Information about Empa
Composition:

Each Film-coated tablet contains 10 or 25 mg Empagliflozin .

Mechanism of Action:

Sodium-glucose co-transporter 2(SGLT2) is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Empagliflozin is aninhibitor of SGLT2. By inhibiting SGLT2, empagliflozin reduces renalreabsorption of filtered glucose and lowers the renal threshold for glucose,and thereby increases urinary glucose excretion.

Pharmacokinetics:

Absorption: After oral administration, peak plasma concentrations of empagliflozin were reached at 1.5 hours post-dose.  The observed effect of food on empagliflozin pharmacokinetics was not considered clinically relevant and empagliflozin may be administered with or without food.

Distribution: plasma protein binding was 86.2%.

Metabolism: In vitro studies suggested that the primary route of metabolism of empagliflozin in humans is glucuronidation by UGT2B7, UGT1A3, UGT1A8, and UGT1A9.

Elimination: The apparent terminalelimination half-life of empagliflozin was estimated to be 12.4 h. Following administration of an oral [14C]-empagliflozin solution to healthy subjects approximately 95.6% of the drug-related radio activity was eliminated in feces (41.2%) or urine (54.4%).

INDICATIONS:

It is indicated:

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus,

To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Limitations of Use: it is not recommended for patients with type 1 diabetes or for the treatment of diabeticketoacidosis.

DOSAGE AND ADMINISTRATION:

The recommended dose is 10 mg once daily in the morning, taken with or without food. In patients tolerating this drug, the dose may be increased to 25 mg.

In patients with volume depletion,correcting this condition prior to initiation of this drug is recommended

Patients with Renal Impairment:Assessment of renal function is recommended prior to initiation of this drug and periodically thereafter.

No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m2.

This drug should be discontinued if eGFR is less than 45 mL/min/1.73 m2

CONTRAINDICATIONS

History of serious hypersensitivity reaction to empagliflozin.

Severe renal impairment, end-stage renal disease, or dialysis.

WARNINGS AND PRECAUTIONS:

Hypotension: empagliflozin causes intravascular volume contraction. Symptomatic hypotension may occur after initiating of empagliflozin particularly in patients with renal impairment, theelderly, in patients with low systolic blood pressure, and in patients ondiuretics. Before initiating this drug, assess for volume contraction andcorrect volume status if indicated. Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinicalsituations where volume contraction is expected.

Ketoacidosis: Fatal cases ofketoacidosis have been reported in patients taking empagliflozin. empagliflozinis not indicated for the treatment of patients with type 1diabetes mellitus. Patientstreated with empagliflozin who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with empagliflozinmay be present even if blood glucose levels are less than 250 mg/dL. Ifketoacidosis is suspected, empagliflozin should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Treatment ofketoacidosis may require insulin, fluid and carbohydrate replacement.

Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and include dnausea, vomiting, abdominal pain, generalized malaise, and shortness of breath.

Before initiating empagliflozin,consider factors in the patient history that may predispose to ketoacidosisincluding pancreatic insulin deficiency from any cause, caloric restriction,and alcohol abuse. In patients treated with empagliflozin consider monitoringfor ketoacidosis and temporarily discontinuing empagliflozin in clinicalsituations known to predispose to ketoacidosis (e.g., prolonged fasting due toacute illness or surgery).

Acute Kidney Injury and Impairmentin Renal Function: empagliflozin causes intravascular volume contraction and can cause renal impairment. There have been post marketing reports of acutekidney injury, some requiring hospitalization and dialysis, in patientsreceiving SGLT2 inhibitors, including empagliflozin; some reports involvedpatients younger than 65 years of age.

Before initiating empagliflozin,consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure andconcomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). If acutekidney injury occurs, discontinue empagliflozin promptly and institute treatment.

Empagliflozin increases serumcreatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function abnormalities can occur after initiating empagliflozin. Renal function should be evaluated prior to initiationof empagliflozin and monitored periodically thereafter. More frequent renalfunction monitoring is recommended in patients with an eGFR below 60mL/min/1.73 m2.

Urosepsis and Pyelonephritis: There have been post marketing reports of serious urinary tract infections includingurosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including empagliflozin. Treatment with SGLT2 inhibitorsincreases the risk for urinary tract infections. Evaluate patients for signs andsymptoms of urinary tract infections and treat promptly.

Genital Mycotic Infections: this drug increases the risk for genital mycotic infections. Patients with a history of chronic or recurrent genital mycotic infections were more likely to developmycotic genital infections. Monitor and treat as appropriate.

Increased Low-Density Lipoprotein Cholesterol (LDL-C): Increases in LDL-C can occur with this drug.Monitor and treat as appropriate.

8.DRUG INTERACTIONS:

Diuretics: Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

Insulin or Insulin Secretagogues: Coadministration of empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. Therefore, a lower dose of the insulinsecretagogue or insulin may be required to reduce the risk of hypoglycemia whenused concomitantly.

Positive Urine Glucose Test:Monitoring glycemic control with urine glucose tests is not recommended inpatients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucoseexcretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemiccontrol.

Interference with 1, 5-anhydroglucitol(1,5-AG) Assay: Monitoring glycemic control with this assay is not recommendedas measurements of it are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

9.Adverse Reactions:

Adverse Reactions Reported in 2% of Patients in clinical trials:

Urinary tract infection, Femalegenital mycotic infections (vulvovaginal mycotic infection, vaginal infection, vulvitis,vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis,urogenital infection fungal, vaginitis bacterial), Upper respiratory tractinfection, Increased urination, Dyslipidemia, Arthralgia, Male genital mycoticinfections (balanoposthitis, balanitis, genital infections fungal,genitourinary tract infection, balanitis candida, scrotal abscess, penile infection), Nausea.

Other adverse reactions:

Thirst (including polydipsia), VolumeDepletion (empagliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volumedepletion), Hypoglycemia (The incidence of hypoglycemia increased whenempagliflozin was administered with insulin or sulfonylurea), Increase inHematocrit.

Pregnancy:

Based on animal data showing adverse renal effects, this drug is not recommended during the second and thirdtrimesters of pregnancy.

Limited data available with this drug in pregnant women are not sufficient to determine a drug-associated risk for major birth defects and miscarriage.

Lactation:

There is no information regarding the presence of this drug in human milk.

Because of the potential for serious adverse reactions in infant, advise women that use of this drug is not recommended while breastfeeding.

Pediatric Use:

The safety and effectiveness of this drug in pediatric patients under 18 years of age have not been established.

Geriatric Use:

No dosage change is recommended based on age. This drug is expected to have diminished glycemic efficacy in elderly patients with renal impairment.

Renal Impairment:

The efficacy and safety of this drug have not been established in patients with severe renal impairment, with ESRD, or receiving dialysis.

Hepatic Impairment

This drug may be used in patients with hepatic impairment.

OVER DOSAGE

In the event of an overdose, the Poison Control Center should be contacted. Employ the usual supportive measures(e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment) as dictated by thepatient’s clinical status. Removal of empagliflozin by hemodialysis has not been studied.

Storage conditions:

store at 25 °C

Packaging:

pack of 20 or 30 F.C Tablets .