Sitazan

(Sitagliptin + Metformin HCl)

Sitazan Tablets 50mg/500mg and 50mg/1000mg

Sitazan tablets 50mg/500mg:

Composition:
Each film-coated tablet contains:

Sitagliptin as phosphate...50mg

Metformin HCl………………500mg

(Innovator's Specs.)

Sitazan Tablets 50mg/1000mg:

Composition:
Each film-coated tablet contains:

Sitagliptin as phosphate ……………50mg

Metformin as HCI……………………….1000mg

(Innovator's Specs.)

THERAPEUTIC CLASS:
Sitazan (sitagliptin phosphate/metformin HCI) combines two antihyperglycemic agents with
complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes:
Sitagliptin phosphate, a dipeptidyl peptidase 4 (DPP-4) inhibitor, and metformin hydrochloride, a
member of the biguanide class.
Sitagliptin phosphate:
Sitagliptin phosphate is an orally active, potent, and highly selective inhibitor of the dipeptidyl
peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes.

Metformin hydrochloride:
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2
diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of
action are different from other cases of oral antihyperglycemic agents Metformin decreases hepatic
glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by
increasing glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and
utilization Unlike sulfonylureas, metformin does not produce hypoglycaemia in either patient with
type 2 diabetes.

INDICATIONS:
 Sitazan is indicated as initial therapy in patients with type 2 diabetes mellitus to improve

glycaemic control when diet and exercise do not provide adequate glycemic control.
 Sitazan is indicated as an adjunct to diet and exercise to improve glycemic control in
patients with type 2 diabetes mellitus inadequately controlled on metformin sitagliptin
alone or in patients already being treated with the combination of sitagliptin and
metformin.
 Sitazan is indicated as part of triple combination therapy with a sulfonylurea as an
adjustment to diet and exercise in patients with type 2 diabetes mellitus inadequately
controlled with any two of the three agents: metformin, sitagliptin, or a sulfonylurea.
 Sitazan is inducted as part of triple combination therapy with a PRARy agoinst (i.e.,
thiazolidinediones as an adjunct to diet and exercise in patients with type 2 diabetes
mellitus inadequately controlled with any two of the three agents. metformin, sitagliptin, or
a PPARy agoinst.
 Sitazan is inducted in patients with type 2 diabetes mellitus as an adjunct to diet and
exercise to improve glycemic control in combination with insulin.

DOSAGE AND ADMINISTRATION:

General:
 The dosage of antihyperglycemic therapy with Sitazan should be individualized based on
the patient's current regimen, effectiveness, and tolerability while not exceeding the
maximum recommended daily dose of 100 mg of sitagliptin.
 Sitazan should be given twice daily with meals, with gradual dose escalation to reduce the
gastrointestinal (GI) side effects of metformin.

Dosing Recommendations:
The starting dose of Sitazan should be based on the patient's current regimen. Sitazan should be
given twice daily with meals. The following doses are available. 50mg Sitagliptin/500mg Metformin
Hydrochloride 50mg Sitagliptin/1000mg Metformin Hydrochloride.
As initial therapy:
For Patients with type 2 diabetes Mellitus, whose hyperglycaemia is inadequately controlled with
diet and exercise alone, the recommended starting dose of Sitazan is 50mg sitagliptin/500mg
metformin hydrochloride twice daily. patients may be treated up to 50mg Sitagliptin/1000mg
Metformin Hydrochloride twice daily.

CONTRAINDICATIONS:
Sitazan (Sitagliptin phosphate/Metformin HCI) is contraindicated in patients with:

 Renal disease or renal dysfunction. e.g., as suggested by serum creatinine levels>1.5mg/dl

(males)1.4mg/dl (females) or abnormal creatinine clearance, which may also from
conditions such as cardiovascular collapse (Shock) acute myocardial infarction, and
septicemia.
 Known hypersensitivity to sitagliptin phosphate, or any other component of metformin
hydrochloride Sitazan.
 Acute chronic metabolic acidosis including diabetic Ketoacidosis. Sitazan should be
temporarily discontinued in patients undergoing radiologic studies involving intravascular
administration of iodinated contrast materials, because the use of such products may result
in acute alteration of renal function.

