Addiction Treatment Forum reports on substance abuse news of interest to opioid treatment programs and patients in methadone maintenance treatment.

FAQFrequently Asked Questions (FAQs) - and Answers

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Responses to Frequently Asked Questions (FAQs) were developed by the editorial staff of Addiction Treatment Forum and made possible by an educational grant from Mallinckrodt Pharmaceuticals, a manufacturer of methadone and naltrexone.

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Methadone Prescribing

What Is The Best Dose Of Methadone To Achieve Better Treatment Outcomes?

best dose For most medical conditions, health care practitioners try to prescribe the lowest practical dose of a medication that   will “get the job done.” This conservative approach is believed to help reduce unwanted side effects. But some of methadone’s properties make it different from most other medications, so that the “low dose” approach with methadone is usually not best.

Just how large a dose is “enough” depends on individual patient needs. Numerous clinical trials have compared various doses of methadone for medication-assisted treatment (MAT). A finding reported consistently is that patients receiving higher doses have better outcomes related to illicit-opioid abstinence, retention in treatment, psychosocial rehabilitation, and others.

Minimum and maximum doses decided by clinic policy rather than by medical criteria are contrary to best practices in MAT mandated by federal regulations. Although individual state requirements may vary, federal regulations do not require special permission for patients receiving methadone doses above specific levels.


Donny EC, Brasser SM, Stitzer ML, Bigelow GE, Walsh SL. Relatively high doses of methadone are necessary to suppress heroin self-administration in the human laboratory. Paper presented at: CPDD (College on Problems of Drug Dependence) 65th Annual Meeting; June 2004; San Juan, Puerto Rico.

Federal Register. Opioid Drugs in Maintenance and Detoxification Treatment of Opiate Addiction. Federal Register. January 17, 2001. 21 CFR Part 291; 42 CFR Part 8. Available at: Accessed June 16, 2009.

Leavitt SB. Methadone Dosing & Safety in the Treatment of Opioid Addiction. Addiction Treatment Forum [Special Report]. September 2003. Available at:

Leavitt SB, Shinderman M, Maxwell S, Eap CB, Paris P. When “enough” is not enough: new perspectives on optimal methadone maintenance dose. Mt Sinai J Med. 2000;67(5-6):404-411. Available from AT Forum at:

Revised July 2009

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What Can Be Done If My Methdone Dose Doesn't Hold Me All Day?

An adequate daily methadone dose will prevent withdrawal symptoms and drug craving for at least 24 hours. The simple fact is, however, that patients respond differently to methadone and there is no single best dose that works for everyone. Dosage needs to be individualized.

Some patients need higher doses of methadone to hold them for a day. This can be due to the amount and purity of street heroin the person was used to. It can also be due to a current physical ailment or interactions of methadone with prescription medicines or other drugs. Also, some patients are “fast metabolizers” – they digest the methadone more quickly – due to how their digestive tract and liver function.

blood testA blood test can measure the amount of methadone in a patient’s system. When blood is tested just before taking the dose and 3 to 4 hours later, it helps indicate how fast the methadone is being metabolized. This test alone, however, rarely tells the whole story. An important measure is how the patient feels throughout the day: Withdrawal sickness and drug craving coming at the same time each day are good indicators that a dose adjustment is needed.

Some patients in medication-assisted treatment (MAT) are not prescribed sufficient daily methadone doses. Research has shown that there really is no upper limit as to what certain patients may require and find beneficial, with some needing as much as 200 to 300 mg/day, or even much more.

Another approach helpful for some patients is splitting the dose: for example, taking half early in the day and half in the evening. This allows them to have a steady blood level of methadone throughout the day, without an extremely low period that produces withdrawal or craving. However, dose splitting is not done commonly, except in special circumstances, because of logistical problems. Patients must be honest with clinic staff in describing problem symptoms and work patiently with staff in arriving at a methadone dose and dosing schedule that is best.

For further information and references, see:

Understanding Methadone Split Dosing. Addiction Treatment Forum. 2003;12(4):3. Available at:

Leavitt SB. Methadone Dosing & Safety in the Treatment of Opioid Addiction. Addiction Treatment Forum [Special Report]. September 2003. Available at:

Revised July 2009

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Does The Formulation Or Brand Of Methadone Make A Difference?

As with many medications, several forms of methadone make dispensing and administration more convenient. Pharmacologically – that is, the way they work in the body – the different formulations must be equivalent to be approved by the Food and Drug Administration (FDA).

FormulationSome patients may sense that one formulation is easier on the stomach or seemingly more rapid acting. This may be due to individual differences in how the methadone is absorbed into the body and digested (metabolized), but it is not due to differences in the essential methadone ingredient. It also could be due to how the liquid or dispersible tablets are mixed (eg, with juice or with plain water). Finally, the preservatives or fillers – inactive ingredients – used in the various formulations may differ and some people can be sensitive to one of those compounds for unknown reasons.

methadone blood levelsPractitioners and patients have often debated whether methadone liquid, tablets, or dispersible tablets are more potent. Patients sometimes complain when switched to a different formulation, but pharmacologic advantages of one formulation over another are not supported by evidence.

