Synjardy XR Side Effects

Generic name: empagliflozin / metformin

Medically reviewed by Drugs.com. Last updated on Dec 31, 2023.

Note: This document provides detailed information about Synjardy XR Side Effects associated with empagliflozin / metformin. Some dosage forms listed on this page may not apply specifically to the brand name Synjardy XR.

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

Precautions

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Tell your doctor if you are pregnant or planning to become pregnant. It is not safe to take this medicine during the second and third trimester of pregnancy. It could harm an unborn baby. This medicine may cause some women who do not have regular monthly periods to ovulate. This can increase the chance of pregnancy if you are sexually active. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

Under certain conditions, too much metformin can cause a serious condition called lactic acidosis. Lactic acidosis usually occurs when other serious health problems are present, such as a heart attack or kidney failure. The symptoms of lactic acidosis include: stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If you have more than one of these symptoms together, you should get immediate emergency medical help.

Dizziness, lightheadedness, or fainting may occur with this medicine. This is more common if you have kidney disease, low blood pressure, or if you are taking a diuretic (water pill). Taking plenty of fluids each day may help. Drink plenty of water during exercise or in hot weather. Check with your doctor if you have severe nausea, vomiting, or diarrhea that does not stop. This may cause you to lose too much water.

Ketoacidosis (high ketones and acid in the blood) may occur while you are using this medicine. This can be life-threatening and requires immediate medical attention. Your doctor may give you insulin, fluid, and carbohydrate replacement to treat this condition. Tell your doctor right away if you have nausea, vomiting, trouble breathing, increased thirst or urination.

Tell your doctor if you have bloody urine, decrease in how much or how often you urinate, painful or difficult urination, lower back or side pain, fever, chills, or swelling of the face, finger, or lower legs. These may be symptoms of a serious kidney problem.

This medicine may cause serious allergic reactions, including angioedema, which can be life-threatening and require medical attention. Call your doctor right away if you have large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs while you are using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine at least 3 days before having major surgery, other procedures that require fasting, or diagnostic tests, especially tests that use a contrast dye. This medicine may also affect the results of certain medical tests (eg, urine glucose tests may not be accurate).

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with other diabetes medicines (eg, insulin, glipizide, or glyburide). The symptoms of low blood sugar must be treated before they cause you to pass out. People feel different symptoms with low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Some symptoms of low blood sugar include: behavior changes that are similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, a fast heartbeat, headaches that continue, nausea, shakiness, slurred speech, or unusual tiredness or weakness. Talk to your doctor about how to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your diabetes medicine, overeat or do not follow your diet plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

This medicine may cause vaginal yeast infections in women and yeast infections of the penis in men. This is more common in patients who have a history of genital yeast infections or in men who are not circumcised. Women may have a vaginal discharge, itching, or odor. Men may have redness, itching, swelling, or pain around the penis, or a discharge with a strong odor from the penis. Check with your doctor right away if you have any of these symptoms.

This medicine may increase your risk of having urinary tract infections, including pyelonephritis or urosepsis. Check with your doctor right away if you have bladder pain, bloody or cloudy urine, difficult, burning, or painful urination, or lower back or side pain.

This medicine may cause a rare but serious bacterial infection, called necrotizing fasciitis of the perineum or Fournier's gangrene, which can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). Fournier's gangrene may lead to hospitalization, multiple surgeries, or death. Check with your doctor right away if you have fever, unusual tiredness or weakness, or pain, tenderness, redness, or swelling of the area between and around your anus and genitals.

This medicine may increase your risk of having lower leg, foot, or toe amputation. Check with your doctor right away if you have pain, tenderness, sores or ulcers, or infections on your leg or foot.

Limit the amount of alcohol you drink while you are using this medicine. Heavy alcohol use can increase your chances of serious side effects.

There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes with a list of all your medicines.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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:

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:

For healthcare professionals

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

General adverse events

The most common adverse reactions associated with empagliflozin were urinary tract infection and female genital mycotic infections. The most common adverse reactions associated with metformin were diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.^[Ref]

Cardiovascular

Empagliflozin:

• Frequency not reported: Decreased blood pressure (ambulatory), decreased systolic blood pressure, hypotension, orthostatic hypotension

Adverse reactions related to volume depletion included decreased blood pressure (ambulatory), decreased systolic blood pressure, hypotension, and orthostatic hypotension.

Dermatologic

• Common (1% to 10%): Rash
• Uncommon (0.1% to 1%): Urticaria, angioedema

Empagliflozin:

• Common (1% to 10%): Generalized pruritus
• Postmarketing reports: Angioedema, skin reactions (e.g., rash, urticaria)

Metformin:

• Common (1% to 10%): Pruritus, generalized pruritus
• Very rare (less than 0.01%): Erythema, urticaria

Gastrointestinal

• Common (1% to 10%): Constipation

Empagliflozin:

• Common (1% to 10%): Nausea
• Postmarketing reports: Constipation

Metformin:

• Very common (10% or more): Gastrointestinal symptoms
• Frequency not reported: Diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion

Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, abdominal pain, loss of appetite) occurred most often during initiation of metformin therapy and resolved spontaneously in most cases.