PRECAUTIONS:
Sitazan should not be used in patients with type 1 diabetes or for the treatment of diabetic
ketoacidosis.

Pancreatitis: In post-marketing experience, there have been reports of acute pancreatitis, including
fatal and non-fatal haemorrhagic or necrotizing pancreatitis Because these reports are made
voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their
frequency or establish a causal relationship to drug exposure. Patients should be informed of the
characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. resolution of
pancreatitis has been observed after discontinuation of sitagliptin.

Monitoring of renal function:

Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin
accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus,
patients with serum creatinine levels above the upper limit of normal for their age should not receive
Sitazan in patients with advanced age, Sitazan should be carefully titrated to establish the minimum
dose for adequate glycemic effect, because ageing can be associated with reduced renal function. In
elderly patients, particularly those >80 years of age, renal function should be monitored regularly.

Before the initiation of therapy with Sitazan and at least annually thereafter, renal function should be
assessed and verified as normal. In patients in whom the development of renal dysfunction is
anticipated, renal function should be assessed more frequently and Sitazan discontinued If evidence
of renal impairment is present.

PREGNANCY:
Sitazan
There are no adequate and well-controlled studies on pregnant women with Sitazan or its
component: therefore, the safety of Sitazan in pregnant women is not known. Sitazan like other oral
antihyperglycemic agents, is not recommended for use in pregnancy.

NURSING MOTHERS:
No studies in lactating animals have been conducted with the combined components of Sitazan. In
studies performed with the individual components, both sitagliptin and metformin are secreted in
the milk of lactation rats. It is not known whether sitagliptin is excreted in human milk. Therefore,
Sitazan should not be used by a woman who is nursing.

PEDIATRIC USE:
The safety and effectiveness of Sitazan in paediatric patients under 18 years have not been
established.

ELDERLY USE:
Sitazan
Because sitagliptin and metformin are substantially excreted by the kidney and because ageing can
be associated with reduced renal function, Sitazan should be used with caution as age increases.
Care should be taken in dose selection and should be based on careful and regular monitoring of
renal function.

DRUG INTERACTIONS:
Sitagliptin and metformin
Co-administration of multiple doses of sitagliptin (50 mg b.i.d) and metformin (1000 mg b.i.d) did not
meaningfully alter the pharmacokinetics of either sitagliptin or metformin in patients with type 2
diabetes.

Pharmacokinetics drug interaction studies Sitazan have not been performed; however, such studies
have been conducted with the individual components of Sitazan, sitagliptin and metformin.

Sitagliptin phosphate
In drug interaction studies, sitagliptin did not have clinically meaningful effects on the
pharmacokinetics of the following: metformin, rosiglitazone, glyburide, simvastatin, warfarin and oral
contraceptive. Based on these data, sitagliptin does not inhibit CYP isozyme CYP3A4,2C8, or 2C9.
Based on in Vitro data, sitagliptin is also not expected to inhibit CYP2D6,1A2,2C19 or 2B6 or to
induce CYP3A4.

Metformin hydrochloride
Glyburide; In a single-dose interaction study in type 2 diabetes patients, co-administration of
metformin and glyburide did not result in any changes in either metformin pharmacokinetics or
pharmacodynamics. Decrease in glyburide AUG and Cmax were observed, but were highly variable.
The single-dose nature of this and the lack of correlation between glyburide blood levels and
pharmacodynamic effects make the clinical significance of this interaction uncertain.

Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects

demonstrated that the pharmacokinetics parameters of both compounds were affected by co-
administration. Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC
by 15% without any significant change alone. and the terminal half-life was decreased by 32%
without any significant change in furosemide renal clearance. No information is available about the
interaction of Sitazan and furosemide when co-administered chronically.

Cationic drugs: cationic drugs (e.g., amiloride, digoxin, morphine, procainamide. quinidine, quinine,
ranitidine, triamterene, trimethoprim or vancomycin) that are eliminated by renal tubular secretion
theoretically have the potential for interaction with metformin by competing for common renal
tubular transport systems.

AVAILABILITY:
 Sitazan 50mg/500mg tablets are available in a blister pack of 2x7 tablets.
 Sitazan 5Omg/1000mg tablets are available in a blister pack of 2 x7 tablets.

Sitazan (Sitagliptin + Metformin HCl)

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