Synjardy XR Side Effects
Generic name: empagliflozin / metformin
Medically reviewed by Drugs.com. Last updated on Jul 26, 2023.
Note: This document contains side effect information about empagliflozin / metformin. Some dosage forms listed on this page may not apply to the brand name Synjardy XR.
Applies to empagliflozin / metformin: oral tablet, oral tablet extended release.
Oral route (Tablet; Tablet, Extended Release)
Lactic AcidosisPostmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally greater than 5 mcg/mL. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.If metformin-associated lactic acidosis is suspected, immediately discontinue empagliflozin/metformin hydrochloride and institute general supportive measures in the hospital setting. Prompt hemodialysis is recommended.
Serious side effects of Synjardy XR
Along with its needed effects, empagliflozin / metformin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking empagliflozin / metformin:
- Bladder pain
- bloody or cloudy urine
- blurred vision
- cool, pale skin
- decreased appetite
- difficult, burning, or painful urination
- fast heartbeat
- fast, shallow breathing
- feeling sad or empty
- frequent urge to urinate
- general feeling of discomfort
- increased hunger
- lack of appetite
- loss of consciousness
- loss of interest or pleasure
- lower back or side pain
- muscle pain or cramping
- slurred speech
- stomach discomfort
- trouble concentrating
- trouble sleeping
- unusual tiredness or weakness
- Bad-smelling discharge from the penis
- itching of the vagina or genitals
- itching, stinging, or redness of the vaginal area
- redness, itching, swelling, or pain of the penis
- thick, white vaginal discharge with mild or no odor
Incidence not known
- Dark urine
- decreased frequency or amount of urine
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- dry mouth
- flushed, dry skin
- fruit-like breath odor
- increased thirst
- itching, skin rash
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
- light-colored stools
- pain, tenderness, redness, or swelling of the area between the anus and genitals
- redness of the skin
- stomach pain, continuing
- unexplained weight loss
- weight gain
- yellow eyes or skin
Other side effects of Synjardy XR
Some side effects of empagliflozin / metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
- Bloated or feeling of fullness
- excess air or gas in stomach or bowels
- passing gas
- stomach discomfort
For Healthcare Professionals
Applies to empagliflozin / metformin: oral tablet, oral tablet extended release.
Empagliflozin: The most frequently reported side effects included urinary tract infections and female genital mycotic infections.
Metformin: The most frequently reported side effects included diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.[Ref]
Empagliflozin is known to cause osmotic diuresis, leading to intravascular volume contraction and adverse reactions related to volume depletion. Adverse reactions related to volume depletion such as decreased ambulatory/systolic blood pressure, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope were reported in 0.5% and 0.3% of patients receiving empagliflozin 10 mg (n=999) or 25 mg (n=977) orally once a day, respectively.[Ref]
Uncommon (0.1% to 1%): Hypotension, orthostatic hypotension, syncope, decreased systolic blood pressure, decreased ambulatory blood pressure[Ref]
During a 24 week study of empagliflozin in combination with metformin plus a sulfonylurea, urinary tract infections (UTIs) were reported in 9.4% and 6.9% of patients receiving empagliflozin 10 mg (n=224) or 25 mg (n=217) once a day, respectively. Pooled data from 5 studies showed the incidence of UTIs (e.g., UTI, asymptomatic bacteriuria, and cystitis), was increased in empagliflozin-treated patients compared to placebo, more frequent in females compared to males, and more likely to occur in patients with a history of chronic or recurrent UTIs. Treatment discontinuation due to UTIs occurred in 0.2% and 0.1% of patients receiving empagliflozin 10 mg or 25 mg once a day, respectively.
