-Hypersensitivity to the active substances or to any of the component of Sitament®

-Any type of acute or chronic metabolic acidosis (such as lactic acidosis, diabetic

ketoacidosis); diabetic pre-coma;

-Moderate or severe renal impairment(GFR< 30 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.

-Consumption of alcohol and medicinal products containing alcohol should be

avoided

-Cationic medicinal products that are eliminated by renal tubular secretion (e.g.,

Cimetidine) may interact with metformin by competing for common renal tubular

transport systems.

-Combinations requiring precautions for use : Glucocorticoids (given by systemic

and local routes) beta-2-agonists, and diuretics and ACE-inhibitors.

-Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic

control. These drugs include the thiazides and other diuretics, corticosteroids,

phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin,

nicotinic acid, sympathomimetics, calcium channel blockingdrugs, and isoniazid.

When such drugs are administered to a patient receiving Sitament® the patient

should be closely observed to maintain adequate glycemic control.

-Potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir,

clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with

severe renal impairment or ESRD.

-Digoxin: patients at risk of digoxin toxicity should be monitored for this when

sitagliptin and digoxin are administered concomitantly.

-Carbonic anhydrase inhibitors may increase risk of lactic acidosis.

-Drugs that reduce metformin clearance (such as ranolazine, vandetanib,

dolutegravir, and cimetidine) may increase the accumulation of metformin.

Use in Pregnancy And lactation

-Sitament® should not be used during pregnancy.

-It must not be used in women who are breast-feeding.

-Common adverse reaction include: hypoglycemia, diarrhea, upper respiratory tract

infection, headache, nausea, flatulence, vomiting, osteoarthritis, arm or leg pain, a

metallic taste, stuffy or runny nose and sore throat.

-Uncommon reaction such as somnolence, constipation, upper abdominal pain and

 pruritus.

-Very rare: decreased vitamin B12 levels, hepatitis (a problem with your liver),

hives, redness of the skin (rash) or itching.

-Some adverse reactions were observed more frequently in studies of combination

use of sitagliptin and metformin with other anti-diabetic medicinal products than in

studies of sitagliptin and metformin alone. These included hypoglycaemia

(frequency very common with sulphonylurea or insulin), constipation (common

with sulphonylurea), peripheral oedema (common with pioglitazone), and

headache and dry mouth (uncommon with insulin).

Overdose

-The most effective method to remove lactate and metformin is haemodialysis.

-In the event of an overdose, it is reasonable to employ the usual supportive

measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ

clinical monitoring and institute supportive therapy if required.

- Sitament® should not be used in patients with type1diabetes or for the treatment

of diabetic ketoacidosis.

- Acute pancreatitis: use of DPP-4 inhibitors has been associated with a risk of

developing acute pancreatitis. Patients should be informed of the characteristic

symptom of acute pancreatitis: persistent, severe abdominal pain  which may or may

not be accompanied with vomiting.. If pancreatitis is suspected, Sitament® should

be discontinued; caution should be exercised in patients with a history of

pancreatitis. Gallstones, alcohol dependence or very high levels of triglycerides (a

form of fat) in the blood can increase the chance of getting pancreatitis

-Lactic acidosis: There have been postmarketing cases of metformin-associated

lactic acidosis, including fatal cases. If metformin-associated lactic acidosis is

suspected, general supportive measures should be instituted promptly in a hospital

setting, along with immediate discontinuation of Sitament® . Symptoms of lactic

acidosis include: vomiting, stomach ache (abdominal pain), muscle cramps, a

general feeling of not being well with severe tiredness, difficulty in breathing,

reduced body temperature and heartbeat.

-Heart Failure: An association between dipeptidyl peptidase-4 (DPP-4) inhibitor

treatment and heart failure has been observed in cardiovascular outcomes trials for

two other members of the DPP-4 inhibitor class. Consider the risks and benefits of

Sitament® prior to initiating treatment in patients at risk for heart failure

-Renal function: GFR should be assessed before treatment initiation and regularly

thereafter. Sitament® is contraindicated in patients with GFR < 30 mL/min and

should be temporarily discontinued during conditions with the potential to alter renal

function

-Hypoglycaemia: if sulphonylurea, insulin or diabetes medicines are taken together

with Sitament® , the dose of sulphonylurea or insulin may be reduced.

-Hypersensitivity reactions: include anaphylaxis, angioedema, and exfoliative skin

conditions including Stevens-Johnson syndrome. If a hypersensitivity reaction is

suspected, Sitament® should be discontinued.

-Surgery: as Sitament® contains the metform in hydrochloride , the treatment

should be discontinued 48 hours before elective of surgery with general, spinal or

epidural anaesthesia.

-Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. Measurement

of hematologic parameter on annual basis is advised in patients on Sitament®.

-Severe and Disabling Arthralgia.

-Bullous Pemphigoid.

Effects on ability to drive and use machines

- Sitament® has no or negligible influence on the ability to drive and use machines.

However, dizziness and drowsiness have been reported with sitagliptin, which may

affect the ability to drive or use machines. In addition, patients should be alerted to

the risk of hypoglycaemia when Sitament® is used in combination with a

sulphonylurea or with insulin.

-Sitament® 50 /1000: Blister of 5 tablets, pack of 6m blisters.

-Sitament® 50 /500: Blister of 5 tablets, pack of 6m blisters.

-Store in dry place, below 25ºC.