The U.S. Food and Drug Administration warns that dapagliflozin (the active ingredient in Farxiga) can cause acute kidney injury and a condition of too much acid in the blood called ketoacidosis.
Safety reviews link the drug to low blood pressure and serious urinary tract infections. Farxiga’s label also includes a bladder cancer warning.
The FDA initially denied drugmakers AstraZeneca and Bristol-Myers Squibb permission to sell Farxiga in the U.S. because of cancer concerns. However, in 2014, the FDA approved the drug, making it the second sodium-glucose cotransporter 2 inhibitor — or SGLT2 inhibitor — available to Americans with Type 2 diabetes. The risks associated with the drug remain a concern.
Serious side effects associated with Farxiga include:
Serious urinary tract infections (UTIs)
Bladder Cancer and Farxiga
People who took Farxiga in studies were five times more likely to develop bladder cancer than people who took a placebo or other diabetes medication. Researchers also concluded Farxiga might make existing bladder cancer worse or speed up the development of bladder cancer in people who are at risk.
The fear is that patients take diabetes drugs for years, and the longer someone takes this drug, the greater their risk of cancer”
- Diana Zuckerman, president of the National Research Center for Women & Families, wrote in The Huffington Post.
Bladder cancer occurs when cells in the bladder grow uncontrollably and form a tumor. Bladder cancer can be deadly and is particularly dangerous in diabetics.
The American Cancer Society estimates that in 2017, about 79,000 people will be diagnosed with bladder cancer, and about 12,240 men and 4,630 women will die from the disease.
Farxiga Bladder Cancer Clinical Studies
Researchers investigated a link between Farxiga and bladder cancer in 22 clinical studies. Results show there were more newly diagnosed cases of bladder cancer in people who were taking Farxiga than in people who were taking other diabetes medications.
Ten out of 6,045 patients treated with Farxiga were diagnosed with new cases of bladder cancer.
One out of 3,512 patients treated with a placebo or another diabetes drug faced the same diagnosis.
In other words, about 0.17 percent of patients taking Farxiga developed bladder cancer compared to 0.03 percent of patients taking other diabetes drugs.
Researchers then ruled out patients who were diagnosed with bladder cancer after taking Farxiga for less than one year. They were left with: Four cases of bladder cancer with Farxiga and no cases with placebo or other diabetes drugs.
“There were too few cases to know if bladder cancer is related to Farxiga,” according to the drug’s label. AstraZeneca also says there is not enough data to determine whether Farxiga has an effect on pre-existing bladder tumors.
Still, the FDA notes “an imbalance in bladder cancers was observed in clinical trials.” The agency warns patients with active bladder cancer not to take Farxiga because it might cause the cancer to get worse. Farxiga should be used with caution in patients with a prior history of bladder cancer.
Symptoms of Bladder Cancer
Blood in urine is typically the first sign of bladder cancer. Urine may turn orange, pink or even darker red. It is possible for urine to be normal in color but small amounts of blood may be found in a urine test.
Possible signs of bladder cancer include:
- Blood in urine
- Having to urinate more frequently
- Burning or pain when urinating
- An urgency to urinate, even when the bladder is not full
- Difficulty urinating or having a weak urine stream
Patients taking Farxiga should tell their doctor immediately if they experience signs or symptoms potentially related to bladder cancer. Bladder cancer can be harder to treat if it becomes more advanced. Bladder cancer that spreads to other parts of the body normally reaches the lymph nodes, the bones, the lungs or the liver first.
Signs that the cancer has spread to other parts of the body include:
- An inability to urinate
- Pain on one side of the lower back
- Decreased appetite and weight loss
- Tiredness or weakness
- Swollen feet
- Bone pain
Diagnosing Bladder Cancer
Physical exams, urine lab tests and a procedure that involves inserting a tube into the bladder are among the ways doctors confirm a bladder cancer diagnosis. Doctors then use additional tests, such as X-rays and scans, to determine the severity of the cancer.
Diagnosis starts with getting a patient’s medical history. Doctors typically perform a physical exam, which may involve a rectal exam for men and a pelvic exam for women. These exams sometimes allow a doctor to feel a bladder tumor, assess its size and figure out if the cancer has spread.
