`
`Merck Provides Update on Combination Medicine
`JUVISYNC™ (sitagliptin and simvastatin) Tablets
`Terms:
`Company Statements diabetes Januvia Juvicor Juvisync Merck MRK MSD simvastatin sitagliptin
`Published Date and Time:
`9/26/13 8:00 am EDT
`News Organization:
`Merck
`News Organization Location:
`WHITEHOUSE STATION, N.J.
`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.
`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.
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`Novo Nordisk Exhibit 2517
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00001
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`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.
`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 and connect with us on Twitter, Facebook and YouTube.
`Forward-Looking Statement
`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
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`Novo Nordisk Exhibit 2517
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00002
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`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).
`
`T he P rescribing Inf o rmat io n and Medicat io n Guide f o r JUVISYNC™ (sit aglipt in and simvast at in) are available at
`ht t p://www.merck.co m/pro duct /usa/pi_circulars/j/juvisync/juvisync_pi.pdf and
`ht t p://www.merck.co m/pro duct /usa/pi_circulars/j/juvisync/juvisync_mg.pdf .
`
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`Source URL: https://www.mrknewsroom.com/news/company-statements/merck-provides-update-combination-medicine-juvisync-
`sitagliptin-and-simvasta
`
`Novo Nordisk Exhibit 2517
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00003
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