How a prescription drug moves to the drugstore shelf

The most recent entry on FDA's list of prescription-to-nonprescription switches is dated June 16, 2026: a 4 mg naloxone hydrochloride nasal spray, the opioid overdose reversal drug, approved for sale without a prescription. The FDA list¹ has 47 entries, starting with a topical antifungal in December 2001. Naloxone first crossed over on March 29, 2023, when FDA approved a 4 mg spray as "the first naloxone product approved for use without a prescription," the agency said at the time².

A switch changes where a medicine sits, who can buy it and, often, who pays for it. The molecule, and often the strength, stays the same while the legal status, the label and the price move. This explainer walks through the legal test FDA applies, the consumer studies a sponsor has to run, the molecules that have made the trip since 2001, what pharmacies pay for the prescription and OTC versions of two acid reducers, and the 2024 rule meant to widen the path.

The legal line between prescription and OTC

Federal law drew the split in 1951. The Durham-Humphrey Amendment "defines the kinds of drugs that cannot be safely used without medical supervision and restricts their sale to prescription by a licensed practitioner," FDA's history of food and drug law³ says. GxRadar's article on the Durham-Humphrey Amendment covers that law, and the explainer on "Rx only" covers the prescription legend on labels today.

A drug stays prescription-only until FDA exempts it. Under 21 CFR 310.200(b)⁴, the exemption comes when FDA finds the prescription requirement "not necessary for the protection of the public health by reason of the drug's toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use," and that the drug "is safe and effective for use in self-medication as directed in proposed labeling." Once exempted, a product may not carry the Rx-only legend; using it would be misbranding, the same section says. A second route runs through the OTC monograph system, covered in GxRadar's piece on the 2020 monograph reform.

What a switch application has to show

FDA recognizes two kinds of switch, according to its switch overview⁵. In a full switch, the sponsor moves the whole product to nonprescription status through an efficacy supplement or a 505(b)(2) application, and afterward the drug is sold only OTC. In a partial switch, the sponsor files a new application covering some conditions of use, such as certain indications, while others stay prescription-only.

Either way the application needs efficacy and safety data for the nonprescription setting, data showing consumers can use the drug safely "without the supervision of a healthcare professional," and postmarketing safety surveillance data, the same page says. The consumer evidence usually comes from three kinds of studies. A label comprehension study tests whether people understand the proposed Drug Facts label, under FDA's August 2010 guidance⁶. A self-selection study "assesses the ability of consumers to apply drug labeling information to their personal health situation" to decide whether the drug is right for them, under an April 2013 guidance⁷. When FDA needs to see how people behave under real-world conditions, an actual use study is the tool, both guidances say.

Norgestrel, a progestin-only daily oral contraceptive switched in 2023, shows how the pieces fit. Its effectiveness had been established when it was approved for prescription use in 1973, and studies showed consumer understanding of its Drug Facts label "was high overall," FDA said in its July 13, 2023 announcement⁸ of the first nonprescription daily oral contraceptive.

Switches by molecule, 2001 to 2026

FDA's list names products by brand. The table below gives the active ingredients instead, matched by application number to FDA's Orange Book data files⁹, for a selection of the 47 entries. FDA flags a few acid reducer entries, marked with an asterisk, as not true switches because those conditions of use had not been marketed as prescription products under an approved application first.

By year, the list's busiest stretches were 2002 (six entries), 2011 and 2020 (five each). It has no entries for 2018, 2019, 2024 or 2025. The list does not include every OTC drug, and FDA notes that switching is only one of several ways to bring a nonprescription drug to market.

One molecule, two shelves

A full switch leaves no prescription version behind. A partial switch, or a prescription strength that never moved, can leave both. GxRadar counted active listings in the October 2026 Orange Book data for six switched single-ingredient drugs; each strength of each application counts once.

Costs can differ sharply between the two versions. CMS's NADAC survey¹⁰, which records what pharmacies pay to acquire drugs, tracks prescription and OTC products separately. In the file dated Nov. 4, 2026 (rates effective Oct. 21), the gap was large for two acid reducers. These are pharmacy acquisition costs, not shelf or counter prices.

Because the omeprazole rows compare different dosage forms, the famotidine pair is the closer match. GxRadar's pages for famotidine and omeprazole track the prescription rows over time, and the acid reducer price history covers all three common acid reducers.

Coverage follows the legal status. Federal Medicaid law lists "nonprescription drugs" among the classes a state may exclude or restrict, though a state that covers them when prescribed must treat them as covered outpatient drugs, under 42 U.S.C. 1396r-8(d)¹¹. Medicare Part D's definition of a covered drug leaves out drugs Medicaid may exclude, apart from a few named exceptions, under 42 U.S.C. 1395w-102(e)¹². Whether a particular plan pays for an OTC product is a question for the plan or the pharmacist.

Generic makers have to follow a full switch. Prescription and nonprescription versions of the same drug without a clinically meaningful difference cannot be marketed at the same time, and generic holders should update their labeling within six months after FDA approves the brand's full switch, under FDA's MAPP 5200.11¹³, effective Dec. 8, 2025. GxRadar's piece on why generic labeling must match the brand explains the underlying rule.

The ACNU rule, and what it has produced so far

For some drugs, a label alone cannot give consumers everything they need to choose and use the product correctly, FDA says¹⁴. The agency's answer is a rule on nonprescription drug products with an "additional condition for nonprescription use," or ACNU, published as a final rule on Dec. 26, 2024¹⁵. An ACNU is an extra step a consumer must complete before buying the drug, such as a questionnaire, to show the product is appropriate for them. The rule's preamble describes a hypothetical "Drug X" whose buyers answer questions on a secure website that calculates a risk score before allowing the purchase.

Originally the rule was to take effect Jan. 27, 2025; it was delayed twice and took effect May 27, 2025, according to a March 2025 notice¹⁶. FDA's primary estimate was that the rule would cut consumers' access costs, such as doctor visits and copays, by $33.62 per purchase, with a range of $0 to $67.23, the final rule says¹⁵.

No product has used it yet. "Right now, there are no FDA-approved nonprescription drugs with an ACNU," FDA's ACNU page¹⁴ said as of its Aug. 13, 2026 update.