The active ingredient of GLUCOEMP is Empagliflozin, other blood glucose lowering drugsselective competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2).
Each Tablet contains 10mg/25mg of Empagliflozin.
Pack size: 10*10 Blisters.
Pharmacodynamic properties:
Pharmacotherapeutic group: Drugs used in diabetes, other blood glucose lowering drugs, and excl. insulin. Mechanism of action: Empagliflozin is a reversible, highly potent (IC50 of 1.3 nmol) and selective competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2). Empagliflozin does not inhibit other glucose transporters important for glucose transport into peripheral tissues and is 5000 times more selective for SGLT2 versus SGLT1, the major transporter responsible for glucose absorption in the gut. SGLT2 is highly expressed in the kidney, whereas expression in other tissues is absent or very low. It is responsible, as the predominant transporter, for the reabsorption of glucose from the glomerular filtrate back into the circulation. In patients with type 2 diabetes and Hyperglycemia a higher amount of glucose is filtered and reabsorbed.
Empagliflozin improves Glycaemic control in patients with type 2 diabetes by reducing renal glucose reabsorption. The amount of glucose removed by the kidney through this Glucuretic mechanism is dependent on blood glucose concentration and GFR. Inhibition of SGLT2 in patients with type 2 diabetes and Hyperglycaemia leads to excess glucose excretion in the urine. In addition, initiation of Empagliflozin increases excretion of sodium resulting in osmotic diuresis and reduced intravascular volume.
In patients with type 2 diabetes, urinary glucose excretion increased immediately following the first dose of Empagliflozin and is continuous over the 24 hour dosing interval. Increased urinary glucose excretion was maintained at the end of the 4-week treatment period, averaging approximately 78 g/day. Increased urinary glucose excretion resulted in an immediate reduction in plasma glucose levels in patients with type 2 diabetes.
Empagliflozin improves both fasting and post-prandial plasma glucose levels. The mechanism of action of Empagliflozin is independent of beta cell function and insulin pathway and this contributes to a low risk of Hypoglycemia. Improvement of surrogate markers of beta cell function including Homeostasis Model Assessment-β (HOMA-β) was noted. In addition, urinary glucose excretion triggers calorie loss, associated with body fat loss and body weight reduction. The Glucosuria observed with Empagliflozin is accompanied by diuresis which may contribute to sustained and moderate reduction of blood pressure. The Glucosuria, Natriuresis and Osmotic Diuresis observed with Empagliflozin may contribute to the improvement in cardiovascular outcomes.
Pharmacokinetic properties:
Absorption: The pharmacokinetics of Empagliflozin has been extensively characterized in healthy volunteers and patients with type 2 diabetes. After oral administration, Empagliflozin was rapidly absorbed with peak plasma concentrations occurring at a median tmax of 1.5 hours post-dose. Thereafter, plasma concentrations declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. The steady state mean plasma AUC and Cmax were 1870 nmol.h/l and 259 nmol/l with Empagliflozin 10 mg and 4740 nmol.h/l and 687 nmol/l with Empagliflozin 25 mg once daily. Systemic exposure of Empagliflozin increased in a dose-proportional manner. The single-dose and steady-state pharmacokinetic parameters of Empagliflozin were similar suggesting linear pharmacokinetics with respect to time. There were no clinically relevant differences in Empagliflozin pharmacokinetics between healthy volunteers and patients with type 2 diabetes. Administration of Empagliflozin 25 mg after intake of a high-fat and high calorie meal resulted in slightly lower exposure; AUC decreased by approximately 16% and Cmax by approximately 37% compared to fasted condition. The observed effect of food on Empagliflozin pharmacokinetics was not considered clinically relevant and Empagliflozin may be administered with or without food.
Distribution: The apparent steady-state volume of distribution was estimated to be 73.8 l based on the population pharmacokinetic analysis. Following administration of an oral. Empagliflozin solution to healthy volunteers, the red blood cell partitioning was approximately 37% and plasma protein binding was 86%.
Biotransformation: No major metabolites of Empagliflozin were detected in human plasma and the 4 most abundant metabolites were three Glucuronide conjugates (2-, 3-, and 6-O Glucuronide). Systemic exposure of each metabolite was less than 10% of total drug-related material. In vitro studies suggested that the primary route of metabolism of Empagliflozin in humans is Glucuronidation by the Uridine 5'-Diphospho-GlucuronosylTransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9.
