2/13/2016
`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`
`(http://www.merck.com/index.html)
`
`MERCK MAKING NEWS
`
`Merck Provides Update on Combination Medicine JUVISYNC™
`(sitagliptin and simvastatin) Tablets
`
`Thursday, September 26, 2013 8:00 am EDT
`
`Merck, known as MSD outside the United States and Canada, today said that the company will voluntarily discontinue
`distributing JUVISYNC™ (sitagliptin and simvastatin) tablets to pharmacies and wholesalers in the United States and
`Puerto Rico. This decision is for business reasons only and is not due to the efficacy or safety profile of JUVISYNC or the
`individual components. JUVISYNC is a treatment that combines the glucose-lowering medication sitagliptin, the active
`®
`component of JANUVIA (sitagliptin), with the cholesterol-lowering medication simvastatin. Sitagliptin and simvastatin
`will continue to be available as separate medicines.
`
`During their next visit, patients taking JUVISYNC should discuss treatment options with their prescribing physician.  
`®
`JUVICOR , the brand name of the sitagliptin/simvastatin combination tablet outside the United States, will continue to be
`marketed and distributed outside the United States. JUVICOR is currently approved in 10 countries, and Merck plans to
`continue filing applications in additional countries.
`
`About JUVISYNC™ (sitagliptin and simvastatin) tablets 
`
`JUVISYNC is indicated in patients for whom treatment with both sitagliptin and simvastatin is appropriate.
`
`Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
`mellitus.
`
`Simvastatin is indicated as an adjunct to diet to reduce the risk of total mortality by reducing coronary heart disease (CHD)
`deaths, the risk of nonfatal myocardial infarction and stroke, and the need for coronary and noncoronary revascularization
`procedures in patients at high risk of coronary events because of existing CHD, diabetes, peripheral vessel disease,
`history of stroke, or other cerebrovascular disease. Simvastatin is also indicated as an adjunct to diet to reduce elevated
`total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and
`to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia or mixed dyslipidemia; to
`reduce elevated TG in patients with hypertriglyceridemia; to reduce elevated TG and VLDL-C in patients with primary
`dysbetalipoproteinemia; and to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an
`adjunct to other lipid-lowering treatments or if such treatments are unavailable.
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`1/6
`
`AstraZeneca Exhibit 2123
`Mylan v. AstraZeneca
`IPR2015-01340
`
`Page 1 of 6
`
`

`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`2/13/2016
`JUVISYNC should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, and
`JUVISYNC has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of
`pancreatitis are at increased risk for the development of pancreatitis while using JUVISYNC.
`
`JUVISYNC has not been studied in conditions in which the major abnormality is elevation of chylomicrons (i.e.,
`hyperlipidemia Fredrickson types I and V).
`
`Because doses of JUVISYNC appropriate for patients with severe renal impairment or end-stage renal disease (ESRD) are
`not available in this combination product, JUVISYNC is not recommended in these patients.
`
`Selected Important Risk Information About JUVISYNC™ (sitagliptin and simvastatin) tablets
`
`JUVISYNC is contraindicated in patients with a history of a serious hypersensitivity reaction, such as anaphylaxis or
`angioedema, to any component of JUVISYNC; in those receiving concomitant administration of strong CYP3A4 inhibitors
`(eg, itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin,
`clarithromycin, telithromycin, and nefazodone), gemfibrozil, cyclosporine, or danazol; or in those with active liver disease.
`JUVISYNC is also contraindicated in women who are or may become pregnant and nursing mothers. JUVISYNC should be
`administered to women of childbearing age only when such patients are highly unlikely to conceive.
`
`There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing
`pancreatitis, in patients taking sitagliptin. After initiating JUVISYNC, observe patients carefully for signs and symptoms of
`pancreatitis. If pancreatitis is suspected, promptly discontinue JUVISYNC and initiate appropriate management. It is
`unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking
`JUVISYNC.
`
`Simvastatin occasionally causes myopathy, manifested as muscle pain, tenderness or weakness with creatine kinase (CK)
`above 10 times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without
`acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy
`include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. The risk of
`myopathy, including rhabdomyolysis, is dose related. All patients starting therapy with JUVISYNC, or whose dose of
`JUVISYNC is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained
`muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms
`persist after discontinuing JUVISYNC. Therapy with JUVISYNC should be discontinued immediately if markedly elevated
`CK levels occur or myopathy is diagnosed or suspected.
`
`In addition to the drugs that are contraindicated, because of an increased risk of myopathy/rhabdomyolysis, grapefruit
`juice should be avoided. Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin
`coadministered with colchicine, and caution should be exercised when prescribing JUVISYNC with colchicine.
`
`The dose of simvastatin should not exceed 10 mg (100 mg/10 mg or 50 mg/10 mg JUVISYNC) daily in patients receiving
`verapamil, diltiazem, or dronedarone, and 20 mg (100 mg/20 mg or 50 mg/20 mg JUVISYNC) daily in patients receiving
`amiodarone, amlodipine, or ranolazine. The benefits of combined use of JUVISYNC with these drugs, other fibrates, or
`niacin (≥1 g/day) should be carefully weighed against the potential risk of myopathy/rhabdomyolysis. Caution should be
`used when treating Chinese patients with JUVISYNC 100 mg/40 mg or 50 mg/40 mg per day coadministered with lipid-
`modifying doses of niacin-containing products.
`
`Persistent increases to more than 3 times the ULN in serum transaminases have occurred in approximately 1 percent of
`patients who received simvastatin in clinical studies. Liver function tests should be performed before initiating treatment
`and thereafter when clinically indicated. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or
`jaundice occurs during treatment with JUVISYNC, promptly interrupt therapy and do not restart unless an alternate
`etiology is found.
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`2/6
`
`Page 2 of 6
`
`

