Drug Index


Dolophine, Methadose

fizzies, amidone, chocolate chip cookies

Methadone hydrochloride is a synthetic opioid analgesic (pain killer) that binds to the mu(µ) opioid receptor with multiple actions. It is a central nervous system depressant and relaxes smooth muscle. Examples of other opioid agonists include substances such as heroin, morphine, oxymorphone, hydromorphone, hydrocodone, and oxycodone. Methadone is primarily metabolized in the liver by N-demethylation to an inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP). Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, 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. Methadone is lipophilic (dissolves in fat) and can be stored in liver and fatty tissue. This may delay the elimination of methadone from the body. There is much variation concerning the studies done on the half-life. Estimates range from 8 to 59 hours in different studies.

Methadone is a long acting opiate. It is used for: (1) Detoxification off of other opioid medications such as heroin or other powerful opiates. (2) Maintenance treatment of opioid medication addiction. Simply put, methadone is given to prevent opiate withdrawal and craving. It occupies the same mu(µ) opioid receptor as other opiate agonists. It is substitution of a long acting opiate for shorter acting opiates. (3) It is also used in treatment of chronic pain. Methadone prescriptions for the treatment of drug addiction are not easily available. The prescriptive authority by physicians is highly controlled and monitored. Only a few selected registered physicians have the ability to prescribe the drug for " drug maintanence" and physicians have to make a special application to the FDA and the Drug Enforcement Agency. The Department of Health & Human Services and the FDA also decide dosage regimens, how, and under what circumstances methadone maintenance may be used to treat opiate addiction. Most methadone clinics must obtain an extra license and comply with extra set of both federal and state regulations. All this has made it difficult for opioid addicts to get methadone. Although there are over 700 active methadone clinics in the nation, many states don‚Äôt allow methadone clinics, forcing some patients to drive hundreds of miles each day to get their required daily dosage. Clinics in states that do allow methadone often have strict morning hours that make it difficult for patients to stick to the regimen.


Use of methadone poses a high risk for abuse or dependence. It should be used with caution in patients with a history of alcohol or substance dependence as this may highly predisposed to becoming addicted to this drug. A symptom that is easily detected with opiate use is pinpoint pupils (miosis). Psychological dependence may occur early in use of this medication, but physical dependence and tolerance may develop upon repeated administration over several weeks or months (requiring larger or more frequent dosages of methadone to achieve the same effect). When methadone is abused, the individual is seeking the euphoric effect ("high"). Mild signs of withdrawal can occur in some individuals after using methadone for several days consecutively. Methadone dependence usually occurs, even if taken as prescribed, when used for several weeks or months consecutively. Once an individual has become dependent on methadone, a primary driving force to continue using methadone (or substituting other opiate agonists) is to prevent the very unpleasant neurochemical and physical withdrawal syndrome associated with discontinuing this drug. Symptoms associated with withdrawal may include:

  • • Abdominal pain
  • • Muscle aches
  • • Joint pain
  • • Sleep problems (insomnia)
  • • Agitation, restlessness, irritability
  • • Diarrhea, intestinal spasm
  • • Dilated pupils
  • • Goose bumps
  • • Nausea
  • • Runny nose
  • • Sweating, dehydration
  • • Vomiting
  • • Restlessness
  • • Yawning, sneezing
  • • Loss of appetite (anorexia)
  • • Rapid heart rate
  • • Elevated blood pressure or temperature
  • • Rapid breathing
  • • Eyes or nose watering

(Note: the term "going cold turkey" comes from the goose-flesh that occurs during withdrawal that looks like the skin of a plucked turkey) Withdrawal of methadone should always be done under the care of a physician that is skilled at assisting patients with opiate detoxification. The withdrawal symptoms encountered detoxing off methadone usually last much longer than with withdrawal off short acting opiates. Medications are usually necessary to help control symptoms of withdrawal.

Acute overdose of methadone can cause respiratory depression, extreme drowsiness, prolonged sleeping, stupor or coma, muscle flaccidity, cold/clammy skin, constricted pupils, slow heart rate (bradycardia), low blood pressure (hypotension), coma, and death. When methadone is used in combination with alcohol or other central nervous system depressants, the two drugs potentiate one another and can greatly enhance the risk for overdose. Deaths associated with illicit use of methadone frequently have involved concomitant benzodiazepine abuse. Because of the dangers associated with overdose, immediate medical attention should be sought.


Deaths have been reported during initiation of methadone treatment for opioid dependence. In some cases, drug interactions with other drugs, both licit and illicit, have been suspected. However, in other cases, deaths appear to have occurred due to the respiratory or cardiac effects of methadone and too-rapid titration (progressive dose increases) without appreciation for the accumulation of methadone over time. Do not take methadone with any of the following unless advised to do so by your physician:

  • • antibiotics like chloroquine, clarithromycin, erythromycin, grepafloxacin, pentamidine,
  • • cisapride
  • • droperidol
  • • halofantrine
  • • haloperidol
  • • medicines for irregular heart beat like amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol
  • • pimozide
  • • ranolazine
  • • rasagiline
  • • selegiline
  • • sertindole
  • • ziprasidone
  • • alcohol
  • • alfuzosin
  • • antibiotics like gatifloxacin, gemifloxacin, levofloxacin, mefloquine, moxifloxacin, ofloxacin, telithromycin
  • • antihistamines for allergy, cough and cold
  • • desipramine
  • • MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate
  • • medicines for depression, anxiety, or psychotic disturbances
  • • medicines for irregular heart beat like flecainide, propafenone
  • • medicines for nausea or vomiting like dolasetron, ondansetron, palonosetron
  • • medicines for seizures like carbamazepine, phenobarbital, phenytoin
  • • medicines for sleep
  • • muscle relaxers
  • • narcotic medicines for pain
  • • octreotide
  • • peginterferon Alfa-2b
  • • phenothiazines like chlorpromazine, mesoridazine, prochlorperazine, thioridazine
  • • rifampin, rifapentine
  • • some medicines for cancer like dasatinib, lapatinib, sunitinib
  • • some medicines for HIV like delavirdine, didanosine, efavirenz, nevirapine
  • • St. John's wort
  • • tacrolimus
  • • tramadol
  • • vardenafil
  • • vorinostat

This list may not describe all possible interactions. Give your health care providers a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use before taking methadone.

The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. Other reactions use may include constipation, headache, and itching (pruritus). Adverse effects may include allergic reaction, irregular heartbeat, migraine, confusion, agitation, dry mouth, nervousness, tremor, rash, blurred vision, mental clouding, lethargy, mood changes, urinary retention, anxiety, fear, respiratory depression, and personality changes.


*This is a condensed description of methadone. For more details check with your physician, pharmacist, or resources such as The Physicians' Desk Reference (PDR)



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