Applies to empagliflozin / linagliptin / metformin: oral tablet extended release.

Get emergency medical help if you have signs of an allergic reaction: hives, itching, flaking or peeling skin; trouble swallowing, difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical attention right away if you have signs of a serious genital infection (penis or vagina): burning, itching, odor, discharge, pain, tenderness, redness or swelling of the genital or rectal area, fever, not feeling well. These symptoms may get worse quickly.

Stop taking this medicine and call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• severe or ongoing pain in your joints;

• lactic acidosis--unusual muscle pain, trouble breathing, stomach pain, vomiting, irregular heart rate, dizziness, feeling cold, or feeling very weak or tired;

• serious skin reaction--itching, blisters, breakdown of the outer layer of skin;

• ketoacidosis (too much acid in the blood)--nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing;

• pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting;

• dehydration--dizziness, confusion, feeling very thirsty, less urination;

• signs of a bladder infection--pain or burning when you urinate, blood in your urine, pain in pelvis or back; or

• symptoms of heart failure--shortness of breath (even while lying down), swelling in your legs or feet, rapid weight gain.

Common side effects may include:

• stomach pain, diarrhea, constipation;

• a bladder infection;

• headache; or

• cold symptoms such as runny or stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to empagliflozin/linagliptin/metformin: oral tablet extended release.

General

The most commonly reported adverse reactions have included upper respiratory tract infection, urinary tract infection, nasopharyngitis, diarrhea, constipation, headache, and gastroenteritis.^[Ref]

Metabolic

Dose-related increases in low-density lipoprotein cholesterol (LDL-C) were observed in patients treated with empagliflozin; increases of 2.3%, 4.6%, and 6.5% occurred in patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Mean baseline LDL-C level increases of 90.3 to 90.6 mg/dL were observed.

Empagliflozin/linagliptin/metformin:

-Uncommon (0.1% to 1%): Hypoglycemia

Empagliflozin:

-Common (1% to 10%): Dyslipidemia

-Postmarketing reports: Ketoacidosis

Linagliptin:

-Common (1% to 10%): Increased uric acid

Metformin:

-Common (1% to 10%): Subnormal vitamin B12 levels

-Postmarketing reports: Lactic acidosis

Empagliflozin, Linagliptin, or Metformin

-Postmarketing reports: Ketoacidosis

Renal

Empagliflozin:

-Frequency not reported: Increased serum creatinine, decreased eGFR

-Postmarketing reports: Acute kidney injury

Hypersensitivity

Linagliptin:

-Frequency not reported: Hypersensitivity (urticaria, angioedema, localized skin exfoliation, or bronchial hyperreactivity)

Empagliflozin, Linagliptin, or Metformin

-Postmarketing reports: Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions

Musculoskeletal

Empagliflozin:

-Common (1% to 10%): Arthralgia

Linagliptin:

-Frequency not reported: Myalgia

Empagliflozin, Linagliptin, or Metformin

-Postmarketing reports: Severe and disabling arthralgia, rhabdomyolysis

Dermatologic

Empagliflozin, Linagliptin, or Metformin

Postmarketing reports: Bullous Pemphigoid, skin reactions (e.g., rash, urticaria)

Gastrointestinal

Empagliflozin / linagliptin / metformin:

-Common (1% to 10%): Diarrhea, constipation, gastroenteritis

Empagliflozin:

-Common (1% to 10%): Nausea, thirst, polydipsia

Linagliptin:

-Common (1% to 10%): Increased lipase levels

-Postmarketing reports: Acute pancreatitis, including fatal pancreatitis

Metformin:

-Common (1% to 10%): Nausea, vomiting, flatulence, abdominal discomfort, indigestion

Empagliflozin, Linagliptin, or Metformin

-Postmarketing reports: Mouth ulceration, stomatitis

Cardiovascular

Empagliflozin / linagliptin / metformin:

-Common (1% to 10%): Volume depletion (hypotension, syncope)

Respiratory

Empagliflozin / linagliptin / metformin:

-Very common (10% or more): Upper respiratory tract infection (up to 10.3%)

-Common (1% to 10%): Nasopharyngitis

Linagliptin:

-Common (1% to 10%): Cough

Hepatic

Empagliflozin, Linagliptin, or Metformin

Postmarketing reports: Cholestatic, hepatocellular, and mixed hepatocellular liver injury

Other

Metformin:

-Common (1% to 10%): Asthenia

Hematologic

Empagliflozin:

-Common (1% to 10%): Increased hematocrit

Genitourinary

Empagliflozin / linagliptin / metformin:

-Very common (10% or more): Urinary tract infection (up to 10.2%)

Empagliflozin:

-Common (1% to 10%): Genital mycotic infections, increased urination, male genital infections

Empagliflozin, Linagliptin, or Metformin

-Postmarketing reports: Urosepsis, pyelonephritis, necrotizing fasciitis of the perineum (Fournier's gangrene)

Nervous system

Empagliflozin / linagliptin / metformin:

-Common (1% to 10%): Headache