Current Class Of Risk Evaluation & Mitigation Strategies

Here is a general outline of the REMS FDA has mandated so far, as well as a listing of drugs where it has been announced that REMS are being developed or drugs with safety issues that could invoke a REMS.

Drug & Sponsor		Reason for REMS	Elements of REMS		Timetable for Assessments	Post-marketing Requirements
Abstral (fentanyl, transmucosal) ProStrakan		Drug associated with risk of overdose, abuse, addiction and serious complications due to medication errors	Medication Guide; elements to assure safe use, including restricted distribution; implementation system Abstral REMS is the first approval of FDA's vision for a transmucosal fentanyl class REMS that will use the same template and offer a shared system for implementation		Every six months for the first year and annually thereafter 7/7/2011, 1/7/2012 and annually thereafter
Accutane (isotretinoin) and generics Roche (program is administered by Covance)		To prevent fetal exposure to isotretinoin and to communicate the serious risks and safe-use conditions of the iPLEDGE program	Medication Guide, elements to assure safe use and implementation system based on the previous iPLEDGE program		5/1/2011 and annually thereafter
Actemra (tocilizumab) Roche		Drug associated with risks of serious infections, gastrointestinal perforations, changes in liver function, decreases in peripheral neutrophil counts, decreases in platelet counts, elevations in lipid parameters in peripheral blood, demyelinating disorders, and malignancies	MedGuide and communication plan		18 months, 3 years and 7 years 7/8/2011, 1/8/2013, 1/8/2017	Conduct non-clinical animal studies
Actiq (fentanyl citrate) Cephalon		Drug associated with risk of overdose, abuse, addiction and serious complications due to medication errors	Medication Guide; elements to assure safe use, including restricted distribution; implementation system		Every six months for the first year and annually thereafter
Actonel (risedronate) Warner Chilcott [Released from REMS 8/25/2011]		Possible risk of unusual thigh bone fracture with the bisphosphonate class	Medication Guide		18 months, 3 years and 7 years 7/25/2012, 1/25/2014 and 1/25/2018
ActoPlus Met & ActoPlus Met XR (pioglitazone/metformin) Takeda		Drug associated with increased risk of fracture in women	MedGuide		18 months, 3 years and 7 years 11/12/2010, 5/12/2012 and 5/12/2016
Actos (pioglitazone) Takeda		Due to reports of congestive heart failure in both the clinical trial and post-marketing setting for pioglitazone-containing products	MedGuide		18 months, 3 years and 7 years 8/3/2012, 2/3/2014 and 2/3/2017
Advair Diskus, Advair HFA (fluticasone/salmeterol) GlaxoSmithKline		New safety information from three controlled clinical trials identified an increased risk of pneumonia in COPD patients who take Advair Diskus	MedGuide		1^st: Oct. 2009 2^nd: April 2011 3^rd: April 2015
Ampyra (dalfampridine) Acorda Modified 11/17/2011		Drug associated with an increased risk of seizure	MedGuide and communication plan consisting of Dear Health Care Provider letters annually for the first three years on the market		7/22/2011, 1/22/2014 and 1/22/2017
Anti-epileptic class: Carbamazepine (Shire's Carbatrol, Validus' Equetro, Novartis' Tegretol and Tegretol XR, and generics), Clonazepam (Roche's Klonopin and Klonopin ODT), Felbamate (Meda's Felbatol), Lacosamide (Schwarz’s Vimpat), Levetiracetam (UCB’s Keppra and Keppra XR and generics), Levofloxacin (J&J’s Levaquin), Oxcarbazepine (Novartis’ Trileptal and generics), Norfloxacin (Merck’s Noroxin), Tiagabine (Cephalon’s Gabitril), Zonisamide (Eisai’s Zonegran and generics) Not yet finalized: Divalproex sodium (Abbott’s Depakote franchise and generics), Gabapentin (generics), Mephenytoin (formerly marketed as Novartis’ Mesantoin), Trimethadione (Abbott’s Tridione), Valproic Acid (Abbott’s Depakene, Banner’s Stavzor ER) [Released from REMS: Clorazepate (Ovation’s Tranxene and generics), Ethosuximide (Pfizer’s Zarontin and generics), Ethotoin (Ovation’s Peganone), Pregabalin (Pfizer’s Lyrica), Lamotrigine (GlaxoSmithKline’s Lamictal and generics), Methsuximide (Pfizer’s Celontin), Rufinamide (Eisai’s Banzel), Phenytoin (Pfizer’s Dilantin and generics), Primidone (Valeant’s Mysoline and generics), Gabapentin (Pfizer's Neurontin and Abbott's Gralise), Topiramate (J&J’s Topamax)]		Drugs associated with risk of suicidality	MedGuide and timetable for submission of assessments		18 months, 3 years and 7 years
Aplenzin (bupropion) Biovail Laboratories [Released from REMS 4/29/2011]		Antidepressants are associated with an increased risk of suicidality in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders	MedGuide		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015
Atelvia (risedronate delayed-release) Warner Chilcott [Released from REMS 8/22/2011]		Possible risk of unusual thigh bone fracture with the bisphosphonate class	Medication Guide		18 months, 3 years and 7 years
Avandamet (rosiglitazone/metformin) & Avandaryl (rosiglitazone/glimepiride) GlaxoSmithKline Updated with final ETASU for Avandia		Increased risk of ischemic cardiovascular events in certain patients receiving rosiglitazone-containing products	Medication Guide, communication plan, elements to assure safe use including prescriber certification, controlled distribution and an implementation system		6 months, 12 months and annually thereafter
