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.

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 Contraindications and Warnings:

It is contraindicated or should be used with caution in the following group of patients:

• Hypersensitivity:

Allergy to the drug, Empagliflozin, or its ingredients of it. Allergic reactions may be mild in which cases, it can be used with caution. In severe cases such as angioedema, it should be avoided.

• Type 1 and diabetic ketoacidosis:

Patients with low pancreatic reserves are more likely to develop ketoacidosis, even though their plasma glucose level is below 250 mg/dl. This is known as euglycemic ketoacidosis.

• 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 and monitor/ adjust diabetes medications when they are started on Empagliflozin.

• Dialysis, or advanced renal disease:

It is contraindicated in 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. 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 checked 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 death if not recognized early in the course of the disease.

• Hypoglycemia and Hyperglycemia:

Patients who are prone to develop hypoglycemia like those with adrenal, thyroid, and pituitary diseases should take the drug with caution. Patients with these conditions should start on a lower dose at first. In addition, it can cause hypoglycemia when combined with insulin or other potent diabetes drugs.

Hyperglycemia can also occur if a person is switched from a potent diabetes drug to Jardiance, which has intermediate efficacy according to ADA. In addition, conditions that predispose patients to develop hyperglycemia like burns, hyperthyroidism, surgery, and infections may alter its efficacy.

Hyperglycemia can be caused by drug interactions, hormonal changes in females, psychological stress, and endocrine disorders as well. Patients with these conditions should have their blood glucose monitored more often.

• Hypercholesterolemia:

Jardiance use is associated with lipid abnormalities. It causes an increase in LDL and Triglycerides and a decrease in HDL. Patients might need to adjust statin doses or seek out alternative therapies such as a GLP-1 analog like Ozempic, a DPP-IV like Sitagliptin/ Vildagliptin, or a Sulfonylurea like Glipizide.

After starting therapy, monitor and treat LDL-C according to the recommendations.

• Older people:

Older patients should use it with caution, as there are greater risks of adverse reactions.

• Pregnancy:

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

Empagliflozin (Jardiance) dose in adults:

• 10 mg taken orally once daily, preferably in the morning, with or without a meal.
• If glycemic goals are not met, the dose may be increased to 25 mg once daily.

The maximum daily dose is 25 mg.

Empagliflozin Use in Children:

Dapagliflozin got approved for use in children and obese type 1 diabetic patients by the European Commission and NICE. However, this recommendation has been recently withdrawn. Empagliflozin has not been approved for use in children. 

Empagliflozin dosage in Renal disease:

With a creatinine clearance of greater than 45 ml/min, no dosage change is necessary. If the creatinine clearance falls to < 45 ml/minute but is above 30 ml/minute, Empagliflozin can be given with caution.

Patients with a creatinine clearance of under 30 ml/min should avoid it.

Jardiance Dose in liver disease:

No dose adjustment is necessary.

How to take Empagliflozin?

You can take the drug with or without meals, but it is best to take it in the morning as you may need to pee more than usual after taking Jardiance.

Empagliflozin Pregnancy Category C 

Using it while pregnant is not advised, especially in the second and third trimesters. Mothers who are nursing should also avoid taking it.

Side effects of empagliflozin (Jardiance):

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

Monitor:

• Blood Glucose
• Renal functions (Urea, creatinine, and uric acid)
• 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.

 Empagliflozin (Jardiance) Mechanism of action:

It inhibits the sodium-glucose transporter 2 (SGLT2) within the proximal renal tubes, inhibiting glucose reabsorption from the kidneys. When glucose is lost in the urine, it also results in a loss of water, resulting in osmotic diuresis and dehydration.

This may prove beneficial for hypertensive patients, those suffering from cardiac disease or fluid overload. However, it can cause dehydration in patients already taking diuretics or those working in hot weather.

It can also lead to recurrent infections of the urinary tract, as well as genital infections which may sometimes be very severe and necessitate treatment discontinuation.

Pharmacokinetics of Empagliflozin:

Empagliflozin Brands:

• Jardiance (Boehringer-Ingelheim)

Empagliflozin in combination with metformin:

• Glyxambi
• Synjardy,
• Synjardy XR

Empagliflozin in combination with Linagliptin and Metformin XR:

• TRIJARDY XR

Empagliflozin brands in Pakistan:

• Diampa (Getz Pharma)
• Diampa-M (empagliflozin + metformin)
• Empa (Horizon)
• Jardy (CCL)
• 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.)

Check prices in Pakistan here: https://wa.me/message/HV6M3JGTA6RJB1