Zensita D 50 Tablets

Sitagliptin and Dapagliflozin Tablets

Zensita-D 50/5

Each film coated tablet contains :

Sitagliptin Phosphate Monohydrate IP equivalent to Sitagliptin 50 mg

Dapagliflozin Propanediol Monohydrate equivalent to Dapagliflozin 5 mg

Excipients q.s.

Colours : Titanium Dioxide IP & Ferric Oxide Red USP NF

Zensita-D 100/10

Each film coated tablet contains :

Sitagliptin Phosphate Monohydrate IP equivalent to Sitagliptin 100 mg

Dapagliflozin Propanediol Monohydrate equivalent to Dapagliflozin 10 mg

Excipients q.s.

Colours : Titanium Dioxide IP & Ferric Oxide Red USP NF

Film coated tablet

4.1 Therapeutic Indication

Sitagliptin and Dapagliflozin are indicated for the treatment of type 2 diabetes mellitus inadequately controlled on Metformin monotherapy.

4.2 Posology & Method of Administration

The dosage of Sitagliptin and Dapagliflozin should be individualized on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin and 10 mg Dapagliflozin. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.

Method of administration

Sitagliptin and Dapagliflozin can be taken with or without food.

4.3 Contraindications

Sitagliptin and Dapagliflozin is contraindicated in patients with: Sitagliptin Patients with a history of a hypersensitive reaction to Sitagliptin or to any ingredient in the formulation. Prohibited Medications Strong CYP2C8 inhibitors (e.g., Gemfibrozil), CYP2C8 inducers (e.g., Rifampin) and Topiramate. Drugs increasing hypoglycemic action: β-blocking agents, Salicylic acid and Monoamine oxidase inhibitor. Drugs decreasing hypoglycemic action: Adrenalin and adrenocortical hormone. Drugs known to cause QT prolongation: Class IA antiarrhythmic drug Quinidine sulfate hydrate, Procainamide Hydrochloride, Class III antiarrhythmic drugs Amiodarone Hydrochloride, Sotalol Hydrochloride. Digoxin and Oral hypoglycemic agents other than study medication. Diuretics, Insulin and insulin secretagogues, such as sulphonylureas, Rifampicin and Mefenamic Acid. Oral hypoglycemic agents other than study medication.

Dapagliflozin

• Patients with a history of hypersensitivity reaction to the active substance or to any of the excipients.

• Patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m , severe renal impairment, end-stage renal disease (ESRD) or patients on dialysis

4.4 Warning & Precautions

Volume depletion: Before initiating Sitagliptin and Dapagliflozin, assess volume status and renal function in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. Ketoacidosis in Patients with Diabetes Mellitus: Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis regardless of blood glucose level. If suspected, discontinue Sitagliptin and Dapagliflozin, evaluate and treat promptly. Before initiating Sitagliptin and Dapagliflozin, consider risk factors for ketoacidosis. Patients on Sitagliptin and Dapagliflozin may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. Urosepsis and Pyelonephritis: Evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Hypoglycemia: Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with Sitagliptin and Dapagliflozin. Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Serious, life-threatening cases have occurred in patients with diabetes, both females and males. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment.

Genital Mycotic Infections: Monitor and treat if indicated. There have been post marketing reports of acute pancreatitis, including fatal and non-fatal haemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue Sitagliptin and Dapagliflozin. There have been post marketing reports of acute renal failure, sometimes requiring dialysis. Dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with ESRD. Assessment of renal function is recommended prior to initiating Sitagliptin and Dapagliflozin and periodically thereafter. There is an increased risk of hypoglycaemia when Sitagliptin and Dapagliflozin is added to an insulin secretagogue (e.g., sulfonylurea) or insulin therapy. Consider lowering the dose of the sulfonylurea or insulin to reduce the risk of hypoglycemia. There have been post marketing reports of serious allergic and hypersensitivity reactions in patients treated with Sitagliptin and Dapagliflozin such as anaphylaxis, angioedema, and exfoliative skin conditions including Steven Johnson syndrome. In such cases, promptly stop Sitagliptin and Dapagliflozin, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. There have been no clinical studies establishing conclusive evidence of macro vascular risk reduction with Sitagliptin and Dapagliflozin or any other anti-diabetic drug

