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Dapagliflozin / metformin Side Effects

In Summary

Commonly reported side effects of dapagliflozin/metformin include: lactic acidosis. Other side effects include: cystitis, pyelonephritis, urinary tract infection, vulvovaginal candidiasis, bacterial vaginosis, genital candidiasis, genitourinary infection, nasopharyngitis, prostatitis, urethritis, vaginal infection, vulvitis, vulvovaginitis, nausea, and vomiting. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to dapagliflozin / metformin: oral tablet, oral tablet extended release

In addition to its needed effects, some unwanted effects may be caused by dapagliflozin / metformin. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking dapagliflozin / metformin:

More common:
  • Bladder pain
  • bloody or cloudy urine
  • change in the color, amount, or odor of vaginal discharge
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • lower back or side pain
Rare
  • Abdominal or stomach discomfort
  • decreased appetite
  • diarrhea
  • fast, shallow breathing
  • general feeling of discomfort
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • muscle pain or cramping
  • nausea
  • shortness of breath
  • sleepiness
  • unusual tiredness or weakness
Incidence not known:
  • Anxiety
  • blurred vision
  • chills
  • cold sweats
  • coma
  • confusion
  • cool, pale skin
  • depression
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fast heartbeat
  • fever
  • headache
  • hives, itching, or rash
  • hoarseness
  • increased hunger
  • irritation
  • joint pain, stiffness, or swelling
  • nightmares
  • redness of the skin
  • seizures
  • shakiness
  • slurred speech
  • sweating
  • swelling of the eyelids, face, lips, hands, or feet
  • tightness in the chest
  • troubled swallowing

Minor Side Effects

Some of the side effects that can occur with dapagliflozin / metformin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:
  • Muscle aches
  • sore throat
  • stuffy or runny nose
Less common:
  • Back pain
  • body aches or pain
  • congestion
  • difficulty having a bowel movement (stool)
  • tender, swollen glands in the neck
  • voice changes

For Healthcare Professionals

Applies to dapagliflozin / metformin: oral tablet extended release

General

The most common adverse reactions reported with this combination drug included female genital mycotic infection, nasopharyngitis, urinary tract infection, diarrhea, and headache.[Ref]

Metabolic

Hypoglycemia was reported more frequently when this drug was added to sulfonylurea or insulin (up to 43%). Hypoglycemia was not reported in dapagliflozin monotherapy trials, and was reported infrequently in add-on trials with metformin, or dipeptidyl peptidase-4 inhibitors.

Twenty reports of acidosis 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 diabetic ketoacidosis (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]

Dapagliflozin-Metformin:
Very common (10% or more): Hypoglycemia (when used with sulfonylurea or insulin)

Dapagliflozin:
Common (1% to 10%): Hyperphosphatemia, increases in low-density lipoprotein cholesterol (LDL-C)
Uncommon (0.1% to 1%): Decreased weight, thirst
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis

Metformin:
Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency[Ref]

Gastrointestinal

Dapagliflozin-Metformin:
Common (1% to 10%): Diarrhea, nausea, constipation

Dapagliflozin:
Uncommon (0.1% to 1%): Constipation, dry mouth

Metformin:
Very common (10% or more): Gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite occurring most frequently during initiation[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Adverse reactions related to reduced intravascular volume (dehydration, hypovolemia, orthostatic hypotension, or hypotension)[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, cough, pharyngitis[Ref]

Dermatologic

Metformin:
Very rare (less than 0.01%): Urticaria, erythema, pruritus[Ref]

Endocrine

Small increases in serum parathyroid hormone (PTH) levels were observed with increases larger in subjects with higher baseline PTH concentrations. Bone mineral density in patients with normal or mildly impaired renal function did not indicate bone loss over a period of 2 years.[Ref]

Dapagliflozin:
Frequency not reported: Small increases in serum parathyroid hormone levels[Ref]

Oncologic

Dapagliflozin:
Uncommon (0.1% to 1%): Bladder cancer[Ref]

Newly diagnosed bladder cancer was reported in 10 of 6045 (0.17%) patients receiving dapagliflozin in clinical trials compared with 1 of 3512 (0.3%) patients receiving placebo or comparator. Upon excluding patients in whom exposure to study drug was less than 1 year at time of diagnosis, there were no cases associated with placebo and 4 cases with this drug. Due to the low number of cases, further studies are needed.[Ref]

Genitourinary

Common (1% to 10%): Female genital mycotic infections (including vulvovaginal mycotic infection, vaginal infection, genital infection, vulvovaginitis, fungal genital infection, vulvovaginal candidiasis, vulval abscess, genital candidiasis, and vaginitis bacterial), urinary tract infections (including urinary tract infection cystitis, pyelonephritis, urethritis, and prostatitis), male genital mycotic infections (including balanitis, fungal genital infection, balanitis candida, genital candidiasis, balanoposthitis, balanoposthitis infective, genital infection, posthitis), increased urination, discomfort with urination
Uncommon (0.1% to 1%): Vulvovaginal pruritus[Ref]

Genital mycotic infections have been commonly reported with dapagliflozin treatment. Discontinuation due to genital infection occurred in 0.2% of patients in dapagliflozin clinical trials. Infections were more frequently reported in females than males, and patients with a history of genital mycotic infections were more likely to have an infection than those without a history.[Ref]

Hematologic

Dapagliflozin:
Common (1% to 10): Hematocrit increased

Metformin:
Very rare (less than 0.01%): Decreased vitamin B12 serum levels[Ref]

Hepatic

Metformin:
Very rare (less than 0.01%): Liver function disorders, liver function tests abnormalities, hepatitis[Ref]

Hypersensitivity

Dapagliflozin:
Rare (less than 0.1%): Serious anaphylactic reactions, severe cutaneous reactions, and angioedema[Ref]

Musculoskeletal

Common (1% to 10%): Back pain[Ref]

Nervous system

Dapagliflozin-Metformin:
Common (1% to 10%): Headache, dizziness,

Metformin:
Common (1% to 10%): Taste disturbance[Ref]

Renal

Dapagliflozin:
Uncommon (0.1% to 1%): serum creatinine increased, blood urea increased
Frequency not reported: Decreases in eGFR[Ref]

Immunologic

Common (1% to 10): Influenza[Ref]

References

1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. Cerner Multum, Inc. "Australian Product Information." O 0

3. "Product Information. Xigduo XR (dapagliflozin-metFORMIN)." Astra-Zeneca Pharmaceuticals, Wilmington, DE.

4. FDA. U.S. Food and Drug Administration "FDA: SGLT2 inhibitors: Drug Safety Communication - FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood Available from: URL: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm44699" (2015 May 15):

Not all side effects for dapagliflozin / metformin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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