• alcohol
• antipsychotics, eg haloperidol, chlorpromazine
• barbiturates, eg phenobarbital, amobarbital
• benzodiazepines, eg diazepam, temazepam
• other opioid painkillers, eg codeine, morphine, fentanyl
• sedating antihistamines, eg chlorphenamine, hydroxyzine
• sleeping tablets, eg zopiclone
• tricyclic antidepressants, eg amitriptyline.

The following medicines may reduce the breakdown of methadone by the body and thus increase the level of methadone in the blood and the risk of its side effects:

• azole antifungals, eg itraconazole, ketoconazole, fluconazole, voriconazole
• cimetidine
• ciprofloxacin
• SSRI antidepressants, eg fluvoxamine, fluoxetine, paroxetine, sertraline
• macrolide antibiotics, eg erythromycin, clarithromycin.

The following medicines may increase the breakdown of methadone in the body and so could cause withdrawal symptoms if given to someone dependent on methadone:

• antiretrovirals for HIV infection, eg abacavir, nelfinavir, ritonavir, nevirapine, efavirenz, amprenavir (methadone may also lower the blood level of amprenavir and could make it less effective)
• carbamazepine
• phenobarbital
• phenytoin
• primidone
• rifampicin
• rilpivirine
• the herbal remedy St John's wort (Hypericum perforatum).

The following medicines oppose the effects of methadone and can cause withdrawal symptoms if given to someone dependent on methadone:

• buprenorphine
• nalmefene
• naloxone
• naltrexone
• pentazocine.

Methadone slows down activity in the gut and could oppose the effect of domperidone or metoclopramide, which work by increasing muscle contractions in the gut.

There may be an increased risk of abnormal heartbeats (seen on an ECG as a 'prolonged QT interval') if methadone is taken in combination with other medicines that can also potentially cause this problem, such as the following:

• arsenic trioxide
• atomoxetine
• boceprevir
• bosutinib
• certain medicines to treat abnormal heartbeats (antiarrhythmics), eg amiodarone, procainamide, quinidine, disopyramide, sotalol, dronedarone
• certain antidepressants, eg citalopram, escitalopram, clomipramine
• certain antipsychotics, eg haloperidol, chlorpromazine, sertindole, thioridazine, pimozide, amisulpride, droperidol
• certain antimalarials, eg quinine, mefloquine, chloroquine, Riamet
• certain other anti-infectives, eg clarithromycin, telithromycin, voriconazole, pentamidine, moxifloxacin
• cisapride
• delamanid
• ranolazine
• saquinavir
• telaprevir
• terfenadine
• tolterodine
• vandetanib
• vardenafil.

There may also be an increased risk of abnormal heartbeats if methadone is taken in combination with medicines that can cause disturbances in the levels of electrolytes (eg potassium and magnesium) in the blood, for example:

• corticosteroids such as prednisolone
• diuretics such as furosemide or bendroflumethiazide
• stimulant laxatives such as senna or bisacodyl.

References:

https://www.webmd.com/mental-health/addiction/what-is-methadone#1

https://www.netdoctor.co.uk/medicines/brain-nervous-system/a8009/methadone/

http://www.drugs.ie/phone

https://spunout.ie/health/article/methadone

https://en.wikipedia.org/wiki/Methadone

https://www.dtcb.ie/faq/article.asp?FID=37&T=F