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Synjardy is a brand name for Empagliflozin. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE SYNJARDY SYNJARDY is a combination of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor and metformin hydrochloride (HCl) immediate-release, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. 1 ) Individualize the starting dosage based on the patient's current regimen and renal function.
4 ) The maximum recommended dosage is 25 mg/day of empagliflozin and 2,000 mg/day of metformin HCl. 73 m 2 , due to the metformin HCl component. 4 ) SYNJARDY: take orally twice daily with meals, with gradual dosage escalation to reduce the gastrointestinal adverse reactions due to metformin HCl.
3 ) SYNJARDY XR: take orally once daily with a meal in the morning, with gradual dosage escalation to reduce the gastrointestinal adverse reactions due to metformin HCl. Swallow whole; do not split, crush, dissolve, or chew. 2 ) SYNJARDY or SYNJARDY XR may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.
5 ) Withhold SYNJARDY or SYNJARDY XR at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. 3) ] . Assess volume status. 6) ] . 2 Recommended Dosage and Administration of SYNJARDY or SYNJARDY XR in Adults When switching to SYNJARDY or SYNJARDY XR from: Metformin HCl: initiate SYNJARDY or SYNJARDY XR at a similar total daily dosage of metformin HCl and a total daily empagliflozin dosage of 10 mg.
Empagliflozin: initiate SYNJARDY or SYNJARDY XR at the same total daily dosage of empagliflozin and a total daily metformin HCl dosage of 1,000 mg. Empagliflozin and metformin HCl: initiate SYNJARDY or SYNJARDY XR at the same total daily dosages of each component.
Recommended dosage of SYNJARDY or SYNJARDY XR:
The recommended total daily dosage of empagliflozin is 10 mg. 1) ]. Take SYNJARDY orally twice daily with meals. Take SYNJARDY XR orally once daily with a meal in the morning. Swallow each tablet whole. Do not split, crush, dissolve, or chew.
3 Recommended Dosage and Administration of SYNJARDY in Pediatric Patients Aged 10 Years and Older Individualize the dosage of SYNJARDY based on the patient's current regimen. Monitor effectiveness and tolerability, and adjust dosage as appropriate, not to exceed the maximum total daily dosage of empagliflozin 25 mg and metformin HCl 2,000 mg .
8) ] Most common adverse reactions associated with empagliflozin (5% or greater incidence) were urinary tract infections and female genital mycotic infections. 1 ) Most common adverse reactions associated with metformin HCl (>5%) are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.
1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of concomitantly administered empagliflozin (daily dosage 10 mg or 25 mg) and metformin HCl (mean daily dosage of approximately 1,800 mg) has been evaluated in 3,456 adult patients with type 2 diabetes mellitus treated for 16 to 24 weeks, of which 926 patients received placebo, 1,271 patients received a daily dosage of empagliflozin 10 mg, and 1,259 patients received a daily dosage of empagliflozin 25 mg.
9% for placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Adverse Reactions in a Clinical Trial with Empagliflozin (Add-On Combination Therapy with Metformin HCl and Sulfonylurea) for Glycemic Control in Adults with Type 2 Diabetes Mellitus In a 24-week placebo-controlled trial of empagliflozin 10 mg or 25 mg administered once daily added to metformin HCl and sulfonylurea, adverse reactions reported in ≥5% of empagliflozin-treated patients and more commonly than in placebo-treated patients are presented in Table 1 (see also Table 4 ).
0 Empagliflozin Clinical Trials in Adults with Type 2 Diabetes Mellitus The data in Table 2 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with basal insulin in adult patients with type 2 diabetes mellitus.
5 WARNINGS AND PRECAUTIONS Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk of ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue SYNJARDY or SYNJARDY XR if ketoacidosis is suspected.
Monitor patients for resolution of ketoacidosis before restarting. 2 ) Volume Depletion: Before initiating SYNJARDY or SYNJARDY XR, assess volume status and renal function in patients with impaired renal function, elderly patients, or patients on loop diuretics.
