Xigduo XR Side Effects, Cost, Dosing, And Prescribing Information For Type 2 Diabetes

Xigduo XR (dapagliflozin, metformin ER) Side Effects, Cost, Dosing, Approval, And Prescribing Information For Type 2 Diabetes Category: Diabetes by Nhan Le, PharmD - May 28, 2015 | Views: 49376 | Likes: 1 | Comment: 1

Xigduo XR for type 2 diabetes

Brand Name: Xigduo XR
Generic Name: Dapagliflozin and Metformin Extended-Release

Drug Class: Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor
Similar Medications: Invokament (canagliflozin/metformin)
Manufacturer: AstraZeneca
FDA Approval Date: October 29, 2014

What is Xigduo XR and its mechanism of action?

Xigduo XR is an oral combination drug used for treating type 2 diabetes. It contains dapagliflozin, an SGLT2 inhibitor, and metformin ER, a biguanide. Dapagliflozin reduces glucose reabsorption in the kidneys by blocking the sodium-glucose co-transporter-2 (SGLT2). The sodium-glucose co-transporter-2 is a protein in the kidney that is responsible for reabsorbing glucose back into the body. Metformin improves glucose tolerance and utilization. According to the American Diabetes Association 2015 guidelines, metformin is the preferred initial drug of choice for treating type 2 diabetes. Dapagliflozin and metformin have complementary mechanisms that contribute to insulin-independent blood glucose control.

What is Xigduo XR used for treating?

Xigduo XR is approved for the treatment of adults with type 2 diabetes who require dapagliflozin and metformin.

Type 2 diabetes is a chronic condition characterized by elevated blood glucose and increased risk of cardiovascular diseases, blindness, kidney disease, and amputations. In 2012, diabetes affected about 29.1 million people in the US with type 2 diabetes accounting for 90-95% of cases. In 2012, the total costs of diagnosed diabetes was $245 billion in the US.

Xigduo XR is not indicated for treatment of type 1 diabetes or diabetic ketoacidosis.

How effective is Xigduo XR in controlling type 2 diabetes?

The effect of Xigduo is similar to the effect of taking metformin plus dapagliflozin as separate tablets. Xigduo increases convenience by combining both agents into a single pill. In addition, bioequivalence tests show equivalence between Xigduo XR tablets and its individual components.

In a dapagliflozin study A1C reduction was 0.58% with the 2.5 mg dose, 0.77% with the 5 mg dose, and 0.89% with the 10 mg dose compared to a 0.23% reduction with placebo. In a metformin study patients taking metformin attained lower mean fasting blood glucose (FBG) of 189 mg/dL and A1C of 7.1% compared to FBG of 244 mg/dL and A1C of 8.6% for the placebo group.

In a study of dapagliflozin as add-on therapy to metformin, there was a -0.5% difference in A1C with dapagliflozin 10 mg and -0.4% difference in A1C with the 5 mg dose when compared to placebo. In addition, there was a -17.5 mg/dL difference in FBG with the 10 mg dose and -15.5 mg/dL difference with the 5 mg dose when compared to placebo.

Interesting facts about Xigduo XR

Xigduo XR is a once-daily dosing combination agent with an SGLT2 inhibitor.
Xigduo XR can be used in any stage of diabetes because dapagliflozin and metformin reduce blood glucose via insulin-independent mechanisms.
Xigduo XR provides modest weight loss and blood pressure reduction.

The inactive ingredients may appear in feces as a soft, hydrated mass that may look like the original tablet.

What is the dosage of Xigduo XR?

Xigduo XR combination tablets are available in the following strengths:

5 mg dapagliflozin/500 mg metformin ER
5 mg dapagliflozin/1000 mg metformin ER
10 mg dapagliflozin/500 mg metformin ER
10 mg dapagliflozin/1000 mg metformin ER

Xigduo XR starting doses are individualized per patient based on their medical history, conditions, and treatment. The dose should be gradually increased and the maximum dose is 10 mg dapagliflozin and 2000 mg metformin.

