The document discusses Risk Evaluation and Mitigation Strategies (REMS) implemented by the FDA for certain drugs that pose serious safety risks. REMS can include medication guides, communication plans, and elements to assure safe use. Examples provided include specific REMS programs for drugs like alosetron, clozapine, isotretinoin, thalidomide, and dofetilide that require enrollment of prescribers and pharmacies, patient counseling and monitoring, and other restrictions to ensure the safe use of the medication. REMS are intended to help ensure the benefits of medications outweigh the risks when serious safety issues have been identified.

1. RESTRICTED DRUGS
Risk Evaluation and Mitigation Strategies--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. RESTRICTED 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. RESTRICTED 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. RESTRICTED 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

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