Avandia (rosiglitazone) GlaxoSmithKline		Increased risk of myocardial infarction	Medication Guide, communication plan, elements to assure safe use including prescriber certification, controlled distribution and an implementation system		6 months, 12 months and annually thereafter
Avelox (moxifloxacin hydrochloride) Bayer [Released from REMS 8/3/2011]		Fluoroquinolone antibiotic carries increased risk of tendonitis and tendon rupture	MedGuide		10/27/2010, 4/27/2012, 4/27/2016
Banzel (rufinamide) Eisai [Released from REMS 6/10/2011]		Drug associated with increased the risk of suicidal thoughts or behavior	MedGuide and timetable for assessments		1^st: May 2010 2^nd: November 2011 3^rd: November 2015	Conduct non-clinical trial
Boniva (ibandronate) Roche/Genentech [Release from REMS 7/1/2011]		Possible risk of unusual thigh bone fracture with the bisphosphonate class	Medication Guide		7/25/2012, 1/25/2014 and 1/25/2018
Botulinum toxin class: Allergan’s Botox (botulinum toxin type B), Ipsen/Medicis’ Dysport (abobotulinum toxin A),Solstice Neurosciences’ Myobloc (botulinum toxin type B), Merz’s Xeomin (incobotulinumtoxin A)		Drugs carry risk of adverse events when the effects of the toxin spread beyond the site where it was injected; REMS also warns the products are not interchangeable	MedGuide, communication plan including Dear Health Care Provider letters and survey		18 months, 3 years and 7 years
Butrans (buprenorphine transdermal system) Purdue Pharma		To inform patients and healthcare professionals of the potential for misuse, abuse and overdose, and addiction, from use of the partial opioid agonist	MedGuide and elements to assure safe use including a training program		Every six months for the first year and annually thereafter
Byetta (exenatide) Amylin [Released from REMS 8/5/2011]		To mitigate the potential risk of undiagnosed and/or complicated pancreatitis and to mitigate the potential risk of renal failure	MedGuide and communication plan		5/30/2011, 10/30/2012 and 10/30/2016
Cambia (diclofenac) Kowa Pharma [Released from REMS 7/20/2011]		Drug associated with increased risk of cardiovascular events and gastrointestinal toxicity	MedGuide		December 2010, June 2012, June 2016
Caprelsa (vandetanib) AstraZeneca		Drug associated with risk of QT prolongation, Torsades de pointes and sudden death	MedGuide, communication plan, elements to assure safe use and implementation plan		Every six months for the first year and annually thereafter	Long-term rodent carcinogenicity studies, a randomized dose-finding study of 150 mg and 300 mg doses in patients with progressive or symptomatic medullary thyroid cancer to assess known serious risk of vortex keratopathy and corneal stromal changes and other serious risks that could affect overall survival, and submission of the overall survival results of the pivotal study
Chantix (varenicline) Pfizer		Serious risks include potential for neuropsychiatric symptoms	MedGuide		1^st: 4/19/2011 2^nd: 10/19/2012 3^rd: 10/19/2016
Cimzia (certolizumab pegol) UCB		To ensure the benefits of the drug outweigh the risks of opportunistic infections, development of lymphoma, other malignancies and demyelinating and autoimmune disorders in Crohn’s patients	MedGuide and communication plan		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015	Conduct four clinical trials and one observational study
Cipro (ciprofloxacin) Bayer [Released from REMS 8/3/2011]		Fluoroquinolone antibiotic carries increased risk of tendonitis and tendon rupture	MedGuide		10/27/2010, 4/27/2012, 4/27/2016
Colcrys (olchicines) Mutual Pharmaceutical [Released from REMS 7/20/2011]		Risks include increased susceptibility to colchicine toxicity in patients with renal or hepatic impairment and potential serious drug-drug interactions	MedGuide		1/30/2011, 7/30/2012, 7/30/2016
Copegus (ribavirin) Roche [Released from REMS 5/9/2011]		Risks include teratogenicity and anemia	Medication guide		12/9/2011, 6/9/2013, 6/9/2017
Creon (pancrelipase) Solvay [Released from REMS 5/9/2011]		Porcine-derived pancreatic enzyme products carry risk of fibrosing colonopathy with high doses, and the theoretical risk of transmission of viral disease to patients	MedGuide		10/30/2010, 4/30/2012, 4/30/2016	Two observational studies; clinical study; seven reports on risk, prevention, quality and surveillance
Duetact (pioglitazone/glimepiride) Takeda		Due to reports of congestive heart failure in both the clinical trial and post-marketing setting for pioglitazone-containing products	Medication guide		March 2011, September 2012, September 2016
Dulera (mometasone furoate/formoterol fumarate) Schering (Merck)		To inform health care providers and patients of the increased risk of asthma-related death and serious outcomes with the long-acting beta2-adrenergic agonists (LABA) class, as well as other serious risks, and inform them about appropriate use	Medication guide and communication plan consisting of a “Dear Health Care Provider” letter and website		Annually
Edluar (zolpidem) Meda [Released from REMS 8/10/2011]		To ensure the benefits of the drug outweigh the risks of complex sleep-related behaviors, such as sleep-driving and sleep-eating, and severe anaphylactic reactions	Medication guide		9/13/2010, patient survey 6/11/2011, 3/13/2012 and 3/13/2017
