قرص پگلیمت 5/500 میلی گرم

What is Paglimet?
Paglimet® is a prescription medication combining two antidiabetic agents: Empagliflozin and Metformin HCl. It can be used along with diet and exercise to improve blood sugar in adults and children ten years of age and older with type 2 diabetes. 
One of the medicines in Paglimet®, Empagliflozin, can also be used in adults with type 2 diabetes:
- Who have known cardiovascular disease to reduce the risk of cardiovascular death
- Who have heart failure to reduce the risk of cardiovascular death and hospitalization for heart failure

General Product Information
•    Pharmacologic Category
Empagliflozin: Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
Metformin: Antidiabetic Agent, Biguanide
 
•    Dosage Forms & Strengths
Immediate release tablet, oral:
o    5 mg Empagliflozin/ 500 mg Metformin HCl
o    5 mg Empagliflozin/ 1000 mg Metformin HCl
o    12.5 mg Empagliflozin/ 500 mg Metformin HCl
o    12.5 mg Empagliflozin/ 1000 mg Metformin HCl

•    Mechanism of Action
Empagliflozin: By inhibiting Sodium-Glucose Cotransporter 2 (SGLT2) in the proximal renal tubules, Empagliflozin reduces the reabsorption of filtered glucose from the tubular lumen. SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption results in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations. Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule, which may lower both the preload and afterload of the heart and downregulate sympathetic activity.

Metformin: It decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. 

•    Use: Labeled Indications
Diabetes mellitus, type 2, treatment
Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years of age with type 2 diabetes mellitus; risk reduction of cardiovascular mortality in adults with type 2 diabetes mellitus and established cardiovascular disease; risk reduction of cardiovascular mortality and hospitalization for heart failure in adults with type 2 diabetes mellitus and heart failure.

•    Dosing: Kidney Impairment

o    Adult
-    eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment is necessary. Monitor kidney function at least annually.
-    eGFR 30 to 45 mL/minute/1.73 m2: It is not recommended to initiate therapy.
-    eGFR <30 mL/minute/1.73 m2, end-stage renal disease, or dialysis: Use is contraindicated.
-    Acute kidney injury during therapy: If acute kidney injury occurs or risk factors are present (e.g., severe vomiting or diarrhea), instruct the patient to temporarily hold the medication due to the Metformin component.

o    Pediatric (Children ≥10 years and Adolescents)
-    eGFR >60 mL/minute/1.73 m2: No dosage adjustment is necessary.
-    eGFR 45 to <60 mL/minute/1.73 m2: No dosage adjustment is necessary based on the Metformin component; however, in pediatric trials with Empagliflozin, patients with eGFR <60 mL/minute/1.73 m2 were excluded.
-    eGFR 30 to 45 mL/minute/1.73 m2: Based on the Metformin component: Preexisting kidney impairment: Initiation of therapy is not recommended.
-    eGFR <30 mL/minute/1.73 m2, end-stage renal disease, or dialysis: Use is contraindicated.

•    Dosing: Liver Impairment
Empagliflozin may be used in patients with hepatic impairment. It is recommended to avoid Metformin because liver disease is considered a risk factor for the development of lactic acidosis during Metformin therapy; however, Metformin may be used depending on the severity of hepatic impairment. 

•    Administration: Adult
Oral: Administer immediate release tablets twice daily with meals. 

•    Warnings/ Precautions
o    Special populations:
-    Older adult: Use with caution; risk of Metformin associated lactic acidosis increases with age. The risk of intravascular volume contraction and symptomatic hypotension is also increased in older adults treated with Empagliflozin, especially if kidney function is compromised.

o    Other warnings/ precautions:
-    Appropriate use: Not for use in patients with diabetic ketoacidosis or for glycemic control in patients with type 1 diabetes mellitus.
-    Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate Metformin's effect on lactate metabolism.
-    Surgical procedures: Consider temporary discontinuation of Empagliflozin-containing products ≥3 days prior to surgery; ensure risk factors for ketoacidosis are resolved prior to reinitiating therapy.

•    Contraindications
-    Hypersensitivity (e.g., angioedema) to Empagliflozin, Metformin, or any component of the formulation
-    Severe renal impairment (eGFR <30 mL/minute/1.73 m2), end-stage renal disease (ESRD), or patients on dialysis
-    Acute or chronic metabolic acidosis (including diabetic ketoacidosis).

•    Drug Interactions
Risk X: Avoid combination
-    Alcohol (Ethyl): May enhance the adverse/toxic effect of Metformin. Specifically, excessive alcohol ingestion (acute or chronic) may potentiate the risk of lactic acidosis.
Risk D: Consider therapy modification
-    Cimetidine: May increase the serum concentration of Metformin. Management: Consider alternatives to cimetidine in patients receiving Metformin due to a potential for increased Metformin concentrations and toxicity (including lactic acidosis). 
-    Insulins: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. 
-    Iodinated Contrast Agents: May enhance the adverse/toxic effect of Metformin. Renal dysfunction that may be caused by iodinated contrast agents may lead to Metformin-associated lactic acidosis. 
-    Ranolazine: May increase the serum concentration of Metformin. Management: Limit the Metformin dose to a maximum of 1,700 mg per day when used together with ranolazine 1,000 mg twice daily. Monitor patients for Metformin toxicities, including lactic acidosis, and carefully weigh the risks and benefits of this combination. 
-    Sulfonylureas: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor and monitor patients for hypoglycemia. 

•    Pregnancy and Breastfeeding Considerations
It’s not recommended to use Empagliflozin/Metformin during the second and third trimesters or in patients who are breastfeeding.
Metformin crosses the placenta and is present in breast milk; excretion of Empagliflozin is not known.

FAQ
-    What happens if I miss a dose?
Take the medicine (with food) as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

-    What should I avoid while taking Paglimet®?
Avoid drinking alcohol. It may increase your risk of lactic acidosis.
Avoid getting up too fast from a sitting or lying position.

-    What other drugs will affect Paglimet®?
some drugs may increase or decrease the effects of Empagliflozin and Metformin on lowering your blood sugar. 
Tell your doctor about all your other prescription and over-the-counter medicines, vitamins, and herbal products, especially insulin or other oral diabetes medicines or a diuretic.