4.5 Drug Interactions

Digoxin

There was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (C , 18%) of digoxin with the co-administration of 100 mg sitagliptin for 10 days. Patients receiving max digoxin should be monitored appropriately. No dosage adjustment of digoxin or Sitagliptin and Dapagliflozin is recommended. Positive Urine Glucose Test Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

4.6 Special populations

Pregnancy

There are no adequate and well-controlled studies in pregnant women with Sitagliptin and Dapagliflozin or its individual components; therefore, the safety of Sitagliptin and Dapagliflozin in pregnant women is not known.

Sitagliptin and Dapagliflozin should be used during pregnancy only if clearly needed. Reproduction studies have been performed in rats and rabbits. Doses of sitagliptin up to 125 mg/kg (approximately 12 times the human exposure at the maximum recommended human dose) did not impair fertility or harm the foetus.

The data are based on findings in studies performed with Sitagliptin and Dapagliflozin individually

Nursing woman

No studies in lactating animals have been conducted with the combined components of Sitagliptin and Dapagliflozin.

In studies performed with the individual components, both Sitagliptin and Dapagliflozin are secreted in the milk of lactating rats. It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sitagliptin and Dapagliflozin is administered to a nursing woman.

Paediatric Use

Safety and effectiveness of Sitagliptin and Dapagliflozin in paediatric patients under 18 years have not been established.

Geriatric Use

No Sitagliptin and Dapagliflozin dosage change is recommended based on age.

4.7 Effects on ability to drive and use machines

Sitagliptin and Dapagliflozin has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable Effects

Undesirable Effects Adverse reactions reported in 5% of patients treated with Sitagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, nasopharyngitis and headache. In the add on to sulfonylurea and add-on to insulin studies, hypoglycemia was also more commonly reported in patients treated with Dapagliflozin compared to placebo. The most common adverse reactions associated with Dapagliflozin (5% or greater incidence) were female genital mycotic infections, nasopharyngitis, and urinary tract infection. Arthralgia ADR is reported with sitagliptin

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com Website: http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Sitagliptin

During controlled clinical trials in healthy subjects, single doses of up to 800 mg Sitagliptin were administered.

Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg Sitagliptin, a mean effect that is not considered clinically important. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with Sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days. 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 (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4- hour haemodialysis session. Prolonged haemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Dapagliflozin

There were no reports of overdose during the clinical development program for dapagliflozin. In the event of an overdose, contact the Poison Control Centre. It is also reasonable to employ supportive measures as dictated by the patient's clinical status. The removal of dapagliflozin by haemodialysis has not been studied.

5.1 Mechanism of Action

Sitagliptin and Dapagliflozin combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes: sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride, a member of the biguanide class. Sitagliptin and Dapagliflozin are indicated for the treatment of type 2 diabetes mellitus inadequately controlled on Metformin monotherapy.

Dapagliflozin

Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity.

Sitagliptin

Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signalling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucosedependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

5.2 Pharmacodynamic Properties

Dapagliflozin

Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin. Dapagliflozin doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at Week 12. A near maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume. After discontinuation of dapagliflozin, on average, the elevation in urinary glucose excretion approaches baseline by about 3 days for the 10 mg dose.

Sitagliptin

General

In patients with type 2 diabetes, administration of sitagliptin led to inhibition of DPP-4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased responsiveness of insulin release to glucose, resulting in higher C-peptide and insulin concentrations. The rise in insulin with the decrease in glucagon was associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal. In studies with healthy subjects, sitagliptin did not lower blood glucose or cause hypoglycemia.