Investigators at Albert Einstein College of Medicine, Bronx, NY, enrolled patients on methadone maintenance treatment in an experiment in which each received methadone liquid, tablets, or dispersible tablets for a period of 3 weeks. Each subject was then switched to one of the other formulations for a similar period of time.

There were no significant differences in methadone blood levels among the 3 formulations during a 24-hour dosing period (see graph). Additionally, patient-reported opioid-withdrawal symptoms did not differ at any time by methadone formulation.

The researchers concluded that patient intolerance to changes in methadone formulation appear to have no basis in the pharmacologic action of methadone itself, whether in liquid or solid form. Any difficulties attributed solely to a particular methadone formulation may be due more to patient-specific psychosocial factors.

Brand—Furthermore, some people may think that Methadose and methadone are different drugs, and may have different effects. But Methadose is simply an FDA-approved brand name of the generic product – methadone – produced by Covidien Mallinckrodt, Inc. of St. Louis, MO. Covidien uses the brand name for marketing purposes. At equivalent doses, both the branded product and the generic version have the same potency and effects – that is, 10 mg of Methadose should have the same pharmacologic action and effect as 10 mg of generic methadone.


Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone. Implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41(14)1153-1193.

Gourevitch MN, Hartel D, Tenore P, et al. Three oral formulations of methadone. A clinical and pharmacodynamic comparison. J Substance Abuse Treatment. 1999;17(3):237-241.

Revised July 2009

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medicationsIs It Safe To Take Methadone With Other Medications?

Many drugs, including methadone, are digested (metabolized) by chemicals in the liver called enzymes. Other drugs broken down by the same liver enzymes may interfere with the break down of methadone and change its effects – this    is called a “drug interaction.”

A drug interaction occurs when the amount or action of a drug in the body is altered – usually increased or decreased – by the presence of one or more other drugs. During clinical use spanning more than 45 years, oral methadone has proven to be well-tolerated with minor side effects when prescribed in appropriate doses and taken daily as a component of medication-assisted treatment (MAT). However, there are potential methadone-drug interactions – involving prescribed medications, illicit drugs, OTC products, and other substances – that sometimes can be difficult to predict. Such interactions may be harmful, or can lead to treatment failures, or both.

Given the individual variability in methadone absorption and metabolism, it becomes difficult to accurately predict the effects of drug combinations in any one patient, or how the methadone dose may need adjustment. Several points to keep in mind:

Also, it is always best for MAT patients to inform their health care providers that they are taking methadone and to express concern about possible interactions with any prescribed medications. MAT clinic staff should become familiar with drugs or drug combinations that may affect methadone so they can advise these outside providers.

For more information and references about drugs that might interact with methadone, see:

Leavitt SB. Methadone-Drug Interactions. Addiction Treatment Forum [Special Report]. November 2005. Available at:

Revised July 2009

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hourglass Does Methadone Spoil Or Go Bad?

Up to 30 days of methadone may be prescribed at one time in the U.S. for take-home—will it spoil in that time? Manufacturers can provide little guidance once the seal of the original container is broken and opioid treatment program (OTP) staff add other ingredients to the product.

Methadone itself is stable and usually does not spoil – problems have more to do with how it is diluted when it is dispensed, due to possible contamination.

Bacterial growth can occur. Storage of methadone mixtures at room temperature can show unacceptable bacterial growth within 2 weeks, unless preservatives are included. As for potency, methadone mixed with Kool-Aid, Tang, apple juice, or Crystal Light and refrigerated (41°F) maintained its strength for 30 days or much longer in laboratory tests.

Based on a review of existing literature and a consensus of opinion among consulted pharmacists, the American Association for the Treatment of Opioid Dependence, Inc. (AATOD) issued several recommendations in June 2004:

  1. Dilution of methadone products should be with distilled water only.
  2. New, clean, air-tight, light-resistant containers should be used for dispensing.
  3. Take-home containers should be securely refrigerated as soon as possible, and remain refrigerated until used.

AATOD specified that by following these procedures, liquid methadone should remain stable for up to 30 days from the date of OTP dispensing.

However, there may be a question as to whether dilution at the time of clinic dispensing is required or necessary. Federal Regulations do not specifically require dilution. Typically, product labeling specifies, “to be diluted with water or other liquid to 30 mL (1 fluid oz.) or more before oral administration.” This could mean dilution “just before the dose is taken,” in which case the patient might be the one to add liquid for dilution. Tap water or other fluid could be used, since storage is not a concern. Dilution simply makes it easier to consume the full amount of otherwise thick, undiluted methadone that is in the take-home container.


Allen LV, Stiles ML. Methadone lemonade. U.S. Pharmacist. 1988(September):82.

Lauriault G, LeBelle MJ, Lodge BA, Savard C. Stability of methadone in four vehicles for oral administration. AJHP. 1991;48:1252-1256.

Parinno MW. Shelf life for methadone hydrochloride products following OTP compounding [memo]. June 11, 2004. AATOD.

Federal Register. Opioid drugs in maintenance and detoxification treatment of opiate addiction; final rule. 2001 (Jan 17);66(11):4085. 42 CFR Part 8,

Package Insert. Methadose® Oral Concentrate. 2001. Mallinckrodt, Inc.; St. Louis.

Revised July 2009

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