Synjardy (empagliflozin/metformin): Diabetes Drug Side Effects

Generic drug: empagliflozin and metformin

Brand name: Synjardy

What is Synjardy (empagliflozin and metformin), and how does it work?

Synjardy (empagliflozin and metformin) is a prescription medicine used to treat the symptoms of Type 2 Diabetes Mellitus. Synjardy may be used alone or with other medications.

Synjardy belongs to a class of drugs called Antidiabetics, Biguanides; Antidiabetics, SGLT2 Inhibitors.

It is not known if Synjardy is safe and effective in children younger than 18 years of age.

What are the side effects of Synjardy?

WARNING

LACTIC ACIDOSIS

Postmarketing 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 (>5 mmol/Liter), anion gap
acidosis (without evidence of ketonuria or ketonemia), an increased
lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., 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
Synjardy and institute general supportive measures in a hospital setting. Prompt hemodialysis
is recommended.

Synjardy may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• burning or painful urination,
• frequent or urgent urination,
• pink or bloody urine,
• little or no urination,
• unusual vaginal discharge, burning, itching, or odor,
• redness, itching, swelling of the penis,
• unusual discharge from the penis,
• pain, redness, or swelling in or around the genital or anal area,
• fever,
• feeling unwell,
• sudden sweating,
• shaking,
• fast heartbeat,
• hunger,
• blurred vision,
• dizziness,
• tingling hands or feet,
• thirst,
• increased urination,
• confusion,
• drowsiness,
• flushing,
• rapid breathing,
• fruity breath odor,
• vomiting,
• diarrhea,
• heavy sweating,
• dry mouth,
• thirst,
• lightheadedness, and
• fainting

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Synjardy include:

• headache,
• diarrhea,
• nausea,
• vomiting,
• runny nose, and
• sore throat

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Synjardy. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Synjardy?

Prior To Initiation Of Synjardy

• Assess renal function before initiating Synjardy and as clinically
  indicated.
• In patients with volume depletion, correct this condition before
  initiating Synjardy.

Recommended Dosage And Administration

• Individualize the starting dose of Synjardy based on the patient’s current regimen:
  • In patients on metformin HCl, switch to Synjardy containing empagliflozin 5 mg with a similar total daily dose of metformin HCl;
  • In patients on empagliflozin, switch to Synjardy containing metformin HCl 500 mg with a similar total daily dose of empagliflozin;
  • In patients already treated with empagliflozin and metformin HCl, switch to
    Synjardy containing the same total daily doses of each component.
• Monitor effectiveness and tolerability, and adjust dosing as appropriate, not to exceed the maximum recommended daily dose of empagliflozin 25 mg and metformin HCl 2000 mg.
• Take Synjardy twice daily with meals; with gradual dose escalation to reduce the gastrointestinal side effects due to metformin.

Dosage Recommendations In Patients With Renal Impairment

• Initiation of Synjardy is not recommended in patients with an eGFR less than 45 mL/min/1.73 m², due to the metformin component.
• Synjardy is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m²
  or in patients on dialysis.

Discontinuation For Iodinated Contrast Imaging Procedures

Discontinue Synjardy at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR less than 60 mL/min/1.73 m²;
in patients with a history of liver disease, alcoholism or heart failure; or in
patients who will be administered intra-arterial iodinated contrast. Re-evaluate
eGFR 48 hours after the imaging procedure; restart Synjardy if renal function is
stable.

What drugs interact with Synjardy?

Table 4 Clinically Relevant Interactions with Synjardy

Carbonic Anhydrase Inhibitors

Clinical Impact
Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

Intervention
Concomitant use of these drugs with Synjardy may increase the risk of lactic acidosis. Consider more frequent monitoring of these patients.

Drugs that Reduce Metformin Clearance

Clinical Impact
Concomitant use of drugs that interfere with common renal
tubular transport systems involved in the renal elimination of
metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug
and toxin extrusion [MATE] inhibitors such as ranolazine,
vandetanib, dolutegravir, and cimetidine) could increase systemic
exposure to metformin and may increase the risk for lactic acidosis.

Intervention
Consider the benefits and risks of concomitant use.

Alcohol

Clinical Impact
Alcohol is known to potentiate the effect of metformin on lactate metabolism.

Intervention
Warn patients against excessive alcohol intake while receiving
Synjardy.

Diuretics

Clinical Impact
Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

Intervention
Before initiating Synjardy, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating
Synjardy. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.

Insulin or Insulin Secretagogues

Clinical Impact
The risk of hypoglycemia is increased when empagliflozin is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. Metformin may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue.

Intervention
Coadministration of Synjardy with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.

Drugs Affecting Glycemic Control

Clinical Impact
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.

Intervention
When such drugs are administered to a patient receiving Synjardy, the patient should be closely observed to maintain adequate glycemic control. When such drugs are withdrawn from a patient receiving
Synjardy, the patient should be observed closely for hypoglycemia.

Positive Urine Glucose Test

Clinical Impact
SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests.

Intervention
Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

Interference with 1,5-anhydroglucitol (1,5-AG) Assay

Clinical Impact
Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors.

Intervention
Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control.

Is Synjardy safe to use while pregnant or breastfeeding?

• Advise pregnant patients, and patients of reproductive potential, of the
  potential risk to a fetus with treatment with Synjardy.
• Instruct patients to report pregnancies to their physicians as soon as
  possible. Advise patients that breastfeeding is not recommended during
  treatment with Synjardy.