Effient (prasugrel) Lilly/Daiichi Sankyo [Updated 9/26/2011]		Drug associated with serious risk of major bleeding and a signal of a serious risk of increased incidence of malignancies	MedGuide and communication plan for the first two years of launch, to address bleeding risk and guide appropriate patient selection		Jan. 31, 2011, Jan. 31, 2012, and Jan. 31, 2016	Conduct six trials (two mandatory), including a potential way to control excess bleeding
Embeda (abuse-resistant morphine) King Pharmaceuticals		Drug poses a high abuse risk and places undue burden on the health care system	MedGuide, communication plan, prescriber training program, and patient monitoring and prescription tracking		2/13/2010, 8/13/2010 and annually thereafter
Enbrel (etanercept) Amgen [Released from REMS 8/10/2011]		New safety information shows that serious infections, including tuberculosis, have occurred in patients taking Enbrel	MedGuide		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015
Entereg (alvimopan) Adolor		Drug associated with the risk of myocardial infarction	Communication plan, elements to ensure safe use, an implementation system, a timetable for assessments and assessments of REMS		Quarterly for first 18 months and annually thereafter	Conduct one clinical trial
Epzicom (abacavir/lamivudine) Viiv [Released from REMS 5/27/2011]		To communicate increased risks of abacavir-containing products, particularly the increased risk of hypersensitivity reactions	Medication guide		9/9/2010, 3/9/2012 and 3/9/2016
Erythropoiesis-stimulating agent class		Drugs accelerates tumor growth and results in earlier deaths in some cancer patients	MedGuide, communication plan, elements to assure safe use and implementation system		8 months, 1 year, 18 months and annually thereafter
Exalgo (hydromorphone) Alza		Drug has potential for abuse, misuse, overdose and addiction	MedGuide, elements to assure safe use and implementation system (including dear doctor letter)		9/1/2010, 3/1/2011 and annually thereafter	Conduct two carcinogenicity studies (one in mice and one in rats)
Extavia (interferon beta-1b) Novartis [Released from REMS 6/22/2011]		To inform patients regarding the serious risks associated with interferon beta-1b	MedGuide		2/28/2011, 8/31/2012 and 831/2016
Extraneal (icodextrin peritoneal solution) Baxter		Risk of morbidity and mortality associated with the use of non-specific glucose monitors and test strips in patients using Extraneal due to drug/device interaction	MedGuide, elements to assure safe use and implementation system		3/8/2012 and annually thereafter
Exubera (inhaled insulin) Pfizer [No longer marketed]		New safety information from a clinical trial shows an imbalance in lung cancer cases between Exubera and controls	MedGuide, communication plan and timetable for assessments		18 months, 3 years and 7 years after REMS is approved	Conduct four comparative trials, one clinical trial and a study of the PPI
Fentora (fentanyl citrate) Cephalon		Drug associated with risk of overdose, abuse, addiction and serious complications due to medication errors	Medication Guide; elements to assure safe use, including restricted distribution; implementation system		Every six months for the first year and annually thereafter
Forteo (teriparatide) Lilly		Drug associated with increased risk of bone cancer	MedGuide and communication plan		January 2011, July 2012 and July 2016
Fosamax (alendronate) Merck [Released from REMS 7/1/2011]		Possible risk of unusual thigh bone fracture with the bisphosphonate class	Medication Guide		18 months, 3 years and 7 years
Fluoroquinilones Multiple manufacturers		Antibiotic class associated with increased risk of tendonitis and tendon rupture	MedGuide		18 months, 3 years and 7 years
Gilenya (fingolimod) Novartis		Risk of bradyarrhythmia and atrioventricular block at treatment initiation, infections, macular edema, respiratory effects, hepatic effects, and fetal risk	Medication Guide and communication plan			A prospective, randomized, controlled trial of fingolimod 0.5 mg and 0.25 mg and an appropriate control of at least one year duration to establish safety and efficacy
Gralise (gabapentin) Abbott [Released from REMS 4/28/2011]		Anti-epileptic drug associated with risk of suicidality	Medication Guide		1^st: 7/28/2012 2^nd: 1/28/2014 3^rd: 1/28/2018
HalfLytely (bisacodyl bowel prep kit) Braintree [Released from REMS 7/6/2011]		To communicate the risks of serious fluid and serum chemistry abnormalities associated with osmotic bowel preparations to patients	Medication guide		1/16/2012, 7/16/2013 and 7/16/2017
H.P. Acthar Gel (repository corticotrophin) Questcor		Risk of adrenal insufficiency, infections and blood pressure elevation	Medication guide		18 months, 3 years and 7 years
Humira (adalimumab) Abbott		To alert and warn healthcare providers about unrecognized histoplasmosis and other invasive fungal infections associated with Tumor Necrosis Factor (TNF) blocker use	Medication guide and communication plan		10/8/2011, 4/8/2013, 4/8/2017
Infergen (interferon alfacon-1) Intermune [Released from REMS 6/1/2011]		To inform patients regarding the serious risks associated with interferon alfacon-1	MedGuide		2/7/2011, 8/7/2012, 8/7/2016
Intron A (interferon alfa-2a) Schering-Plough [Released from REMS 5/13/2011]		New safety information shows cases of cerebrovascular complications due to stroke in patients with few or no expected risk factors for stroke	MedGuide		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015
