EMPALIN 10MG/5MG TABLET

Indications

• Type 2 diabetes mellitus as monotherapy (if metformin is inappropriate)
• Type 2 diabetes mellitus in combination with insulin or other antidiabetic drugs (if existing treatment fails to achieve adequate glycaemic control)
• Symptomatic chronic heart failure

Dosage

Adults: 10 mg once daily, increased to 25 mg once daily if necessary and tolerated.

Mechanism of action

Empagliflozin inhibits the SGLT2 transporters in the proximal tubules of the kidneys. By blocking the co-transport of sodium and glucose into the blood, it increases glucosuria, leading to lower blood glucose levels. Additionally, it may offer cardiovascular benefits by mechanisms yet to be fully elucidated, including effects on myocardial sodium/hydrogen exchangers and diuretic actions.

Pharmacodynamics

Empagliflozin effectively reduces blood glucose levels through increased urinary glucose excretion, necessitating once-daily dosing due to its prolonged action. Patients should be monitored for ketoacidosis, as it can occur even in the absence of significantly elevated blood glucose. The drug also poses a risk of urogenital infections due to the elevated glucose levels in urine.

Pharmacokinetics

Empagliflozin is absorbed after oral administration, with peak plasma concentrations occurring within 1.5 hours. It has a volume of distribution of approximately 73 liters and is primarily excreted via urine. Renal function should be monitored, as impaired renal function may affect drug efficacy and safety.

Contra-indications

• Diabetic ketoacidosis
• Severe renal impairment (eGFR < 30 mL/min)
• Hypersensitivity to empagliflozin or any of the excipients

Adverse effects

• Genital infections
• Urinary tract infections
• Dehydration
• Hypotension
• Diabetic ketoacidosis (rare)
• Fournier's gangrene (necrotizing fasciitis of the genitalia)

Interactions

• Antiepileptics (unknown effect on exposure)
• Rifamycins (unknown effect on exposure)
• Insulin and insulin secretagogues (may require dose adjustments)

Precautions

• Monitor for signs of diabetic ketoacidosis, particularly in patients with risk factors
• Consider temporary interruption in patients with complicated urinary tract infections
• Caution in elderly patients due to risk of hypotension and volume depletion
• Monitor renal function periodically

Pregnancy

Empagliflozin is not recommended during pregnancy due to potential risks to the fetus. Consult a healthcare provider for alternatives.

Breast-feeding

Empagliflozin is not recommended for use while breastfeeding. The effects on a nursing infant are unknown.

Storage

Store below 30°C. Protect from moisture. Keep out of reach of children.

Formulations

• Tablets: 10 mg, 25 mg

Indications

• Type 2 diabetes mellitus
• Hyperglycemia in patients inadequately controlled on diet and exercise alone

Dosage

Children: Safety and efficacy in children have not been established; therefore, linagliptin is not recommended for use in patients under 18 years of age.

Adults: The usual recommended dose of linagliptin is 5 mg once daily, taken orally, with or without food.

Mechanism of action

Linagliptin is a competitive, reversible DPP-4 inhibitor. By inhibiting DPP-4, linagliptin slows the degradation of incretin hormones, specifically GLP-1 and GIP. This leads to increased insulin secretion from pancreatic beta cells in a glucose-dependent manner and decreased glucagon secretion from alpha cells. These actions together promote lower hepatic glucose output and improved glycemic control.

Pharmacodynamics

A 5mg oral dose of linagliptin results in more than 80% inhibition of DPP-4 for at least 24 hours. This inhibition leads to elevated levels of GLP-1, which correlates with decreased glycosylated hemoglobin (HbA1c) and lower fasting plasma glucose levels, contributing to effective management of blood glucose levels in patients with type 2 diabetes.

Pharmacokinetics

Linagliptin is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 1.5 hours post-dose. It has a long half-life of around 12 hours, allowing for once-daily dosing. Linagliptin is extensively distributed in the body and is primarily metabolized by the liver, with minimal renal excretion, which means it does not require dose adjustments in patients with renal impairment.

Contra-indications

• Hypersensitivity to linagliptin or any of its excipients
• Type 1 diabetes mellitus
• Diabetic ketoacidosis

Adverse effects

• Hypoglycemia
• Nausea
• Diarrhea
• Abdominal pain
• Headache
• Upper respiratory tract infections
• Pancreatitis

Interactions

• May enhance the hypoglycemic effect of other antidiabetic medications
• Concomitant use with strong CYP3A4 inducers may reduce linagliptin effectiveness

Precautions

• Renal impairment may require dose adjustment
• Monitor for signs of pancreatitis
• Use with caution in patients with a history of severe allergic reactions

Pregnancy

Limited data on the use of linagliptin in pregnancy. Animal studies have shown no harm, but its safety has not been established in pregnant women.

Breast-feeding

It is not known if linagliptin is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature (20-25°C). Protect from moisture.

Formulations

• Tablets: 5 mg

Mechanism of action

The vast majority of glucose filtered through the glomerulus is reabsorbed within the proximal tubule, primarily via SGLT2 (sodium-glucose linked co-transporter-2) which is responsible for ~90% of the total glucose reabsorption within the kidneys. Na⁺/K⁺-ATPase on the basolateral membrane of proximal tubular cells utilize ATP to actively pump Na+ ions into the interstitium surrounding the tubule, establishing a Na⁺ gradient within the tubular cell. SGLT2 on the apical membrane of these cells then utilize this gradient to facilitate secondary active co-transport of both Na+ and glucose out of the filtrate, thereby reabsorbing glucose back into the blood – inhibiting this co-transport, then, allows for a marked increase in glucosuria and decrease in blood glucose levels. Empagliflozin is a potent inhibitor of renal SGLT2 transporters located in the proximal tubules of the kidneys and works to lower blood glucose levels via an increase in glucosuria. Empagliflozin also appears to exert cardiovascular benefits - specifically in the prevention of heart failure - independent of its blood glucose-lowering effects, though the exact mechanism of this benefit is not precisely understood. Several theories have been posited, including the potential inhibition of Na⁺/H⁺ exchanger (NHE) 1 in the myocardium and NHE3 in the proximal tubule, reduction of pre-load via diuretic/natriuretic effects and reduction of blood pressure, prevention of cardiac fibrosis via suppression of pro-fibrotic markers, and reduction of pro-inflammatory adipokines.

Pharmacodynamics

Empagliflozin lowers blood glucose levels by preventing glucose reabsorption in the kidneys, thereby increasing the amount of glucose excreted in the urine. It has a relatively long duration of action requiring only once-daily dosing. Patients should be monitored closely for signs and symptoms of ketoacidosis regardless of blood glucose level as empagliflozin may precipitate diabetic ketoacidosis in the absence of hyperglycemia. As its mechanism of action is contingent on the renal excretion of glucose, empagliflozin may be held in cases of acute kidney injury and/or discontinued in patients who develop chronic renal disease. The overexcretion of glucose creates a sugar-rich urogenital environment which increases the risk of urogenital infections in both male and female patients - monitor closely for signs and symptoms of developing infection.

Mechanism of action

Linagliptin is a competitive, reversible DPP-4 inhibitor. Inhibition of this enzyme slows the breakdown of GLP-1 and glucose-dependant insulinotropic polypeptide (GIP). GLP-1 and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic beta cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose. Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta-cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha-cells, resulting in a reduction in hepatic glucose output.

Pharmacodynamics

A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose.