Empagliflozin and metformin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For empagliflozin and metformin, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to empagliflozin and metformin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of empagliflozin and metformin combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of empagliflozin and metformin combination in the elderly. However, elderly patients are more likely to have kidney problems, which may require caution and an adjustment in the dose for patients receiving empagliflozin and metformin combination.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using empagliflozin and metformin.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking empagliflozin and metformin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using empagliflozin and metformin with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Acetrizoic Acid
• Diatrizoate
• Ethiodized Oil
• Iobenzamic Acid
• Iobitridol
• Iocarmic Acid
• Iocetamic Acid
• Iodamide
• Iodipamide
• Iodixanol
• Iodohippuric Acid
• Iodopyracet
• Iodoxamic Acid
• Ioglicic Acid
• Ioglycamic Acid
• Iohexol
• Iomeprol
• Iopamidol
• Iopanoic Acid
• Iopentol
• Iophendylate
• Iopromide
• Iopronic Acid
• Ioseric Acid
• Iosimide
• Iotasul
• Iothalamate
• Iotrolan
• Iotroxic Acid
• Ioxaglate
• Ioxitalamic Acid
• Ipodate
• Metrizamide
• Metrizoic Acid
• Tyropanoate Sodium

Using empagliflozin and metformin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aspirin
• Balofloxacin
• Besifloxacin
• Bupropion
• Ciprofloxacin
• Dasabuvir
• Dofetilide
• Dolutegravir
• Enoxacin
• Fleroxacin
• Flumequine
• Gatifloxacin
• Gemifloxacin
• Ioversol
• Lanreotide
• Levofloxacin
• Lomefloxacin
• Moxifloxacin
• Nadifloxacin
• Norfloxacin
• Octreotide
• Ofloxacin
• Ombitasvir
• Paritaprevir
• Pasireotide
• Pazufloxacin
• Pefloxacin
• Pioglitazone
• Prulifloxacin
• Ritonavir
• Rufloxacin
• Sparfloxacin
• Thioctic Acid
• Tosufloxacin
• Vandetanib

Using empagliflozin and metformin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Atenolol
• Betaxolol
• Bisoprolol
• Bitter Melon
• Carteolol
• Carvedilol
• Celiprolol
• Esmolol
• Fenugreek
• Furazolidone
• Glucomannan
• Guar Gum
• Iproniazid
• Isocarboxazid
• Labetalol
• Levobunolol
• Linezolid
• Methylene Blue
• Metipranolol
• Metoprolol
• Moclobemide
• Nadolol
• Nebivolol
• Nialamide
• Oxprenolol
• Patiromer
• Penbutolol
• Phenelzine
• Pindolol
• Practolol
• Procarbazine
• Propranolol
• Psyllium
• Ranolazine
• Rasagiline
• Rifampin
• Safinamide
• Selegiline
• Sotalol
• Timolol
• Tranylcypromine
• Verapamil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of empagliflozin and metformin. Make sure you tell your doctor if you have any other medical problems, especially:

• Adrenal gland problem (underactive) or
• Alcohol abuse, history of or
• Cardiovascular collapse (shock) or
• Congestive heart failure or
• Dehydration, severe or
• Heart attack, acute or
• Pancreatic insulin deficiency, history of or
• Pituitary gland problem (underactive) or
• Poorly nourished condition or
• Sepsis (severe infection) or
• Weakened physical condition—Use with caution. May cause side effects to become worse.

• Anemia (low red blood cells) or
• Dehydration or
• Genital yeast (fungus) infection (eg, balanitis, balanoposthitis, vulvovaginitis), history of or
• Hypercholesteremia (high levels of cholesterol) or
• Hypotension (low blood pressure) or
• Hypovolemia (low blood volume) or
• Kidney disease or
• Urinary tract infections (eg, pyelonephritis, urosepsis), history of or
• Vitamin B12 deficiency—Use with caution. May make these conditions worse.

• Diabetic ketoacidosis (high ketones and acid in the blood) or
• Kidney disease, moderate to severe or
• Liver disease or
• Metabolic acidosis (acid in the blood) or
• Patients receiving dialysis or
• Type I diabetes—Should not be used in patients with these conditions.

• Fever or
• Infection or
• Surgery or
• Trauma—Use with caution. These conditions may cause problems with blood sugar control.

• Empagliflozin/Metformin HCl
• Metformin and Empagliflozin

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Synjardy: Empagliflozin 5 mg and metformin hydrochloride 500 mg, Empagliflozin 5 mg and metformin hydrochloride 1000 mg, Empagliflozin 12.5 mg and metformin hydrochloride 500 mg, Empagliflozin 12.5 mg and metformin hydrochloride 1000 mg [contains corn starch]

Tablet Extended Release 24 Hour, Oral:

Synjardy XR: Empagliflozin 5 mg and metformin hydrochloride 1000 mg, Empagliflozin 10 mg and metformin hydrochloride 1000 mg [scored]

Synjardy XR: Empagliflozin 25 mg and metformin hydrochloride 1000 mg, Empagliflozin 12.5 mg and metformin hydrochloride 1000 mg [scored; contains fd&c blue #2 aluminum lake]

Empagliflozin: By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, empagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

Metformin: Decreases hepatic glucose production, decreases intestinal absorption of glucose, improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Note: If present, correct volume depletion prior to initiation.

Diabetes mellitus, type 2: Oral:

Initial: Individualize initial dose based on patient's current antidiabetic regimen. May gradually increase dose based on effectiveness and tolerability.

Patients on metformin: Empagliflozin 10 mg/day plus similar total daily dose of metformin, administered in 2 divided doses (immediate release) or once daily (extended release)

Patients on empagliflozin: Metformin 1,000 mg/day plus similar total daily dose of empagliflozin, administered in 2 divided doses (immediate release) or once daily (extended release)

Maximum: Empagliflozin 25 mg/metformin 2,000 mg per day, administered in 2 divided doses (immediate release) or once daily (extended release).

Concomitant use with insulin and/or insulin secretagogues (eg, sulfonylureas): Reduced dose of insulin and/or insulin secretagogues may be needed.

Blood glucose, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change (ADA 2017a); LDL-C; renal function (baseline and annually thereafter or when clinically indicated); volume status (eg, blood pressure, hematocrit, electrolytes); hematologic parameters (annually); blood pressure; genital mycotic infections, urinary tract infections, and vitamin B12 (periodically with long term therapy); folate (if megaloblastic anemia is suspected); signs and symptoms of metabolic acidosis

Metformin crosses the placenta. Use of empagliflozin/metformin combination product is not recommended during the second and third trimesters. Refer to individual monographs.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flatulence, loss of strength or energy, headache, rhinitis, or pharyngitis. Have patient report immediately to prescriber signs of dehydration (dry skin, dry mouth, dry eyes, increased thirst, tachycardia, dizziness, fast breathing, or confusion), signs of acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), vaginal yeast infection, penile yeast infection, severe dizziness, passing out, or severe abdominal pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m2 ) or ESRD: Use is contraindicated

IODINATED CONTRAST PROCEDURE:
-Stop this drug at time of, or prior to, an iodinated contrast imaging procedure for patients with an eGFR between 45 and 60 mL/min/1.73 m2 .
-Stop this drug in patients who will be administered intra-arterial iodinated contrast.
-Stop this drug in patients with a history of hepatic impairment, alcoholism, or heart failure.
-Reevaluate eGFR 48 hours after the imaging procedure; this drug may be restarted once adequate renal function is confirmed.

Avoid use in patients with clinical or laboratory evidence of hepatic disease.