Elimination: Based on the population pharmacokinetic analysis, the apparent terminal elimination half-life of Empagliflozin was estimated to be 12.4 hours and apparent oral clearance was 10.6 l/hour. The inter-subject and residual variabilities for Empagliflozin oral clearance were 39.1% and 35.8%, respectively. With once-daily dosing, steady-state plasma concentrations of Empagliflozin were reached by the fifth dose. Consistent with the half-life, up to 22% accumulation, with respect to plasma AUC, was observed at steady-state. Following administration of an oral .Empagliflozin solution to healthy volunteers, approximately 96% of the drug-related radioactivity was eliminated in faeces (41%) or urine (54%). The majority of drug-related radioactivity recovered in faeces was unchanged parent drug and approximately half of drug related radioactivity excreted in urine was unchanged parent drug.
Pharmacodynamic interactions:
Diuretics: Glucoemp may add to the diuretic effect of Thiazide and Loop Diuretics and may increase the risk of Dehydration and Hypotension.
Insulin and Insulin Secretagogues: Insulin and Insulin Secretagogues, such as Sulphonylureas, may increase the risk of Hypoglycemia. Therefore, a lower dose of insulin or an insulin Secretagogue may be required to reduce the risk of Hypoglycemia when used in combination with Glucoemp.
Pharmacokinetic interactions:
-treatment with known inducers of UGT enzymes should be avoided due to a potential risk of decreased efficacy.
Effects of Glucoemp on other medicinal products: Based on in vitro studies, Glucoemp does not inhibit, inactivate, or induce CYP450 isoforms.
Glucoemp does not inhibit UGT1A1, UGT1A3, UGT1A8, UGT1A9, or UGT2B7. Drug-drug interactions involving the major CYP450 and UGT isoforms with Glucoemp and concomitantly administered substrates of these enzymes are therefore considered unlikely.
Glucoemp does not inhibit P-gp at therapeutic doses. Based on in vitro studies, Glucoemp is considered unlikely to cause interactions with active substances that are P-gp substrates. Co-administration of digoxin, a P-gp substrate, with Glucoemp resulted in a 6% increase in AUC and 14% increase in Cmax of digoxin. These changes were not considered to be clinically meaningful.
It is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and
As monotherapy when Metformin is considered inappropriate due to intolerance
In addition to other medicinal products for the treatment of diabetes.
Special populations:
Renal impairment: Due to the mechanism of action, the Glycaemic efficacy of Glucoemp is dependent on renal function. No dose adjustment is required for patients with an eGFR ≥60 ml/min/1.73 m2 or CrCl ≥60 ml/min.
Glucoemp should not be initiated in patients with an eGFR < 60 ml/min/1.73 m2 or CrCl < 60 ml/min. In patients tolerating Empagliflozin whose eGFR falls persistently below 60 ml/min/1.73 m2 or CrCl below 60 ml/min, the dose of Empagliflozin should be adjusted to or maintained at 10 mg once daily. Glucoemp should be discontinued when eGFR is persistently below 45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min.
Glucoemp should not be used in patients with end stage renal disease (ESRD) or in patients on dialysis as it is not expected to be effective in these patients.
Hepatic Impairment: No dose adjustment is required for patients with Hepatic Impairment. Glucoemp exposure is increased in patients with severe Hepatic Impairment. Therapeutic experience in patients with severe Hepatic Impairment is limited and therefore not recommended for use in this population.
Elderly: No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for volume depletion should be taken into account. In patients aged 85 years and older, initiation of Glucoemp therapy is not recommended due to the limited therapeutic experience.
Pediatrics population: The safety and efficacy of Glucoemp in children and adolescents has not yet been established. No data are available.
Method of administration:
The tablets can be taken with or without food, swallowed whole with water. If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day.
Possible signs of severe allergic reaction may include:
These are the signs of diabetic ketoacidosis
Contact your doctor as soon as possible if you notice the following side effects:
Low blood sugar (hypoglycemia), seen very commonly (may affect more than 1 in 10 people)
If you take Glucoemp with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher.
The signs of low blood sugar may include:
Urinary tract infection, seen commonly (may affect up to 1 in 10 people)
The signs of urinary tract infection are:
An urge to pass urine or more frequent urination may be due to the way Empagliflozin works, but they can also be signs of urinary tract infection.