In the 5 years (2013 to 2018) since SGLT2 inhibitor approval, 12 cases of Fournier's gangrene have been reported. Reports were almost equal in men and women (men=7; women=5), ages ranged from 38 to 78 years, and the average time to onset after starting an SGLT2 inhibitor was 9.2 months (range 7 days to 25 months). All SGLT2 inhibitor drugs except ertugliflozin were included in the reports. Ertugliflozin being the most recently approved agent, is expected to have the same risk, but insufficient patient use to assess risk. All patients were hospitalized, all required surgery, all required surgical debridement, 5 required more than 1 surgery and 1 required skin grafting. Four cases were complicated by diabetic ketoacidosis, acute kidney injury, and septic shock, leading to prolonged hospitalization, and death in 1 case. In the general population, Fournier's gangrene occurs in about 1.6 out of 100,000 males annually, with the highest incidence in men 50 to 79 years. Since diabetes is a risk factor for Fournier's gangrene, a review of the FAERS database for the last 34 years was done and only 6 cases (all males, median age 57 years) were found with several other classes of antidiabetic drugs. Findings with SGLT2 inhibitors appear to show an association over a shorter time frame and involve both males and females.[Ref]
Common (1% to 10%): Urinary tract infections
Common (1% to 10%): Urinary tract infections, female genital mycotic infections, male genital mycotic infections, increased urination (e.g., polyuria, pollakiuria, and nocturia)
Uncommon (0.1% to 1%): Dysuria
Rare (less than 0.1%): Phimosis
Postmarketing reports: Urosepsis, pyelonephritis, Fournier's gangrene[Ref]
The frequency of hypoglycemia depended on the type of background therapy used. When empagliflozin was used as monotherapy, hypoglycemia was reported in 0.4% of patients taking the 10 mg and 25 mg doses. In combination with metformin, hypoglycemia was reported in 1.8% taking 10 mg and 1.4% taking 25 mg. In combination with metformin and a sulfonylurea, hypoglycemia was reported in 16.1% taking the 10 mg dose and 11.5% taking the 25 mg dose. In combination with basal insulin, hypoglycemia was reported in 19.5% taking the 10 mg dose and 28.4% taking the 25 mg dose.
Twenty reports of acidosis, including diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT-2 inhibitors have been identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database during the period March 2013 through 06 June 2014. All patients required emergency room treatment or hospitalization. These cases were not typical of ketoacidosis or DKA in that they occurred in patients with type 2 diabetes and their blood sugar levels were only slightly increased. Some factors identified as potentially triggering the acidosis included major illness, reduced food and fluid intake, and reduced insulin dose.[Ref]
Very common (10% or more): Hypoglycemia (15.6%)
Common (1% to 10%): Dyslipidemia, polydipsia, increased LDL-C
Uncommon (0.1% to 1%): Dehydration, hypovolemia, hypoglycemia
Frequency not reported: Increased serum creatinine
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis
Very rare (less than 0.01%): Lactic acidosis[Ref]
Common (1% to 10%): Pruritus
Postmarketing reports: Skin reactions (e.g., rash, urticaria)
Very rare (less than 0.01%): Erythema, urticaria[Ref]
Common (1% to 10%): Nausea
Common (1% to 10%): Nausea, vomiting, diarrhea, flatulence, abdominal discomfort, indigestion[Ref]
Common (1% to 10%): Increased hematocrit
Common (1% to 10%): Subnormal vitamin B12 levels
Postmarketing reports: Hematologic reactions possibly related to subnormal Vitamin B12 levels[Ref]
Very rare (less than 0.01%): Hepatitis, abnormal liver function tests
Postmarketing reports: Cholestatic, hepatocellular, mixed hepatocellular liver injury[Ref]
Common (1% to 10%): Arthralgia[Ref]
Common (1% to 10%): Headache, taste disturbances
Postmarketing reports: Neurologic reactions possibly related to subnormal Vitamin B12 levels[Ref]
Postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, have been received for patients treated with SGLT2 inhibitors including empagliflozin. Some reports involved patients younger than 65 years old.[Ref]
Frequency not reported: Decreased eGFR
Postmarketing reports: Acute Kidney Injury[Ref]
Common (1% to 10%): Nasopharyngitis
Common (1% to 10%): Upper respiratory tract infection[Ref]
Common (1% to 10%): Asthenia[Ref]
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Related treatment guides
1. Cerner Multum, Inc. UK Summary of Product Characteristics.
2. Cerner Multum, Inc. Australian Product Information.
3. Product Information. Synjardy (empagliflozin-metformin). Boehringer Ingelheim. 2015.
4. FDA. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM618466.pdf 2018.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.