Empagliflozin ( Jardiance, Jardy, Diampa) – Dose, Side effects, Brands

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582
empagliflozin brands worldwide

Empagliflozin (Jardiance) is used to treat adults with type 2 diabetes mellitus. It belongs to the SGLT2 inhibitor class of anti-diabetic medicines.

It acts by inhibiting the filtered glucose from the renal tubules back into the circulation. This results in the loss of calories, loss of fluid, and sodium from the body.

It thus reduces the extra fluid from the body, apart from improving hyperglycemia. It reduces the risk of cardiovascular death in patients with established cardiovascular disease.

Other drugs belonging to the same class (SGLT 2 inhibitors) are Dapagliflozin, canagliflozin, and ertugliflozin.

The efficacy of Jardiance in the treatment of Diabetes Mellitus in Comparison with Metformin, Placebo, and other Diabetes Medicines

Empagliflozin metformin & Empagliflozin, linagliptin, & metformin Combinations:

Empagliflozin is available as a single drug and in combination with metformin (Synjardy).

It has recently been approved as a triple combination regimen by the name of TRIJARDY XR that contains empagliflozin, linagliptin, and metformin extended-release.

Compared to sitagliptin, empagliflozin is associated with significantly lower cardiovascular-related mortality, all-cause mortality, and hospitalizations due to heart failure [Ref].

It is also associated with significantly greater weight loss and is more cost-effective [Ref].

Empagliflozin (Jardiance) dose in adults:

  • 10 mg orally once daily with or without food, preferably in the morning.
  • The dose may be increased to 25 mg orally once daily if glycemic targets are not achieved.
  • The maximum dose is 25 mg per day.

 

Empagliflozin Use in Children:

Dapagliflozin has recently been approved for use in children and obese type 1 diabetic patients by the European Commission and NICE.

Empagliflozin has not been approved for use in children.

 

Empagliflozin dose in Renal disease:

No dosage adjustment needed with a creatinine clearance of more than 45 ml/min. Patients with a creatinine clearance of less than 45 ml/min and more than 30 ml/min may be given the drug with caution

It is contraindicated in patients with a creatinine clearance of less than 30 ml/min.

 

Jardiance Dose in liver disease:

No dose adjustment is necessary.

 

Empagliflozin Pregnancy Category C 

It is not recommended to use during pregnancy, especially in the second and third trimesters.

It should not be advised to breastfeeding mothers.

 

Empagliflozin Contraindications and Warnings:

It is contraindicated in the following group of patients:

Allergies:

  • Patients who are allergic to empagliflozin or any of its ingredients. Individuals who have a history of prior allergic reactions in the form of angioedema.

T1DM:

  • Type 1 Diabetes and patients with diabetic ketoacidosis. Patients with low pancreatic reserves are more likely to develop ketoacidosis, even though their plasma glucose level may be lower than 250 mg/dl. This is known as euglycemic ketoacidosis. Euglycemic ketoacidosis can occur with any SGLT2 inhibitors.

Dehydration, volume depletion, and hypotension:

  • Because SGLT2 inhibitors prevent glucose absorption from your kidneys, they can also cause fluid loss and osmotic dilution. If patients are taking diuretics or ACE inhibitors concurrently, hypotension may occur.
  • Patients should be instructed to drink adequate fluids while on treatment. It is better to withhold the drug during episodes of illnesses that may result in fluid loss or dehydration such as those with nausea, vomiting, and diarrhea.

Dialysis, or advanced renal disease:

  • It is contraindicated in individuals with severe renal impairment, defined as a creatinine clearance below 30ml/min/1.73m2, end-stage renal failure, and dialysis patients.
  • Acute renal failure can also be caused by volume contraction, hence SGLT2 inhibitors can exacerbate the condition.
  • After initiating treatment, patients should be checked for signs of renal dysfunction.

Recurrent urinary tract infections, and urogenital infections including severe tissue necrosis:

  • Patients with diabetes are more likely to get genitourinary infections. These infections should be treated if patients experience flank pain, fever, burning micturition, and urgency.
  • It has been associated with severe genital infections such as Necrotizing fasciitis, which can lead to fatalities.

Hypoglycemia:

  • Patients who are prone to developing hypoglycemia like those with adrenal, thyroid, and pituitary diseases should take the drug with caution.
  • Patients with these conditions should be started on a lower dose at first. The dose may be then titrated to the desired response.

Avoid in stressful conditions:

  • Conditions that predispose patients to develop hyperglycemia like burns, hyperthyroidism, surgery, and infections may alter its efficacy. Such patients should best be treated with insulin.
  • Hyperglycemia can be also be caused by drug interactions, hormonal changes in females, psychological stress, and endocrine disorders. Patients with these conditions should have their blood glucose monitored more often.

Hypercholesterolemia:

  • Hypercholesterolemia and an increase in LDL-C may occur with SGLT2 inhibitors. It is important to be cautious when initiating treatment in patients who have risk conditions such as advanced atherosclerosis, cardiovascular diseases, and peripheral arterial diseases. Patients might need to adjust their statin doses if they are already on a statin or seek out alternative diabetes medications.
  • After starting therapy, monitor and treat LDL-C according to the recommendations.

