Two medicines, side by side
Methadone vs tramadol
Methadone and tramadol are both labeled for pain. Drugs@FDA records approvals of methadone since 1947 and of tramadol since 1995. Pharmacies paid $0.177 per methadone HCl 10 mg tablet and $0.0248 per tramadol HCl 50 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. 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 …”; Tramadol, “Tramadol hydrochloride extended-release tablet contains tramadol, an opioid agonist and an inhibitor of reuptake of norepinephrine and serotonin.”
Check it at the source: the methadone FDA label on DailyMed (effective December 8, 2025); the tramadol FDA label on DailyMed (effective March 5, 2026).
Highlights of the methadone record
Methadone (Diskets) · label of December 8, 2025
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: indicationsMethadone 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 tramadol record
Tramadol (Ultram) · label of March 5, 2026
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of Tramadol hydrochloride extended-release tablet 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: indicationsTramadol hydrochloride extended-release tablet is indicated for the 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
- March 3, 1995
- Generic labelers
- 39 labelers
- Pharmacy cost
- $0.0248 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 8
Source: FDA drug labels via openFDA (Methadone label of December 8, 2025, Tramadol label of March 5, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do methadone and tramadol differ on the record?
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 …”; Tramadol, “Tramadol hydrochloride extended-release tablet contains tramadol, an opioid agonist and an inhibitor of reuptake of norepinephrine and serotonin.”
Both are in FDA's class opioid agonists.
Both labels carry a boxed warning; the records quote them.
Generics: methadone since 1981; tramadol since 2002 (Drugs@FDA).
DEA schedule: methadone CII; tramadol CIV.
| Methadone | Tramadol | |
|---|---|---|
| Labeled for | Pain, Opioid use disorder | Pain |
| Pharmacologic class | Opioid Agonist | Opioid Agonist |
| 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. | Tramadol hydrochloride extended-release tablet contains tramadol, an opioid agonist and an inhibitor of reuptake of norepinephrine and serotonin. |
| 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 … | n/a |
| Earliest approval on file (Drugs@FDA) | August 13, 1947 | March 3, 1995 |
| First generic approved | May 22, 1981 | June 19, 2002 |
| Generic labelers (NDC) | 18 labelers | 39 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.177 per tablet (Methadone HCl 10 mg tablet) | $0.0248 per tablet (Tramadol HCl 50 mg tablet) |
| 12-month price change | -7% | -1% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 4 | 8 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 45,988 | 37,421 |
| DEA schedule | CII | CIV |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
What do the labels say about using others of their kind?
Methadone label, warnings and precautionsRisks 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 …
Tramadol label, warnings and precautionsRisks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of tramadol hydrochloride extended-release tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics …
Source: FDA drug labels via openFDA
What next?
- Alternatives to methadone
- every medicine labeled for the same conditions