In clinical trials of metformin, diarrhea, nausea/vomiting, flatulence, abdominal discomfort, and indigestion were reported in greater than 5% of patients. In clinical trials of extended-release metformin plus glyburide, diarrhea and nausea were reported in 12.5% and 6.7% of patients, respectively.

Genitourinary

• Common (1% to 10%): Urinary tract infection
• Very rare (less than 0.01%): Tubulointerstitial nephritis

Empagliflozin:

• Common (1% to 10%): Female genital mycotic infections, increased urination, male genital mycotic infections, vaginal moniliasis, vulvovaginitis, balanitis, other genital infection, urinary tract infection
• Uncommon (0.1% to 1%): Nocturia, dysuria
• Rare (0.01% to 0.1%): Phimosis
• Postmarketing reports: Urosepsis, phimosis

Urinary tract infection included (but was not limited to) asymptomatic bacteriuria, cystitis, and urinary tract infection. Urinary tract infections occurred more often in female patients and were more likely to occur in patients with history of chronic or recurrent urinary tract infections.

Female genital mycotic infections included vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, fungal genital infection, genitourinary tract infection, vulvovaginitis, cervicitis, fungal urogenital infection, and bacterial vaginitis. Genital mycotic infections occurred more frequently in female than male patients.

Increased urination included (but was not limited to) polyuria, pollakiuria, and nocturia.

Male genital mycotic infections included balanoposthitis, balanitis, fungal genital infections, genitourinary tract infection, Candida balanitis, scrotal abscess, and penile infection.

Hematologic

Empagliflozin:

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

Hepatic

Metformin:

• Very rare (less than 0.01%): Abnormal liver function tests, hepatitis
• Postmarketing reports: Cholestatic liver injury, hepatocellular liver injury, mixed hepatocellular liver injury

Hypersensitivity

Empagliflozin:

• Postmarketing reports: Serious hypersensitivity reactions (e.g., angioedema)

Metabolic

• Very common (10% or more): Hypoglycemia (up to 15.6%)

Empagliflozin:

• Common (1% to 10%): Dyslipidemia
• Uncommon (0.1% to 1%): Hypoglycemia, volume depletion, volume depletion-related adverse reactions
• Frequency not reported: Dehydration, hypovolemia
• Postmarketing reports: Ketoacidosis

Metformin:

• Common (1% to 10%): Decreased vitamin B12 levels
• Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency
• Frequency not reported: Hypoglycemia
• Postmarketing reports: Drug-associated lactic acidosis

The incidence of hypoglycemia increased when empagliflozin was administered with insulin or sulfonylurea. The incidence of overall hypoglycemic events (plasma/capillary glucose 70 mg/dL or less) was 0.4% with empagliflozin monotherapy, up to 1.8% with empagliflozin plus metformin, up to 16.1% with empagliflozin plus metformin plus sulfonylurea, up to 2.4% with empagliflozin plus pioglitazone (with/without metformin), up to 28.4% with empagliflozin plus basal insulin (with/without metformin), and up to 41.3% with empagliflozin plus multiple daily injections of insulin (with/without metformin).

In clinical trials in adults, adverse reactions related to volume depletion (e.g., decreased blood pressure [ambulatory], decreased systolic blood pressure, dehydration, hypotension, hypovolemia, orthostatic hypotension, syncope) were reported in up to 0.5% of patients treated with empagliflozin.

In clinical trials of extended-release metformin plus glyburide, hypoglycemia was reported in 13.7% of patients.

Musculoskeletal

Empagliflozin:

• Common (1% to 10%): Arthralgia
• Frequency not reported: Lower limb amputation
• Postmarketing reports: Necrotizing fasciitis of the perineum (Fournier's gangrene)

Across 4 empagliflozin outcome trials, lower limb amputation event rates were 4.3 and 5 events per 1000 patient-years in the placebo and empagliflozin groups, respectively. In a long-term cardiorenal outcome trial in patients with chronic kidney disease, lower limb amputations event rates were 2.9 and 4.3 events per 1000 patient-years in the placebo and empagliflozin arms, respectively.

Nervous system

Empagliflozin:

• Frequency not reported: Syncope

Metformin:

• Common (1% to 10%): Taste disturbance
• Frequency not reported: Headache

Adverse reactions related to volume depletion included syncope.

In clinical trials of metformin, headache was reported in greater than 5% of patients.

Other

Empagliflozin:

• Common (1% to 10%): Thirst, increased serum lipids
• Frequency not reported: Increased low-density lipoprotein cholesterol, increased total cholesterol, increased high-density lipoprotein cholesterol, increased triglycerides

Metformin:

• Frequency not reported: Asthenia

Thirst included polydipsia.

In clinical trials of metformin, asthenia was reported in greater than 5% of patients.

Renal

Empagliflozin:

• Frequency not reported: Increased serum creatinine, decreased estimated GFR, osmotic diuresis
• Postmarketing reports: Pyelonephritis, acute kidney injury

Respiratory

• Common (1% to 10%): Nasopharyngitis

Empagliflozin:

• Common (1% to 10%): Upper respiratory tract infection

See also:

Further information

Synjardy XR side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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