Invirase (saquinavir mesylate) Roche [Released from REMS 5/26/2011]		Risk of QT and PR prolongation and thus potential for heart rrhythmias	Medication Guide		4/6/2012, 10/6/2013, 10/6/2017
Janumet (sitagliptin/metformin) Merck [Released from REMS 4/14/2011]		Drug associated with risk of pancreatitis	MedGuide		8/26/2011, 2/26/2013, 2/26/2017
Januvia (sitagliptin) Merck [Released from REMS 4/14/2011]		Drug associated with risk of pancreatitis	MedGuide		8/26/2011, 2/26/2013, 2/26/2017
Kalbitor (ecallantide) Dyax		Drug associated with hypersensitivity reaction	MedGuide and communication plan		6/1/2011, 12/1/2012, 12/1/2016
Kaletra (lopinavir/ritonavir) Abbott [Released from REMS 5/6/2011]		Drug carries increased risk of cardiac abnormalities	MedGuide		8/24/2012, 2/24/2014, 2/24/2018
Krystexxa (pegloticase) Savient		To inform health care providers about anaphylaxis, infusion reactions and contraindication of use in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency and other serious risks associated with Kystrexxa	Medication Guide and communication plan, including Dear Healthcare Provider letters and publication of “information pieces” in certain professional journals twice yearly for first three years		9/14/2011, 9/14/2012, 9/14/2013, 9/14/2015, 9/14/2017 1 year, 2 years, 3 years, 5 years and 7 years	Eight required trials, including an observational safety study in 500 patients, various preclinical studies on fetal and cardiac toxicity and trials on the IgE assay
Lariam (mefloquin) Roche [Released from REMS 4/29/2011]		Potential for drug-drug interaction with ketoconazole, either during use or within 15 weeks, causing increased plasma concentration and half-life of mefloquin and increasing the risk of QTc prolongation, among other serious risks associated with mefloquin	MedGuide		2/20/2011, 8/20/2012, 8/20/2016
Lazanda (fentanyl nasal spray) Archimedes		Risk of overdose, misuse, abuse, addiction and serious complications due to medication errors	Medication guide, elements to assure safe use and implementation system		Six months and annually thereafter
Letairis (ambrisentan) Gilead		Drug associated with hepatoxicity, teratogenicity and reduced sperm counts	MedGuide, elements to assure safe use and implementation system		Annually on Aug. 13
Lotronex (alosetron) Prometheus		To mitigate the risk of ischemic colitis and serious complications of constipation associated with Lotronex by ensuring that the drug is used in only severely affected patients for whom benefits exceed the risks and to ensure that those risks are communicated to patients, pharmacists and prescribers	Medication Guide, elements to assure safe use and implementation system		After six months and then annually on Sept. 2
Lumizyme (alglucosidase alfa) Genzyme [Updated 9/12/2011]		To ensure that the known risks of anaphylaxis and severe allergic reactions, as well as the potential risks of severe cutaneous and systemic immune mediated reactions, associated with use of Lumizyme are communicated to patients and prescribers, and to mitigate the potential risk of rapid disease progression in patients less than 8 years of age for whom the safety and effectiveness of Lumizyme have not been evaluated	Communication plan, elements to assure safe use, and implementation system for the Lumizyme ACE program		At six months and one year from approval, and annually thereafter on May 24
Meridia (sibutramine) Abbott [Drug withdrawn 10/8/2010]		To inform patients about serious risks associated with sibutramine, including cardiovascular risks	Medication Guide		18 months, 3 years and 7 years
Metoclopramide Class: Alavan’s Reglan and generics; Quantam Pharmics’ Clopra; Baxter’s injectable formulation and generics; Salix’s Metozolv ODT[Released from REMS 8/22/2011]		Drugs associated risk of tardive dyskinesia	MedGuide		18 months, 3 years and 7 years
Mifeprex (mifepristone) Danco Labs		To educate patients about serious risks and to minimize risk of serious complications by requiring physician certification	Medication guide, elements to assure safe use and implementation system		One year and every three years thereafter
Morphine sulfate oral solution Roxane Laboratories		Drug associated with risk of medication errors due to 20 mg dose being filled as 20 mL, causing life-threatening overdoses	MedGuide
Multaq (dronedarone) Sanofi Aventis		Drug associated with increased risk of death in people with severe heart failure	MedGuide and communication plan		Aug. 31, 2010 and each year thereafter until 2014, and Aug. 31, 2016	Conduct post-marketing surveillance
Nplate (romiplostim) Amgen		Drug associated with risk of bone marrow fibrosis, worsened thrombocytopenia after cessation of Nplate, thromboembolic complications, hematological malignancy or myelodysplastic syndrome, and serious complications due to medical error	MedGuide, communication plan, elements to assure safe use and implementation system		Every six months for the first two years, and annually thereafter on Aug. 22	Conduct three registry studies and one clinical trial
Nucynta ER (tapentadol extended-release) Johnson & Johnson [NEW]		Drug associated with risk of opioid abuse, misuse, overdose and addiction	MedGuide and elements to assure safe use