Cardiac Electrophysiology In a randomized, placebo-controlled crossover study, 79 healthy subjects were administered a single oral dose of sitagliptin 100 mg, sitagliptin 800 mg (8 times the recommended dose), and placebo. At the recommended dose of 100 mg, there was no effect on the QTc interval obtained at the peak plasma concentration, or at any other time during the study. Following the 800-mg dose, the maximum increase in the placebo-corrected mean change in QTc from baseline at 3 hours post dose was 8.0 msec. This increase is not considered to be clinically significant. At the 800-mg dose, peak sitagliptin plasma concentrations were approximately 11 times higher than the peak concentrations following a 100-mg dose. In patients with type 2 diabetes administered sitagliptin 100 mg (N=81) or sitagliptin 200 mg (N=63) daily, there were no meaningful changes in QTc interval based on ECG data obtained at the time of expected peak plasma concentration.

5.3 Pharmacokinetic properties

Absorption

Sitagliptin

The absolute bioavailability of sitagliptin is approximately 87%. Co-administration of a high-fat meal with sitagliptin had no effect on the pharmacokinetics of sitagliptin

Dapagliflozin

Following oral administration of dapagliflozin, the maximum plasma concentration (C ) is usually max attained within 2 hours under fasting state. The C and AUC values increase dose proportionally with max increase in dapagliflozin dose in the therapeutic dose range. The absolute oral bioavailability of dapagliflozin following the administration of a 10 mg dose is 78%. Administration of dapagliflozin with a high-fat meal decreases its C by up to 50% and prolongs T by approximately 1 hour, but does not alter max max AUC as compared with the fasted state. These changes are not considered to be clinically meaningful and dapagliflozin can be administered with or without food.

Distribution

Sitagliptin

The mean volume of distribution at steady state following a single 100-mg intravenous dose of sitagliptin to healthy subjects is approximately 198 litres. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).

Dapagliflozin

Dapagliflozin is approximately 91% protein bound. Protein binding is not altered in patients with renal or hepatic impairment.

Biotransformation

Sitagliptin

Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway. Approximately 79 % of sitagliptin is excreted unchanged in the urine. Following a sitagliptin oral dose, approximately 16 % of the radioactivity was excreted as metabolites of sitagliptin. Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin. In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8. In vitro data showed that sitagliptin is not an inhibitor of CYP isozymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6, and is not an inducer of CYP3A4 and CYP1A2.

Dapagliflozin

Dapagliflozin is approximately 91% protein bound. Protein binding is not altered in patients with renal or hepatic impairment.

Elimination

Sitagliptin

Following administration of an oral sitagliptin dose to healthy subjects, approximately 100 % of the administered radioactivity was eliminated in faeces (13 %) or urine (87 %) within one week of dosing. The apparent terminal t following a 100-mg oral dose of sitagliptin was approximately 12.4 hours. Sitagliptin accumulates only minimally with multiple doses. The renal clearance was approximately 350 mL/min. Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion. Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin. The clinical relevance of hOAT-3 in sitagliptin transport has not been established. Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin. However, ciclosporin, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin. Sitagliptin is not a substrate for OCT2 or OAT1 or PEPT1/2 transporters. In vitro, sitagliptin did not inhibit OAT3 (IC50=160 μM) or p-glycoprotein (up to 250 μM) mediated transport at therapeutically relevant plasma concentrations. In a clinical study sitagliptin had a small effect on plasma digoxin concentrations indicating that sitagliptin may be a mild inhibitor of p-glycoprotein.

Dapagliflozin

Dapagliflozin and related metabolites are primarily eliminated via the renal pathway. Following a single 14 50 mg dose of [ C]-dapagliflozin, 75% and 21% total radioactivity is excreted in urine and faces, respectively. In urine, less than 2% of the dose is excreted as parent drug. In faces, approximately 15% of the dose is excreted as parent drug. The mean plasma terminal half-life (t½) for dapagliflozin is approximately 12.9 hours following a single oral dose of Dapagliflozin 10 mg.