Monitor for signs and symptoms during therapy. 3 ) Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections: Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated.
Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis and if suspected, discontinue SYNJARDY or SYNJARDY XR, and promptly institute appropriate medical and/or surgical intervention.
4 ) Hypoglycemia: Adult patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher regardless of insulin use. Consider lowering the dosage of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating SYNJARDY or SYNJARDY XR.
5 ) Lower Limb Amputation: Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment. , angioedema) have occurred with empagliflozin. If hypersensitivity reactions occur, discontinue SYNJARDY or SYNJARDY XR, treat promptly, and monitor until signs and symptoms resolve.
6) ]. 1) ]. 7) ] . 73 m 2 ) ( 4 ) Metabolic acidosis, including diabetic ketoacidosis ( 4 ) Hypersensitivity to empagliflozin, metformin HCl or any of the excipients in SYNJARDY or SYNJARDY XR ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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1) ]. 73 m 2 , due to the metformin HCl component. 6) ] . 73 m 2 ; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. 1) ] . 6 Temporary Interruption for Surgery Withhold SYNJARDY or SYNJARDY XR for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting.
2) ] . 7 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose.
1) ] . These data reflect exposure of 1,976 adult patients to empagliflozin with a mean exposure duration of approximately 23 weeks. Patients received placebo (N=995), empagliflozin 10 mg (N=999), or empagliflozin 25 mg (N=977) once daily.
The mean age of the population was 56 years and 3% were older than 75 years of age. More than half (55%) of the population was male; 46% were White, 50% were Asian, and 3% were Black or African American. At baseline, 57% of the population had diabetes mellitus more than 5 years and had a mean hemoglobin A1c (HbA1c) of 8%.
Established microvascular complications of diabetes mellitus at baseline included diabetic nephropathy (7%), retinopathy (8%), or neuropathy (16%). 73 m 2 ). Table 2 shows adverse reactions (excluding hypoglycemia) that were not present at baseline, occurred more commonly in empagliflozin-treated patients than placebo-treated patients, and occurred in greater than or equal to 2% of empagliflozin-treated patients.
Table 2 Adverse Reactions Reported in ≥2% of Adults with Type 2 Diabetes Mellitus Treated with Empagliflozin and Greater than Placebo in Pooled Placebo-Controlled Clinical Trials of Empagliflozin Monotherapy or Combination Therapy Adverse Reactions Placebo (%) N=995 Empagliflozin 10 mg (%) N=999 Empagliflozin 25 mg (%) N=977 a Predefined adverse event grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis b Female genital mycotic infections include the following adverse reactions: vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis, urogenital infection fungal, vaginitis bacterial.
Percentages calculated with the number of female subjects in each group as denominator: placebo (N=481), empagliflozin 10 mg (N=443), empagliflozin 25 mg (N=420). c Predefined adverse event grouping, including, but not limited to, polyuria, pollakiuria, and nocturia d Male genital mycotic infections include the following adverse reactions: balanoposthitis, balanitis, genital infections fungal, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection.
Percentages calculated with the number of male subjects in each group as denominator: placebo (N=514), empagliflozin 10 mg (N=556), empagliflozin 25 mg (N=557). 5% for placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.
Volume Depletion Empagliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. 3% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.
6) ]. , polyuria, pollakiuria, and nocturia) occurred more frequently on empagliflozin than on placebo (see Table 2 ). 8% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Hypoglycemia in Clinical Trials with Empagliflozin for Glycemic Control in Adults with Type 2 Diabetes Mellitus The incidence of hypoglycemia in adults by trial is shown in Table 3.
The incidence of hypoglycemia increased when empagliflozin was administered with insulin or sulfonylurea. 7% of patients randomized to placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. 2% of patients treated with either empagliflozin 10 mg or 25 mg.
Genital mycotic infections occurred more frequently in female than male patients (see Table 2 ). 1%) than placebo (0%). , urinary tract infection, asymptomatic bacteriuria, and cystitis) was increased in patients treated with empagliflozin compared to placebo (see Table 2 ).
