Methadone Dosage

Medically reviewed by Drugs.com. Last updated on Aug 2, 2023.

Applies to the following strengths: 5 mg; 10 mg; 10 mg/mL; 40 mg; 5 mg/5 mL; 10 mg/5 mL; 1 mg/mL-NaCl 0.9%; 5 mg/mL-NaCl 0.9%

Usual Adult Dose for:

Pain
Opiate Withdrawal
Chronic Pain

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Adult Dose for Pain

Individualize dose; dosing recommendations should only be considered as suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient; this drug has a narrow therapeutic index, especially when combined with other drugs; monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy.

Parenteral:
Initiation in Opioid Non-Tolerant Patients:
Initial dose: 2.5 mg to 10 mg IV every 8 to 12 hours
Maintenance dose: Slowly titrate to effect; more frequent administration may be required to maintain adequate analgesia during initiation, however, extreme caution is necessary to avoid overdosing.

Comments:

May be administered IV, IM or subcutaneously, although the absorption of IM or subcutaneous injections has not been well studied and appears to be unpredictable; local tissue reactions may occur.
Oral methadone is not indicated as an as-needed analgesic; due to increased risk of overdose and death with this long-acting opioid, its use is limited to chronic pain management.

CONVERSION: Switching a patient from another chronically administered opioid to methadone requires caution due to the uncertainty of dose conversion ratios and incomplete cross-tolerance; deaths have occurred in opioid tolerant patients during conversion. When prescribing this drug for pain, might be best to consider all patients opioid naive; limit dose adjustments to once a week to allow steady state levels to develop.

From ORAL Methadone to PARENTERAL Methadone:

Start with a 2:1 ratio of oral to parenteral (e.g., oral methadone 10 mg to parenteral methadone 5 mg)

From Other Chronic Opioids to PARENTERAL Methadone:

Individualize dose taking into account the patient's prior opioid exposure, general medical condition, concomitant medications, and anticipated breakthrough medication use.
Manufacturer's product information may be consulted for tables that aid in converting chronic pain patients from oral morphine doses to oral and parenteral methadone doses.

Uses: For the treatment of moderate to severe pain not responsive to non-narcotic analgesics.

Usual Adult Dose for Opiate Withdrawal

For detoxification and maintenance of opioid dependence, the drug should be administered in accordance with the treatment standards cited in 42 CFR (Code of Federal Regulations) Section 8.12, including limitations on unsupervised administration.

Oral:
Day 1: Administer initial dose under supervision when symptoms of withdrawal are present.

Initial dose: 20 to 30 mg orally; an additional 5 to 10 mg may be given orally after 2 to 4 hours if withdrawal symptoms have not been suppressed or if symptoms reappear.
Maximum initial dose: 30 mg
Maximum day 1 dose: 40 mg
Adjust dose over the first week based on control of withdrawal symptoms at 2 to 4 hours after dosing; titrate carefully as methadone levels will accumulate over the first several days of dosing.

Short-term Detoxification:

For a brief course of stabilization followed by a period of medically supervised withdrawal, titrate to a total daily dose around 40 mg per day in divided doses; after 2 to 3 days, gradually decrease the dose at 2-day intervals maintaining sufficient dose to keep withdrawal symptoms at a tolerable level.

Titration and Maintenance of Opioid Dependence Detoxification:

Titrate to a dose that prevents opioid withdrawal, reduces drug hunger or cravings, and blocks or attenuates the euphoric effects of self-administered opioids while ensuring the patients is tolerant to the sedative effects.
Target range: 80 to 120 mg orally per day is a range that is commonly associated with therapeutic effectiveness.
Cessation of therapy: There is considerable variability in the rate at which patients taper off; abrupt discontinuation is not advised. Dose reductions should generally be in increments of less than 10% every 10 to 14 days.

Parenteral:

Injectable methadone products may be used in the temporary treatment of opioid dependence in patients unable to take oral medication.
The patient's oral dose should be converted to the parenteral dose based on a 2:1 ratio (e.g., oral methadone 10 mg = parenteral methadone 5 mg)
Injectable products are not approved for the outpatient treatment of opioid dependence.

Comments:

Use lower dose for patients whose tolerance is expected to be low at treatment entry.
Patients who have not taken opioids for more than 5 days may no longer be tolerant; initial doses should not be based on previous treatment episodes.
Patients receiving methadone maintenance for opioid dependence cannot be expected to derive analgesia from their methadone; if acute pain occurs and requires treatment, these patients may require higher and/or more frequent doses than non-tolerant patients due to the opioid tolerance induced by methadone.
During pregnancy, an increase in dose or a decrease in dosing interval may be required due to altered kinetics.