Special populations

Renal Insufficiency

Sitagliptin

An approximately 2-fold increase in the plasma AUC of sitagliptin was observed in patients with moderate renal insufficiency, and an approximately 4-fold increase was observed in patients with severe renal insufficiency including patients with ESRD on haemodialysis, as compared to normal healthy control subjects

Dapagliflozin

At steady-state (20 mg once daily dapagliflozin for 7 days), patients with type 2 diabetes with mild, moderate, or severe renal impairment (as determined by eGFR) had geometric mean systemic exposures of dapagliflozin that were 45%, 2.04-fold, and 3.03-fold higher, respectively, as compared to patients with type 2 diabetes mellitus with normal renal function. Higher systemic exposure of dapagliflozin in patients with type 2 diabetes mellitus with renal impairment did not result in a correspondingly higher 24-hour urinary glucose excretion. The steady-state 24-hour urinary glucose excretion in patients with type 2 diabetes mellitus and mild, moderate, and severe renal impairment was 42%, 80%, and 90% lower, respectively, than in patients with type 2 diabetes mellitus with normal renal function. The impact of haemodialysis on dapagliflozin exposure is not known.

Hepatic Insufficiency

Sitagliptin

In patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), mean AUC and C of sitagliptin max increased approximately 21% and 13%, respectively, compared to healthy matched controls following administration of a single 100-mg dose of sitagliptin. These differences are not considered to be clinically meaningful. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9).

Dapagliflozin

In subjects with mild and moderate hepatic impairment (Child-Pugh classes A and B), mean C and AUC max of dapagliflozin were up to 12% and 36% higher, respectively, as compared to healthy matched control subjects following single-dose administration of 10 mg dapagliflozin. These differences were not considered to be clinically meaningful. In patients with severe hepatic impairment (Child-Pugh class C), mean C_max and AUC of dapagliflozin were up to 40% and 67% higher, respectively, as compared to healthy max matched controls

Gender

Sitagliptin

Gender had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.

Geriatric

Sitagliptin

When the effects of age on renal function are taken into account, age alone did not have a clinically meaningful impact on the pharmacokinetics of sitagliptin based on a population pharmacokinetic analysis

Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.

Dapagliflozin

Based on a population pharmacokinetic analysis, age, gender, race, and body weight do not have a clinically meaningful effect on the pharmacokinetics of dapagliflozin and thus, no dose adjustment is recommended.

Paediatric

Sitagliptin

Race had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of available pharmacokinetic data, including subjects of white, Hispanic, black, Asian, and other racial groups.

Dapagliflozin

Pharmacokinetics in the paediatric population has not been studied.

6.1 Animal Toxicology or Pharmacology

No animal studies have been conducted with the combined products in Sitagliptin and Dapagliflozin to evaluate effects. Sitagliptin reproduction studies have been performed in rats and rabbits. Doses of sitagliptin up to 125 mg/kg (approximately 12 times the human exposure at the maximum recommended human dose) did not impair fertility or harm the foetus. There are, however, no adequate and wellcontrolled studies with sitagliptin in pregnant women. Sitagliptin administered to pregnant female rats and rabbits from gestation day 6 to 20 (organogenesis) was not teratogenic at oral doses up to 250 mg/kg (rats) and 125 mg/kg (rabbits), or approximately 30 and 20 times human exposure at the maximum recommended human dose (MRHD) of 100 mg/day based on AUC comparisons. Higher doses increased the incidence of rib malformations in offspring at 1000 mg/kg, or approximately 100 times human exposure at the MRHD. Sitagliptin administered to female rats from gestation day 6 to lactation day 21 decreased body weight in male and female offspring at 1000 mg/kg. No functional or behavioural toxicity was observed in offspring of rats. Placental transfer of sitagliptin administered to pregnant rats was approximately 45% at 2 hours and 80% at 24 hours post dose. Placental transfer of sitagliptin administered to pregnant rabbits was approximately 66% at 2 hours and 30% at 24 hours.

