When a drug can save your life but also carry a serious risk-like causing birth defects, organ failure, or deadly blood disorders-how do you make sure it’s used safely? That’s where REMS programs come in. These aren’t just paperwork or red tape. They’re legally required safety nets put in place by the U.S. Food and Drug Administration (FDA) to let patients get life-saving medicines while minimizing the chance of harm.
What Exactly Is a REMS Program?
REMS stands for Risk Evaluation and Mitigation Strategies. It’s a formal system created by Congress in 2007 under the Food and Drug Administration Amendments Act (FDAAA). The FDA can require a REMS for any prescription drug that has serious safety risks that can’t be managed with just a standard warning label.
Think of it this way: some drugs are so powerful-or so dangerous-that the FDA won’t approve them unless there’s a plan to control how they’re prescribed, dispensed, and used. Examples include drugs like isotretinoin (for severe acne, which can cause birth defects), clozapine (for treatment-resistant schizophrenia, which can wipe out white blood cells), and thalidomide (used for cancer and leprosy, infamous for causing limb deformities in babies in the 1950s).
Today, about 120 REMS programs are active in the U.S., covering roughly 185 different drugs. That’s about 5.7% of all prescription medications. Most of these are in cancer, autoimmune diseases, and neurology-areas where the benefits are huge, but the risks are too high to leave to chance.
The Three Main Parts of a REMS Program
Not all REMS are the same. But every one includes at least one of these three components:
- Medication Guides - These are printed handouts given to patients when they pick up their prescription. They explain the risks in plain language, what symptoms to watch for, and what to do if something goes wrong. About 78% of REMS programs require these.
- Communication Plans - These are tools to educate doctors and pharmacists. They might include letters, training videos, or safety alerts sent out by the drug maker. About 62% of REMS programs use these to make sure prescribers understand the dangers.
- Elements to Assure Safe Use (ETASU) - This is the strictest level. About 45% of REMS programs have ETASU, and they’re the ones that cause the most headaches-for patients, doctors, and pharmacies alike.
ETASU can include things like:
- Doctors needing special certification before they can prescribe
- Pharmacies having to be specially licensed to dispense the drug
- Patients being enrolled in a registry to track their health over time
- Requiring pregnancy tests before each dose for drugs that cause birth defects
- Only allowing the drug to be given in a hospital or clinic
For example, the REMS for lenalidomide (Revlimid®) and pomalidomide (Pomalyst®)-both used for multiple myeloma-require doctors to be certified, patients to sign forms agreeing to birth control, and monthly pregnancy tests for women of childbearing age. That’s not just a formality. It’s a legal requirement.
Who’s Responsible for Making REMS Work?
The drug manufacturer has to design the REMS and pay for it. On average, each program costs a company $2.7 million per year. That includes building websites, training materials, certification systems, and hiring staff to manage compliance.
But the real work happens on the ground:
- Doctors have to complete certification for each REMS they prescribe under. It takes about 45 minutes per program, and many oncologists and hematologists manage 5 or more REMS drugs at once.
- Pharmacists have to check online portals before dispensing. For drugs like Entyvio, that can add 15-20 minutes per prescription just to verify certification status and document everything.
- Specialty pharmacies handle 89% of REMS drugs. These aren’t your local CVS-they’re high-touch centers that track patient outcomes, manage inventory, and coordinate with doctors.
- Patients are expected to follow strict rules: take pregnancy tests, attend follow-ups, report side effects, and sometimes travel to a hospital just to get one dose.
And it’s not just inconvenient-it’s expensive. The whole system costs the U.S. healthcare system about $1.2 billion a year. But the FDA says it prevents $8.4 billion in avoidable hospitalizations and complications. That’s a 7-to-1 return on investment.
Why Do REMS Programs Cause So Much Frustration?
Despite their safety benefits, REMS programs are widely criticized for being messy, slow, and outdated.
Generic drug makers say REMS are being used as a barrier to competition. A 2024 study in Health Affairs found that 78% of generic manufacturers faced delays averaging 14.3 months just to get samples of the brand-name drug to test their version. That’s not safety-it’s a monopoly tactic.
Doctors and nurses are drowning in paperwork. A 2023 survey by the American Society of Hematology found that 68% of hematologists spend more than 5 hours a week just managing REMS requirements for drugs like Revlimid and Pomalyst. That’s 5 hours they could spend seeing patients.