Uses: For detoxification and maintenance treatment of opioid addiction in conjunction with appropriate social and medical services.

Usual Adult Dose for Chronic Pain

Individualize dose; dosing recommendations should only be considered as suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient; this drug has a narrow therapeutic index, especially when combined with other drugs; monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy.

As the First Opioid Analgesic:
Initial dose: 2.5 mg orally every 8 to 12 hours

Conversion from Other Oral Opioids:

Upon initiation, discontinue all other around-the-clock opioid drugs.
The following conversion factors can be used to convert from another oral opioid analgesic to methadone, however do not use these conversion factors to convert from methadone to another opioid as doing so will result in an overestimation of the opioid dose and may result in fatal respiratory depression.
Conversion is based on oral morphine equivalents; to estimate a patient's 24-hour oral morphine requirement, use published potency tables.
It is best to underestimate a patient's 24-hour oral morphine requirement and use rescue medication as the dose is titrated due to substantial inter-patient variability.
Suggested Maximum Starting Dose: 20 mg per day (10 mg for the elderly or infirmed).

For patients receiving a total daily baseline ORAL morphine equivalent dose less than 100 mg: estimate the daily oral methadone requirement at 20% to 30%.
For patients receiving a total daily baseline ORAL morphine equivalent dose of 100 to 300 mg: estimate the daily oral methadone requirement at 10% to 20%.
For patients receiving a total daily baseline ORAL morphine equivalent dose of 300 to 600 mg: estimate the daily oral methadone requirement at 8% to 12%.
For patients receiving a total daily baseline ORAL morphine equivalent dose of 600 to 1000 mg: estimate the daily oral methadone requirement at 5% to 10%.
For patients receiving a total daily baseline ORAL morphine equivalent dose greater than 1000 mg: estimate the daily oral methadone requirement at less than 5%.
Divide the total daily methadone dose by the number of doses permitted based on dosing interval; always round down, if necessary.

Conversion from Parenteral Methadone to Oral Methadone:

Use a conversion ratio of 2:1 for oral to parenteral (e.g., oral methadone 10 mg to parenteral methadone 5 mg)

TITRATION and MAINTENANCE:

Titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments should be no sooner than every 1 to 2 days (manufacturer); preferably no more than once a week (Institute for Safe Medical Practices (ISMP)); with repeated dosing the potency of methadone increases due to systemic accumulation
Breakthrough Pain: If the level of pain increases after dose stabilization, attempt to identify the source before increasing dose; rescue medication with appropriate immediate-release analgesia may be helpful.

Comments:

ISMP suggests when prescribing this drug for pain, consider all patients as opioid naive; consider limiting the starting dose to oral doses not exceeding 20 mg per day (10 mg for the elderly or infirmed) and limit dose adjustments to once a week to allow steady state levels to develop.
Prescribe oral liquid doses in milligrams (mg) to avoid confusion.
Dose conversion should be done carefully and with close monitoring due to large patient variability to opioid analgesic response.
This drug is not indicated as an as-needed analgesic.
Upon cessation of therapy, gradually taper dose in physically dependent patient.
Because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risk of overdose and death with long-acting opioids, this drug should be reserved for use in patients for whom alternative analgesic treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management.

Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Renal Dose Adjustments

Renal impairment: Start at the low end of the dosing range using longer dosing intervals and titrate slowly; closely monitor for signs of respiratory and CNS depression.

Liver Dose Adjustments

Hepatic impairment: Start at the low end of the dosing range and titrate slowly; closely monitor for signs of respiratory and CNS depression.

Dose Adjustments

Elderly patients: Start at the low end of the dosing range and closely monitor for signs of respiratory and CNS depression.

Concomitant use with CNS depressants:

Assess the appropriateness of concomitant use
If the decision is made to begin this drug: Initial dose: 2.5 mg every 12 hours
Monitor for signs of sedation and respiratory depression; consider a lower dose of the concomitant CNS depressant.

Cessation of chronic pain therapy:

In physically-dependent patient: Gradually reduce dose every 2 to 4 days

Cessation of opiate-dependence therapy:

There is considerable variability in the rate at which patients taper off; abrupt discontinuation is not advised.
Dose reductions should generally be in increments of less than 10% every 10 to 14 days.