Patients with a history of chronic or recurrent urinary tract infections were more likely to experience a urinary tract infection. 1% for placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Urinary tract infections occurred more frequently in female patients.
0%, respectively. 5) ] . 36). 3 events per 1,000 patient-years in the placebo, and empagliflozin 10 mg treatment arms, respectively. 2) ] . 7%). 1 years. 6% were aged 15 years and older. Approximately, 50% were White, 6% were Asian, 31% were Black or African American, and 38% were of Hispanic or Latino ethnicity.
0. Approximately 25% of the trial population had microalbuminuria or macroalbuminuria. The risk of hypoglycemia was higher in pediatric patients treated with empagliflozin regardless of concomitant insulin use. 5%) patients treated with empagliflozin and placebo, respectively.
No severe hypoglycemic events occurred (severe hypoglycemia was defined as an event requiring the assistance of another person to actively administer carbohydrates, glucagon or take other corrective actions). Adverse Reactions with Clinical Trials of Metformin HCl The most common (>5%) established adverse reactions due to initiation of metformin HCl therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.
2%). Pediatric Patients In clinical trials with metformin HCl immediate-release tablets in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults. Laboratory Test Abnormalities in Clinical Trials of Empagliflozin or Metformin HCl Empagliflozin Increases in Serum Creatinine and Decreases in eGFR: Initiation of empagliflozin causes an increase in serum creatinine and decrease in eGFR within weeks of starting therapy and then these changes stabilize.
In a trial of adults with moderate renal impairment, larger mean changes were observed. 73 m 2 , respectively, at Week 4, and reversed after treatment discontinuation, suggesting acute hemodynamic changes may play a role in the renal function changes observed with empagliflozin.
Increase in Low-Density Lipoprotein Cholesterol (LDL-C):
Dose-related increases in low-density lipoprotein cholesterol (LDL-C) were observed in adults treated with empagliflozin. 5% in patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. 6 mg/dL across treatment groups.
8% in empagliflozin 25 mg treated patients. 5% of patients with hematocrits initially within the reference range had values above the upper limit of the reference range with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.
Metformin HCl Decrease in Vitamin B 12 :
In metformin HCl clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients. 2 Postmarketing Experience Additional adverse reactions have been identified during postapproval use.
Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. , rash, urticaria) Metformin HCl Hepatobiliary Disorders: Cholestatic, hepatocellular, and mixed hepatocellular liver injury
7 ) Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematologic parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. 1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases.
These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension, and resistant bradyarrhythmias have occurred with severe acidosis.
Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:pyruvate ratio; metformin plasma levels generally >5 mcg/mL.
Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of SYNJARDY or SYNJARDY XR.
In SYNJARDY or SYNJARDY XR-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin is dialyzable, with a clearance of up to 170 mL/minute under good hemodynamic conditions).
Hemodialysis has often resulted in reversal of symptoms and recovery . Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to discontinue SYNJARDY or SYNJARDY XR and report these symptoms to their healthcare provider.
For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal Impairment: The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment.
The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. 3) ] : Before initiating SYNJARDY or SYNJARDY XR, obtain an estimated glomerular filtration rate (eGFR).
73 m 2 [see Contraindications (4) ]. Obtain an eGFR at least annually in all patients taking SYNJARDY or SYNJARDY XR. , the elderly), renal function should be assessed more frequently.
Drug Interactions:
The concomitant use of SYNJARDY or SYNJARDY XR with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance or increase metformin accumulation [see Drug Interactions (7) ] .
Therefore, consider more frequent monitoring of patients.
Age 65 or Greater:
The risk of metformin-associated lactic acidosis increases with the patient's age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. 5) ] .
Radiological Studies with Contrast:
Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. 73 m 2 ; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast.
Re-evaluate eGFR 48 hours after the imaging procedure, and restart SYNJARDY or SYNJARDY XR if renal function is stable.