Urine lab tests usually follow physical exams that show signs of cancer.
- Urinalysis is a quick test that checks for blood and other substances in a sample of a patient’s urine.
- Urine cultures check for bacteria in the urine to determine whether infection, not cancer, is the cause of the symptoms.
- Urine tumor marking tests look for specific substances released by bladder cancer cells to help determine if a patient has bladder cancer.
A cystoscopy is the next test for bladder cancer after urine labs tests. It is essentially a scope of the bladder. It involves a cystoscope, which is a hollow tube that has a light and a small camera on the end. Doctors insert the cystoscope through the opening of the urethra up into the bladder. They then inject sterile salt water to expand the bladder so that doctors can examine its inner lining.
Fluorescence cystoscopy uses a light-activated drug and a special blue light to make cancer cells in the bladder glow.
Sometimes doctors will also inject a light-activated drug into the bladder to make sure they are not overlooking cancer. Cancer cells absorb the drug and will glow when the doctors shine a blue light through the cystoscope. This is called fluorescence cystoscopy or blue light cystoscopy.
Doctors perform cystoscopies in a doctor’s office or in an operating room. The location depends on whether the patient is asleep and on how much of the body is numbed (just the urethra and bladder or the whole lower body).
Testing to See if Bladder Cancer has Spread
Doctors use imaging tests to determine if cancer has spread from the bladder to other parts of the body. Tests that show signs cancer has spread are usually followed by a biopsy, which is when a doctor takes a tissue or cell sample from part of the body.
Types of imaging tests used to see if bladder cancer has spread include:
Intravenous pyelogram (IVP):
Doctors inject a special dye into the vein. The dye goes from the bloodstream into the kidneys and then to the ureters and bladder. A doctor then takes an X-ray. The dye outlines the organs and allows doctors to see urinary tract tumors on X-rays. This test is also called intravenous urogram (IVU). It is not for everyone. Patients should tell their doctor if they have any allergies or have ever had a reaction to X-ray dyes, or if they have any type of kidney problems.
This test is less common than IVP. It is used along with an ultrasound of the kidneys to look for urinary tract tumors in patients who can’t have an IVP. It involves inserting a catheter through the urethra and up into the bladder or a ureter. Like IVP, this test also uses dye to outline the bladder, ureters and kidneys to make them easier to see on X-rays.
This test takes X-rays of the kidney, ureters and bladder to show how big a urinary tract tumor is, what shape it is and where it is located. CT urogram can also provide information on other organs in the abdomen and pelvis. It can show enlarged lymph nodes that might contain caner. A CT scan of the chest will show if the cancer has spread to the lungs.
This test uses radio waves and strong magnets to create images of soft tissue in the bladder, ureters and kidneys. It can be used as an alternative to having an IVP to look at the upper part of the urinary system. It can also show whether cancer has spread from the bladder to nearby tissue or lymph nodes.
This test uses sound waves (not radiation) to create images of the bladder, kidneys and other nearby organs. Doctors use it to determine the size of a bladder cancer. Ultrasounds are also useful in determining whether cancer has spread outside the bladder.
Bladder Cancer Treatment
Treatment options for people with bladder cancer can include surgery, intravesical therapy, chemotherapy, radiation therapy and immunotherapy. Doctors consider the individual patient and how advanced the cancer is at the time of diagnosis when determining how to treat it.
Doctors may recommend one or more of following treatments:
Surgery is part of treatment for most bladder cancers. Doctors may recommend surgery to remove early-stage bladder tumors or to remove the entire bladder (radical cystectomy).
Intravesical therapy is used to treat only early-stage bladder cancer. A doctor uses a catheter to put a liquid drug directly into the bladder.
Chemotherapy uses drugs to treat bladder cancer. Doctors may use it alone
to treat advanced bladder cancers or in combination with surgery or radiation therapy.
Radiation therapy kills cancer cells using high-energy radiation. External beam radiation therapy is the type of radiation most often used to treat bladder cancer. A source outside of the body generates beams that are targeted at the tumors.
Immunotherapy uses a catheter to put bacteria directly into the bladder to trigger a person’s immune system to destroy bladder cancer cells.
It is important to discuss with your medical team the possible side effects of each treatment option so that you can make the best possible health care decision.
