This document discusses Risk Evaluation and Mitigation Strategies (REMS) which are required by the FDA to help ensure that a drug's benefits outweigh its risks. It provides details on the different components of a REMS which may include medication guides, communication plans, and elements to assure safe use. Examples are given of several drugs that require a REMS due to serious safety risks, including alosetron, clozapine, isotretinoin, thalidomide, and dofetilide. For each drug, the document outlines the specific REMS program and its requirements for prescribers, patients, and pharmacies.

1. RiskR EEvaSluTatIioCn TanEd DMi tiDgaRtioUn SGtrSategies--REMS
With each drug/biologic safety issue posing a
serious risk, the question for FDA will be: to REM or
not to REM?
REMS---Food and Drug Administration
Amendments Act of 2007
in 2006 the FDA listed 156 REMS for prescription
medicines (128) and biologics (28)
intended to ensure the benefits of the medication
outweigh its risk
why REMS??--Public outcry over revelations of
unforeseen risks from trusted medicines(rofecoxib,
valdecoxib, and salmeterol

2. RESTICTED DRUGS
 FDA can require a manufacturer to implement a
REMS
 Components of REMS
 1--Medication Guides--required for drugs and
biologics when the FDA determines that: (a)
certain information is necessary to prevent
serious adverse effects, (b) patient decision-making
should be informed by information
about a known serious side effect of a product,
or (c) patient adherence to directions for the
use of a product is essential to its
effectiveness.

3. RESTICTED DRUGS
 2--Communication Plans--
 Letters to healthcare providers;
 Disseminating information about the REMS to
encourage implementation; and
 Disseminating information through professional
societies about any serious risks of the drug
and any protocol to assure safe use.

4. RESTICTED DRUGS
 3--Elements to Assure Safe Use(ETASU)
 may include one or more of the following
 Special training, certifications, or demonstration of
experience for prescribers of the drug/biologic
 Certification of pharmacies, practitioners, or
healthcare settings that dispense the drug/biologic
 Limitations as to the healthcare settings where the
drug/biologic may be dispensed
 Evidence of special safe-use conditions--patients
receive the drug/biologic only after specified
authorization,proof of counseling, periodic blood tests
 monitor the number of prescriptions dispensed,
adverse events,

5. Examples of Drugs with REMS
 alosetron (Lotronex)
 clozapine (Clozaril, Fazaclo)
 isotretinoin (Accutane, Amnesteem,
Claravis, Sotret)
 thalidomide (Thalomid)
 dofetilide (Tikosyn)

6. Alosetron
 Treats a type of irritable bowel syndrome
(IBS)
 Serious adverse reactions of
gastrointestinal tract
 some necessitate a blood transfusion or surgery
 some even lead to death
 Restricted by Prescription Program for
Lotronex (PPL)
 requires physician enrollment & submission of
Patient-Physician Agreement Form
 Prescriptions must be written by physician &
must include PPL sticker on face of prescription

7. Clozapine
 Treats patients with schizophrenia
 Can cause serious drop in white blood
cells
 monitoring must be done regularly
 Pharmacies must register to dispense
clozapine
 Specific day supply may be dispensed
 (1, 2, or 3 weeks depending on monitoring
frequency)
 Pharmacy must receive documentation
of blood work

8. Isotretinoin
 Treats severe acne & can cause serious
birth defects
 iPledge Program
 registration required by
 doctors
 patients
 Pharmacies
 must meet specific requirements / answer
questions with iPledge Program each time
drug dispensed
 quantity dispensed is limited
 prescription must be picked up within
limited time

9. Thalidomide
 Treats multiple myeloma/erythema
nodosum leprosum
 Causes birth defects
 Thalidomide Education & Prescribing
Safety (S.T.E.P.S.) Program
 prescribers, patients, pharmacies must
register
 pharmacy must verify that the prescriber is
registered with S.T.E.P.S. before
dispensing medication

10. Dofetilide
 Treats irregular heart rhythms
 Can cause serious complications
 Patients must be hospitalized to initiate
therapy
 Tikosyn in Pharmacy System (T.I.P.S.)
 prescribers & pharmacists must register
 pharmacy must verify the prescriber’s
registration