Objectives By completing the lesson, the pharmacist will be able to: • Discuss the history of the REMS program • Describe the elements of the REMS program • Identify when a REMS might be used for a particular drug • Identify REMS elements employed with medications dispensed in community pharmacy • Discuss selection provision in Ohio law related to REMS requirements

1. Page 1 of 11
REMS in the Community Pharmacy1
Objectives2
By completing the lesson, the pharmacist will be able to:3
 Discuss the history of the REMS program4
 Describe the elements of the REMS program5
 Identify when a REMS might be used for a particular drug6
 Identify REMS elements employed with medications dispensed in community pharmacy7
 Discuss selection provision in Ohio law related to REMS requirements8
9
Introduction10
Federal law requires prescription drugs to be safe and effective. Clinical trials and testing before11
a drug’s labelling is approved involves significant time and expense. What happens after a12
drug’s labelling is approved? Post-marketing surveillance plays a more significant role than ever13
in assuring each drug is used in a manner considered to be safe and effective. FDA’s current14
post-marketing effort is referred to as Risk Evaluation and Mitigation Strategies (REMS).15
16
This program will outline the REMS elements and show them in use with medications17
commonly dispensed in community pharmacy settings. The discussion will focus on:18
 Accutane19
 Testosterone (topical) e.g. Androgel, Axiron20
 Chantix21
 Suboxone22
23
In addition to REMS, this lesson will discuss:24
 OAC 4729-5-18 Patient Profiles25
 OAC 4729-5-20 Prospective Drug Utilization Review26
 OAC 4729-5-21 Manner of Processing a Prescription (legitimate medical purpose)27
 OAC 4729-5-22 Patient Counseling28
29
History of REMS30
In 2007, a new law that gave FDA many new authorities and responsibilities to enhance drug31
safety was enacted. The Food and Drug Administration Amendments Act (FDAAA) and one of32
its provisions gave FDA the authority to require a REMS from manufacturers to help ensure that33
the benefits of a drug or biological product outweigh its risks.34
35
Other, similar and less formal mechanisms were already in place. For example, in 1989 FDA36
and Hoffman-LaRoche established the well-known system for monitoring the use of Accutane in37
woman of child-bearing age. See www.ipledgeprogram.com. In 2005, FDA also created a risk38
management system called Risk Minimization Action Plan (RiskMAP). A few drugs were39
selected for RiskMAP monitoring, including:40
 Clozaril® Patient Management System41

2. Page 2 of 11
 Thalidomide (Thalomid ®) STEPS program (System for Thalidomide Education and1
Prescribing Safety)2
 Isotretinoin (Accutane ®) iPLEDGE program3
 Dofetilide (Tikosyn ®) T.I.P.S.4
5
Some regulators felt that a more structured system was needed to decide when and whether ALL6
medications might be subject to more stringent post-marketing surveillance requirements. This7
provided the impetus for REMS. See 21 U.S. Code §355.1.8
9
General Overview of REMS10
Not all drugs require a REMS. Some drugs are so toxic that the small amount of benefits11
provided are insufficient to permit distribution, even when some patients would benefit from use.12
Likewise, some drugs are very effective and have relatively few or minor toxicities or secondary13
effects. It is those chemical entities “in between” where REMS comes into play. The FDA14
views some drugs as being effective enough to be prescribed, provided certain mandatory15
strategies or elements are in effect to monitor use.16
17
FDA is required to consider the following factors in deciding whether to require a REMS:18
 estimated size of the population likely to use the drug involved19
 seriousness of the disease or condition that is to be treated with the drug20
 expected benefit of the drug with respect to such disease or condition21
 expected or actual duration of treatment with the drug22
 seriousness of any known or potential adverse events that may be related to the drug and23
the background incidence of such events in the population likely to use the drug24
 whether the drug is a new molecular entity25
See 21 U.S. Code §355.1(a)(1).26
27
The four elements that may be included in any REMS, each discussed herein, are:28
 Medication Guide29
 Communication Plan30
 Elements To Assure Safe Use31
 Implementation System32
33
A REMS may be required by the FDA as part of the approval of a new product, or for an34
approved product when new safety information arises. For purposes of consistency, the REMS35
follow a standard template. See Guidance for Industry Format and Content of Proposed Risk36
Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS37
Modifications at:38
www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm1841239
8.pdf. Last accessed September 11, 2015. It is of interest to note that foreign-language versions40
of REMS elements, such as Medication Guides, patient package inserts, communication and41
education materials, enrollment forms, prescriber and patient agreements, and others, are not42
considered part of the approved REMS. FDA will not review foreign-language versions of43
REMS.44

