Low-Dose Naltrexone: EMA vs FDA Regulatory Approach

By HealthRX.com Editorial Team

Published Jan 28, 2025Updated Nov 7, 2026Last reviewed Jan 28, 2025

15 linked public sourcesEditorial, sourcing, and corrections policy

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No low-dose naltrexone product is FDA-approved

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Key numbers

0.5 to 6 mg a dayTypical off-label LDN dose range, far below the 50 mg tabletSource: pmc.ncbi.nlm.nih.gov, as cited Nov 7, 2026
48 hoursLongest duration of opioid precipitated withdrawal on the naltrexone tablet labelSource: dailymed.nlm.nih.gov, as cited Nov 7, 2026
380 mgMonthly injection strength of Vivitrol, an FDA-approved naltrexone product that is not LDNSource: accessdata.fda.gov, as cited Nov 7, 2026

From the public record

Patents and generic approvals for naltrexone

The FDA Orange Book lists 8 approved generic applications for naltrexone, the first approved on 1998-05-08. 1 listed patent on specific brand products has not yet expired, the last on 2029-10-15; generics of other versions are already approved.

Patents and generic approvals for naltrexone: the figures
Measure	Value	Note
Brand-name applications (NDA)	2
Approved generic applications (ANDA)	8	first approved 1998-05-08
Companies with a generic not marked discontinued	7
Listed patents not yet expired	1
Latest listed patent expiry	2029-10-15	on any product; may cover only one brand formulation
Earliest approval date on file	1984-11-20
Products not marked discontinued	10 of 12

Source: FDA, Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), data as of Oct 9, 2026

How this was calculated

Selected Orange Book products whose only active ingredient is this substance, then counted applications by type and the distinct patents and exclusivities listed against them. Expired patents are left out.

Scope: All single-ingredient naltrexone products in the Orange Book, every brand and strength, files dated 2026-10-09

An approved generic or an expired patent does not show that a generic is on sale. Launch timing also depends on litigation, settlements and supply. Biologics and compounded products are not in the Orange Book.

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From the public record

FDA approval history for naltrexone

The earliest FDA approval on file for a naltrexone product is 1984-11-20. Drugs@FDA lists 10 applications for it and 56 approved supplements, the most recent on 2025-12-22.

FDA approval history for naltrexone: the figures
Measure	Value	Note
Earliest FDA approval on file	1984-11-20
Applications with an approval on file	10
New drug applications (NDA)	2
Generic applications (ANDA)	8
Approved supplements	56	label, manufacturing and efficacy changes
Most recent supplement approval	2025-12-22
Sponsoring companies	10

Source: FDA, Drugs@FDA, data as of Nov 11, 2026

How this was calculated

Selected applications with a product whose only active ingredient is this substance, then counted approved original and supplemental submissions. The earliest approved original submission is the first approval.

Scope: Applications with a single-ingredient naltrexone product in Drugs@FDA, all sponsors and strengths

Older approvals can be missing dates, and tentative approvals are not counted. An approved application does not mean the product is currently marketed.

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From the public record

FDA drug recalls naming naltrexone

FDA enforcement reports list 15 drug recall entries naming naltrexone from 2013 to 2022-06-15. 14 of them are for compounded or other unlisted products and 1 for products FDA lists under a label. The most common stated reason was lack of sterility assurance (5 of 15).

FDA drug recalls naming naltrexone: the figures
Measure	Value	Note
Recall entries on record	15
For products FDA lists under an approved or registered label	1
For compounded or other unlisted products	14	matched by the name in the product description
Class I (most serious)	0
Class II	15
Class III	0
Most recent recall reported	2022-06-15
Most common stated reason	lack of sterility assurance	5 of 15 entries

Source: FDA, Enforcement Reports (drug recalls) via openFDA, data as of Nov 10, 2026

How this was calculated

Counted enforcement report entries matched by FDA's listed active substance, or by the name in the product description where FDA lists none. Reasons were grouped by keywords in FDA's stated reason.

Scope: Recalls of single-ingredient naltrexone products, plus compounded or unlisted products whose description names it

Each recall covers specific lots from one firm and is not a statement about every product with this ingredient. One event can appear as several entries, one per product.

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At a glance

FDA-approved naltrexone / 50 mg tablets (1984) and 380 mg monthly injection (2006) [7][8]
Other approved naltrexone product / Contrave, naltrexone plus bupropion, for weight management — not LDN [3]
FDA-approved low-dose naltrexone product / None [4][6]
Typical off-label LDN dose / 0.5 to 6 mg a day, most often 4.5 mg [4]
How LDN is supplied / Off-label, mainly through compounding pharmacies [4][5]
Compounded drugs / Not FDA-approved; safety, effectiveness and quality not verified before marketing [6]

What has the FDA approved?

Revia 50 mg tablets were approved on 20 November 1984 under NDA 018932; the brand is now marked discontinued and generics are approved [7]. The current generic tablet label covers alcohol dependence and blockade of the effects of exogenously administered opioids [1]. Vivitrol, a 380 mg extended-release intramuscular injection, was approved on 13 April 2006 under NDA 021897 [8]. Contrave, naltrexone extended-release plus bupropion extended-release, is a separate approved weight-management product and is not LDN [3].

Is low-dose naltrexone an approved product?

