Introduction to Risk Evaluation and Mitigation Strategy (REMS) a US FDA Program

What is REMS? | Risk Evaluation and Mitigation Strategy | What is the Risk Evaluation and Mitigation Strategies?

A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that is required for certain medications with serious safety concerns to ensure the benefits of the medication outweigh its risks. REMS program is initiated to strengthen medication use behaviours and actions that support the safe use of medicine.  

 

The Food and Drug Administration Amendments Act of 2007 gave FDA the right to have need of a Risk Evaluation and Mitigation Strategy (REMS) from drug manufacturers to ensure that the benefits of a drug or biological medicine outweigh its risks.

 

Despite the fact that all medications have labeling (Prescribing Information) that informs health care professionals about medication risks, only a few medications require a REMS.

 

Objective of REMS

• REMS are not designed to alleviate all the adverse events of a medication.

• REMS objective is to prevent, monitor and/or manage a specific serious risk by informing, educating and/or reinforcing actions to diminish the frequency and/or severity of the event.

• REMS ensures all treated patients receive special monitoring during the treatment period when a side effect is most likely to occur so it can be detected and treated.

Example of REMS

·         Olanzapine depot injection is a long-acting injectable anti-psychotic medication.

·         Olanzapine is used to treat schizophrenia in adults.

·         Olanzapine depot injection can cause serious delirium sedation syndrome.

·         Symptoms include feeling sleepier than usual, coma, and feeling confused or disoriented.

·     The risk of delirium sedation syndrome is present with every post-injection, although the risk is small - less than 1 %.

·       To reduce the risk of post-injection delirium sedation syndrome, FDA required the manufacturer of  Olanzapine depot injection to develop a REMS.

·       The purpose of the REMS is to make sure that the drug is administered only in certified health care facilities that can monitor patients for at least three hours and provide the medical care necessary in case of an adverse event.

 

Parts of a REMS

 

A REMS can have one or more of the following components:

·       Medication Guide (MG) or Patient Package Insert

Contains Patient/Consumer-friendly information to promote safe and effective use of medicine

·       Communication Plan (CP) for Healthcare Providers

Contains “Dear Healthcare Professional” letters, additional information about the REMS, and other educational materials directed toward the healthcare professionals

·       Elements to Assure Safe Use (ETASU)

Contains Provider/Pharmacy certifications, dispensing/administration information, patient monitoring, patient enrollment into registries

  

·       Implementation System

How ETASU will be enacted, along with requirements for monitoring and evaluating ETASU implementation by healthcare providers, pharmacists, and others.

Table: Examples of the Types of Risk   

Risk Example	Possible REMS Action
Serious infection	Patient education on initial warning signs prior to prescribing
Severe allergic reaction	Healthcare professional must be certified prior to administer the product
Liver damage	Liver function monitoring while patient is taking the drug
Severe birth defects	Negative pregnancy test prior to dispensing each prescription

 

Table: Drug Products with Approved Risk Evaluation and Mitigation Strategies (REMS)

S. No.	Product Name
1.	Acetaminophen and codeine phosphate Acetaminophen and hydrocodone bitartrate Acetaminophen and oxycodone
2.	Alemtuzumab
3.	Alosetron
4.	Alosetron hydrochloride
5.	Alvimopan
6.	Ambrisentan
7.	Axicabtagene ciloleucel Brexucabtagene autoleucel
8.	Belantamab mafodotin
9.	Bosentan
10.	Brexanolone
11.	Brodalumab
12.	Buprenorphine Buprenorphine and naloxone Buprenorphine hydrochloride
13.	Buprenorphine extended-release
14.	Buprenorphine hydrochloride
15.	Calcium, magnesium, potassium, and sodium oxybates Sodium oxybate
16.	Ciltacabtagene autoleucel
17.	Clozapine
18.	Collagenase clostridium histolyticum
19.	Denosumab
20.	Duvelisib
21.	Eculizumab
22.	Esketamine
23.	Fenfluramine hydrochloride
24.	Fentanyl Fentanyl buccal Fentanyl citrate
25.	Flibanserin
26.	Idecabtagene vicleucel
27.	Inotersen
28.	Isotretinoin
29.	Lenalidomide
30.	Lisocabtagene maraleucel
31.	Lomitapide
32.	Loxapine
33.	Macitentan
34.	Mavacamten
35.	Metreleptin
36.	Mifepristone
37.	Mycophenolate acid delayed-release Mycophenolate mofetil for injection Mycophenolate mofetil for oral suspension
38.	Natalizumab
39.	Olanzapine
40.	Panobinostat
41.	Parathyroid hormone
42.	Peanut (Arachis hypogaea) Allergen Powder-dnfp
43.	Pegcetacoplan
44.	Pegvaliase-pqpz
45.	Pexidartinib
46.	Phentermine and topiramate
47.	Pomalidomide
48.	Pomalidomide capsule
49.	Ravulizumab-cwvz
50.	Riociguat
51.	Sodium oxybate
52.	Sparsentan
53.	Sufentanil
54.	Teclistamab-cqyv
55.	Teduglutide [rDNA origin]
56.	Testosterone undecanoate
57.	Thalidomide
58.	Tisagenlecleucel
59.	Tolvaptan
60.	Vandetanib
61.	Vigabatrin

Conclusions

 

For certain drugs that might otherwise not be approvable based upon their benefit-risk profile, the REMS may offer a practical solution for tipping the balance in favour of approvability by introducing additional safeguards to mitigate risk.