3. Page 3 of 11
Medication Guide1
Since 1998, FDA had the authority to require distribution of medication guides. See 21 CFR2
208.20. [63 FR 66396, Dec. 1, 1998, as amended at 73 FR 404, Jan. 3, 2008.] FDA can require3
the development of, or changes to, a medication guide and can require these to be completed4
quickly, whether or not a medication guide is part of a REMS. Medication guides are part of5
labeling (21 CFR 201.57(c)) and are subject to the safety labeling change provisions of section6
505(o)(4) of the FD&C Act, added by FDAAA.7
Where required, a medication guide must be provided to the patient or the patient’s agent in the8
following four situations:9
1. When the patient or the patient’s agent requests a medication guide.10
2. When a drug is dispensed in an outpatient setting (e.g., retail pharmacy, hospital11
ambulatory care pharmacy) and the product will then be used by the patient without12
direct supervision by a healthcare professional.13
3. The first time a drug is dispensed to a healthcare professional for administration to a14
patient in an outpatient setting, such as in a clinic or dialysis or infusion center.15
4. The first time a drug is dispensed in an outpatient setting of any kind, after a Medication16
Guide is materially changed (e.g., after addition of a new indication, new safety17
information). FDA will provide notice when this occurs.18
The two most common instances where a medication guide is not required are:19
 for inpatients, unless the patient requests one20
 for outpatients refills when the drug is dispensed to a healthcare professional for21
administration to a patient, such as in a clinic or dialysis or infusion center22
23
For the typical community pharmacist, the medication guide is required for each dispensing of24
the drug. Of course, when the patient is discharged from the hospital or inpatient setting with a25
new prescription for administration at home, the appropriate medication guide(s) should be26
provided when the outpatient prescription is dispensed. The manufacturer of a drug product for27
which a medication guide is required must obtain FDA approval of the medication guide before28
the medication guide may be distributed. See 21 CFR 208.2429
Communication Plan30
When REMS requires a Communication Plan, the information will be directed to one of more31
members of the healthcare team or drug distribution chain. For example, prescribers may be sent32
written material to review. Also, prescribers may be sent material to review in person with each33
patient – a sort of checklist to make sure patients understand proper use, monitoring, laboratory34
testing, record keeping, and the like. In such a case, documenting review by both patient and35
prescriber together is employed. These materials will be available on both the FDA.gov website36
and websites provided by the manufacturers. The isotretinoin REMS includes a number of37
letters and communications, as discussed in the examples below.38

4. Page 4 of 11
Elements To Assure Safe Use1
FDA believes that sometimes, providing information alone is not enough. In such cases,2
additional Elements To Assure Safe Use (ETASU) will be required. ETASU are essentially3
mechanisms to restrict distribution of the drug. Requiring that patients not only receive4
information but formally “enroll” in a monitoring program may be required. Similarly,5
prescribers and pharmacists may face similar enrollment requirements. Mandatory laboratory6
testing may be required. Requiring that certain “certification stickers” are placed on written7
prescriptions is another mechanism to document compliance with an ETASU program. As a8
related aside, some third party payers may audit and refuse to pay for prescriptions not showing9
these stickers. The REMS for Suboxone includes a number of ETASU, as discussed in the10
examples below.11
12
The first drug with an ETASU under the REMS program was Entereg, used to treat disruption of13
normal motor activity of the gastrointestinal tract after surgery. The REMS for Entereg limited14
its dispensing to short-term use (no more than fifteen 15 doses for seven days) only for inpatients15
of certified hospitals. The REMS for Entereg served as a sort of prototype for subsequent16
approvals of high risk products that were felt to need an element to ensure safe use.17
18
Implementation System19
FDA may require the implementation system to include a description of how applicable products20
will be distributed. In addition, as part of the implementation system, FDA may require the21
certification of wholesalers and/or distributors to ensure the product is distributed only to22
certified or otherwise specified pharmacies, practitioners, or healthcare settings that dispense the23
drug, or only to patients who meet the requirements of the REMS. The implementation system24
may include:25
 a description of how the drug will be distributed26
 certification of wholesalers and distributors27
 a database of all entities certified to use the drug28
 periodic audits of those certified entities29
30
Each REMS requires ongoing assessment by the manufacturer and FDA review. The standard31
timetable for submission of assessments is:32
 eighteen (18) months after the REMS is approved33
 three (3) years after the REMS is approved34
 seven (7) years year after the REMS is approved35
36
The manufacture can also submit a voluntary REMS assessment at any time. The REMS37
assessment must also provide the status of all studies the manufacturer is conducting as well as38
any difficulties that have been encountered.39
40
REMS and Selected Outpatient Medications41
The FDA website has a wealth of information available for the REMS program. As of the time42
of this writing, there are eighty-four (84) medications active in the REMS program, with a43
history of two-hundred forty-four (244) listings since its beginning. The common community44