Patients get caught in the middle. A GoodRx survey in 2023 showed that 42% of people prescribed a REMS drug experienced at least one delay in getting their medication. One patient described waiting 11 days for a pregnancy test result before her doctor could refill her prescription for a multiple sclerosis drug.
And it’s worse for non-English speakers. Many Medication Guides aren’t translated. Patients who don’t speak English often don’t understand the risks-or the steps they need to take.
Is the System Getting Better?
Yes-and it needs to.
The FDA launched the REMS Modernization Initiative in 2023. The goal? Cut the red tape without cutting safety. That means:
- Standardizing forms and documentation across all REMS programs
- Building a central digital dashboard to track compliance and outcomes
- Using electronic health records to auto-verify prescriber certification
- Allowing pharmacies to check REMS status in real time instead of logging into 10 different portals
The 21st Century Cures Act Reauthorization (2022) also requires the FDA to create a new REMS Assessment Standard by December 2025. That means REMS programs will be evaluated based on actual patient outcomes-not just how many forms were filled out.
Some drug companies are already testing digital tools. One company uses text reminders to prompt patients to take their pregnancy tests. Another uses AI to flag when a patient’s lab results show early signs of dangerous side effects.
The FDA has also started removing REMS when they’re no longer needed. In March 2023, they dropped the REMS for the MS drug Zeposia after data showed the risks were low and well-managed with standard warnings.
What Should You Do If You’re Prescribed a REMS Drug?
If your doctor prescribes a drug with a REMS program:
- Ask: “What do I need to do to get this medication?” Don’t assume it’s like any other prescription.
- Find out if your pharmacy is certified to dispense it. Many regular pharmacies can’t.
- Check if you need to sign forms, join a registry, or get regular blood tests.
- Keep a copy of your Medication Guide. Read it. Keep it with your other medical records.
- If you’re delayed, ask your doctor to call the REMS program’s support line. They can help troubleshoot.
REMS programs aren’t perfect. But they’ve kept thousands of people safe. The goal isn’t to eliminate them-it’s to make them smarter, faster, and less of a burden for everyone involved.
What Happens If a REMS Program Fails?
The FDA doesn’t just approve a REMS and walk away. Manufacturers have to submit regular reports showing whether the program is working. Did fewer patients have side effects? Were prescriptions delayed too often? Did doctors actually complete training?
If a REMS isn’t helping, the FDA can change it-or remove it entirely. Since 2007, only three REMS programs have been fully discontinued. That’s rare, because the FDA only removes them when evidence shows the risks are now low enough to manage without extra steps.
But if a company doesn’t follow the rules? The FDA can issue a Warning Letter. In fiscal year 2023, they issued 17 such letters-up 22% from the year before. That’s not a slap on the wrist. It’s a legal notice that could lead to fines, product recalls, or even withdrawal from the market.
What drugs require a REMS program?
Drugs with serious, life-threatening risks that can’t be managed by standard labeling require a REMS. Common examples include isotretinoin (for acne), clozapine (for schizophrenia), thalidomide (for cancer and leprosy), lenalidomide and pomalidomide (for multiple myeloma), and alemtuzumab (for multiple sclerosis). The FDA maintains a public list of all active REMS programs on its REMS@FDA website.
Can I get a generic version of a REMS drug?
Yes, but it’s often delayed. Generic manufacturers must get access to the brand-name drug for testing, and some branded companies use REMS requirements to block that access. A 2024 study found generic makers face delays averaging 14.3 months. New laws aim to fix this by requiring branded companies to provide samples within 90 days.
Do REMS programs actually make drugs safer?
Evidence shows they do. For example, the REMS for isotretinoin reduced the rate of fetal exposure by more than 90% since its implementation. The FDA estimates REMS programs prevent $8.4 billion in healthcare costs annually by avoiding hospitalizations and complications. But their effectiveness depends on how well they’re implemented.
Why do pharmacists hate REMS programs?
Because they add hours of manual work. Pharmacists must verify prescriber certification, check patient enrollment status, maintain special inventory logs, and complete extra documentation for each REMS drug. For drugs like Entyvio or Lemtrada, this can add 15-20 minutes per prescription. Many say the systems are outdated and don’t talk to each other.
Are REMS programs the same in other countries?
No. The U.S. is one of the few countries with a formal, legally mandated REMS system. Other countries use risk management plans, but they’re often less rigid and don’t require prescriber certification or pharmacy licensing. The FDA’s system is more complex and more costly, but also more tightly enforced.
