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Take command of HbA1c when metformin is no longer enough.


Januvia is indicated for improvement of glycaemic control in adults with type 2 diabetes mellitus


JANUVIA® sitagliptin. PRESCRIBING INFORMATION.


Refer to Summary of Product Characteristics (SPC) before prescribing.


Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/ yellowcard. Adverse events should also be reported to MSD (tel: 01992 467272).


PRESENTATION: Film-coated tablets containing either 25 mg, 50 mg or 100 mg of sitagliptin. USES: For adult patients with type 2 diabetes mellitus Januvia is indicated to improve glycaemic control: as monotherapy • in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance as dual oral therapy in combination with • metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control


• a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contra-indications or intolerance


• a PPARγ agonist (i.e. a thiazolidinedione) when use of a PPARγ agonist is appropriate and when diet and exercise plus the PPARγ agonist alone do not provide adequate glycaemic control as triple oral therapy in combination with • a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control


• a PPARγ agonist and metformin when use of a PPARγ agonist is appropriate and when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control. Januvia is also indicated as add-on to insulin (with or without metformin) when diet and exercise plus stable dosage of insulin do not provide adequate glycaemic control.


DOSAGE AND ADMINISTRATION: One 100 mg tablet once daily, with or without food. When sitagliptin is used in combination with metformin and/or a PPARγ agonist, maintain the dosage of metformin and/or PPARγ agonist, and administer sitagliptin concomitantly. When used in combination with a sulphonylurea or with insulin, consider a lower dose of sulphonylurea or insulin, to reduce risk of hypoglycaemia. If a dose of Januvia is missed, take


DIAB-1159588-0007.


as soon as the patient remembers. Do not take a double dose on the same day. Renal impairment: when considering use in combination with other anti- diabetic medicinal products, check conditions for use in patients with renal impairment. No dosage adjustment required for mild renal impairment (creatinine clearance [CrCl] ≥50 ml/min). For patients with moderate renal impairment (CrCl ≥30 to <50 mL/min), the dose of Januvia is 50 mg once daily. For patients with severe renal impairment (CrCl <30 mL/min) or with end-stage renal disease (ESRD) requiring haemodialysis or peritoneal dialysis, the dose of Januvia is 25 mg once daily. Januvia may be administered without regard to the timing of dialysis. Because of the above dosage adjustment, assessment of renal function is recommended prior to initiation of Januvia and periodically


thereafter. Hepatic impairment: no dosage


adjustment necessary for patients with mild to moderate hepatic impairment. Januvia has not been studied in patients with severe hepatic impairment and care should be exercised. Elderly: no dosage adjustment necessary. Exercise care in patients ≥ 75 years of age as there are limited safety data in this group. Children: The safety and efficacy of sitagliptin in children and adolescents under 18 years of age have not yet been established. CONTRA-INDICATIONS: Hypersensitivity to active substance or excipients. PRECAUTIONS: General: do not use in patients with type 1 diabetes or for diabetic ketoacidosis. Acute pancreatitis: Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. Inform patients of the symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin, but very rare cases of necrotizing or haemorrhagic pancreatitis and/or death have been reported. If pancreatitis is suspected, Januvia and other potentially suspect medicinal products should be discontinued; if acute pancreatitis is confirmed, Januvia should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Hypoglycaemia when used with other anti-hyperglycaemic medicinal products: Rates of hypoglycaemia reported with sitagliptin were generally similar to rates in patients taking placebo. On addition of sitagliptin to insulin or a sulphonylurea, consider a lower dose of insulin or sulphonylurea


to reduce the risk of hypoglycaemia. Renal


impairment: Januvia is renally excreted. To achieve plasma concentrations of Januvia similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal impairment,as well as in ESRD patients requiring haemodialysis or peritoneal dialysis (see section ‘Dosage and administration’ above and section 4.2 and 5.2 of the SmPC). Hypersensitivity reactions: Serious hypersensitivity reactions have been reported, including anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome. Onset occurred within the first 3 months after initiation of treatment with some reports occurring after the first dose. If suspected, discontinue Januvia, assess for other potential causes and initiate alternative treatment for diabetes.


DRUG INTERACTIONS: Digoxin: sitagliptin had a small effect on plasma digoxin concentrations. No dosage adjustment of digoxin is recommended, but monitor patients at risk of digoxin toxicity if the two are used together. PREGNANCY AND LACTATION: Do not use during pregnancy or breast-feeding. SIDE EFFECTS: Refer to SPC for complete information on side effects. Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. Hypoglycemia has been reported in combination with sulphonylurea and insulin. Adverse reactions are listed under drug combination and frequency using the categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (cannot be estimated from the available data). Sitagliptin monotherapy: Common: upper respiratory tract infection, nasopharyngitis, osteoarthritis, pain in extremity, hypoglycaemia, headache. Combination with metformin: Common: nausea, flatulence,


vomiting. Combination with a sulphonylurea: Common:


hypoglycaemia. Combination with metformin and a sulphonylurea: Very common: hypoglycaemia; Common: constipation. Combination with a PPARγ agonist (pioglitazone): Common: flatulence, peripheral oedema. Combination with a PPARγ agonist (pioglitazone) and metformin: Common: peripheral oedema. Combination with insulin with/without metformin: Common: hypoglycaemia, influenza. Serious adverse events with sitagliptin during post- approval use alone and/or with other diabetes medicines where frequency is not known: hypersensitivity reactions including anaphylactic responses (see precautions), interstitial lung disease, acute pancreatitis, fatal and non-fatal haemorrhagic and necrotizing pancreatitis, angioedema, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome, impaired renal function, acute renal failure. PACKAGE QUANTITIES AND BASIC NHS COST: 28 Tablets: £33.26. Marketing Authorisation Number: EU/1/07/383/002 –25 mg; EU/1/07/383/008 –50 mg; EU/1/07/383/014 –100 mg. Marketing Authorisation Holder: Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK.


POM Date of review of prescribing information: July 2015.


© Merck Sharp & Dohme Limited 2016. All rights reserved. PI.JAN ALL.15.UK.4638.IB-046, PSUR-032 & WS-0741


Reference: 1. Valensi P, et al. Treatment maintenance duration of dual therapy with metformin and sitagliptin in type 2 diabetes: The ODYSSEE observational study. Diabetes Metab. 2015;41(3):231–238. The ODYSSEE Study: a prospective, observational (n=2607) study with > 3 years of real-life experience on dual therapy.


Date of preparation: January 2016.


JANUVIA plus metformin maintains treatment for over twice as long versus sulphonylurea plus metformin dual therapy (median treatment maintenance 43.2 months vs 20.2 months).


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