Reviewed on 7/19/2022

What Is Methadone and How Does It Work?

Methadone is a prescription medication used for the management of severe pain. 

What Are Dosages of Methadone?

Adult dosage

Injectable solution: Schedule II

  • 10 mg/mL

Tablet: Schedule II

  • 5 mg
  • 10 mg

Dispersible tablet: Schedule II

  • 40 mg

Oral solution: Schedule II

  • 5 mg/5 mL
  • 10 mg/5 mL

Oral concentrate solution: Schedule II

  • 10 mg/mL

Pain Management

Adult dosage

  • Opioid-naive patients: 2.5 mg orally every 8-12 hours; titrate slowly to dose increases no more frequent than every 3-5 days


Adult dosage

  • 20-30 mg orally once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”.

What Are Side Effects Associated with Using Methadone?

Common side effects of Methadone include:

  • dizziness, 
  • drowsiness, 
  • nausea, 
  • vomiting,
  • constipation,
  • tiredness,
  • headache,
  • increased sweating, and
  • pain, redness, or swelling at the injection site

Serious side effects of Methadone include:

  • hives, 
  • difficulty breathing, 
  • swelling in the face, lips, tongue, or throat, 
  • slow breathing with long pauses, 
  • blue colored lips, 
  • difficult to wake up, 
  • weak or shallow breathing, 
  • breathing that stops during sleep, 
  • severe constipation, 
  • lightheadedness
  • fast or pounding heartbeats, 
  • fluttering in the chest, 
  • shortness of breath, 
  • nausea, 
  • vomiting, 
  • loss of appetite, 
  • dizziness, 
  • worsening tiredness or weakness, 
  • agitation, 
  • hallucinations, 
  • fever, 
  • muscle stiffness, 
  • twitching
  • loss of coordination, and
  • diarrhea

Rare side effects of Methadone include:

  • none 

Seek medical care or call 911 at once if you have the following serious side effects:

  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.
This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Methadone?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist about all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What are warnings and precautions for Methadone?


Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Methadone?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Methadone?”


  • Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioids present (see Black Box Warnings)
  • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases the risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
  • Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black Box Warnings)
  • Serious, life-threatening, or fatal respiratory depression was reported (see Black Box Warnings)
  • May cause constipation, which could cause problems in patients with unstable angina and patients post-myocardial infarction; consider preventive measures (stool softener, increased fiber in diet) to reduce the potential for constipation
  • Accidental exposure was reported, including fatalities (see Black Box Warnings)
  • Do not abruptly discontinue buprenorphine in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
  • Neonatal opioid withdrawal syndrome was reported with long-term use during pregnancy (see Black Box Warnings)
  • Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, and other opioids) can cause additive effects and increase the risk for respiratory depression, profound sedation, and hypotension; deaths reported due to methadone abuse in conjunction with benzodiazepines
  • Monitor for hypotension during dose initiation and titration; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may significantly increase hypotensive effects
  • In patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock
  • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
  • Serotonin syndrome may occur with concomitant administration of serotonergic agents; monitor patients for symptoms of serotonin syndrome such as mental status changes, autonomic instability, neuromuscular changes, and/or GI symptoms
  • Risk of QT interval prolongation at high doses
  • Use caution in cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, prostatic hyperplasia/urethral stricture, hepatic impairment, thyroid dysfunction, increased intracranial pressure, prostatic hypertrophy, adrenal insufficiency, history of depression or suicidal tendencies, renal function impairment, seizures with epilepsy, urethral stricture, patients who are morbidly obese, urinary tract surgery
  • May cause CNS depression; use caution in performing tasks, which require mental alertness
  • Not recommended to treat abdominal conditions; may obscure diagnosis or clinical course of patients with acute abdominal conditions
  • Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist; mixed agonists/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy
  • May obscure diagnosis or clinical course of patients with acute abdominal conditions; avoid use in patients with obstruction
  • Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of the sphincter of Oddi
  • Use with caution in patients with delirium tremens

Opioid analgesic risk evaluation and mitigation strategy (REMS)

  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
  • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG):
  • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
  • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
  • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to; the FDA Blueprint can be found at

Concomitant use with benzodiazepines or other CNS depressants

  • If concomitant use with benzodiazepines is warranted, strongly consider prescribing naloxone for emergency treatment of opioid overdose, as is recommended for all patients in methadone treatment for opioid use disorder
  • Concomitant use of methadone and benzodiazepines or other CNS depressants increases the risk of adverse reactions including overdose and death; medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs; prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to opioid use disorder alone
  • Educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, or alcohol
  • Develop strategies to manage the use of prescribed or illicit benzodiazepines or other CNS depressants at admission to methadone treatment, or if it emerges as a concern during treatment; adjustments to induction procedures and additional monitoring may be required
  • There is no evidence to support dose limitations or arbitrary caps of methadone as a strategy to address benzodiazepine use in methadone-treated patients; if a patient is sedated at the time of methadone dosing, ensure that a medically trained healthcare provider evaluates the cause of sedation, and delays or omits the methadone dose if appropriate
  • Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use; in some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  • For patients in methadone treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia; before co-prescribing benzodiazepines, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments to address anxiety or insomnia
  • Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient’s methadone treatment and coordinate care to minimize the risks associated with concomitant use
  • In addition, take measures to confirm that patients are taking the medications prescribed and not diverting or supplementing with illicit drugs; toxicology screening should test for prescribed and illicit benzodiazepines

Patient access to naloxone for emergency treatment of opioid overdose

  • Discuss the availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver
  • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
  • Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider prescribing naloxone for emergency treatment of opioid overdose, both when initiating and renewing treatment
  • Also, consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose
  • Advise patients and caregivers that naloxone may also be administered for a known or suspected overdose with therapy
  • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, or as part of a community-based program)
  • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose

Pregnancy and Lactation

  • There are no adequate and well-controlled studies on pregnant women; untreated opioid addiction is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death; in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use; neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy
  • Pregnant women in methadone maintenance programs may have a reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs; untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes and risk of continued or relapsing illicit opioid use; these risks should be considered in women receiving maintenance treatment of opioid addiction; for women treated with pain severe enough to require daily, around-the-clock, long-term opioid treatment, therapy should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus


  • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible; reproductive function in human males may be decreased by methadone treatment; reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals; in addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported. 
  • Methadone present at low levels in human milk; did not show adverse reactions in breastfed infants; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for methadone and any potential adverse effects on the breastfed child from the drug or underlying maternal condition; advice breastfeeding women taking methadone to monitor the infant for increased drowsiness and breathing difficulties
Medscape. Methadone.

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