Doctors Who Treat Bladder Cancer
Doctors who treat bladder cancer include urologists, radiation oncologists and medical oncologists. Your treatment team may also include other health professionals such as physician assistants, nurse practitioners, nurses, psychologists and nutrition specialists.
Each type of doctor has a specific role in treating bladder cancer:
These doctors are surgeons who are trained specifically to treat diseases that affect the urinary system and male reproductive system.
These doctors use radiation therapy to treat cancer.
These doctors use chemotherapy and immunotherapy to treat cancer.
FDA Rejected Farxiga Over Cancer Concerns
The FDA rejected Farxiga in 2012 because of cancer concerns and questions about how well the drug works.
The agency later selected an advisory committee to review data on the drug. Doctors and scientists on the committee expressed concerns about risks and benefits, and experts and FDA scientists noted several unanswered questions.
Nonetheless, the committee recommended the drugmakers could sell Farxiga so long as they continued to study the drug’s risks after the FDA approved it.
The FDA approved the drug in 2014 and required the drugmakers to study 17,000 diabetes patients for at least four years to determine how the drug affects patients when taken for a longer period of time.
The study was to look at whether and how often patients taking farxiga are diagnosed with:
Ketoacidosis Caused by Farxiga
Type 2 diabetes patients taking Farxiga have died from ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones. People who develop ketoacidosis often need to be hospitalized.
Between March 2013 and May 2015, the FDA identified 73 cases of ketoacidosis in patients treated with SGLT2 inhibitors such as Farxiga.
Patients in all cases were admitted to a hospital or treated in an emergency room. The FDA said at the time there were likely more cases the agency was not aware of.
The FDA put out a safety alert in May 2015 warning that Farxiga’s active ingredient, dapagliflozin, may lead to ketoacidosis. The agency conducted a safety review, and in December 2015, it added a ketoacidosis warning to Farxiga’s label.
Anyone who takes Farxiga should pay close attention for signs of ketoacidosis. Patients should get medical help immediately if they experience symptoms of too much acid in their blood.
Signs and symptoms of ketoacidosis include:
- Difficulty breathing
- Abdominal pain
- Abnormal fatigue or sleepiness
Test for ketones in your urine if you experience any symptoms of ketoacidosis while taking Farxiga, even if your blood sugar is less than 250 mg/dL. Farxiga users may have ketoacidosis even if blood glucose levels are below those typically expected for diabetic ketoacidosis.
Ketone tests are available at local pharmacies. A doctor may also do a physical exam and order blood tests and a urinalysis. Chest X-rays and an electrocardiogram (a recording of the electricity of the heart) will help check for complications and any underlying health problems.
Patients who develop ketoacidosis should get medial help right away. Patients should not stop taking Farxiga without first talking to the doctor who prescribed it. A doctor who suspects ketoacidosis may stop treating a patient with Farxiga, then evaluate and treat the condition.
Treatment of ketoacidosis may include:
Consider Ketoacidosis Risk Before Taking Farxiga
Certain factors may make a person more likely to develop ketoacidosis. It is important to consider these before taking Farxiga. A doctor will be able to help you weigh the risk and benefits of using the drug.
Factors in the patient history that may predispose to ketoacidosis include:
- Pancreatic insulin deficiency from any cause
- Caloric restriction
- Alcohol abuse
A doctor may consider telling a patient to temporarily stop taking Farxiga in certain situations, such as prolonged fasting due to acute illness or surgery.
Kidney Injury and Farxiga
Some people who took Farxiga suffered from acute kidney injury and were admitted to the hospital and needed dialysis. Acute kidney injury occurs when the kidneys suddenly stop working. This can lead to dangerous levels of waste building up in the body.
The FDA identified 28 people who took dapagliflozin (Farxiga) and developed acute kidney injury between March 2013 and October 2015.
- Nearly all of the people were hospitalized, some in the intensive care unit.
- About half of the people developed acute kidney injury within one month of starting dapagliflozin.
- Most patients improved after stopping the drug.
Taking certain medications at the same time as Farxiga could be dangerous to the kidneys. Patients should tell their doctor if they are taking other medicines that may also affect the kidneys. These include water pills, blood pressure medicines, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen or naproxen.
FDA Reports of Farxiga Acute Kidney Injury
The FDA received 101 reports of people who developed acute kidney injury related to canagliflozin (73 patients) and dapaglifozin (28 patients) between March 29, 2013 and Oct. 19, 2015. More than half suffered acute kidney injury within one month or less of starting the drugs.
needed to go to the hospital
ended up in an intensive care unit
people received dialysis
Half of the patients were also taking an angiotensin-converting-enzyme (ACE) inhibitor, a drug used to treat hypertension and congestive heart failure. Twenty-six patients were taking a diuretic at the same time as Farxiga, and six reported NSAID use. Ten patients reported a prior history of chronic kidney disease.
Of the 78 people who stopped taking the drugs, 56 got better. Eleven people did not recover, including the four who died. Two of them died of cardiac-related issues.
Three patients recovered after stopping the drugs but still experienced consequences of acute kidney injury. Researchers say this suggests that kidney injury may not be completely reversible in certain situations.
Kidney Injury Symptoms
Symptoms of kidney injury can range from decreased urine and swelling in the legs to seizures or coma in severe cases. They differ based on the cause of the illness.
Signs and symptoms of acute kidney injury may include:
Too little urine leaving the body
Swelling in legs, ankles and around the eyes
Fatigue or tiredness
Shortness of breath
Seizures or coma in severe cases
Chest pain or pressure
Patients should get medical help right away if they experience symptoms of acute kidney injury. They should not stop taking Farxiga without first talking to a doctor because it may cause dangerous changes in blood sugar levels.
It is important to also alert a doctor if a patient is eating or drinking less due to illness or fasting, or if the patient is vomiting, having diarrhea or experiencing excessive exposure to heat.
Diagnosing Kidney Injury
A doctor may analyze a sample of urine and/or monitor the amount of urine a patient excretes in a day to diagnose kidney injury and determine its cause.
Another method for diagnosing kidney injury is to measure kidney function by testing a sample of blood for rising levels of creatinine. Creatinine is a waste product produced by the muscles. A high creatinine level indicates impaired kidney function.
Doctors may use an ultrasound or CT scan to look at a patient’s kidneys. Some may insert a needle through a patient’s skin and into the kidney to remove a sample of tissue for lab testing (biopsy).
Treatment for Kidney Injury
A person with acute kidney injury might need to stay in a hospital for treatment. The cause of the kidney injury and how quickly the kidneys recover will determine how long a patient stays in the hospital.
Doctors may recommend dialysis in more serious cases. Dialysis helps replace kidney function until the kidneys recover. Some people may need to undergo dialysis treatments for the remainder of their lives.
Five to 10 years is the average life expectancy for people on dialysis. Still, many patients have lived for 20 or 30 years on dialysis.
Patients can undergo dialysis in a hospital, in a separate dialysis unit or at home. Dialysis is very expensive. Eighty percent of all dialysis costs for most patients are paid for by the U.S. government.
Dialysis treatments help many patients feel better. Patients often can go back to work and travel. They do need to be on a special diet, however.
Treatment involves needles so there may be some discomfort. Some patients experience a drop in blood pressure, which can lead to vomiting, headache or cramps. These reactions usually go away the more a patient has dialysis.
There are two types of dialysis: hemodialysis and peritoneal dialysis. Both have been around since the mid-1940s.
Hemodialysis uses an artificial kidney to remove waste from a patient’s blood.
There are different ways the blood gets into the artificial kidney:
- Patients may have a minor surgery to an arm or leg to create an access to the blood vessels.
- A doctor may join an artery to a vein under the skin to create a fistula, or a bigger blood vessel.
- A patient may receive a graft (a soft plastic tube) that connects an artery and a vein under the skin.
- A doctor may insert a catheter into a large vein in the neck.
Most patients undergo treatment three times per week. Hemodialysis generally lasts about four hours. There is a type of hemodialysis that takes less time. It is called high-flux dialysis.
Many factors affect how long dialysis lasts. Some include how well a person’s kidneys function, a person’s size, the type of artificial kidney used, the amount of waste in a person’s body and how much fluid weight a person gains between treatments.
Two major types of peritoneal dialysis are Continuous Ambulatory Peritoneal Dialysis (CAPD) and Automated Peritoneal Dialysis (APD).