`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`2/13/2016
`JUVISYNC is not recommended for use in patients with severe renal impairment or ESRD because doses of sitagliptin
`appropriate for these patients are not available in this combination product. Assessment of renal function is
`recommended prior to initiation of JUVISYNC™ (sitagliptin and simvastatin) and periodically thereafter.
`
`There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring
`dialysis, in patients treated with sitagliptin. A subset of these reports involved patients with renal impairment, some of
`whom were prescribed inappropriate doses of sitagliptin.
`
`When JUVISYNC is used in combination with a sulfonylurea or insulin, a lower dose of sulfonylurea or insulin may be
`required to reduce the risk of hypoglycemia.
`
`The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2 percent (0.59
`episodes/patient-year) for sitagliptin 100 mg in combination with glimepiride (with or without metformin), 1.8 percent
`(0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5 percent (1.06
`episodes/patient-year) for sitagliptin 100 mg in combination with insulin (with or without metformin), and 7.8 percent
`(0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).
`
`There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin, such as
`anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions
`occurred within 3 months after initiation of treatment with sitagliptin, with some reports occurring after the first dose. If a
`hypersensitivity reaction is suspected, discontinue JUVISYNC, assess for other potential causes, and institute alternative
`treatment. Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a
`patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be
`predisposed to angioedema with JUVISYNC.
`
`Increases in A1C and fasting serum glucose levels have been reported with statins, including simvastatin.
`
`In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in >5 percent of
`patients treated with sitagliptin as monotherapy and in combination therapy and more commonly than in patients treated
`with placebo, were upper respiratory tract infection (sitagliptin, 15.5%; placebo, 6.2%); nasopharyngitis (11.0%, 9.3%);
`peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%).
`In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in ≥5 percent of
`patients treated with simvastatin were upper respiratory tract infection (9.0%), headache (7.4%), abdominal pain (7.3%),
`constipation (6.6%), and nausea (5.4%).
`
`The dosages for therapy with JUVISYNC are 100 mg/10 mg, 100 mg/20 mg, 100 mg/40 mg, 50 mg/10 mg, 50 mg/20 mg,
`and 50 mg/40 mg (sitagliptin/simvastatin) once daily. The recommended starting dose of JUVISYNC is 100/40 mg once
`daily in the evening.
`
`About Merck
`
`Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the
`United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and
`animal health products, we work with customers and operate in more than 140 countries to deliver innovative health
`solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies,
`programs and partnerships. For more information, visit www.merck.com (http://www.merck.com/) and connect with us on
`Twitter (https://twitter.com/Merck), Facebook (http://www.facebook.com/MerckBeWell) and YouTube
`(http://www.youtube.com/Merck).
`
`Forward-Looking Statement
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`3/6
`
`Page 3 of 6
`
`