Nulojix (belatacept) Bristol-Myers Squibb		Serious risks include post-transplant lymphoproliferative disorder (PTLD) and progressive multifocal leukoencephalopathy (PML)	Medication guide and communication plan including Dear Healthcare Professional letters and educational materials		Annually for five years and again at seven years	Observational studies of transplant patients to assess prevalence of belatacept use and risk of PTLD, including EBV status and CMV serostatus, to assess incidence rates of PTLD versus CNI-based regimens and assess CNS-based PTLD and PML in EBV-seropositive patients; manufacturing study
Nuvigil (armodafinil) Cephalon		Risk of serious skin rash and other hypersensitivity reactions, particularly in pediatric patients	Medication Guide and communication plan, including Dear Healthcare Professional letter and prescriber brochure, Pharmacist Action letter and REMS program website		10/21/2011, 10/21/2012, 10/21/2013 and 10/21/2017
Oleptro (trazodone extended-release) Angiolini Labopharm [Released from REMS 5/11/2011]		Drug associated with risk of suicidality in children, adolescents and young adults; serotonin syndrome; and QT prolongation	Medication Guide		8/2/2011, 2/2/2013, 2/2/2017
Onsolis (buccal fentanyl) BioDelivery Sciences International		Drug associated with risk of overdose, abuse, addiction and serious complications due to medication errors	MedGuide, communication plan, elements to assure safe use and implementation system		1/16/2010, 7/16/2010 and annually thereafter
OsmoPrep (oral sodium phosphate) Salix Pharmaceuticals		Drug associated with the risk of acute phosphate nephropathy	MedGuide and communication plan		4/13/2011, 10/13/2012, 10/13/2016	Conduct one clinical trial
Oxycodone HCl, oral solution Lehigh Valley Technologies		Drug associated with risk of abuse, misuse, overdose and addiction	Medication Guide		4/20/2011, 10/20/2013, 10/20/2017 18 months, 3 years and 7 years
OxyContin (oxycodone controlled-release) Purdue Pharma		Drug associated with risk of abuse, misuse, overdose and addiction; also concern about use of doses greater than 60 mg in non-opioid tolerant patients	MedGuide and elements to assure safe use (including prescription only by trained physicians)		10/5/2010, 4/5/2011 and annually thereafter	Conduct post-marketing studies, including epidemiological studies, to assess whether the changes made to the OxyContin formulation result in a decrease in misuse and abuse
Pancreaze (pancrelipase) Ortho McNeil Janssen [Released from REMS 6/20/2011]		Drug associated with risk of fibrosing colonopathy and theoretical risk of transmission of porcine viral disease, among other serious risks	MedGuide		10/12/2011, 4/12/2013, 4/12/2017
Pegasys (peginterferon alfa-2a) Roche [Released from REMS 5/9/2011]		Drug associated with increased risk of cerebrovascular complications due to stroke in patients with few or no expected risk factors for stroke	MedGuide		4/31/2010, 10/31/2011, 10/31/2015
PegIntron (peginterferon alfa-2b) Schering-Plough (Merck) [Released from REMS 5/13/2011]		Drug associated with increased risk of cerebrovascular complications due to stroke in patients with few or no expected risk factors for stroke	MedGuide		6/11/2010, 12/11/2011, 12/11/2015
PegIntron Rebetrol Combopack (peginterferon alfa-2b/ribavirin) Schering-Plough (Merck)		Drug associated with increased risk of cerebrovascular complications due to stroke in patients with few or no expected risk factors for stroke	MedGuide		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015
Pennsaid (diclofenac topical solution) Mallinckrodt [Released from REMS 7/14/2011]		Drug associated with increased risk of cardiovascular events and gastrointestinal toxicity	MedGuide		3/4/2011, 11/4/2012, 11/4/2016
Perforomist (formoterol inhalation solution) Dey Pharma		To inform health care providers and patients of the increased risk of asthma-related death and serious outcomes with the long-acting beta2-adrenergic agonists (LABA) class, as well as other serious risks, and inform them about appropriate use	Medication guide and communication plan consisting of “Dear Health Care Provider” and “Dear Medical Society” letters and website		Annually
Plavix (clopidogrel) Sanofi-Aventis/Bristol-Myers Squibb [Released from REMS 5/3/2011]		Co-administration with a drug that inhibits CYP450 2C19 results in a reduction in blood levels of clopidogrel’s active metabolite and a loss of the desired anti-platelet effect	Medication Guide		1^st: 6/1/2012 2^nd: 2/1/2014 3^rd: 2/1/2018
Potiga (ezogabine) Valeant		Risk of acute urinary retention	Communication plan including Dear Healthcare Professional letter		Annually for three years and again at seven years	A prospective cohort study to better define the risk of urinary retention in epilepsy patients treated with ezogabine, a controlled urodynamic trial and various preclinical studies
Pradaxa (dabigatran etexilate mesylate) Boehringer Ingelheim [Released from REMS 4/5/2011]		Risk of serious and sometimes fatal bleeding, among others	Medication Guide		4/19/2012, 10/19/2013, 10/19/2017	In vitro study of dabigatran as a substrate or inhibitor of a panel of certain drug solute carrier transporters; in vitro study of the effects of amiodarone and dronedarone on active transport of dabigatran
Prolia (denosumab) Amgen [Updated 9/16/2011 with revised materials]		Drug associated with risk of serious infections, dermatologic adverse reactions and suppression of bone turnover	Medication Guide and communication plan		18 months, 3 years and 7 years