Surgery and Other Procedures:
Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension and renal impairment. SYNJARDY or SYNJARDY XR should be temporarily discontinued while patients have restricted food and fluid intake.
Hypoxic States:
Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia.
When such events occur, discontinue SYNJARDY or SYNJARDY XR.
Excessive Alcohol Intake:
Alcohol potentiates the effect of metformin on lactate metabolism and this may increase the risk of metformin-associated lactic acidosis. Warn patients against excessive alcohol intake while receiving SYNJARDY or SYNJARDY XR.
Hepatic Impairment:
Patients with hepatic impairment have developed cases of metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore, avoid use of SYNJARDY or SYNJARDY XR in patients with clinical or laboratory evidence of hepatic disease.
2 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, empagliflozin, a component of SYNJARDY or SYNJARDY XR, significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate.
In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose co-transporter 2 (SGLT2) inhibitors compared to patients who received placebo and fatal ketoacidosis has occurred with empagliflozin.
SYNJARDY and SYNJARDY XR are not indicated for glycemic control in patients with type 1 diabetes mellitus. , history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including SYNJARDY or SYNJARDY XR.
Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.
Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. , less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected.
2) ] ; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation.
Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue SYNJARDY or SYNJARDY XR, promptly evaluate, and treat ketoacidosis, if confirmed.
Monitor patients for resolution of ketoacidosis before restarting SYNJARDY or SYNJARDY XR. Withhold SYNJARDY or SYNJARDY XR, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. 6) ] . Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue SYNJARDY or SYNJARDY XR and seek medical attention immediately if signs and symptoms occur.
1) ] . There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including empagliflozin. 73 m 2 ), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.
Before initiating SYNJARDY or SYNJARDY XR in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating SYNJARDY or SYNJARDY XR.
Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy. 1) ] . 2) ] . Cases have required hospitalization . In patients with Fournier's gangrene, serious outcomes have included multiple surgeries and death.
SYNJARDY and SYNJARDY XR are only indicated for use in patients with type 2 diabetes mellitus. Patients with a history of chronic or recurrent genitourinary infections are more likely to develop genitourinary infections when using SYNJARDY or SYNJARDY XR.
Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated. Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis.
If suspected, discontinue SYNJARDY or SYNJARDY XR and promptly institute appropriate medical and/or surgical intervention. 5 Hypoglycemia Insulin and insulin secretagogues are known to cause hypoglycemia. , sulfonylurea) or insulin. 1) ] .
The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications and pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
6 Lower Limb Amputation In some clinical studies with SGLT2 inhibitors an imbalance in the incidence of lower limb amputation has been observed. 36). 3 events per 1,000 patient-years in the placebo, and empagliflozin 10 mg treatment arms, respectively.
Amputation of the toe and mid-foot were most frequent (21 out of 28 empagliflozin 10 mg treated patients with lower limb amputations), and some involving above and below the knee. Some patients had multiple amputations. Peripheral artery disease, and diabetic foot infection (including osteomyelitis), were the most common precipitating medical events leading to the need for an amputation.
The risk of amputation was highest in patients with a baseline history of diabetic foot, peripheral artery disease (including previous amputation) or diabetes. Counsel patients about the importance of routine preventative foot care.
Monitor patients receiving SYNJARDY or SYNJARDY XR for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.
, angioedema) in patients treated with empagliflozin. If a hypersensitivity reaction occurs, discontinue SYNJARDY or SYNJARDY XR; treat promptly per standard of care, and monitor until signs and symptoms resolve. SYNJARDY and SYNJARDY XR are contraindicated in patients with hypersensitivity to empagliflozin or any of the excipients in SYNJARDY or SYNJARDY XR [see Contraindications (4) ] .
8 Vitamin B 12 Deficiency In metformin HCl clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of metformin-treated patients. Such decrease, possibly due to interference with B 12 absorption from the B 12 -intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin or vitamin B 12 supplementation.
Certain individuals (those with inadequate vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B 12 levels. 1) ].