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Farxiga

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Farxiga (dapagliflozin) belongs to a class of drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It effectively treats Type 2 diabetes by excreting extra sugar in the urine. But medical studies and FDA safety communications link it to diabetic ketoacidosis, kidney problems and bladder cancer.

AstraZeneca and Bristol-Myers Squibb’s Farxiga (dapagliflozin) is an oral Type 2 diabetes medication that belongs to a class called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It is the second drug approved in its class. Originally approved in 2014, Farxiga controls blood sugar by preventing the kidneys from reabsorbing sugar and releasing it into the blood. The excess sugar then leaves the body through the urine. The same year, the U.S. Food & Drug Administration approved Xigduo XR, an extended release formula that combines dapagliflozin and metformin.

Each year, more people receive prescriptions for Farxiga. In 2015 alone, AstraZeneca reported $492 million in revenue from the drug. That is more than double what it made in 2014. In the first quarter of 2016, it has already made $165 million worldwide — $94 million in the U.S. alone.

While Farxiga is effective at controlling blood-sugar levels, studies also link it to a number of serious side effects. The FDA released several safety communications warning patients and doctors that Farxiga and other SGLT2 inhibitors may lead to a potentially fatal condition called diabetic ketoacidosis (DKA). If left untreated, DKA can lead to coma and death.

Patients who developed DKA and other serious side effects filed lawsuits against AstraZeneca and other manufacturers of SGLT2 inhibitors such as Johnson & Johnson’s Janssen Pharmaceuticals. Plaintiffs who filed against AstraZeneca said Farxiga caused them to suffer DKA and kidney failure, according the company’s 2015 Annual Report.

Farxiga’s Serious Side Effects

While the most common side effect found in studies is female yeast infections, FDA warnings and recent studies link Farxiga to side effects that can be fatal. According to FDA reports, several patients required hospitalization.

Diabetic Ketoacidosis

In May 2015, the FDA warned Farxiga and other SGLT2 inhibitors may lead to diabetic ketoacidosis (DKA), a condition that occurs when the body breaks down fat for energy. The breakdown of fat produces waste produces called ketones. Ketones become toxic when they build up in the blood.

The FDA received about 20 reports of ketoacidosis in patients treated with SGLT2 inhibitors, including Farxiga, from March 2013 to June 6, 2014. The agency ordered manufacturers to add warnings to the drugs’ labels in December 2015. The FDA is still receiving reports of DKA associated with these drugs.

DKA is a serious condition and patients who notice any of these symptoms should contact a doctor or emergency room immediately.

Symptoms of DKA include:

  • Aching muscles or muscle stiffness
  • Confusion
  • Difficulty breathing
  • Flushed face
  • Frequent urination or thirst that lasts for a day or more
  • Fruity-smelling breath
  • Stomach pain
  • Unusual fatigue or sleepiness
  • Vomiting and nausea

Kidney Injury

In June 2016, the FDA strengthened the acute kidney injury (AKI) warning for Farxiga and Xigduo XR. According to the FDA, more than 100 people reported suffering kidney injuries after taking Farxiga or Invokana, between March 2013 and October 2015. These cases are the only ones reported to the FDA Adverse Event Reporting System, and there may be more unreported cases. About 50 percent of the cases occurred within one month of starting the drug.

The FDA recommends patients with signs of kidney injuries to seek medical attention immediately.

Symptoms of AKI include:

  • Chest pain or pressure
  • Confusion
  • Fatigue or tiredness
  • Nausea
  • Seizures or coma in severe cases
  • Shortness of breath
  • Swelling in legs, ankles and around the eyes
  • Too little urine leaving the body

Bladder Cancer

During clinical trials, an increased number of patients suffered bladder cancers. As a result, the FDA does not recommend Farxiga for people with active bladder cancer. People with a history of bladder cancer should talk to their doctor. The FDA previously rejected Farxiga’s approval based on bladder and breast-cancer concerns.

In clinical trials, researchers discovered 10 out of 6,045 people who took Farxiga had new cases of bladder cancer, compared to one case in a patient who took a placebo. According to AstraZeneca’s medication insert, “There were too few cases to determine whether the emergence of these events is related to Farxiga.”

The most common side effects include:

  • Female and male yeast infections
  • Colds
  • Back pain
  • Increased urination
  • Nausea
  • Flu
  • Increased cholesterol
  • Constipation
  • Discomfort urinating
  • Drop in blood pressure
  • Dehydration

Farxiga Use in Pregnant Women

Farxiga has not been tested adequately in pregnant women. In animal studies, researchers found Farxiga affects kidney development in fetuses. Birth defects occurred at doses 1,441 times the maximum clinical dose in rats. These included malformations of ribs, vertebra, skeletons and blood vessels. Studies also showed Farxiga is excreted in rat milk and juvenile rats exposed to the drug risked problems with kidney development.

“Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney,” according to safety information. Nursing mothers should decide whether to discontinue use of Farxiga.

FDA-Required Postmarket Studies

Scientists evaluated Farxiga’s safety and efficacy in 16 clinical trials with about 9,400 people with Type 2 diabetes. Trials showed an improvement in HbA1C — an indication of blood-sugar control. But the FDA flagged some outcomes that might pose potential risks to patients and require more data. After the agency approved the drug, it ordered AstraZeneca to conduct postmarket studies to determine more safety points and efficacy outcomes.

According to the FDA, it is requiring six post-marketing studies including:

  • An assessment of bladder-cancer risk
  • A cardiovascular outcomes trial to check heart safety in patients with risks
  • Animal studies for bladder tumor growth
  • Program to monitor liver abnormalities and pregnancy outcomes
  • Two clinical studies for Farxiga use in pediatric patients

One trial called DECLARE is already underway. This trial will collect data to determine if Fraxiga presents an increased risk in cardiovascular or liver problems. This trial will follow more than 17,000 people for four to five years.

Clinical Trials

Researchers studied Farxiga as a standalone therapy and in combination with other drugs to treat Type 2 diabetes. Some of the drugs studied in combination include metformin, Actos (pioglitazone), glimepiride, Januvia (sitagliptin ) and insulin.

In a study, 840 patients with inadequately controlled diabetes received Farxiga or placebo. After 24 weeks, people who took the 10 mg dose achieved the best results. About 50 percent achieved HbA1C levels of less than 7 percent, which is the recommended target point for adults with diabetes. About 44 percent of patients who took a 5 mg dose achieved the same results.

Patients with kidney problems did not have any benefits in studies.

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