Promacta (eltrombopag) GSK		Drug associated with risks of hepatoxicity, bone marrow fibrosis, worsened thrombocytopenia and hemorrhage	MedGuide, elements to assure safe use and implementation system		5/20/2010, 11/20/2011, 11/20/2015	Conduct prospective pregnancy registry and one clinical trial
Propoxyphene-containing products Darvon, Darvocet and generics Xanodyne [Drugs withdrawn 11/2010]		Drug associated with a high level of cardiotoxicity	MedGuide			Conduct five total studies – one by sponsor and others through FDA collaborations
Provigil (modafinil) Cephalon		Risk of serious skin rash and other hypersensitivity reactions, particularly in pediatric patients	Medication Guide and communication plan, including Dear Healthcare Professional letter and prescriber brochure, Pharmacist Action letter and REMS program website		10/21/2011, 10/21/2012, 10/21/2013, 10/21/2017
Qualaquin (quinine sulfate) AR Scientific		To curb off-label use of the antimalaria drug to treat or prevent night-time leg cramps and improve awareness of potential side effectis, including thrombocytopenia	Medication Guide and communication plan consisting of a “Dear Health Care Provider” letter
Raptiva (efalizumab) Genentech [Drug withdrawn 6/2009]		New safety information shows an increase in the risk of serious fungal and viral infections	MedGuide
Rebetol (ribavirin) Roche [Released from REMS 5/6/2011]		Risks include teratogenicity and anemia	Medication guide		12/9/2011, 6/9/2013, 6/9/2017
Reclast (zoledronic acid) Novartis [Released from REMS 8/15/2011]		Possible risk of unusual thigh bone fracture with the bisphosphonate class	Medication Guide		18 months, 3 years and 7 years
Revlimid (lenalidomide) Celgene		Drug associated with teratogenicity	Medication Guide, elements to assure safe use including patient and prescriber registration and controlled distribution (RevAssist), and implementation system		6 months and annually thereafter
Roferon-A (interferon alfa-2a) Roche [Released from REMS 6/16/2011]		To inform patients regarding the serious risks associated with interferon alfa-2a	Medication Guide		2/28/2011, 8/28/2012, 8/28/2016
Sabril (vigabatrin) Lundbeck		Drug associated with risk of permanent vision loss and the class risk of suicidality	MedGuide and elements to assure safe use
Samsca (tolvaptan) Otsuka [Updated 9/23/2011 with revised material and removal of MedGuide from the REMS]		Drug associated with risk of overly rapid correction of serum sodium leading to osmotic demyelination	Communication plan			A validation report
Savella (milnacipran) Forest [Released from REMS 4/26/2011]		SNRIs are associated with an increased risk of suicidality in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders	MedGuide			Conduct lactation trials and run a pregnancy registry
Silenor (doxepin) Somaxon [Released from REMS 10/30/2011]		Hypnotic sleep medication can cause patients to fail to remember activities occurring while medicated (such as driving and eating)	MedGuide
Simponi (golimumab) Centocor Ortho Biotech [Released from REMS 3/17/2011]		Tumor necrosis factor inhibitor carries risks of serious infections, including tuberculosis, invasive fungal infections, other opportunistic infections, malignancies, congestive heart failure and peripheral demyelinating disorders	MedGuide, communication plan			Optimize the existing adventitious virus assay
Soliris (eculizumab) Alexion		To limit the occurrence and morbidity associated with meningococcal infections, to mitigate serious outcomes for patients who develop Neisseria meningitides and other systemic infections and to impart important safety information before initiating treatment with Soliris and ensure proper use	Medication guide and elements to assure safe use, including prescriber certification (original RiskMAP that was a “deemed REMS” did not include the certification requirement)		Every 6 months for 1 year and then annually
Stelara (ustekinumab) Centocor Ortho Biotech		Drug associated with risk of serious infections, including those caused by viruses, fungi and bacteria	MedGuide, communication plan including dear prescriber letters, an adverse event reporting awareness campaign and other outreach efforts
Suboxone (buprenorphine/naloxone sublingual film) Reckitt Benckiser		To mitigate the risks of accidental overdose, misuse and abuse and to Inform patients of the serious risks associated with Suboxone film	Medication Guide, elements to assure safe use and implementation system		After six months and then annually
Sucraid (sacrosidase) QOL Medical [Released from REMS 12/9/2010]		To ascertain if there is an increased risk of allergy-related adverse events	MedGuide, communication plan, elements to assure safe use and implementation system
Sutent (sunitinib) Pfizer [Released from REMS 5/20/2011]		Risk of severe hepatotoxicity resulting in death observed in clinical trials and post-marketing experiences	Medication guide		18 months, 3 years and 7 years
Symbicort (budesonide/ formoterol) AstraZeneca		Drug associated with increased incidence of lower respiratory tract infections in patients with COPD	MedGuide and timetable for assessments
Tapentadol Johnson & Johnson		Drug associated with opioid abuse	MedGuide and timetable for assessments
Tasigna (nilotinib) Novartis		New safety information revealed cases of QT prolongation	MedGuide, communication plan and timetable for assessments
