Janumet pi jmt 13 uk 3853-047-renewal-final text 25 march 2013

JANUMET®
sitagliptin/metformin hydrochloride
PRESCRIBING INFORMATION
Refer to Summary of Product Characteristics (SmPC) 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 50 mg sitagliptin and 1000 mg metformin hydrochloride.

USES
For patients with type 2 diabetes mellitus:
-
as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximal tolerated dose of metformin alone or those already being treated with the combination of sitagliptin and metformin. - in combination with a sulphonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea. - as triple combination therapy with a PPARγ agonist (i.e., a thiazolidinedione) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a PPARγ agonist. - as add-on to insulin (i.e., triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when stable dosage of insulin and metformin alone
do not provide adequate glycaemic control.

DOSAGE AND ADMINISTRATION - Take twice daily with meals. When used in
combination with a sulphonylurea, or with insulin a lower dose of the sulphonylurea or
insulin may be required to reduce the risk of hypoglycaemia. Patients with renal impairment:
not to be used in patients with moderate or severe renal impairment (creatinine clearance
< 60 ml/min). Patients with hepatic impairment: not to be used. Elderly: use with caution as
age increases. Monitoring of renal function is necessary to aid in prevention of metformin-
associated lactic acidosis. Exercise care in patients > 75 years of age due to limited safety
data in this population. Children: not recommended below 18 years of age.
CONTRA-INDICATIONS - Hypersensitivity. Diabetic ketoacidosis and diabetic pre-coma.
Moderate and severe renal impairment (creatinine clearance < 60 ml/min). Acute conditions
with the potential to alter renal function such as dehydration, severe infection, shock.
Intravascular administration of iodinated contrast agents. Acute or chronic disease which
may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction,
shock. Hepatic impairment. Acute alcohol intoxication, alcoholism. Lactation.

PRECAUTIONS - General: Do not use in patients with type 1 diabetes or for treatment of
diabetic ketoacidosis. Pancreatitis: Post-marketing experience - spontaneously reported
adverse reactions of 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, Janumet and other potentially suspect medicinal products should be discontinued. Lactic acidosis: a very rare, but serious, metabolic complication can occur due to metformin accumulation. Cases in patients on metformin have occurred primarily in diabetic patients with significant renal failure. Reduce incidence by assessing other associated risk factors. If suspected, discontinue treatment and hospitalise patient immediately. Renal function: metformin-related lactic acidosis increases with the degree of impairment of renal function. Determine serum creatinine concentrations regularly, i.e. at least once a year in patients with normal renal function and at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in elderly patients. Decreased renal function in elderly patients is frequent and asymptomatic. Exercise special caution where renal function may become impaired, e.g. when initiating antihypertensive or diuretic therapy or when starting treatment with a non-steroidal anti-inflammatory drug (NSAID). Hypoglycaemia: patients receiving Janumet in combination with a sulphonylurea or with insulin may be at risk of hypoglycaemia. Reduction of the dose of sulphonylurea or insulin may be necessary. Hypersensitivity reactions: serious hypersensitivity reactions have been reported including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson Syndrome. Onset occurred within first 3 months after initiation of treatment with some reports occurring after the first dose. If suspected discontinue Janumet, assess for other potential causes and institute alternative treatment of diabetes. Surgery: due to metformin hydrochloride content of Janumet, discontinue treatment 48 hours before elective surgery with general, spinal or epidural anaesthesia. Do not resume earlier than 48 hours afterwards and only after renal function is normal. Change in clinical status of patients with previously controlled type 2 diabetes: any patient with type 2 diabetes, previously well controlled on Janumet who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness), evaluate promptly for evidence of ketoacidosis or lactic acidosis. If acidosis of either form occurs, stop Janumet immediately and initiate corrective measures. Drug interactions: Alcohol: avoid alcohol and medicinal products containing alcohol due to risk of lactic acidosis. Cationic medicinal products that are eliminated by renal tubular secretion (e.g., cimetidine): these may interact with metformin by competing for common renal tubular transport systems. Consider close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment when these agents are co-administered. Iodinated contrast agents in radiological studies: intravascular administration of these agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Discontinue Janumet prior to, or at the time of the test and do not reinstitute until 48 hours afterwards, and only after renal function is found to be normal. Combination requiring precautions for use: glucocorticoids (given by systemic and local routes), beta-2-agonists and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust dose of the anti-hyperglycaemic medicine during therapy with, or on discontinuation of the other medicine. ACE-inhibitors: as these may decrease the blood glucose levels, if necessary, adjust dose of the antihyperglycaemic during therapy with, or on discontinuation of the other medicine. Effects of other medicinal products on sitagliptin: low risk of clinically meaningful interactions with other medicinal products and ciclosporin. Meaningful interactions would not be expected with other p-glycoprotein inhibitors. The primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8. Effects of sitagliptin on other medicinal products: Digoxin: sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p-glycoprotein in vivo. No dose adjustment of digoxin is recommended, but monitor patients at risk of digoxin toxicity if used together. Pregnancy and Lactation: Do not use during
pregnancy. Do not use during breast-feeding.
SIDE EFFECTS - Refer to SmPC for complete information on side effects
There have been no therapeutic clinical trials conducted with Janumet tablets however
Janumet is bioequivalent to co-administered sitagliptin and metformin. 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 and metformin: common: hypoglycaemia, nausea, flatulence, vomiting;
Sitagliptin with metformin and sulphonylurea: very common: hypoglycaemia; common:
constipation. Sitagliptin with metformin and a PPARγ agonist (pioglitazone): common:
hypoglycaemia, peripheral oedema. Sitagliptin with metformin and insulin: very common:
hypoglycaemia. Adverse events identified through post-marketing use where frequency not
known: hypersensitivity reactions including anaphylactic responses (see precautions),
interstitial lung disease, acute pancreatitis (see precautions), fatal and non-fatal haemorrhagic
and necrotizing pancreatitis, angioedema, rash, urticaria, cutaneous vasculitis, exfoliative skin
conditions including Stevens-Johnson syndrome, arthralgia, myalgia, pain in extremity, back
pain, impaired renal function, acute renal failure. Additional information on the individual
active substances - Sitagliptin: In studies of sitagliptin 100 mg once daily alone compared to
placebo, drug-related adverse reactions reported were: headache, hypoglycaemia, constipation
and dizziness. Also, adverse events reported, regardless of causal relationship to medication
and occurring in at least 5% included: upper respiratory tract infection and nasopharyngitis.
In addition, osteoarthritis and pain in extremity were reported with frequency uncommon
(> 0.5 % higher among sitagliptin users than that in the control group). Metformin: Clinical
Trial Data and Post-Marketing Data: very common: gastro-intestinal disorders; common:
metallic taste; very rare: urticaria, erythema, pruritis, lactic acidosis, vitamin B12 deficiency,
liver function disorders, hepatitis.
PACKAGE QUANTITIES AND BASIC NHS COST - 56 Tablets: £33.26
Marketing Authorisation Number - 50 mg/1000 mg: EU/1/08/455/010
Marketing Authorisation Holder
Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK

Date of review of prescribing information: March 2013
Merck Sharp & Dohme Limited, 2013. All rights reserved. PI.JMT.13.UK.3853-047-renewal

Source: http://www.msdproduct.co.uk/api/janumet.pdf