Geriatric patients:

  • Older patients should use empagliflozin with caution, as there are greater risks of adverse reactions. These adverse reactions may include hypotension, fluid depletion, hypoglycemia, dyslipidemia, and urogenital infections.

Pregnancy:

  • It is not recommended for pregnant women, lactating mothers, or children under 18 years old as the drug has not yet been extensively studied in this population.

 

Severe side effects of empagliflozin (Jardiance):

  • Rapid:

    • Angioedema
  • Early:

    •  Tissue necrosis
  • Delayed:

    • Phimosis,
    • diabetic ketoacidosis,
    • renal failure,
    • necrotizing fasciitis

Empagliflozin Side effects (Moderate):

  • Rapid:

    • Hypotension
  • Early:

    • Hypovolemia and
    • Hypoglycemia
  • Delayed: 

    • Cystitis,
    • Hypercholesterolemia,
    • candidiasis,
    • vaginitis,
    • hyperlipidemia,
    • balanitis, and
    • dehydration

Jardiance side effects (Mild):

  • Rapid:

    • Urticaria
  • Early:

    • Rash,
    • Syncope,
    • Diuresis,
    • Nocturia,
    • Nausea,
    • Polydipsia,
    • Polyuria, and
    • Increased urinary frequency
  • Delayed:

    • Infections,
    • Pharyngitis,
    • Arthralgias, and
    • Orthostatic hypotension

 

Empagliflozin: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use
    Risk Factor C (Monitor therapy)
    Alpha-Lipoic Acid May enhance the hypoglycemic effect of Antidiabetic Agents.
    Androgens May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol.
    Direct Acting Antiviral Agents (HCV) May enhance the hypoglycemic effect of Antidiabetic Agents.
    Guanethidine May enhance the hypoglycemic effect of Antidiabetic Agents.
    Hyperglycemia-Associated Agents May diminish the therapeutic effect of Antidiabetic Agents.
    Hypoglycemia-Associated Agents Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
    Loop Diuretics Empagliflozin may enhance the hypotensive effect of Loop Diuretics.
    Maitake May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Monoamine Oxidase Inhibitors May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Pegvisomant May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Prothionamide May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Quinolones May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use.
    Ritodrine May diminish the therapeutic effect of Antidiabetic Agents.
    Salicylates May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Selective Serotonin Reuptake Inhibitors May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
    Teriflunomide May increase the serum concentration of OAT3 Substrates.
    Thiazide and Thiazide-Like Diuretics May diminish the therapeutic effect of Antidiabetic Agents.
    Risk Factor D (Consider therapy modification)
    Insulins Sodium-Glucose Cotransporter 2 (SLGT2) 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.
    Sulfonylureas Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia.
    Tolvaptan May increase the serum concentration of OAT3 Substrates.

 

Monitor:

  • Glycemic control,
  • urea & creatinine
  • volume status of the patient and lipid profile.
  • Patients with deep breathing and symptoms of hyperglycemia like polyuria and polydipsia should be investigated for diabetic ketoacidosis.

 

How to take Empagliflozin?

You can take the drug with or without meals, but it is best to do so in the morning.

 

Empagliflozin (Jardiance) Mechanism of action:

It inhibits sodium-glucose transporter 2 (SGLT2) within the proximal renal tubes. It also inhibits glucose reabsorption from the kidneys. Osmotic diuresis is when excess glucose is eliminated via the kidneys.

This may prove beneficial for hypertensive patients, those suffering from cardiac disease or fluid overload. It can also lead to recurrent infections of the urinary tract, volume depletion, and dehydration.

Pharmacokinetics:

It can be taken orally. 86.2% of it is protein-bound, and it is metabolized by glucuronidation.

Half-life is estimated to be 12.4 hours.

Affected cytochrome P450 (CYP450) enzymes and drug transporters: None

Peak plasma concentrations (Cmax): 1.5 hours post-dose.

 

Empagliflozin Brands (International):

Jardiance (Boehringer-Ingelheim)

Empagliflozin in combination with metformin:

  • Glyxambi
  • Synjardy,
  • Synjardy XR

Empagliflozin in combination with Linaglipptin and Metformin XR:

 

Empagliflozin brands in Pakistan:

Diampa (Getz Pharma)

14 tablets pack:

10 mg: Rs. 266

25 mg: Rs. 336

Diampa-M (empagliflozin + metformin)

12.5/1000 mg: Rs. 308


Empa (Horizon)

14 tablets Pack

10 mg: Rs. 238


Jardy (CCL)

14 tablets pack

10 mg: Rs. 275

25 mg: Rs. 383


Xenglu 10 & 25 mg

Xenglu-met 10/500 mg, 10/850 mg, 12.5/1000 mg, 25/1000 mg


Empozin 10 & 25 mg


Erli 10 & 25 mg (Pharmevo PVT LTD.)