A small number of medications approved by the Food and Drug Administration (FDA) are known to be dangerous if their use is not carefully controlled. In these situations, FDA has the authority to require stringent safety precautions called “Elements to Assure Safe Use” or ETASU as part of a REMS program.
ETASU are carefully planned safety systems that control how a medication is administered by health professionals and taken by patients. Additionally, ETASU may also add training requirements for pharmacists and doctors and may require special patient counseling or monitoring.
Currently, there are 51 REMS programs with ETASU involving 3 percent of the medicines used in the U.S. (As of August 2019)
The Different Elements to Ensure Safe Use
Just as no two medicines are the same, every REMS is unique and tailored to address the potential dangers associated with a specific medication. Therefore, FDA may require manufacturers to undertake one or more of the following ETASU elements as part of a REMS program:
Certification or Registration of Health Care Professionals.
As a component of a REMS program, FDA may require that prescribers, pharmacists or other health professionals undergo special training on the risks and safe use of the drug and demonstrate to the manufacturer that they met the training requirements before they can prescribe or dispense the REMS drug. This process is known as attestation. Another possible ETASU requirement may be enrolling certified clinicians in a national database to keep track of how the REMS drug is prescribed and dispensed in real time.
Patient Enrollment and Documentation of Safe Use Conditions
Another possible REMS requirement is for physicians and pharmacists to counsel patients on the safe use, serious risks, and proper storage and disposal of the medicine and then for the patients to acknowledge they understand and accept the risks of taking the drug. In addition, a REMS may require documentation that specific steps were undertaken, such as a negative pregnancy test, before the REMS drug will be dispensed to a patient.
Patient Monitoring and Surveillance
REMS programs may also require a physician to monitor the patient for compliance with medication usage. Additionally, patients may be required to undergo specific testing before the drug is prescribed and refilled. Often, these tests results are entered into a patient registry to provide a higher level of surveillance.
A central registry of patients who take the medicine can play a valuable role in tracking the safe use of a REMS drug and identifying problems quickly. Usually operated by a Patient Registry Coordinating Center, the patient registry provides a database for collecting information from monitoring the outcomes and adverse reactions of patients. This information is summarized by the sponsor and submitted to FDA on a continual basis.
In limited situations, FDA may require stringent controls to manage the use of a potentially dangerous medicine at every point in the process – from the training health professionals receive to where and when the drug is administered to patients. Besides the measures described above, restricted distribution can entail only administering the medicine in a hospital, clinic or infusion center.
The Medicines Marketed with ETASU
While ETASU components can add time and administrative requirements for health professionals and can be expensive for manufacturers to develop and operate, the value of these safety systems is critical to ensuring patient safety and allowing needed medications to be available to the patients who need them, while preventing the dangerous complications these drugs can cause.
The following are the diseases, conditions and medical interventions where medicines carrying ETASU are now important treatment options:
- Acne (severe)
- Acute lymphoblastic leukemia (ALL)
- Atypical hemolytic uremic syndrome (a serious kidney disorder)
- B-cell lymphoma
- Bipolar disorder
- Bowel syndrome and disorders
- Chronic obstructive pulmonary disease (COPD)
- Crohn’s disease
- Cutaneous T-cell lymphoma
- Dupuytren’s contracture (a hand deformity)
- GI recovery after surgery
- Hypogonadism (insufficient testosterone production)
- Hypercholesterolemia (a rare cholesterol disorder)
- Hypoactive sexual desire disorder in women
- Hypoparathyroidism (rare condition involving parathyroid glands in the neck)
- Irritable bowel syndrome (IBS)
- Kidney disease
- Lipodystrophy (a disorder of fatty tissue)
- Mantle cell lymphoma (a blood cancer)
- Myelodysplastic syndrome (a blood disease)
- Multiple myeloma (a blood cancer)
- Multiple sclerosis
- Opioid dependence
- Paroxysmal nocturnal hemoglobinuria (a blood disease)
- Peritoneal dialysis (to treat severe kidney disease)
- Peyronie’s Disease (fibrous scar tissue inside the penis)
- Phenylketonuria or PDK (a rare genetic disease)
- Pulmonary hypertension (high blood pressure affecting arteries in the lungs and heart)
- Severe pain
- Thyroid cancer