Dapagliflozin + Metformin


Concise Prescribing Info
Indications/Uses
Type 2 diabetes mellitus.
Dosage/Direction for Use
Adult : PO Each conventional tab contains dapagliflozin (mg)/metformin (mg): 5/850, 5/1,000: 1 tab bid based on patient’s current regimen, effectiveness, and tolerability. Each extended-release tab contains dapagliflozin (mg)/metformin (mg): 2.5/1,000, 5/500, 5/1,000, 10/500, 10/1,000: 1 tab once daily based on patient’s current regimen, effectiveness, and tolerability. Max: Dapagliflozin 10 mg and metformin 2,000 mg daily.
Dosage Details
Oral
Type 2 diabetes mellitus
Adult: Available preparations:
Conventional tab:
Dapagliflozin 5 mg and metformin 850 mg
Dapagliflozin 5 mg and metformin 1,000 mg

Extended-release tab:
Dapagliflozin 2.5 mg and metformin 1,000 mg
Dapagliflozin 5 mg and metformin 500 mg
Dapagliflozin 5 mg and metformin 1,000 mg
Dapagliflozin 10 mg and metformin 500 mg
Dapagliflozin 10 mg and metformin 1,000 mg

1 tab bid (conventional) or once daily or bid based on patient’s current regimen, effectiveness, and tolerability. Max: Dapagliflozin 10 mg and metformin 2,000 mg daily.
Renal Impairment
CrCl (mL/min) Dosage
<60 Contraindicated.
Hepatic Impairment
Contraindicated.
Contraindications
Acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis, lactic acidosis), diabetic pre-coma, acute alcohol intoxication or alcoholism, 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 moderate to severe renal impairment (CrCl <60 mL/min). Lactation.
Special Precautions
Patient with risk factors for acute kidney injury, history of pancreatitis, bladder cancer, CHF, and those who are on stress-related state (e.g. fever, trauma, infection, surgery). Pregnancy. Not intended for the treatment of diabetic ketoacidosis or type 1 diabetes mellitus.
Adverse Reactions
Significant: Hypoglycaemia, bone fracture, genital mycotic infections, hypotension, ketoacidosis, increased LDL-C, acute renal impairment, urinary infections (e.g. urosepsis, pyelonephritis), vitamin B12 deficiency. Rarely, hypersensitivity reactions (e.g. angioedema, urticaria).
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Headache, taste disturbance, dizziness.
Renal and urinary disorders: UTI, increased urination.
Reproductive system and breast disorders: Vaginal moniliasis, vulvovaginitis, balanitis.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, cough.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Lactic acidosis, diabetic ketoacidosis.
MonitoringParameters
Monitor serum glucose, glycosylated HbA1c low-density lipoprotein-cholesterol (LDL-C), hepatic and renal function, haematologic parameters prior to initiation of therapy and periodically thereafter. Monitor vitamin B12 serum concentration, signs or symptoms of genital mycotic infection, UTI and metabolic acidosis.
Drug Interactions
Dapagliflozin: Increased risk of hypoglycaemia when used in combination with sulfonylureas or insulin. Increased risk of dehydration and hypotension when used with thiazides and loop diuretics.
Metformin: Increased serum concentration with cationic drugs that interfere with renal tubular transport systems (e.g. ranolazine, vandetanib, dolutegravir, cimetidine). Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers and isoniazid may produce hyperglycaemia which may lead to loss of glycaemic control. Increased risk of lactic acidosis with NSAIDs, ACE inhibitors, angiotensin II receptor antagonists and diuretics. May impair vitamin B12 absorption.
Potentially Fatal: Intravascular administration of iodinated contrast agents may cause renal dysfunction, leading to metformin-induced lactic acidosis.
Food Interaction
Alcohol may potentiate the effect of metformin on lactate metabolism.
Lab Interference
May cause false-positive result for urine glucose test. May interfere with 1,54-anhydrogluicitol (1,5-AG) assay.
Action
Description: Dapagliflozin is a reversible 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 the renal threshold for glucose. This results in an 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: Dapagliflozin: Rapidly and well absorbed from the gastrointestinal tract. Absolute bioavailability: 78%. Time to peak plasma concentration: Approx 2 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Reduced absorption if taken with food. Absolute bioavailability (fasting): Approx 50-60%. Time to peak plasma concentration: 2-3 hours (immediate-release); 7 hours (extended-release).
Distribution: Dapagliflozin: Volume of distribution: 118 L. Plasma protein binding: 91%.
Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and gastrointestinal tract. Crosses the placenta and enters breast milk in small amounts. Volume of distribution: 654 ± 358 L.
Metabolism: Dapagliflozin: Extensively metabolised in the liver and kidney by uridine diphosphonate glucuronosyltransferase (UGT)1A9 to an inactive metabolite (dapagliflozin 3-O-glucoronide); also undergoes CYP-mediated metabolism.
Excretion: Dapagliflozin: Via urine (75%, <2% as parent drug); faeces (21%, approx 15% as parent drug). Terminal elimination half-life: Approx 13 hours.
Metformin: Via urine (90% as unchanged drug). Plasma elimination half-life: 6.2 hours.
Chemical Structure

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Click on icon to see table/diagram/image
Storage
Store between 20-25°C.
MIMS Class
ATC Classification
A10BD15 - metformin and dapagliflozin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.
Disclaimer: This information is independently developed by MIMS based on Dapagliflozin + 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 © 2020 MIMS. All rights reserved. Powered by MIMS.com
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