Testosterone gel: Solvay’s AndroGel 1%, Auxillium’s Testim 1% and Lilly/Acrux’s Axiron and Endo’s Fortesta Androgel and Testim REMS updated 11/30/2011 with additional language on secondary exposure in children		Reports of adverse effects in children who were inadvertently exposed to testosterone through contact with another person being treated	MedGuide and timetable for submission of assessments		18 months, 3 years and 7 years	Fortesta: a hand washing and application site washing trial following application to measure the amount of residual testosterone before and after washing on the primary user’s hands and application site
Thalomid (thalidomide) Celgene		Drug associated with teratogenicity	Medication Guide, elements to assure safe use including patient and prescriber registration and controlled distribution (STEPS), and implementation system		6 months and annually thereafter
Tikosyn (dofetilide) Pfizer		Drug associated with risk of ventricular arrhythmias	MedGuide, elements to assure safe use and implementation system		6 months, one year and annually thereafter
Tracleer (bosentan) Actelion		Drug associated with potential for serious liver injury and damage to fetuses	MedGuide, elements to assure safe use and implementation system
Treximet (sumatriptan succinate/naproxen) Pozen [Released from REMS 9/23/2011]		Non-steroidal anti-inflammatory drugs are associated with an increased risk of cardiovascular events and gastrointestinal toxicity	MedGuide		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015	Conduct one clinical trial
Trizivir (abacavir/lamivudine/zidovudine) ViiV [Released from REMS 5/13/2011]		Increased risk of hypersensitivity reactions	Medication guide		18 months, 3 years and 7 years
Tyzeka (telbivudine) Novartis [Released from REMS 5/5/2011]		Patients have reported peripheral neuropathy, in some cases resulting in motor weakness, pain, sensory deficits and/or difficulty walking	MedGuide and timetable for submission of assessments			Develop a dosing cup for distribution of drug
Venlafaxine ER Osmotica		Antidepressants are associated with an increased risk of suicidality in children, adolescents and young adults in short-term studies of MDD and other psychiatric disorders	MedGuide and timetable for assessments		1^st: Nov. 2009 2^nd: May 2011 3^rd: May 2015	Conduct one dose dumping study
Vibativ (telavancin) Theravance/Astellas Updated dissemination plan for Dear Health Care Professional letter, 7/27/2011		FDA concerned about drug's use in high-risk populations	MedGuide, letter to health care professionals
Victoza (liraglutide) Novo Nordisk		Drug associated with development of thyroid C-cell tumors in pre-clinical rodent studies and potential class risk of pancreatitis	MedGuide, communication plans and timetable for assessments			A cardiovascular safety study, a five-year epidemiological trial to evaluate thyroid cancer and panrcreatitis risks, and a 15-year cancer registry to monitor thyroid cancer cases
Viibryd (vilazodone) Trovis [Released from REMS 6/29/2011]		Antidepressants are associated with an increased risk of suicidality in children, adolescents and young adults with major depressive disorder and other psychiatric disorders	Medication Guide		18 months, 3 years and 7 years	Two embryo-fetal studies to assess the potential reproductive toxicity of M17, the major human metabolite of vilazodone
Vimpat (lacosamide) UCB [Released from REMS 8/10/2011]		Drug associated with increased the risk of suicidal thoughts or behavior	MedGuide and timetable for assessments			Conduct non-clinical trial
Viramune (nevirapine) Boehringer Ingleheim [Released from REMS 5/6/2011]		New safety information shows that patients with moderate or severe hepatic impairment should not take Viramune due to the risk of increased nevirapine levels	MedGuide and timetable for assessments		1^st: Dec. 20, 2009 2^nd: June 20, 2011 3^rd: June 20, 2015
Visicol (oral sodium phosphate) Salix Pharmaceuticals		Drug associated with the risk of acute phosphate nephropathy	MedGuide and timetable for assessments			Conduct one clinical trial
Vivitrol (naltrexone) Alkermes		Drug has risk of serious injection site reactions likely caused by incorrect administration of the drug	MedGuide and timetable for assessments
Votrient (pazopanib) GlaxoSmithKline {Released from REMS 4/21/2011]		Drug associated with severe and fatal hepatotoxicity	MedGuide, communication plan and timetable for assessments
Wellbutrin/ Wellbutrin SR (bupropion) GlaxoSmithKline		Drug associated with risk of suicidality-related events	MedGuide, timetable for assessments
Xiaflex (collagenase clostridium histolyticum) Auxilum		Drug associated with rare but serious side effect of tendon rupture if injected into the wrong site	MedGuide, training program and timetable for assessments			Conduct three clinical studies, one non-clinical study, and one in vitro study; submit in vivo data
Yervoy (ipilimumab) Bristol-Myers Squibb		Drug associated with risks of severe and fatal immune-mediated adverse reactions such as fatal immune-mediated enterocolitis (including gastrointestinal perforation), fatal immune-mediated hepatitis (including hepatic failure), fatal immune-mediated toxicities of skin (including toxic epidermal necrolysis), fatal nervous system toxicity, and endocrinopathies	Communication plan targeting oncology associations and health care professionals with letter and educational material, to be issued ahead of launch and every six months for the first three years		1st: 9/25/2012 2nd: 3/25/2014 3rd: 3/25/2018	Developmental study final report, assays for binding and neutralizing antibodies to ipilimumab, an efficacy and safety study of 3 mg/kg and 10 mg/kg doses looking at overall survival, an assessment of those assays in 300 ipilimumab-treated patients in the required study and a pharmacogenomic analysis for genetic determinants of immune-mediated adverse events in the required trial
