What a REMS program requires and which drugs have one in the US

What a REMS program is and which drugs have one

A REMS program is an FDA-required drug safety program for medicines with serious safety concerns, to help ensure benefits outweigh risks. REMS stands for Risk Evaluation and Mitigation Strategy, and FDA REMS requirements go beyond the drug's labeling.

As of October 14, 2026, FDA's REMS@FDA database lists 68 approved programs.

Every medicine carries labeling about its risks. FDA says "only a few medications require a REMS", where labeling alone isn't enough. The manufacturer designs and runs the REMS. FDA approves it.

What a REMS program does

Each REMS addresses a specific serious risk. It aims to prevent, monitor or manage that risk "by informing, educating and/or reinforcing actions to reduce the frequency and/or severity of the event" (FDA).

One FDA example is Zyprexa Relprevv, a long-acting olanzapine injection. It can cause post-injection delirium sedation syndrome. Its REMS requires administration in certified healthcare facilities that can observe the patient for at least three hours.

The legal basis is section 505-1 of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 355-1, added by the Food and Drug Administration Amendments Act of 2007 (signed September 27, 2007; REMS provisions effective March 25, 2008). A March 2008 Federal Register notice listed 16 products with existing safe-use restrictions as "deemed to have" a REMS. A REMS can apply to an NDA, a BLA or an ANDA.

REMS requirements: the elements

A REMS has a risk mitigation goal, communication elements and required activities for prescribers, pharmacists or patients (FDA). Section 505-1 sets out the possible elements and the assessment timetable:

FDA can change the assessment frequency. After three years, it can eliminate assessments if serious risks are adequately identified, assessed and managed.

ETASU

ETASU can restrict who prescribes or dispenses a drug and how patients receive it. The statute lists six types (21 U.S.C. 355-1(f)(3)):

• prescribers need specific training or experience, or special certification
• pharmacies, practitioners or healthcare settings that dispense the drug are specially certified
• the drug is dispensed only in certain settings, such as hospitals
• the drug is dispensed only with evidence of safe-use conditions, such as lab test results
• each patient is subject to certain monitoring
• each patient is enrolled in a registry

FDA can require ETASU only when a drug has been shown effective but is associated with a serious adverse drug experience, and it could not be approved (or would be withdrawn) without them. The ETASU must match the specific risk in the labeling. They must not unduly burden patient access, including patients with serious or life-threatening diseases, rural or medically underserved patients, and patients with functional limitations. Where practical, they should fit other REMS and existing distribution and dispensing systems.

"Serious risk" means a serious adverse drug experience under 21 U.S.C. 355-1. That covers death, an immediate risk of death, inpatient hospitalization or a longer stay, persistent or significant incapacity or a substantial disruption of normal life, and a congenital anomaly or birth defect. An event that may need medical or surgical care to prevent one of those outcomes counts too.

Generics and shared systems

A generic with a REMS is subject only to the reference drug's Medication Guide or patient package insert, packaging and disposal rules, and ETASU (505-1(i)). It has no communication plan or assessment timetable of its own. Some programs cover many products in one shared system. iPLEDGE for isotretinoin is one example.

How FDA decides a drug needs a REMS

FDA requires a REMS when it finds one "necessary to ensure that the benefits of the drug outweigh the risks of the drug" (505-1(a)(1)). The statute gives six factors:

1. the estimated size of the population likely to use the drug
2. the seriousness of the disease or condition
3. the expected benefit
4. the expected or actual duration of treatment
5. the seriousness of known or potential adverse events, and their background rate in that population
6. whether the drug is a new molecular entity

FDA explains how it weighs these in its April 2019 guidance, REMS: FDA's Application of Statutory Factors in Determining When a REMS Is Necessary.

The decision can come before approval. The applicant then submits a proposed REMS with the application. It can also come after approval, if FDA learns of new safety information. The holder then has 120 days to submit a proposed REMS, unless FDA sets another reasonable time (505-1(a)(2)).

The applicant may propose to add, change or remove a goal or element at any time. FDA may require a modification too. FDA generally acts within 180 days, and within 60 days on a minor modification (505-1(g) and (h)). Since 2008, FDA's REMS public dashboard counts more than 300 approved REMS and over 700 modifications.

Who does what in a REMS program

The manufacturer is responsible for running the REMS. Depending on the program, prescribers enroll or certify, pharmacies and healthcare settings certify through an authorized representative, and patients enroll, usually through their provider (FDA).

What happens if a REMS is not followed

A drug is misbranded if the responsible person fails to meet a requirement under 505-1(d), (e) or (f) (21 U.S.C. 352(y)). Civil penalties under 21 U.S.C. 333(f)(4) are up to $250,000 per violation and $1,000,000 for all violations in one proceeding. After written notice, a continuing violation starts at $250,000 for the first 30 days, doubles every 30 days, and is capped at $1,000,000 per 30-day period and $10,000,000 per proceeding.

The 2025 inflation-adjusted figures in 45 CFR 102.3 are $377,701 per violation, $1,510,803 per proceeding, and up to $15,108,023 per proceeding for continuing violations. FDA's REMS Compliance Program runs risk-based inspections. Findings can lead to product seizure, an injunction or civil penalties.

REMS drugs list

REMS@FDA is the live list of approved programs, with elements, dates and released-program data. On October 14, 2026 it listed 68 programs: 56 with ETASU and 12 with a communication plan only (Prolia, the denosumab biosimilars and Copiktra). That counts programs, not drugs. The Opioid Analgesic REMS alone covers many brands and generics.

Dates are month/day/year program dates, not necessarily the drug's first approval.

Zyprexa Relprevv is the oldest program still listed. The newest are the Thalidomide REMS (September 2, 2026) and Zenbexus (iberdomide, August 13, 2026).

Drugs that no longer have a REMS

Older lists online are often out of date, because FDA removed several big programs in 2025:

• Clozapine: FDA stopped expecting participation in February 2025, and the REMS was removed effective June 13, 2025 (FDA).
• CAR-T cell therapies Abecma, Breyanzi, Carvykti, Kymriah, Tecartus and Yescarta: REMS eliminated effective June 26, 2025 (FDA).
• Ambrisentan, macitentan and Tryvio (aprocitentan): REMS eliminated in April 2025. Bosentan and Filspari (sparsentan) still have a REMS, but fall 2025 changes dropped the embryo-fetal toxicity requirements and kept the liver-risk requirements (FDA).
• Caprelsa (vandetanib): REMS removed in September 2025 (FDA).

Mycophenolate, Vivitrol and Addyi are also no longer listed on REMS@FDA. Programs that stay listed can still change. An iPLEDGE modification approved February 9, 2026 allows at-home pregnancy tests after the pre-treatment tests and eases rules for patients who cannot get pregnant. Implementation moved from August 8, 2026 to November 15, 2026.

Common mix-ups

A Medication Guide doesn't by itself mean a drug has a REMS. FDA distinguishes risk information in labeling from a REMS, which requires actions beyond labeling alone. A boxed warning stays in the labeling, while a REMS is a separate program that requires actions. Only a minority of programs on REMS@FDA list a Medication Guide as a REMS element.

REMS is a US requirement under US law. Other regulators use their own risk-minimization tools.

You can ask RegAffairs AI what a REMS program is and which drugs have one and open the cited FDA sources from each answer. Any count of REMS is a snapshot, so check REMS@FDA for the current list before you rely on it.