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Methadone is part of a category called opioids. It was created by German doctors during World War II. When it arrived in the United States, it was used to treat people with extreme pain. Today, your doctor may use it as part of your treatment for an addiction to heroin or narcotic painkillers.
It works a lot like morphine does. You can take it as a tablet, a powder, or a liquid. It must be prescribed by a doctor. People who take it illegally often inject it, which exposes them to diseases like HIV.

Even though it’s safer than some other narcotics, your doctor should keep a close watch on you while you take methadone. Taking it can lead to addiction or abuse.

Methadone changes the way your brain and nervous system respond to pain so that you feel relief. Its effects are slower than those of other strong painkillers like morphine. It blocks the high you get from drugs like codeine, heroin, hydrocodone, morphine, and oxycodone.

Your doctor may prescribe methadone if you’re in a lot of pain from an injury, surgery, or chronic illness.
It can also help if you’re in treatment for addiction to other opioids. It can give a similar feeling and prevent withdrawal symptoms. You may hear this called replacement therapy. Methadone replaces the opioids in your system with milder effects.


Indication
For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain.


 Methadone Warnings

Methadone carries a black-box warning because it may cause serious or life-threatening breathing problems. The risk of breathing problems is highest during the first 72 hours of treatment and any time your dose is increased.

You should tell your doctor if you have or have ever had asthma, slowed breathing, chronic obstructive pulmonary disease (COPD), or any other type of lung disease; a head injury; any condition that increases pressure in your brain; or obstructive or central sleep apnea.

Also, you should watch for any signs of breathing problems, including slowed breathing, long pauses between breaths, or shortness of breath. This medication may also cause a rare heart problem known as a long QT interval. This condition can cause irregular heartbeat, fainting, or sudden death.

You should tell your doctor if you or anyone in your family has or has ever had long QT syndrome.

Also, tell your healthcare provider if you have ever had a slow or irregular heartbeat, heart disease, or low levels of potassium or magnesium in your blood.

Call your doctor right away if you experience a pounding heartbeat, lightheadedness, dizziness, or fainting while taking methadone.

Before taking methadone, you should tell your doctor if you have or have ever had:
  • Paralytic ileus (a condition where digested food doesn't move through the intestines)
  • A blockage in your intestine
  • An enlarged prostate
  • Difficulty urinating
  • Addison's disease (a condition where the adrenal gland doesn't work properly)
  • Seizures
  • Thyroid, pancreas, gallbladder, liver, or kidney disease

Pregnancy and Methadone

Methadone might harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while taking this medicine.
Your baby may also develop life-threatening withdrawal symptoms after birth if you take methadone during pregnancy.
Methadone can pass into breast milk and may harm a breastfeeding baby, so talk to your doctor before breastfeeding while taking this medication.

 Mechanism of action
 
Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. 

 The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.

 Absorptiom
Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%.
Volume of distribution
1.0 to 8.0 L/kg
Protein binding
In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%).

Metabolism
Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine.

Common Side Effects of Methadone
You should tell your doctor if any of the following side effects become severe or don't go away:

Serious Side Effects of Methadone
You should call your doctor immediately or seek emergency medical help if you experience any of the following severe side effects:
  • Seizures
  • Itching, hives, or rash
  • Hoarseness
  • Pounding heartbeat
  • Severe nervousness or restlessness
  • Difficulty swallowing or breathing
  • Extreme drowsiness
  • Fainting
  • Hallucinations (seeing or hearing things that do not exist)
  • Swelling of the eyes, face, mouth, tongue, or throat
Methadone and Alcohol
Consuming alcohol or other drugs that contain alcohol may increase serious side effects of methadone.
Talk to your doctor about the risks of drinking alcohol while taking this drug.

 Methadone and Grapefruit
Consuming grapefruit or grapefruit juice may interact with the way methadone works in your body.
You should talk to your doctor about this potential interaction, or avoid all grapefruit products while taking methadone.

Methadone interactions

Many medications may interact with methadone.
Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:
  • St. John's wort
  • Other narcotic pain drugs
  • Antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil)
  • Certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend)
  • Diuretics (water pills)
  • Erythromycin (Erythrocin)
  • Fludrocortisone
  • Certain laxatives
  • Sleeping pills or tranquilizers
  • Medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone, Nexterone), disopyramide (Norpace), dofetilide (Tikosyn), ibutilide (Corvert), flecainide, procainamide, and quinidine (Quinidex, in Nuedexta)
  • Nicardipine (Cardene)
  • Risperidone (Risperdal)
  • Sertraline (Zoloft)
  • Antihistamines
  • Buprenorphine (Suboxone, in Zubsolv)
  • Butorphanol
  • Calcium channel blocking agents such as carbamazepine (Tegretol)
  • Fluvoxamine (Luvox)
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 References
https://www.drugabuse.gov/sites/default/files/pdf/partb.pdf
http://www.who.int/entity/substance_abuse/activities/proposal_for_inclusion_of_buprenorphine_in_who_list_of_essential_medicines.pdf?ua=1
http://www.cesar.umd.edu/cesar/drugs/methadone.pdf
https://www.aafp.org/afp/2001/0615/p2404.pdf
https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-018-3717-2
http://deadiversion.usdoj.gov/drug_chem_info/methadone/methadone.pdf
https://www.who.int/medicines/news/methadone-programme-tanzania/en/
https://medlineplus.gov/druginfo/meds/a682134.html
https://www.webmd.com/mental-health/addiction/what-is-methadone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070723/