Dehydration, seen uncommonly (may affect up to 1 in 100 people)
The signs of dehydration are not specific, but may include:
Other side effects while taking Glucoemp:
Common
Uncommon
Not known
Diabetic Ketoacidosis: Rare cases of diabetic ketoacidosis (DKA), including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including Glucoemp. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below14 mmol/l (250 mg/dl). It is not known if DKA is more likely to occur with higher doses of Glucoemp.
The risk of Diabetic Ketoacidosis must be considered in the event of non-specific symptoms such as Nausea, Vomiting, Anorexia, Abdominal pain, excessive thirst, difficulty breathing, confusion, unusual Fatigue or sleepiness. Patients should be assessed for Ketoacidosis immediately if these symptoms occur, regardless of blood Glucose level. In patients where DKA is suspected or diagnosed, treatment with Glucoemp should be discontinued immediately.
Before initiating Glucoemp, factors in the patient history that may predispose to ketoacidosis should be considered. Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT-2 inhibitor treatment is not recommended.
Renal impairment: Glucoemp should not be initiated in patients with an eGFR below 60 ml/min/1.73 m2 or CrCl < 60 ml/min. In patients tolerating Empagliflozin whose eGFR is persistently below 60 ml/min/1.73 m2 or CrCl < 60 ml/min, the dose of Glucoemp should be adjusted to or maintained at 10 mg once daily. Glucoemp should be discontinued when eGFR is persistently below 45 ml/min/1.73 m2 or CrCl persistently below 45 ml/min. Glucoemp should not be used in patients with ESRD or in patients on dialysis as it is not expected to be effective in these patients.
Monitoring of renal function: Due to the mechanism of action, the Glycaemic efficacy of Glucoemp is dependent on renal function.
Hepatic injury: Cases of hepatic injury have been reported with Glucoemp in clinical trials. A causal relationship between Glucoemp and hepatic injury has not been established.
Elevated Haematocrit: Haematocrit increase was observed with Glucoemp treatment.
Risk for volume depletion: Based on the mode of action of SGLT-2 inhibitors, osmotic diuresis accompanying therapeutic Glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients for whom an Empagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older.
In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status (e.g. physical examination, blood pressure measurements, laboratory tests including Haematocrit) and electrolytes is recommended for patients receiving Glucoemp. Temporary interruption of treatment with Glucoemp should be considered until the fluid loss is corrected.
Elderly: The effect of Glucoemp on urinary glucose excretion is associated with osmotic diuresis, which could affect the hydration status. Patients aged 75 years and older may be at an increased risk of volume depletion. A higher number of these patients treated with Glucoemp had adverse reactions related to volume depletion as compared to placebo .Therefore, special attention should be given to their volume intake in case of co-administered medicinal products which may lead to volume depletion (e.g. Diuretics, ACE-inhibitors). Therapeutic experience in patients aged 85 years and older is limited. Initiation of Glucoemp therapy in this population is not recommended.
Urinary Tract Infections: In a pool of placebo-controlled double-blind trials of 18 to 24 weeks duration, the overall frequency of urinary tract infection reported as adverse event was similar in patients treated with Glucoemp 25 mg and placebo and higher in patients treated with Glucoemp 10 mg .Post-marketing cases of complicated urinary tract infections including pyelonephritis and Urosepsis have been reported in patients treated with Glucoemp. Temporary interruption of Glucoemp should be considered in patients with complicated urinary tract infections.
Lower limb amputations: An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with another SGLT2 inhibitor. It is unknown whether this constitutes a class effect. Like for all diabetic patients it is important to counsel patients on routine preventative foot-care.
Cardiac failure: The reduction of cardiovascular death in these patients was consistent with the overall study population.
Urine laboratory assessments: Due to its mechanism of action, patients taking Glucoemp will test positive for glucose in their urine.
Pregnancy: There are no data from the use of Glucoemp in pregnant women. Animal studies show that Empagliflozin crosses the placenta during late gestation to a very limited extent but do not indicate direct or indirect harmful effects with respect to early embryonic development. However, animal studies have shown adverse effects on postnatal development. As a precautionary measure, it is preferable to avoid the use of Glucoemp during pregnancy.
Breast-feeding: No data in humans are available on excretion of Empagliflozin into milk. Available toxicological data in animals have shown excretion of Empagliflozin in milk. A risk to the newborns/infants cannot be excluded. Glucoemp should not be used during breast-feeding.
Fertility: No studies on the effect on human fertility have been conducted for Empagliflozin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility