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Empagliflozin / linagliptin Side Effects

In Summary

Commonly reported side effects of empagliflozin/linagliptin include: urinary tract infection. Other side effects include: increased ldl cholesterol. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to empagliflozin / linagliptin: oral tablet, tablet oral

In addition to its needed effects, some unwanted effects may be caused by empagliflozin / linagliptin. 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 empagliflozin / linagliptin:

More common:
  • Bladder pain
  • bloody or cloudy urine
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • lower back or side pain
Incidence not known:
  • Anxiety
  • bloating
  • blurred vision
  • chills
  • cold sweats
  • confusion
  • constipation
  • cool, pale skin
  • darkened urine
  • depression
  • dizziness
  • dry mouth
  • fast heartbeat
  • fever
  • flushed, dry skin
  • fruit-like breath odor
  • headache
  • increased hunger
  • increased thirst
  • indigestion
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • loss of consciousness
  • nausea
  • nightmares
  • pains in the stomach, side, or abdomen, radiating to the back
  • seizures
  • severe joint pain
  • shakiness
  • slurred speech
  • stomach pain
  • sweating
  • troubled breathing
  • unexplained weight loss
  • unusual tiredness or weakness
  • vomiting
  • yellow eyes or skin

Minor Side Effects

Some of the side effects that can occur with empagliflozin / linagliptin 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:
  • Body aches or pain
  • difficulty with breathing
  • ear congestion
  • headache
  • loss of voice
  • runny or stuffy nose
  • sneezing
  • sore throat
Incidence not known:
  • Discharge with a strong odor from the penis
  • redness, itching, swelling, or pain around the penis
  • vaginal discharge, itching, or odor

For Healthcare Professionals

Applies to empagliflozin / linagliptin: oral tablet

Dermatologic

Linagliptin:
Postmarketing reports: Rash[Ref]

Gastrointestinal

Pancreatitis was reported in 15.2 cases per 10,000 patient year exposure in patients receiving linagliptin compared to 3.7 cases per 10,000 patient year exposure in those receiving active comparator (placebo or sulfonylurea), during clinical trials. Following completing of clinical trials, 3 additional cases of pancreatitis were reported in those receiving linagliptin. Postmarketing reports of acute pancreatitis, including fatalities, have been reported.[Ref]

Empagliflozin:
Common (1% to 10%): Nausea

Linagliptin:
Common (1% to 10%): Diarrhea
Frequency not reported: Pancreatitis
Postmarketing reports: Acute pancreatitis[Ref]

Genitourinary

Empagliflozin-Linagliptin:
Very Common (10% or more): Urinary tract infection (up to 12.5%)

Empagliflozin:
Common (1% to 10%): Urinary tract infection, female genital mycotic infections, increased urination, male genital mycotic infections[Ref]

Hematologic

Empagliflozin-Linagliptin:
Frequency not reported: Increased hematocrit

Empagliflozin:
Common (1% to 10%): Increased hematocrit[Ref]

Hypersensitivity

Postmarketing, serious hypersensitivity reactions including angioedema, anaphylaxis, and exfoliative skin conditions have been reported in patients treated with linagliptin. These reactions have occurred within the first 3 months and some have occurred after the first dose.[Ref]

Linagliptin:
Frequency not reported: Hypersensitivity reactions including urticaria, angioedema, localized skin exfoliation, or bronchial hyper-reactivity
Postmarketing reports: Serious hypersensitivity reactions including anaphylaxis[Ref]

Metabolic

When this combination product was added to metformin therapy, the overall incidence of hypoglycemia was 2.2% and 3.6% in patients receiving empagliflozin 10 mg-linagliptin 5 mg and empagliflozin 25 mg-linagliptin 5 mg, respectively. There were no reports of serious hypoglycemia.

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]

Empagliflozin-Linagliptin:
Common (1% to 10%): Hypoglycemia, increased cholesterol

Empagliflozin:
Common (1% to 10%): Increased low-density lipoprotein cholesterol, dyslipidemia
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis

Linagliptin:
Common (1% to 10%): Increased uric acid[Ref]

Musculoskeletal

Between October 2006 and December 2013, thirty-three cases of severe arthralgia have been reported to the FDA Adverse Event Reporting System Database. Each case involved the use of 1 or more dipeptidyl peptidase-4 (DPP-4) inhibitor. In all cases, substantial reduction in prior activity level was reported, 10 patients were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of starting therapy, in 23 cases symptoms resolved less than 1 month after discontinuation. A positive rechallenge was reported in 8 cases, with 6 cases involving use of a different DPP-4 inhibitor. Sitagliptin had the greatest number of cases reported (n=28) followed by saxagliptin (n=5), linagliptin (n=2), alogliptin (n=1), and vildagliptin (n=2).[Ref]

Empagliflozin:
Common (1% to 10%): Arthralgia[Ref]

Renal

Empagliflozin:
Frequency not reported: Increased serum creatinine, decreased eGFR[Ref]

Respiratory

Empagliflozin-Linagliptin:
Common (1% to 10%): Nasopharyngitis, upper respiratory infection

Empagliflozin:
Common (1% to 10%): Upper respiratory infection

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

References

1. "Product Information. Glyxambi (empagliflozin-linagliptin)." Boehringer Ingelheim, Ridgefield, CT.

2. 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):

3. US Food and Drug Administration "FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. Available from: URL: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM460038.pdf." ([2015, Aug 28]):

Not all side effects for empagliflozin / linagliptin 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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