What is Methadone hydrochloride - Meaning and definition

Published by Roberto Wenk. Reviewed by Alison Ramsey. Last updated date: January 9, 2019.

The hydrochloride salt of methadone, a synthetic opioid with analgesic activity.
Similar to morphine and other morphine-like agents, methadone mimics the actions of endogenous peptides at CNS opioid receptors, primarily the mu-receptor, resulting in characteristic morphine-like effects including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence.
Because of the prolonged half-life of methadone compared to other morphine-like agents, such as heroin, the onset of opiate withdrawal symptoms is slower, the duration of opiate withdrawal is prolonged, and opiate withdrawal symptoms are less severe.

National Cancer Institute. NCI Drug Dictionary. Internet. September 15, 2009.

Published by Roberto Wenk. Reviewed by Alison Ramsey. Last updated date: January 6, 2020.

Methadone, a potent opioid agonist, has many characteristics that make it useful for the treatment of pain when continuous opioid analgesia is indicated.
Although available for decades, its use has gained renewed interest due to its low cost and potential activity in neuropathic pain syndromes.
Unlike morphine, methadone is a racemic mix; one stereoisomer acts as a NMDA receptor antagonist, the other is a mu-agonist opioid. The NMDA mechanism plays an important role in the prevention of opioid tolerance, potentiation of opioid effects, and efficacy for neuropathic pain syndromes, although this latter impression is largely anecdotal.

Methadone is highly lipophilic, with rapid GI absorption and onset of action. It has a large initial volume of distribution with slow tissue release. Oral bioavailability is high, ~ 80%. Unlike morphine, there are no active metabolites; biotransformation to an active drug is not required. The major route of metabolism is hepatic with significant fecal excretion; renal excretion can be enhanced by urine acidification (pH <6.0). Unlike morphine, no dose adjustment is needed in patients with renal failure since there are no active metabolites.
Methadone is available in tablet, liquid, and injectable forms; oral preparations can be used rectally. Parenteral routes include IV bolus dosing or continuous infusion.

Compared to morphine, methadone is inexpensive, may provide improved analgesia in neuropathic pain and will provide a longer duration of action.

Unlike morphine, hydromorphone or oxycodone, methadone has an extended terminal half-life, up to 190 hours. This half-life does not match the observed duration of analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments.

Rapid titration guidelines for other opioids do not apply to methadone.
Its apparent potency, compared to other opioids, varies with the the patient’s current exposure to other opioids.

See below for a suggested dosing guide for opioids tolerant patients.

Daily oral morphine dose equivalents. Conversion ratio of oral morphine to oral methadone
< 100 mg = 3:1 (i.e., 3 mg morphine = 1 mg methadone)
101-300 mg = 5:1
301-600 mg = 10:1
601-800 mg = 12:1
801-1000 mg = 15:1
> 1001 mg = 20:1

Due to incomplete cross-tolerance, it is recommended that the initial dose is 50-75% of the equianalgesic dose.

See also Instructions and conversion table and Opioid dose conversions

Adapted from Gazelle G and Fine PG. Palliative Care Network of Wisconsin. Fast facts and concepts #75. Methadone for the treatment of pain. Internet. Accessed on January 25, 2016.

Published by Roberto Wenk. Reviewed by Alison Ramsey. Last updated date: January 9, 2019.

Methadone for neuropathic pain
Prescriptions for methadone have greatly increased. The reason for this increase is likely related to two factors: reduced cost relative to other potent opioids and basic science data suggesting that it may be particularly useful in treating neuropathic pain.

Historical context
- Prior to 1985, when long-acting morphine preparations were introduced, methadone was commonly prescribed for cancer-related pain as it had a longer duration of action than morphine. However, it was well appreciated that methadone had a higher risk of respiratory depression due to drug accumulation with chronic dosing — an effect not associated with other opioids, in which there is no drug accumulation in the setting of normal renal function.
- Prior to 1990 there was a widespread belief that opioids were relatively ineffective in treating neuropathic pain. Since then, there been a much greater understanding that opioids are an effective part of neuropathic pain treatment.

Basic science data
Methadone inhibits reuptake of norepinephrine and serotonin in a similar manner to newer antidepressants, some of which are effective against neuropathic pain (e.g., venlafaxine). Also, methadone binds to the NMDA receptor, a known modulator of neuropathic pain. Finally, methadone has demonstrated efficacy in animal models of neuropathic pain.

Patient data
Small noncontrolled case series and at least one small randomized study (methadone vs. placebo) have demonstrated that methadone can reduce neuropathic pain in both cancer and noncancer patients. There is no data, for or against the proposition, that it is superior to other opioids for neuropathic pain.
A 2004 Cochrane Collaborative review found that, “there is no trial evidence to support the proposal that methadone has a particular role in neuropathic pain of malignant origin.” Furthermore, the review cautioned clinicians about the danger of methadone-induced respiratory depression due to its long terminal half-life.

Adapted from Weissman DE. Palliative Care Network of Wisconsin. Fast facts and concepts #171. Methadone for neuropathic pain. Internet. Accessed on January 25, 2016.

Methadone hydrochloride

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