Xigduo XR tablets are taken once daily with food to minimize gastrointestinal (GI) side effects. The tablet should be swallowed whole and never crushed, cut, or chewed. The inactive ingredients may appear in feces as a soft, hydrated mass that may look like the original tablet.

Store Xigduo XR tablets at room temperature between 68°F and 77°F (20°C and 25°C).

What are side effects of Xigduo XR?

Xigduo has the same side effects as dapagliflozin and metformin. Common side effects of Xigduo include yeast infections, urinary tract infection, stuffy or runny nose, sore throat, headache, nausea, vomiting, and diarrhea. The risk of hypoglycemia increases when it is combined with other diabetes medications.

Learn more about the side effects of dapagliflozin and metformin.

What are Xigduo XR drug interactions?

Cationic drugs may compete with metformin for renal elimination and alter its efficacy and risk of toxicity.

Examples of cationic drugs include:

Cimetidine
Digoxin
Triamterene
Trimethoprim
Vancomycin.

Medications that increase blood glucose will reduce the blood glucose reducing effects of Xigduo XR.

Medications that increase blood glucose include:

Thiazides
Corticosteroids
Thyroid products
Estrogens
Oral contraceptives
Calcium channel blockers
Nicotinic acid

When medications that increase blood glucose are stopped patients should closely monitor their blood glucose to avoid hypoglycemia. The risk of hypoglycemia increases when Xigduo XR is taken with other diabetes medications.

Learn more about medications that increase blood glucose.

What are warnings and precautions for Xigduo XR?

Xigduo XR is should not be used by patients with moderate-to-severe renal impairment (serum creatinine levels >1.5 mg/dL for men and >1.4 mg/dL for women, or CrCL <60 mL/min) due to the risk of metformin accumulation.

Xigduo XR should not be used in patients with hypersensitivity to dapagliflozin or metformin and in patients with acute or chronic metabolic acidosis with or without coma.

Xigduo XR may cause lactic acidosis, a rare but serious complication, caused by metformin accumulation. Excessive alcohol intake, liver or kidney impairment, and acute congestive heart failure increase the risk of lactic acidosis.

Xigduo XR should be stopped temporarily in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids.

Lactic acidosis may lead to complications such as cardiovascular shock, acute congestive heart failure, acute myocardial infarction, and other conditions associated with hypoxemia. The symptoms appear gradually and include weakness, muscle pain, abdominal distress, respiratory distress, and drowsiness. Lactic acidosis is a medical emergency and must be treated in a hospital setting.

Xigduo XR may cause hypotension due to dapagliflozin and symptoms include dizziness, lightheadedness, clammy skin, and loss of consciousness. Patients who have renal impairment or are taking antihypertensive medications are at greater risk for hypotension.

Xigduo XR is not recommended for patients with impaired liver function due to the increased risk of lactic acidosis from metformin.

Xigduo XR may decrease vitamin B₁₂ levels because of the metformin component. Vitamin B₁₂ supplementation may be recommended.

Cases of bladder cancer have been reported in patients treated with dapagliflozin. Dapagliflozin is not recommended for patients with active bladder cancer. For patients with a history of bladder cancer, the benefits of Xigduo XR versus the unknown risks of cancer recurrence should be considered.

SGLT2 inhibitors, including dapagliflozin, have been associated with an increased risk of diabetic ketoacidosis (DKA). Learn more about SGLT2 inhibitors and risk of DKA.

Learn more about contraindications of dapagliflozin and metformin.

Can pregnant or breastfeeding women take Xigduo XR?

Xigduo XR should only be used during pregnancy if the benefits outweigh the risks to the fetus. Breastfeeding women should not take Xigduo XR because both dapagliflozin and metformin are excreted into milk.

What is the cost of Xigduo XR?

The average wholesale price per tablet of Xigduo XR are:

$12.48 for 5/500, 10/500, and 10/1000 mg tablets

$6.24 for 5/1000 mg tablets

How to obtain prescription cost assistance for Xigduo XR

Use these resources for cost assistance:

AZ&Me Prescription Savings Programs

Xigduo Savings Card and Coupon

Call 1-800-AZandMe (292-6363), for any questions regarding AstraZeneca programs, eligibility requirements, or the application process

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