Methadone

How does it work?

Methadone is a type of medicine called an opioid.

Opioids are painkillers such as codeine, morphine and diamorphine (heroin) that 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 phsychologically 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 is 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 cough by decreasing nerve messages from the brain that cause cough.

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.

Warning!

• 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 such as benzodiazepines. 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.
• Your doctor may want to monitor your heartbeat with an ECG before you start treatment with this medicine and after your dose has been stabilised. Anyone taking more than 100mg methadone per day should have their heartbeat monitored with an ECG.
• 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.
• Decreased kidney function.
• Decreased liver function.
• Liver disease.
• People with decreased lung function or breathing difficulties, for example asthma.
• History of convulsions (fits), eg epilepsy.
• Inflammatory bowel disorders, eg Crohn's disease or ulcerative colitis.
• People with constipation or any obstruction in the bowel.
• Diseases of the bile ducts.
• Enlarged prostate gland.
• Underactive thyroid gland (hypothyroidism).
• Lack of production of natural steroid hormones from the adrenal gland (adrenocortical insufficiency).
• Abnormal muscle weakness (myasthenia gravis).
• Low blood pressure (hypotension).
• Reduced blood flow to vital internal organs (shock).
• Heart disease.
• History of problems with the electrical signals in the heart or abnormal heart beats (arrhythmias).
• Personal or family history of an abnormal heart beat, 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).
• Family history of sudden death.
• Disturbance in the levels of electrolytes in the blood (eg low potassium or magnesium levels).

Not to be used in

• Children.
• Slow, shallow breathing (respiratory depression).
• Chronic obstructive airways disease (COPD).
• People having an asthma attack.
• People with a head injury or raised pressure inside the skull.
• 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

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• 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 after birth.
• However, when methadone is prescribed as a substitute for illegal opioids such as heroin, it generally carries a lower risk to the mother and baby than if the mother continues to use illegal drugs. It has been used safely for many years to manage opioid dependence in pregnant women. Withdrawal from methadone (detox) is not generally recommended during the first trimester, as this may increase the risk of miscarriage. Starting withdrawal from methadone is also not generally recommended during the third trimester, as even mild withdrawal symptoms in the mother may cause stress and lack of oxygen to the baby, and sometimes even stillbirth. In the third trimester the metabolism of methadone increases, and as a result it may sometimes be necessary to increase the methadone dose, or split a once daily dose into two doses. It is very important that pregnant women who are prescribed methadone are closely monitored by their doctor and midwife.
• 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. The methadone in the breast milk may also help reduce withdrawal symptoms in a baby born to a methadone dependent mother. It is important that the dose of methadone taken by the mother is kept as low as possible, and the nursing baby should be closely monitored to avoid it being sedated. It is important to seek medical advice from your doctor and midwife.

Label warnings

• This medication may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

• 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.
• False perceptions of 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).

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?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

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, which should be avoided while taking this medicine:

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

The following medicines may increase the blood level of methadone and thus increase the risk of its side effects:

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

The following medicines may reduce the blood level of methadone 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.

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

• buprenorphine
• naltrexone
• naloxone
• 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:

• atomoxetine
• cisapride
• certain medicines to treat abnormal heartbeats (antiarrhythmics), eg amiodarone, procainamide, quinidine, disopyramide, sotalol
• certain antidepressants, eg amitriptyline, imipramine, maprotiline
• certain antipsychotics, eg haloperidol, chlorpromazine, sertindole, thioridazine, pimozide
• certain antimalarials, eg quinine, mefloquine, chloroquine
• certain other anti-infectives, eg erythromycin, telithromycin, voriconazole, pentamidine
• terfenadine.

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 diuretics (water tablets).