Two medicines, side by side

Methadone vs naltrexone

Methadone and naltrexone are both labeled for opioid use disorder. Drugs@FDA records approvals of methadone since 1947 and of naltrexone since 1984. Pharmacies paid $0.177 per methadone HCl 10 mg tablet and $1.14 per naltrexone 50 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. Naltrexone's other strengths are brand-only: $1,716.11 per vial (Vivitrol 380 mg vial-diluent). In FDA's classes, methadone is an opioid agonist and naltrexone an opioid antagonist.

Check it at the source: the methadone FDA label on DailyMed (effective December 8, 2025); the naltrexone FDA label on DailyMed (effective September 4, 2026).

Highlights of the methadone record

Methadone (Diskets) · label of December 8, 2025

Boxed warning

SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE TABLETS: Addiction, Abuse, and Misuse Because the use of methadone hydrochloride tablets 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 reassess all patients regularly for the development of these behaviors and conditions [ see Warnings and Precautions (5.1) ].

Used for

From the label: indications
Methadone hydrochloride tablets are indicated for the: 1. Management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. […]

On the market

Earliest approval on file: August 13, 1947
Generic labelers: 18 labelers
Pharmacy cost: $0.177 per tablet

Supply and safety

Shortage: No current entry
Recalls: 4

Highlights of the naltrexone record

Naltrexone (Revia) · label of September 4, 2026

Used for

From the label: indications
Naltrexone Hydrochloride Tablets, USP are indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Naltrexone Hydrochloride Tablets, USP have not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions.

On the market

Earliest approval on file: November 20, 1984
Generic labelers: 21 labelers
Pharmacy cost: $1.14 per tablet

Supply and safety

Shortage: No current entry
Recalls: 5

Source: FDA drug labels via openFDA (Methadone label of December 8, 2025, Naltrexone label of September 4, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)

How do methadone and naltrexone differ on the record?

In FDA's classes, methadone is an opioid agonist and naltrexone an opioid antagonist.

How each works, in its label's words: Methadone, “Methadone hydrochloride is a mu-agonist; a synthetic opioid with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and …”; Naltrexone, “of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data.”

Half-life, in each label's words: Methadone, “Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged …”; Naltrexone, “The mean elimination half-life (T-1/2) values for naltrexone and 6-β-naltrexol are 4 hours and 13 hours, respectively.”

Only the methadone label carries a boxed warning.

Generics: methadone since 1981; naltrexone since 1998 (Drugs@FDA).

DEA schedule: methadone CII; naltrexone none.

	Methadone	Naltrexone
Labeled for	Pain, Opioid use disorder	Alcohol use disorder, Opioid use disorder
Pharmacologic class	Opioid Agonist	Opioid Antagonist
How it works (label)	Methadone hydrochloride is a mu-agonist; a synthetic opioid with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle.	of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data.
Half-life (label)	Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 …	The mean elimination half-life (T-1/2) values for naltrexone and 6-β-naltrexol are 4 hours and 13 hours, respectively.
Earliest approval on file (Drugs@FDA)	August 13, 1947	November 20, 1984
First generic approved	May 22, 1981	May 8, 1998
Generic labelers (NDC)	18 labelers	21 labelers
Pharmacy cost (NADAC, each one's most listed form; strengths differ)	$0.177 per tablet (Methadone HCl 10 mg tablet)	$1.14 per tablet (Naltrexone 50 mg tablet)
12-month price change	-7%	-11%
Boxed warning	Yes	No
Shortage now	No current entry	No current entry
Recalls recorded	4	5
FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used)	45,988	32,067
DEA schedule	CII	none

Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)

Do their labels mention each other?

Naltrexone label, warnings
Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks.

Source: FDA drug labels via openFDA

What do the labels say about using others of their kind?

Methadone label, warnings and precautions
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Methadone hydrochloride tablets with benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin …

Source: FDA drug labels via openFDA

What next?

Methadone: the full record
Naltrexone: the full record
Alternatives to methadone: every medicine labeled for the same conditions