|COMPOSITION||:||Each film-coated tablet contains 25 mg of Empagliflozin|
|EXCIPIENTS||:||Tablet core: Lactose monohydrate, Microcrystalline cellulose, Hydroxypropylcellulose, Croscarmellose sodium, Colloidal anhydrous silica, Magnesium stearate
Film coating: Hypromellose, Titanium dioxide, Talc, Macrogol (400), Iron oxide yellow.
|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 an inhibitor of SGLT2. By inhibiting SGLT2, empagliflozin reduces renal reabsorption 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 terminal elimination half-life of empagliflozin was estimated to be 12.4 h. Following administration of an oral [14C]-empagliflozin solution to healthy subjects, approximately (41.2%) was eliminated in feces and (54.4%) in urine.
|Indications||:||Diacol 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 diabetic ketoacidosis.
|Dosage & 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.
Diacol should be discontinued if eGFR is less than 45 mL/min/1.73 m2.
|Contraindications||:||• History of serious hypersensitivity reaction to Diacol.
• Severe renal impairment, end-stage renal disease, or dialysis.
|Warnings & precautions||:||Hypotension: Diacol causes intravascular volume contraction. Symptomatic hypotension may occur after initiating of empagliflozin particularly in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Before initiating this drug, assess for volume contraction and correct volume status if indicated. Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected.
Ketoacidosis: Fatal cases of ketoacidosis have been reported in patients taking Diacol. Empagliflozin is not indicated for the treatment of patients with type 1diabetes mellitus. Patients treated 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 empagliflozin may be present even if blood glucose levels are less than 250 mg/dL. If ketoacidosis is suspected, empagliflozin should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement.
Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath.
Before initiating Diacol, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with Diacol consider monitoring for ketoacidosis and temporarily discontinuing Diacol in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).
Acute Kidney Injury and Impairment in Renal Function: Diacol causes intravascular volume contraction and can cause renal impairment. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors, including empagliflozin; some reports involved patients younger than 65 years of age.
Before initiating Diacol, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). If acute kidney injury occurs, discontinue Diacol promptly and institute treatment.
Empagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function abnormalities can occur after initiating Diacol. Renal function should be evaluated prior to initiation of empagliflozin and monitored periodically thereafter. More frequent renal function monitoring is recommended in patients with an eGFR below 60 mL/min/1.73 m2.
Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including Diacol. Treatment withSGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms 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 develop mycotic 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.
|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 insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used concomitantly.
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 this assay is not recommended as measurements of it are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.
|Adverse Reactions||:||Adverse Reactions Reported in 2% of Patients in clinical trials:
Urinary tract infection, Female genital mycotic infections (vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, fungal genital infection, genitourinary tract infection, vulvovaginitis, cervicitis, fungal urogenital infection, vaginitis bacterial), Upper respiratory tract infection, Increased urination, Dyslipidemia, Arthralgia, Male genital mycotic infections (balanoposthitis, balanitis, fungal genital infections, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection), Nausea.
Other adverse reactions:
Thirst (including polydipsia), Volume Depletion (empagliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion), Hypoglycemia (The incidence of hypoglycemia increased when empagliflozin was administered with insulin or sulfonylurea), Increase in Hematocrit.
|Pregnancy||:||Based on animal data showing adverse renal effects, this drug is not recommended during the second and third trimesters 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. Diacol 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||:||Diacol may be used in patients with hepatic impairment.
|OVERDOSAGE||:||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 the patient’s clinical status. Removal of empagliflozin by hemodialysis has not been studied.|
|STORAGE CONDITIONS||:||Store at temperature between (15-30) °C.|
|PACKAGING||:||Diacol 25: 20 film coated tablets packed in 2 PVC/Aluminum blisters inside a carton box with a leaflet.|