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What Is Methadone?
Methadone is an effective opioid analgesic for severe pain. Because of low cost and apparent efficacy in complex pain syndromes, it is increasingly used as a first-line opioid. Retrospective analyses of consecutive patients initiated on methadone in an outpatient palliative care clinic confirm its effectiveness and safety. It is, in effect, a combination drug – part opioid and part NMDA receptor antagonist – although there is yet to be any evidence from controlled trials that it is a superior first-line analgesic to other opioids. Methods of dose conversion to methadone from other opioid analgesics that account for its dual action were discussed. This Fast Fact will describe strategies for beginning methadone when the patient has not been taking a strong opioid. Note: due to its complex pharmacology, clinicians are advised to seek consultation prior to initiating therapy.
Pharmacology Methadone is lipophilic, thus it takes time to develop tissue stores that maintain serum levels. There is enormous interindividual variation in how long this takes. After a single dose there is a short distribution phase (associated with acute pain relief) with a half-life of 2-3 hours and a slow elimination phase (half-life 15-60 hours). Dosing must account for the accumulation of drug over days. It is this accumulation that accounts for most therapeutic misadventures. Liver metabolites are inactive; therefore no dose reduction is required with renal failure. After steady-state is reached, about two-thirds of patients will get adequate pain relief with twice a day dosing. Note: a number of drugs will alter methadone metabolism, so there needs to be close follow-up to drug interactions.
There are several approaches to starting methadone for the treatment of pain. All take into account the long-half life of the drug that leads to drug accumulation over days. Physicians are feeling the heat over the highly publicized national public health crisis stemming from overprescribing oxycodone for non-cancer chronic pain. One result has been a huge shift to using methadone for that indication.
Methadone is widely perceived as an attractive alternative to oxycodone because it’s less euphoria-inducing and thus somewhat less prone to abuse, as well as less expensive. But the reality is it’s a very tricky drug to use safely for pain management, according to Dr. Barak Gaster, a general internist at the University of Washington, Seattle.
Methadone is a highly unusual opiate. The dose-response relationship is far more variable and idiosyncratic than for oxycodone or other opiates. Methadone has numerous active metabolites. And as those active metabolites accumulate during the first 2 weeks on any given dose of the drug, patients will gradually experience greater analgesia and, disturbingly, more respiratory depression as well.
This is one of the most dangerous situations for unintentional overdose. Patients have to understand that this is kind of a dangerous medication, and it’s going to take a couple weeks to kick in during which it’s absolutely essential that they don’t increase the dose on their own. Dr. explained at the annual meeting of the American College of Physicians.
The other major shortcoming of methadone as a treatment for chronic pain is that the drug comes in big-dose tablets designed for once-daily treatment of heroin addiction. The smallest available dose – a 5-mg tablet – is 3-4 times more potent than a 5-mg pill of oxycodone. So patients placed on 5 mg per day of methadone are really being started at 3 times the usual starting dose of oxycodone, hydrocodone, or morphine. Methadone is really more like 200 mg of oxycodone.
An opiate-naive individual should be started on half a 5-mg tablet of methadone twice daily for 2 weeks. Titration should then proceed very slowly, since it takes about 2 weeks for each new dose to reach steady state.
"There’s a weird Catch-22 situation with methadone where on the one hand it’s a short-acting drug in terms of its analgesic effect and needs to be dosed at least 3 times a day, but on the other hand it has this very long-acting risk potential," the internist observed. The burgeoning shift from away from prescribing oxycodone in favor of methadone for chronic pain is fueled by a general recognition that something has gone very much awry nationally with regard to opiate prescribing. Prescriptions for opiates have tripled in the last 10 years. Surveys indicate 1 in 20 American adults has taken prescription opiates to get high. Most disturbingly, the annual number of unintentional fatal overdoses attributed to prescription opiates now exceeds those from heroin and cocaine combined.
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