5. Page 5 of 11
pharmacy based medications listed in this lesson include a brief synopsis of materials available1
from FDA at http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm.2
3
Isotretinoin (Accutane)4
Medication Guide – patient education guide (male and female versions), activation form, consent5
form, pharmacist guide, Website: www.ipledgeprogram.com and toll-free number 1-866-495-6
0654, available Monday to Saturday, 9 AM - 12 AM (Midnight) ET. The medication guide must7
be provided with each prescription or when requested by the patient.8
 Prescribers must register and enter required information (pregnancy test results, 2 forms of9
contraception used, confirmation of patient counseling) in the iPLEDGE system for patients10
to be qualified to receive a prescription. Prescribers must document that all patients meet the11
requirements in the iPLEDGE program.12
 Only patients who are registered by prescribers in the iPLEDGE program can receive13
isotretinoin.14
 Female patients of childbearing potential must enter required information (2 forms of15
contraception used, answer questions on program requirements) in the iPLEDGE system in16
order to be qualified to receive a prescription.17
 Only pharmacies registered with and activated in the iPLEDGE program can dispense18
isotretinoin. Pharmacists must access the iPLEDGE system to receive authorization to fill19
and dispense every isotretinoin prescription.20
 Manufacturers will only ship isotretinoin to iPLEDGE-registered entities (e.g., direct vendor21
pharmacies, wholesalers).22
 Wholesalers must register annually in the iPLEDGE program. A registered wholesaler may23
distribute only FDA-approved isotretinoin products.24
25
Testosterone topical (Androgel)26
Medication Guide only. The medication guide must be provided with each prescription or when27
requested by the patient. Highlights include:28
 Women and children should avoid contact with the unwashed or unclothed area where29
ANDROGEL has been applied to the skin.30
 ANDROGEL is to be applied to the area of the shoulders and upper arms that will be covered31
by a short sleeve t-shirt. Do not apply ANDROGEL to any other parts of the body such as32
your penis or scrotum.33
 To lower the risk of transfer of ANDROGEL to others:34
o Wash hands right away with soap and water after applying ANDROGEL35
o After the gel has dried, cover the application area with clothing. Keep the area36
covered until washing the application area well or showering.37
38
Chantix39
Medication Guide only. The medication guide must be provided with each prescription or when40
requested by the patient. See http://www.chantix.com/. Highlights include:41
Stop taking CHANTIX and call prescriber right away with reports of agitation, hostility,42
depression or changes in behavior or thinking, or with any of the following symptoms:43
 thoughts about suicide or dying, or attempts to commit suicide44
 new or worse depression, anxiety, or panic attacks45
 acting aggressive, being angry, or violent46