Pregnancy:

During pregnancy, a women's methadone dose may need to be increased or the dosing interval decreased to achieve therapeutic effectiveness. This drug should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: ADDICTION, ABUSE, and MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; LIFE-THREATENING QT PROLONGATION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and TREATMENT FOR OPIOID ADDICTION:

ADDICTION, ABUSE, and MISUSE: This drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions.
OPIOID REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur. The peak respiratory depressant effect occurs later, and persists longer than the peak analgesic effect, especially during the initial dosing period. Monitor for respiratory depression, especially during initiation or following a dose increase.
ACCIDENTAL INGESTION: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose.
LIFE-THREATENING QT PROLONGATION: QT interval prolongation and serious arrhythmias (Torsades de pointes) have occurred during treatment. Most cases involve patients being treated for pain with large, multiple daily doses, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration.
INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES: Concomitant use with all CYP450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. In addition, discontinuation of concomitantly used CYP450 3A4 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dose reduction with changes to drugs affecting CYP450 isoenzymes listed above.
NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use of this drug during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for those patients for whom alternatives are inadequate; limit dose and duration to the minimum required for patients being treated for pain; monitor for signs and symptoms of respiratory depression and sedation, if patient is visibly sedated, evaluate the cause and consider delaying or omitting the daily dose.
TREATMENT FOR OPIOID ADDICTION: Conditions for distribution and use of methadone products for detoxification and maintenance of opioid dependence should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.

CONTRAINDICATIONS:

Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Hypersensitivity (e.g., anaphylaxis) to methadone or any product excipients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available; this drug is not dialyzable

Other Comments

Administration advice:

This drug should be taken at approximately the same time every day; taking in the evening one day and the morning the following day can lead to an overdose.
If this drug is not taken for 3 consecutive days, the patient may lose tolerance and be at-risk for an overdose; dose adjustment may be necessary.
Missed doses: Chronic Pain: Take as soon as remembered and take the next dose 8 to 12 hours later, if it is almost time for your next dose, skip the missed dose and continue on regular dosing schedule; do not take more than prescribed amount in a 24 hour period.
Missed doses: Opioid Dependence: Take the next dose the following day as scheduled; do not take extra doses.

Oral:

DISKETS are intended for dispersion in approximately 120 mL of liquid; take immediately after dispersing into water, orange juice, or other acidic fruit beverage.
Each 40 mg DISKET is cross-scored; a single DISKET may be broken in half to yield two 20 mg doses or in quarters to yield four 10 mg doses.

Oral liquid doses:

All orders should include mg strength as there are multiple concentrations available.

Parenteral:

May be administered IV, IM or subcutaneously; IM or subcutaneous injections have not been well studied and absorption appears to be unpredictable; local tissue reactions may occur.

Storage requirements:

Protect from light

General:

Acidification of the urine may enhance urinary excretion of this drug.
Treatment with this drug should be managed by physicians with suitable experience.
Because of the greater risk of overdose and death with this long-acting opioid, when used for pain management, this drug should only be used in patients for whom alternative treatment options are ineffective, not tolerated, or would otherwise be inadequate to provide sufficient pain management.
For patients receiving other opioid analgesics and switching to this drug, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.
During chronic therapy, periodically reassess the continued need for opioid analgesics.

Monitoring:

Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
Monitor regularly for the development of addiction, abuse, and misuse.
Monitor for signs of hypotension upon initiating therapy and following dose increases, especially those whose blood pressure is compromised.
Monitor for signs and symptoms of QT prolongation, if used in at-risk patients or concomitantly with drugs that prolong the QT interval, consider monitoring ECG and electrolytes at baseline and periodically during treatment.
During the induction phase as patients are being withdrawn from illicit opioids, monitor of opioid withdrawal symptoms such as lacrimation, rhinorrhea, sneezing, yawning, excessive perspiration, goose-flesh, fever, chilling, irritability, weakness, anxiety, depression, dilated pupils, tremors, tachycardia, abdominal cramps, body aches, involuntary twitching, anorexia, nausea, vomiting, diarrhea, intestinal spasms.

Patient advice:

Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
Advise patients to seek medical attention immediately if they experience palpitations, near syncope, syncope, or other cardiac symptoms while taking this drug.
This drug should be stored safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
Taking this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest.
This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.