Empagliflozin + Metformin


Generic Medicine Info
Indications and Dosage
Oral
Type 2 diabetes mellitus
Adult: Available preparations:
Conventional tab:
Empagliflozin 5 mg and metformin 500 mg
Empagliflozin 5 mg and metformin 850 mg
Empagliflozin 5 mg and metformin 1,000 mg
Empagliflozin 12.5 mg and metformin 500 mg
Empagliflozin 12.5 mg and metformin 850 mg
Empagliflozin 12.5 mg and metformin 1,000 mg

Extended-release tab:
Empagliflozin 5 mg and metformin 1,000 mg
Empagliflozin 10 mg and metformin 1,000 mg
Empagliflozin 12.5 mg and metformin 1,000 mg
Empagliflozin 25 mg and metformin 1,000 mg

1 tab bid (conventional) or once daily (extended-release) based on patient’s current regimen, effectiveness, and tolerability. Max: Empagliflozin 25 mg and metformin 2,000 mg daily.
Renal Impairment
Severe (GFR <30 mL/min): Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
Should be taken with food. Take w/ meals to reduce GI discomfort.
Contraindications
Diabetic pre-coma, acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis, lactic acidosis), alcoholism or acute alcohol intoxication, acute or chronic disease that may cause hypoxia (e.g. cardiac or respiratory failure, recent MI, shock), conditions which may alter renal function (e.g. severe infection, dehydration). Intravascular administration of iodinated contrast agents. Hepatic and severe renal impairment (GFR <30 mL/min), ESRD, patient on dialysis. Lactation.
Special Precautions
Patient with risk factors for acute kidney injury, congestive heart failure, history of pancreatitis, and those who are exposed to stress (e.g. infection, fever, trauma, surgery). Pregnancy. Not intended for the treatment of diabetic ketoacidosis or type 1 diabetes mellitus.
Adverse Reactions
Significant: Bone fracture, genital mycotic infections, hypersensitivity reactions (e.g. angioedema, rash, urticaria), hypotension, increased LDL-C, urinary infections (e.g. urosepsis, pyelonephritis); vitamin B12 deficiency, acute kidney impairment, hypoglycaemia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain.
Metabolism and nutrition disorders: Thirst, loss of appetite.
Musculoskeletal and connective tissue disorders: Arthralgia.
Nervous system disorders: Taste disturbance.
Renal and urinary disorders: Increased urination.
Reproductive system and breast disorders: Vaginal moniliasis, vulvovaginitis, balanitis.
Respiratory, thoracic and mediastinal disorders: Upper respiratory infection.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Potentially Fatal: Lactic acidosis, diabetic ketoacidosis.
Monitoring Parameters
Monitor glycosylated HbA1c, serum glucose, low-density lipoprotein-cholesterol (LDL-C), haematologic parameters, renal function at baseline and periodically thereafter. Monitor blood pressure, genital mycotic infection, vitamin B12 serum concentration; signs and symptoms of UTI and metabolic acidosis.
Drug Interactions
Empagliflozin: May potentiate diuretic effect and increased risk of hypotension with thiazides and loop diuretics. Increased plasma concentration with UGT enzyme inhibitor (e.g. probenecid). Increased risk of hypoglycaemia with insulin and sulfonylureas.
Metformin: Reduced efficacy with verapamil. Increased gastrointestinal absorption and efficacy with rifampicin. Increased plasma concentration with organic cation transporters (OCT) inhibitors (e.g. ranolazine, vandetanib, dolutegravir, cimetidine). Altered renal elimination with olaparib. Increased risk of lactic acidosis with topiramate or other carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, dichlorphenamide), NSAIDs, ACE inhibitors, angiotensin II receptor antagonists, diuretics. May impair vitamin B12 absorption.
Potentially Fatal: Intravascular administration of iodinated contrast may cause nephropathy and increased risk of metformin-induced lactic acidosis.
Food Interaction
Food decreases and slightly delays absorption. Alcohol may potentiate the effect of metformin on lactate metabolism.
Lab Interference
May cause false-positive result for urine glucose test. May interfere with 1,5-anhydrogluicitol (1,5-AG) assay.
Action
Description: Empagliflozin is an inhibitor of sodium-glucose co-transporter 2 (SGLT2), the main site of filtered glucose reabsorption in the proximal renal tubules, thus reducing reabsorption of filtered glucose and lowering of renal threshold for glucose resulting in increased urinary glucose excretion, thereby reducing glucose concentration in the blood.
Metformin is a biguanide antidiabetic agent that reduces hepatic glucose production by decreasing gluconeogenesis and glycogenolysis, decreases intestinal absorption of glucose and enhances insulin sensitivity by increasing peripheral utilisation and uptake of glucose.
Pharmacokinetics:
Absorption: Empagliflozin: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1.5 hours
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food decreases and slightly delays absorption. Absolute bioavailability: Approx 50-60%. Time to peak plasma concentration: 2-3 hours (immediate-release); 7 hours (extended-release).
Distribution: Empagliflozin: Volume of distribution:73.8 L. Plasma protein binding: 86.2%.
Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and GI tract. Crosses the placenta and enters breast milk (small amounts). Volume of distribution: 654 ± 358 L.
Metabolism: Empagliflozin: Metabolised via glucuronidation by uridine diphosphate glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9 to minor metabolites.
Excretion: Empagliflozin: Mainly via urine (54.4%, 50% as unchanged drug); faeces (41.2%, mostly as unchanged drug). Elimination half-life: 12.4 hours.
Metformin: Via urine (90% as unchanged drug). Plasma elimination half-life: 4-9 hours.
Chemical Structure

Chemical Structure Image
Empagliflozin

Source: National Center for Biotechnology Information. PubChem Database. Empagliflozin, CID=11949646, https://pubchem.ncbi.nlm.nih.gov/compound/Empagliflozin (accessed on Jan. 22, 2020)


Chemical Structure Image
Metformin

Source: National Center for Biotechnology Information. PubChem Database. Metformin, CID=4091, https://pubchem.ncbi.nlm.nih.gov/compound/Metformin (accessed on Jan. 20, 2020)

Storage
Store at 25°C.
MIMS Class
ATC Classification
A10BD20 - metformin and empagliflozin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.
References
Anon. Empagliflozin and Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/02/2018.

Anon. Empagliflozin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/02/2018.

Anon. Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/02/2018.

Buckingham R (ed). Empagliflozin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/02/2018.

Buckingham R (ed). Metformin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/02/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Empagliflozin. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/02/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Metformin Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/02/2018.

Synjardy Tab, Extended Release (Boehringer Ingelheim Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/02/2018.

Synjardy Tablet (Boehringer Ingelheim Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/02/2018.

Disclaimer: This information is independently developed by MIMS based on Empagliflozin + Metformin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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