No. LDN means naltrexone at doses far below the 50 mg tablet — typically 0.5 to 6 mg a day, most often 4.5 mg — used off-label for fibromyalgia, multiple sclerosis, Crohn's disease and long COVID, and supplied mainly through compounding pharmacies [4][5]. FDA states that compounded drugs are not FDA-approved and that it does not verify their safety, effectiveness or quality before they are marketed [6]. Naltrexone is not named on FDA's list of bulk drug substances that may present significant safety risks, current as of 22 April 2026 [9].

What do the naltrexone labels say that matters at a low dose?

The labels were written for 50 mg tablets and a 380 mg injection and give no guidance on LDN doses [1][2].

Opioids. Both labels list as contraindications use in patients receiving opioid analgesics and in people currently dependent on opioids, and the tablet contraindication is written without any dose exception [1][2].
Precipitated withdrawal. When an opioid antagonist abruptly causes withdrawal in an opioid-dependent person, the tablet label says symptoms usually appeared within 5 minutes of ingestion and lasted up to 48 hours, with postmarketing cases severe enough to require hospital admission [1].
Liver injury. Hepatotoxicity sits in the Warnings section, not a boxed warning: in placebo-controlled studies at up to 300 mg a day, five times the recommended dose, naltrexone caused hepatocellular injury in a substantial proportion of patients, and the label links the injury to dose [1].

In LDN trials, reported effects are mostly mild and transient, most often insomnia, vivid dreams, nausea and dizziness [4].

What does the evidence say?

A 2026 review examined 105 studies, including 15 randomized trials, and concluded that current evidence does not support routine clinical use [4]. In fibromyalgia, a 31-woman crossover trial of 4.5 mg found pain fell 28.8% versus 18.0% on placebo (P=0.016) [10], while a 99-woman trial of 6 mg found a between-group pain difference of -0.34 points (95% CI -0.95 to 0.27, p=0.27) [11]. Two further placebo-controlled trials, of 58 and 98 patients, also did not beat placebo on their main outcomes [13][14].

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Frequently asked questions

Is low-dose naltrexone FDA-approved?

No. FDA has approved 50 mg naltrexone tablets, a 380 mg monthly injection and the naltrexone-plus-bupropion product Contrave, but no low-dose product [1][2][3]. LDN is used off-label, and FDA does not verify compounded drugs for safety, effectiveness or quality before marketing [4][6].

Do the naltrexone labels cover a 4.5 mg dose?

No. The tablet and Vivitrol labels were written for 50 mg daily and 380 mg monthly and give no guidance on LDN doses, and the tablet contraindication in people receiving opioid analgesics is written without any dose exception [1][2].

Has any LDN trial produced a positive result?

Yes. A 31-woman fibromyalgia crossover trial of 4.5 mg found pain fell 28.8% versus 18.0% on placebo (P=0.016), and a 40-patient Crohn's trial found a 70-point CDAI fall in 88% versus 40% on placebo (p=0.009) [10][12]. Later fibromyalgia trials did not beat placebo on their main pain outcomes [11][13][14].

References

Show all 15 referencesHide references

U.S. National Library of Medicine, DailyMed. Naltrexone hydrochloride tablets USP 50 mg (generic), SpecGx prescribing information. Naltrexone hydrochloride tablets USP 50 mg (generic), SpecGx label
U.S. National Library of Medicine, DailyMed. Vivitrol (naltrexone for extended-release injectable suspension), Alkermes prescribing information. Vivitrol (naltrexone for extended-release injectable suspension), Alkermes label
U.S. National Library of Medicine, DailyMed. Contrave Extended-Release (naltrexone and bupropion), Azurity (naltrexone hydrochloride and bupropion hydrochloride) prescribing information. Contrave Extended-Release (naltrexone and bupropion), Azurity (naltrexone hydrochloride and bupropion hydrochloride) label
Low-Dose Naltrexone: What is the Evidence? A Narrative Review - PMC.
Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 2018;6(4).
Compounding and the FDA: Questions and Answers | FDA.
Drugs@FDA: FDA-Approved Drugs.
Drugs@FDA: FDA-Approved Drugs.
Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks | FDA.
Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013;65(2):529-38.
Due Bruun K, Christensen R, Amris K, Vaegter HB, Blichfeldt-Eckhardt MR, Bye-Møller L, et al. Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2024;6(1):e31-e39.
Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, et al. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011;56(7):2088-97.
Bested K, Jensen LM, Andresen T, Tarp G, Skovbjerg L, Johansen TSD, et al. Low-dose naltrexone for treatment of pain in patients with fibromyalgia: a randomized, double-blind, placebo-controlled, crossover study. Pain Rep. 2023;8(4):e1080.
Rodríguez-Freire C, Navarrete J, Rozadilla-Sacanell A, Sanabria-Mazo JP, Del Pino-Gaya B, Borràs X, et al. Efficacy of Low-Dose Naltrexone in Women With Fibromyalgia Syndrome: A 12-Month Randomised, Double-Blind, Placebo-Controlled Single-Centre Clinical Trial (INNOVA Study). Eur J Pain. 2026;30(6):e70321.
Reddit participants. LDN in USA (r/LowDoseNaltrexone). Accessed 2026-11-11.

Evidence overview for Low-Dose Naltrexone: EMA vs FDA Regulatory Approach