CAPD does not use machines. Instead, the patient uses a catheter to fill the abdomen with a special mixture called dialysate. The dialysate stays in the body for about four or five hours. The patient then drains the mixture into a bag and throws it away. This is done four of five times a day. During these treatments, patients can go about their daily activities.
APD uses a special machine called a cycler. Patients usually undergo this treatment at home. APD is like CAPD; however, the machine takes care of the process while a patient is asleep at night. Each cycle usually lasts 90 minutes. Patients are typically attached to the machine for about eight hours.
Recurring Kidney Injury and Other Health Problems
Patients who had acute kidney injury have a higher chance of having it again and of developing other health problems. It is important to follow up with a doctor who can monitor kidney function and recovery. Kidney disease and kidney failure become more likely every time a person has acute kidney injury. An acute kidney injury increases the chances of kidney disease, heart disease and strokes.
Serious Urinary Tract Infections (UTIs) Caused by Farxiga
Farxiga increases the risk of urinary tract infections (UTIs). People taking Farxiga have developed two types of serious and potentially fatal urinary tract infections — urosepsis and pyelonephritis. Some people were admitted to the hospital as a result.
Urosepsis vs. Pyelonephritis
Urosepsis happens when bacteria from a UTI infects the bloodstream. Pyelonephritis occurs when bacteria from a UTI invades essential kidney tissue.
Untreated UTIs can turn into urosepsis. Patients should go to the hospital immediately if they experience symptoms of this potentially fatal condition.
Symptoms of urosepsis include:
- Pain on near the kidneys
- Nausea and vomiting
- Extreme tiredness
- Decreased urine
- Inability to think clearly
- Difficulty breathing
- Abnormal heart function
- Abdominal pain
- Rapid heart rate
- High or low body temperature
- Fast breathing
Diagnosising and Treating Urosepsis
Doctors diagnose urosepsis through blood tests, a CT scan to look at the kidneys and an ultrasound of the urinary tract. Antibiotics can kill the bacteria that caused urospesis. Some people may need surgery.
Patients with urosepsis that is not treated right away will need to be closely monitored and treated in an intensive care unit.
Types of urosepsis treatment given to patients in the ICU include:
- Intravenous (iv) fluids
- Supportive medical care
Urosepsis and Spetic Shock
Urosepsis can turn into septic shock, a condition where a patient’s blood pressure drops dangerously low and the body’s organs begin to shut down.
Patients who go into shock may need lifesaving treatments to stabilize heart rate and breathing.
A doctor may also prescribe a type of medications called vasopressors that help increase blood pressure by narrowing blood vessels.
A person who has pyelonephritis has a kidney infected by bacteria. Bacteria that invade the kidney come from the lower urinary tract or the bloodstream.
Symptoms of pyelonephritis include fever, pain in the area of the back right above the kidneys, and nausea and/or vomiting.
Symptoms of acute pyelonephritis do not come all at once. They usually develop over hours or throughout the day. An infection is considered complicated if the symptoms last more than seven days or if the infection occurs in someone who is male, elderly or a child.
Elderly patients may also experience mental status change and their organs and body may begin to deteriorate. Anorexia is common in patients with acute pyelonephritis.
Pyelonephritis Diagnosis and Treatment
Doctors typically start with urine tests to diagnose pyelonephritis. They may also use imaging tests, such as CT scans, MRI scans, ultrasonography and scintigraphy.
Antibiotics, IV fluids and surgery to drain the infected area are treatments for pyelonephritis. The sooner a patient is diagnosed with and treated for pyelonephritis the better the chances for recovery.
Emily Miller is an award-winning writer who has held editorial positions with reputable print and online publications around the U.S. As the editor of Drugwatch.com, Emily draws on her background as both a patient and a journalist to ensure her team of writers provides consumers with the latest and most accurate information on drugs, medical devices, procedures and related lawsuits. Emily holds five Health Literacy certificates from the Centers for Disease Control and Prevention as well as a Bachelor of Science in Journalism from the University of Florida. She is a member of The Alliance of Professional Health Advocates, the American Association for the Advancement of Science, the Society of Professional Journalists and the Society for Technical Communication.