6. Page 6 of 11
 an extreme increase in activity and talking (mania)1
 seeing or hearing things that are not there (hallucinations)2
 feeling people are against you (paranoia)3
4
Suboxone5
Medication Guide: www.SuboxoneFilmREMS.com or call 1‐877‐SUBOXONE (1‐877‐782‐6
6966). The medication guide must be provided with each prescription or when requested by the7
patient.8
Elements to Assure Safe Use: SUBOXONE sublingual film will only be dispensed by the9
prescriber or prescribed to patients with documentation of the following safe use conditions:10
 Verification that the patient meets the diagnostic criteria for opioid dependence11
 Risks described in the professional labeling and the Medication Guide have been12
discussed with the patient13
 Safe storage of the medication has been explained and reviewed with the patient14
 After appropriate induction, the patient is prescribed a limited amount of medication at15
the first visit16
17
Pharmacy: To further reinforce safe use conditions, manufacturer will ensure that within 30 days18
of FDA approval of the SUBOXONE sublingual film REMS, a “Dear Pharmacist Letter” will be19
mailed to all pharmacists on a national mailing list of all retail pharmacies authorized by DEA to20
handle schedule 3 controlled substances on a national mailing list from the National Technical21
Information Service. The pharmacist brochure, “Office‐Based Buprenorphine Therapy for22
Opioid Dependence: Important Information for Pharmacists” will be appended to the “Dear23
Pharmacist Letter.”24
Monitoring25
Each patient using SUBOXONE sublingual film will be subject to the following monitoring:26
 Return visits are scheduled at intervals commensurate with patient stability. Weekly, or27
more frequent, visits are recommended for the first month.28
 Assessment and reinforcement of patient’s compliance with the prescribed medication.29
 Assessment of appropriateness of dosage prescribed.30
 Assessment of whether patient is receiving the necessary psychosocial support.31
 Assessment of whether patient is making adequate progress towards treatment goals.32
Implementation System - Manufacturer will monitor compliance with the requirements to33
document prescribing and dispensing with documentation of safe use conditions through surveys34
of patients and prescribers, evaluations of health care utilization databases, and ongoing35
surveillance.36
37
Ohio Law Provisions38
Ohio law requires that all medication dispensing meet guideline to assure proper medication use.39
The following four rules are particularly important to keep in mind:40
 OAC 4729-5-18 Patient Profiles41
 OAC 4729-5-20 Prospective Drug Utilization Review42
 OAC 4729-5-21 Manner of Processing a Prescription (legitimate medical purpose)43
 OAC 4729-5-22 Patient Counseling44
45

7. Page 7 of 11
Patient profiles must include a “history of or active chronic conditions or disease states.” See1
OAC 4729-5-18 (A) (1) (h). While these disease states may sometimes be inferred from the2
medications themselves, it is best to update these conditions frequently. Mental health3
conditions are particularly important for the pharmacist to know of for patients receiving4
testosterone, Chantix, and Suboxone. Pharmacists should also be mindful of the need for5
monitoring of birth control when isotretinoin is dispensed.6
7
OAC 4729-5-20, Prospective drug utilization review, directs the pharmacist to review all8
prescriptions, both new and refills, prior to dispensing. Regarding the medications discussed9
already, compliance to therapy is particularly important for medications treating addiction issues10
such as Chantix and Suboxone.11
12
OAC 4729-5-22 discusses patient counseling. Due to the nature of REMS drugs, additional and13
potentially more specific, detailed counseling may be appropriate for patients receiving these14
particular medications. The FDA website and the website for each REMS medication include15
detailed materials which may be of value to include during the patient's counseling discussion.16
17
All prescriptions must be issued for a legitimate medical purpose in the usual course of18
professional practice by the prescriber: See OAC 4729-5-21 (A) and 4729-5-30 (A). Some19
REMS require substantial documentation in order for the prescription to be considered legitimate20
and the medication to be supplied to the patient. One such medication is Thalomid. For each21
prescription, the prescriber must obtain a unique prescription authorization number and22
document that number on the prescription. This unique prescription authorization number is23
required for each prescription to be legitimate. The pharmacist needs to obtain a confirmation24
number in order to fill the prescription. Both of these numbers must be provided on the25
prescription when dispensing.26
27
In addition, a legitimate prescription may allow no more than a 28 day supply – with no refills.28
Further, to reduce the prospects of stockpiling, the pharmacist should dispense each new29
prescription only if there are seven (7) days or less remaining on the existing prescription. The30
Thalomid REMS employs a restricted distribution program through enrolled specialty31
pharmacies. Medication is shipped from one of these enrolled pharmacies to the patient. The32
FDA and Celgene also provide an Education and Counseling Checklist for Pharmacies.33
Information about THALOMID and the THALOMID REMS™ program can be obtained by34
calling the Celgene Customer Care Center toll-free at 1-888-423-5436, or at35
www.CelgeneRiskManagement.com. A list of network pharmacies can be obtained at36
http://www.celgene.com/patients/rems-pharmacy-network/. There are currently twenty nine (29)37
pharmacies in the network.38
39
In addition to the medications discussion in this lesson, the following other common medications40
have REMS the pharmacist may want to review:41
 Mycophenolate [CELLCEPT]42
 Rosiglitazone [AVANDIA]43
 Buproprion [ZYBAN]44
45

