【藥品性質提示】 ★LASA藥品：JAR01 Jardiance 錠劑 10mg (形似) 點擊看LASA藥品外觀比較圖

糖尿病 (SGLT2I / Metformin) Diabetes mellitus, type 2
#仿單變更2021

SGLT2 inhibitor/Anti-DM Biguanide

Empagliflozin Distribution: Vd 73.8 L
Protein binding: 86.2%
Metabolism: Primarily through glucuronidation by UGT2B7, UGT1A3, UGT1A8, and UGT1A9 to minor metabolites
Half-life Elimination: 12.4 hours
Time to Peak: 1.5 hours
Excretion: Urine (54.4%; 50% as unchanged drug); feces (41.2%; majority as unchanged drug)

Metformin Onset of action: Within days; maximum effects up to 2 weeks
Distribution: Vd: 654 ± 358 L; partitions into erythrocytes; concentrates in liver, kidney, and GI tract
Protein binding: Negligible
Metabolism: Not metabolized by the liver
Bioavailability: 50% to 60%
Half-life elimination: Plasma: 4 to 9 hours; Blood ~17.6 hours
Time to peak, serum: 2 to 3 hours (range: 4 to 8 hours)
Excretion: Urine (90% as unchanged drug; active secretion)

1. History of serious hypersensitivity to empagliflozin, metformin, or any component of the formulation<2021/5/27>
2. moderate to severe renal impairment (eGFR <45 mL/minute/1.73 m2)
3. end-stage renal disease (ESRD) or patients on dialysis
4. acute or chronic metabolic acidosis (including diabetic ketoacidosis)

Metformin crosses the placenta (ADA 2019).
Use of empagliflozin/metformin combination product is not recommended during the second and third trimesters.

Metformin is excreted into breast milk; excretion of empagliflozin is not known. Due to the potential for serious adverse reactions (eg. may affect renal function of infant) <2021/5/27> in the breastfed infant, the manufacturer does not recommend use of empagliflozin/metformin in women who are breastfeeding.

Empagliflozin

>10%:
Genitourinary: Urinary tract infection (9%; females: 18%; males: 4%)

1% to 10%:
Endocrine & metabolic: Dyslipidemia (4%), increased thirst (2%)
Gastrointestinal: Nausea (2%)
Genitourinary: Increased urine output (3%)
Hematologic & oncologic: Increased hematocrit (3% to 4%)
Infection: Genitourinary fungal infection (2% to 6%)

Frequency not defined:
Endocrine & metabolic: Increased LDL cholesterol

Metformin

>10%:
Gastrointestinal: Diarrhea (10% to 17%), nausea and vomiting (7%), flatulence (4% to 12%)
Infection: Infection (21%)

1% to 10%:
Cardiovascular: Chest discomfort, flushing, palpitations
Central nervous system: Headache (5% to 6%), chills, dizziness, taste disorder
Dermatologic: Diaphoresis, nail disease, skin rash
Endocrine & metabolic: Decreased vitamin B12 serum concentrate (7%), hypoglycemia
Gastrointestinal: Nausea (7% to 9%), dyspepsia (7%), abdominal distress (6%), abdominal pain (3% to 4%)

Warnings/Precautions

Genital mycotic infections: Empagliflozin may increase the risk of genital mycotic infections (eg, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). Patients with a history of these infections are at greater risk.

Ketoacidosis:
1. Risk factors: pancreatic insulin deficiency, dose decreases of insulin, caloric restriction, alcohol abuse, acute febrile illness, surgery<2021/5/27>, any other extreme stress event.
2. Discontinuation: Consider temporary discontinuation of therapy 3 days prior to surgery<2021/5/27> or any event which may precipitate ketoacidosis
3. Reinitiating: Ensure risk factors are resolved prior to reinitiating therapy.<2021/5/27>

Lactic acidosis:
1. Risk factors: renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), >65 years of age, having a radiologic study with contrast, surgery and other procedures, hypoxic states (eg, acute heart failure), excessive alcohol intake, and hepatic impairment.
2. Symptoms: The onset is often subtle, accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain); elevated blood lactate levels (>5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); increased lactate:pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Postmarketing cases have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.
3. Discontinue immediately if lactic acidosis is suspected; prompt hemodialysis is recommended.

Initial:
Individualize initial dose based on patient's current antidiabetic regimen. May gradually increase dose based on effectiveness and tolerability.
1. Patients on metformin: Empagliflozin 5 mg/day plus similar total daily dose of metformin
2. Patients on empagliflozin: Metformin 500 mg/day plus similar total daily dose of empagliflozin
Maximum:
Empagliflozin 25 mg/metformin 2,000 mg per day

Allow 1 to 2 weeks between dose titrations. Generally, clinically significant responses are not seen at doses less than 1,500 to 2,000 mg/day; however, a lower recommended starting dose with a gradual increase in dosage is recommended to minimize gastrointestinal symptoms.

1. eGFR >30 mL/minute/1.73 m²: No dosage adjustment necessary. Monitor renal function at least annually.
2. eGFR <30 mL/minute/1.73 m²<2021/10/13>: Use is contraindicated by the manufacturer; refer also to individual agents.
3. End-stage renal disease (ESRD), Dialysis: Use is contraindicated.

The manufacturer recommends avoiding metformin because liver disease is considered a risk factor for the development of lactic acidosis during metformin therapy. However, continued use of metformin in patients with diabetes with liver dysfunction, including cirrhosis, has been used successfully and may be associated with a survival benefit in carefully selected patients; use cautiously in patients at risk for lactic acidosis (eg, renal impairment, alcohol use)

Store at a controlled room temperature of 25 degrees C , with excursions permitted between 15 and 30 degrees C