`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`2/13/2016
`This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United
`States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and
`expectations of Merck’s management and are subject to significant risks and uncertainties. If underlying assumptions
`prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the
`forward-looking statements.
`
`Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic
`factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation
`and health care legislation in the United States and internationally; global trends toward health care cost containment;
`technological advances, new products and patents attained by competitors; challenges inherent in new product
`development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions;
`manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the
`effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including
`patent litigation, and/or regulatory actions.
`
`Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information,
`future events or otherwise. Additional factors that could cause results to differ materially from those described in the
`forward-looking statements can be found in Merck’s 2012 Annual Report on Form 10-K and the company’s other filings
`with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov
`(http://www.sec.gov)). 
`
`The Prescribing Information and Medication Guide for JUVISYNC™ (sitagliptin and simvastatin) are available at
`http://www.merck.com/product/usa/pi_circulars/j/juvisync/juvisync_pi.pdf
`(http://www.merck.com/product/usa/pi_circulars/j/juvisync/juvisync_pi.pdf) and
`http://www.merck.com/product/usa/pi_circulars/j/juvisync/juvisync_mg.pdf
`(http://www.merck.com/product/usa/pi_circulars/j/juvisync/juvisync_mg.pdf).  
`
`Contact:
`
`Media:
`Pam Eisele, 908-423-5042
`or
`Kim Hamilton, 908-391-0131
`or
`Investors:
`Carol Ferguson, 908-423-4465
`
`SEARCH NEWSROOM
`
`Advanced Search (/advsearch)
`
`FOLLOW US
`
`This #ValentinesDay, show
` (https://twitter.com/merck)
`your loved ones how much
`you care with these #heart
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`4/6
`
`Page 4 of 6
`
`

`
`2/13/2016
`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`healthy recipes:
`https://t.co/garWV4ApHI
`(https://t.co/garWV4ApHI)-1
`day 3 hours ago
`
`#TBT to our own Julie
`Gerberding as an intern at
`San Francisco General
`#WomenInSTEM
`https://t.co/B56iMz7btK
`(https://t.co/B56iMz7btK)-2
`days 2 hours ago
`
`@MarilynOliva
`(http://twitter.com/MarilynOliva)
`sorry to hear about this.
`Please contact our National
`Service Center at 1-800-
`672-6372 or
`wecare@merck.com
`(mailto:wecare@merck.com)
`& they will help.-3 days 1
`hour ago
`
` (http://www.facebook.com/MerckBeWell)
`3.7K
`
`Like
`
`MERCK FOR MOTHERS (HTTP://WWW.MERCKFORMOTHERS.COM/)
`
` (http://www.merckformothers.com/)
`
` (http://www.merck.com/rss/home.html)
`
`Subscribe to RSS Feeds (http://www.merck.com/rss/home.html)
`
`RSS Feed Terms of Use (/rss-terms-of-use)
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`5/6
`
`Page 5 of 6
`
`

`
`2/13/2016
`
`Merck Provides Update on Combination Medicine JUVISYNC™ (sitagliptin and simvastatin) Tablets | Merck Newsroom Home
`
`Copyright (http://www.merck.com/policy/copyright/home.html) © 2009-2016 Merck Sharp & Dohme Corp., a
`subsidiary of Merck & Co., Inc. All rights reserved.
`
`Privacy (http://www.merck.com/about/how-we-operate/privacy/home.html) Terms of Use (http://www.merck.com/policy/terms-of-
`use/home.html) Site Map (http://www.merck.com/map/home.html)
`
`(http://privacy.truste.com/privacy-
`seal/Merck-and-Co-,-Inc-/validation?
`rid=7437b42b-c947-434e-b1f5-
`db06d0327616)
`
`(http://privacy.truste.com/privacy-
`seal/Merck-and-Co-,-Inc-/validation?
`rid=7437b42b-c947-434e-b1f5-
`db06d0327616)
` (https://www.facebook.com/MerckBeWell)
`
`(http://www.essentialaccessibility.com/)
`
`
`
` (https://twitter.com/merck)
`
`SM
`Business Wire NewsHQ (http://www.businesswire.com/portal/site/home/online-newsrooms/)
`
`http://www.mercknewsroom.com/news/company­statements/merck­provides­update­combination­medicine­juvisync­sitagliptin­and­simvasta
`
`6/6
`
`Page 6 of 6