8. Page 8 of 11
Take Away Points1
 Know your patient and history. The medication guide is the most common REMS2
element the community pharmacist will encounter.3
 Inpatient distribution of the medication guide is generally limited to requests for4
information by the patient.5
 Update and review the patient profile and patient history each time before dispensing.6
Look for potential excessively early refills and duplications of therapy.7
 Many REMS considerations are directed to psychiatric disorders and symptoms,8
requiring the pharmacist to deal with these sensitive subjects.9
 Manufacturers and wholesalers may have their own independent REMS requirements in10
addition to those of the pharmacist and pharmacy.11
 Isotretinoin dispensing requires extensive intervention at each dispensing.12
 REMS medications and requirements are updated frequently – refer to REMS website13
frequently. http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm14
 Many dispensing errors can be avoided and detected while the pharmacist is reviewing15
proper use of medication with a patient – another reason to counsel.16

9. Page 9 of 11
Questions – choose the one most correct answer. A passing score is seventy percent.1
1. The pharmacist must determine the legitimate medical need for which of the following2
before dispensing them to a patient.3
a. Suboxone4
b. Testosterone topical products5
c. Chantix6
d. all of the above7
2. Providing the REMS medication guide is optional for community pharmacists dispensing8
Chantix.9
a. true10
b. false11
3. Which of the following is the most commonly used REMS element:12
a. Medication Guide13
b. ETASU14
c. Implementation system15
d. Communication plan16
4. The standard timetable for FDA to review a manufacturer’s assessments of each REMS17
includes:18
a. eighteen (18) months after the REMS is approved19
b. three (3) years after the REMS is approved20
c. seven (7) years year after the REMS is approved21
d. all of the above22
5. The REMS for Chantix provides the patient stop taking Chantix and call the prescriber23
right away with reports of:24
a. Agitation25
b. Dry mouth26
c. Feelings of indigestion27
d. All of the above28
6. The REMS for topical testosterone gel provides the patient do all of the following29
except:30
a. Avoid exposure of women and children to the medication31
b. Apply the medication to the scrotum32
c. Wash hands after application of the medication33
d. Cover the application area with clothing after the gel has dried34
7. The REMS for Suboxone involves which of the following parties:35
a. The pharmacist36
b. The wholesaler37
c. The prescriber38
d. All of the above39
8. Which of the following drugs was the first to employ an ETASU under the REMS40
program:41
a. Suboxone42
b. Entereg43
c. Chantix44
d. Topical testosterone45

10. Page 10 of 11
9. The implementation system for a REMS may include all but:1
a. a description of how the drug will be distributed2
b. coupons to allow discounts for low-income patients3
c. certification of wholesalers and distributors4
d. a database of all entities certified to use the drug5
10. Which of the following best describes when the pharmacist is required to access the6
iPLEDGE system to dispense isotretinoin:7
a. When treatment with isotretinoin is initiated8
b. Each time isotretinoin is dispensed9
c. Whenever a female patient using isotretinoin may be pregnant or fills a prescription10
for birth control medication11
d. Annually along with the wholesaler12
13

11. Page 11 of 11
Lesson number 036-368-15-002-H03 Answer Sheet: Expires September 21, 20171
Approved for one contact hour of Ohio Jurisprudence by the Ohio State Board of Pharmacy2
3
REMS in the Community Pharmacy4
Answer Sheet – circle the one correct best answer. Credit will be granted with seven correct.5
Question Answer Question Answer
1 A B C D 6 A B C D
2 True False 7 A B C D
3 A B C D 8 A B C D
4 A B C D 9 A B C D
5 A B C D 10 A B C D
6
Please return by mail with check for $20 payable to James Lindon at:7
James Lindon, Ph.D.8
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Phone 440-333-001110
You may also send payment via PayPal to JLindon at LindonLaw dot com11
New: Submit answers at: http://www.lindonlaw.com/pharmacy-cpe/12
13
Please fax or e-mail, [specify one, please] my continuing education certificate to:14
Pharmacist Name ____________________________15
Street Address ________________________________________________________16
City ______________ State _______ Zip _____________17
E-Mail ___________________________________ Phone _____________________18
Ohio Pharmacist License Number _____________________19
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21
Copyright 2015 James Lindon, Lindon & Lindon LLC22
Any views expressed are not necessarily those of the author or the law firm of Lindon & Lindon.23
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