PPM Editorial Board Discusses Methadone Prescription Safety Measures
Understand Methadone’s Characteristics
Jennifer Schneider, MD, PhD
Methadone is effective and very inexpensive compared with other opioids, and thus it is very useful. Methadone has been used for decades, usually in doses of 60 to 80 mg per day or higher in the maintenance treatment of opioid addicts. Once-daily dosing is adequate for the prevention of withdrawal, but pain relief requires more frequent dosing, about three times per day. Its use for pain management is increasing, but requires extra care. The use of methadone demands understanding of several of its significant characteristics:
- Methadone has a long and variable serum half-life, up to about 36 hours, which is much longer than most opioids. In consequence, when initiating the use of methadone it is crucial to begin with a low dose and titrate up slowly, no faster than every 3 to 5 days. The FDA has issued warnings in this regard, in the aftermath of many methadone-induced deaths, most of which occurred within days after initiation of this drug and resulted from too-rapid upward titration of methadone.
- Methadone is metabolized by cytochrome P450 3A4 and thus has many drug–drug interactions, some of which (eg, erythromycin and fluoxetine) inhibit the breakdown of the molecule, thereby enhancing the effect of any given dose and risking excessive dosing. Other medications (such as carbamazepine) enhance the metabolism of methadone, with the results that higher-than-usual doses are required for effective analgesia. Therefore, it is important for physicians to familiarize themselves with these interactions and take them into consideration when other medications are prescribed concurrently.
- Unlike most other opioids, methadone does not have a linear conversion ratio with other opioids. For example, an equipotent dose of morphine is always approximately 1.5 times higher than oxycodone, no matter what the beginning dose. With methadone, however, the conversion ratio is highly variable, decreasing markedly as the morphine dose rises. The ratio is nearly 1:1 at extremely low morphine doses, but rises to perhaps 5:1 at 100 mg per day morphine and even 10:1 at higher morphine doses. Conversion to methadone, therefore, needs to be very conservative, with frequent and careful follow-up of the patient and slow upward titration.
- High doses of methadone can cause prolongation of the QT interval in the electrocardiogram (ECG), which can result in torsades de pointes—a potentially fatal arrhythmia. Therefore, it is advisable to obtain an ECG in patients who have been prescribed 100 mg per day or more of methadone to be sure the QT interval is not prolonged. If it is, the dose should be decreased.
Be Familiar With Appropriate Use of Methadone
Gary W. Jay, MD, DAAPM, FAAPM
Raleigh-Durham, North Carolina
The first safety measure I recommend, when I am called in to treat many disasters, is that the prescribing doctor knows how to appropriately use methadone, that is, they should not increase the dose more than every 5 to 7 days when starting it! I’ve seen more than a few patients in trouble because the doctors [prescribing] methadone did not understand this, nor did they understand the extremely varied half-life of the drug. Too many doctors think that methadone is like oxycodone (OxyContin) or morphine, etc, and treat it as such, which is a really bad idea.
The second safety measure I recommend, especially in older patients, is that an electrocardiogram (ECG) be obtained first (or a copy of a recent one be obtained from the patient’s primary care provider) to establish that the patient’s QTc is within normal limits.
Third, many patients understand that methadone is used in opioid detoxification and, therefore, think it isn’t really a good pain drug. A heart-to-heart discussion is called for here to teach the patient that methadone is indeed a good analgesic and to be sure that the patient will give it a real try.
Finally, patients need to understand that they can get into real trouble if they don’t take the drug as prescribed. I have a printed sheet I give to patients explaining in layman’s terms about methadone, how to take it correctly, and why it needs to be taken that way. I do not have any patient problems with it—no one has crashed and burned, and the patients respect the drug and are able to obtain good analgesia.
One other issue is that, as the dose of methadone is slowly increased—particularly, according to some sources, when a patient is up to 100 or 200 mg per day (think cancer patients)—the ECG can be repeated periodically to verify that no cardiovascular changes are “sneaking up on you.”
Handle With Care
Michael J. Brennan, MD, MS
Methadone is not a safe drug if used inappropriately. As an analogy, think about walking on a tight rope. Walking on a tight rope includes two activities: walking and balancing. Just because you can walk doesn’t mean you can walk on a tight rope. A lot of people think they can walk on a tight rope by prescribing methadone, and [most] physicians should not. Methadone is too ungainly a drug for doctors who are not extraordinarily familiar with it to use.
Only Prescribed as Courtesy
Peter Moskovitz, MD
As an orthopedic surgeon, I prescribe methadone only as a courtesy to long-standing patients who are on a stable dose of methadone that was first prescribed and followed by a consulting pain management specialist.
Only Use for Withdrawal From Other Narcotics
C. Norman Shealy, MD, PhD
Fair Grove, Missouri
This is an easy one for me. Methadone is a drug used only for withdrawal from other narcotics, never for long-term use. Of course, I do not believe any narcotic should be prescribed long term, except for terminal cancer pain.