Dapagliflozin

Dapagliflozin is described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4 ethoxyphenyl) methyl]phenyl]-, (1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1). The empirical formula is C₂₁H₂₅ClO₆C₈H₈O₂H₂O and the molecular weight is 502.98. The structural formula is

Sitagliptin

Sitagliptin is an orally-active inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. Sitagliptin is present in the form of sitagliptin phosphate monohydrate. Sitagliptin phosphate monohydrate is described chemically as 7-[(3R)-3- amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8tetrahydro-3- (trifluoromethyl)- 1,2,4- triazolo[4,3-a]pyrazine phosphate (1:1) monohydrate with an empirical formula of C₁₆H₁₅F₆N₅O•H₃PO₄ •H₂O and a molecular weight of 523.32. The structural formula is:

Core Tablet:

Microcrystalline Cellulose

Croscarmellose sodium

PVP K 30

Purified water*

Croscarmellose sodium

Colloidal silicon dioxide

Mannitol

Magnesium Stearate

Film Coating:

Polyvinyl Alcohol

Polyethylene Glycol

Talc

Titanium Dioxide

Ferric Oxide Red

9.1 Incompatibilities

Not Applicable

9.2 Shelf Life

Refer on the pack.

9.3 Packaging Information

Alu-Alu blister strip of 10 tablets.

9.4 Storage and handing Instructions

Store below 30°C. Protect from light.

Keep out of reach of children.

What is the most important information I should know about Sitagliptin and Dapagliflozin Tablets?

• Patients with a history of hypersensitivity reaction to the active substance or to any of the excipients.

• Patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2, severe renal impairment, end-stage renal disease (ESRD) or patients on dialysis

Sitagliptin

Patients with a history of a hypersensitive reaction to Sitagliptin or to any ingredient in the formulation. Prohibited Medications

Strong CYP2C8 inhibitors (e.g., Gemfibrozil), CYP2C8 inducers (e.g., Rifampin) and Topiramate. Drugs increasing hypoglycemic action: β-blocking agents, Salicylic acid and Monoamine oxidase inhibitor. Drugs decreasing hypoglycemic action: Adrenalin and adrenocortical hormone. Drugs known to cause QT prolongation: Class IA antiarrhythmic drug Quinidine sulfate hydrate, Procainamide Hydrochloride, Class III antiarrhythmic drugs

Amiodarone Hydrochloride, Sotalol Hydrochloride. Digoxin and Oral hypoglycemic agents other than study medication. Diuretics, Insulin and insulin secretagogues, such as sulphonylureas, Rifampicin and Mefenamic Acid. Oral hypoglycemic agents other than study medication. Call your doctor right away if you have any of the following symptoms, which could be signs of lactic acidosis:

• you feel cold in your hands or feet

• you feel dizzy or lightheaded

• you have a slow or irregular heartbeat

• you feel very weak or tired

• you have unusual (not normal) muscle pain

• you have trouble breathing

• you feel sleepy or drowsy

• you have stomach pains, nausea or vomiting

Do not take Sitagliptin and Dapagliflozin Tablets:

If you are allergic to Sitagliptin and Dapagliflozin or any of the other ingredients of this medicine. If you think you may be allergic to Sitagliptin and Dapagliflozin or any of the other ingredients of Sitagliptin and Dapagliflozin, do not take this medicine and talk to your doctor.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Sitagliptin and Dapagliflozin. If you take Sitagliptin and Dapagliflozin with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you use Sitagliptin and Dapagliflozin. Signs and symptoms of may include:

• Upper respiratory tract infection,

• Nasopharyngitis

• Headache

• Hypoglycemia

• Female genital mycotic infections

What is type 2 diabetes?

Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that your body produces does not work as well as it should. Your body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems. High blood sugar can be lowered by diet and exercise, and by certain medicines when necessary

How will I receive Sitagliptin and Dapagliflozin Tablets?

Swallow the tablets whole with some water.

If you take more Sitagliptin and Dapagliflozin Tablets than you should?

If you have taken too many tablets, contact your doctor immediately or go to the nearest hospital casualty department taking any remaining medication and this patient information leaflet with you.

If you forget to take Sitagliptin and Dapagliflozin Tablets?

If you miss a dose of Sitagliptin and Dapagliflozin Tablets, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.