Zerit (stavudine) Bristol-Myers Squibb [Released from REMS 5/11/2011]		Class REMS on risks of nucleoside reverse transcriptase inhibitors	MedGuide		18 months, 3 years and 7 years
Ziagen (abacavir) ViiV [Released from REMS 5/13/2011]		New safety information indicates that patients who carry the HLA-B*5701 allele are at significantly increased risk of developing abacavir hypersensitivity, which in some cases may be severe or fatal	MedGuide and timetable for assessments		1^st: Jan. 2010 2^nd: July 2011 3^rd: July 2017
Zipsor (diclofenac) Xandoyne Pharma [Released from REMS 5/4/2011]		Drug associated with increased risk of cardiovascular events and gastrointestinal toxicity	MedGuide and timetable for assessments
Zonegan (zonisamide) Eisai [Released from REMS 5/27/2011]		Revision to the class REMS for anti-epileptic drugs on risk of suicidality to include language in the Zonegran Medication Guide regarding the risk of metabolic acidosis	MedGuide and timetable for submission of assessments
Zortress (everolimus) Novartis [MedGuide eliminated from REMS 11/21/2011]		Drug associated with risk of wound-healing complications, hyperlipidemia, proteinuria, graft thrombosis, as well as nephrotoxicity when co-administered with standard doses of cyclosporine	Communication plan
Zyban (bupropion) GlaxoSmithKline		Drug associated with risk of suicidality-related events	MedGuide, timetable for assessments
REMS To Come	Reason for REMS			REMS Proposal
Acetaminophen-containing products	Drug associated with risk of increased liver injury
Afrezza (insulin human rDNA) MannKind (pending approval)	Drug associated with inhaled insulin class risk of lung cancer
Bydureon (formerly Byetta LAR) (long-acting exenatide) Amylin/Lilly	Drug associated with risk of pancreatitis; unclear whether FDA is also considering there to be a class risk of thyroid C-cell tumors as seen with Novo Nordisk's Victoza (liraglutide)			Existing REMS for Byetta includes MedGuide, communication plan and timetable for assessments
Certican (everolimus) Novartis	Drug associated with proteinuria, delayed wound healing and serum lipid abnormalities			MedGuide, user surveys, communication plan, program evaluation tools, and timetable for assessments.
Clolar (clofarabine) Genzyme (pending approval for label expansion)	Drug associated with increased risk of infection
Contrave (naltrexone/bupropion) Orexigen/Takeda	Concerns about appropriate patient selection and safety profile, especially cardiovascular risk			MedGuide and physician education program that includes an algorithm to guide patient selection and decisions on whether to continue therapy; post-marketing study requirement for cardiovascular outcomes trial
Cymbalta (duloxetine) Pfizer	SNRIs are associated with an increased risk of suicidality in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders
Liraglutide NovoNordisk (pending approval)	Drug associated with pre-clinical thyroid cancer signal in rodents
Long acting beta-2 adrenergic agonists class	Drugs associated with increased risk of severe asthma symptoms, hospitalization and death			MedGuide, education plans for health care professionals, new labeling changes, more safety studies, and timetable for assessments
Opioid Class: Ortho McNeil/Janssen’s Duragesic (fentanyl patch); Purdue’s Palladone (hydromorphone), MS Contin (morphine sulfate) and OxyContin (oxycodone); Roxane’s Dolophine (methadone); King’s Avinza (morphine); Actavis’ Kadian (morphine); Xanodyne’s Oramorph (morphine sulfate); Endo’s Opana (oxymorphone); corresponding generics	The potent opioid products pose a high abuse risk and place undue burden on the health care system
Phenergen (promethazine) Wyeth	The Supreme Court ruled that Wyeth could have added a stronger warning to labeling for the anti-nausea drug after accumulating data about the risk of I.V.-push administration
Qnexa (phentermine/topiramate) Vivus	Potential to cause psychiatric-related, cognitive-related and cardiovascular adverse events and metabolic acidosis, as well as teratogenicity associated with topiramate			Medication Guide and communication plan, plus a voluntary pregnancy registry
Relistor (methylnaltrexone bromide) Wyeth/Progenics	Drug associated with potential risk of QT prolongation
Remoxy (abuse-resistant oxycodone) Pain Therapeutics (pending approval)	Drug poses a high abuse risk and place undue burden on the health care system			Similar to Embeda’s REMS: MedGuide, communication plan, prescriber training program, patient monitoring and prescription tracking
Requip XL (ropinirole) GlaxoSmithKline	Varying serious adverse events correlated to dose level			Post-marketing trial to evaluate whether drug is a P-gp substrate and/or inducer for major CYP enzymes
Sodium oxybate oral solution Jazz	Abuse potential (drug is the sodium salt form of gamma hydroxybutyrate) and potential CNS depressant			Similar to the risk management program in place for Xyrem, the firm's sodium oxybate formulation for narcolepsy, which is a "deemed REMS" that has not yet been approved