Saxagliptin-Metformin

Saxagliptin-Metformin is a combination medicine used for the treatment of type 2 diabetes mellitus.

• Saxagliptin-Metformin is available under the following different brand names: Kombiglyze XR

Common side effects of Saxagliptin-Metformin include:

• diarrhea,
• nausea,
• headache,
• runny or stuffy nose,
• sneezing, and
• sore throat

Serious side effects of Saxagliptin-Metformin include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• itching,
• peeling skin,
• severe pain in the upper stomach spreading to the back,
• nausea,
• vomiting,
• loss of appetite,
• fast heartbeats,
• unusual muscle pain,
• feeling cold,
• dizziness,
• lightheadedness,
• tiredness,
• weakness,
• stomach pain,
• irregular heart rate,
• blisters,
• breakdown of the outer layer of skin,
• severe or ongoing pain in the joints,
• pain or burning while urinating,
• shortness of breath,
• swelling in the legs or feet, and
• rapid weight gain

Rare side effects of Saxagliptin-Metformin include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet, extended-release

• 5 mg/500 mg
• 2.5 mg/1000 mg
• 5 mg/1000 mg

Diabetes Mellitus Type 2

Adult and geriatric dosage

• Individualize starting dose based on the patient’s current regimen
• Adjust dose according to effectiveness and tolerability; not to exceed the daily dose of 5 mg/2000 mg
• Administer every day with evening meal
• Inadequately controlled on metformin alone
• 2.5-5 mg/day saxagliptin oral plus a current dose of metformin
• Inadequately controlled on saxagliptin alone
• 500 mg/day metformin oral plus 5 mg/day oral saxagliptin

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Saxagliptin-Metformin has severe interactions with no other drugs.
• Saxagliptin-Metformin has serious interactions with at least 26 other drugs.
• Saxagliptin-Metformin has moderate interactions with at least 252 other drugs.
• Saxagliptin-Metformin has minor interactions withat least 139 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• History of serious hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions)
• Severe renal disease: eGFR less than 30 ml/min/1.73 m²
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (should be treated with insulin)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Saxagliptin-Metformin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Saxagliptin-Metformin?”

Cautions

• Gradual increase of metformin dose may reduce GI side effects
• Metformin may decrease serum vitamin B12 concentration
• Do not exceed saxagliptin 2.5 mg/day when coadministered with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (eg, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)
• Coadministration of saxagliptin with thiazolidinediones (eg, rosiglitazone, pioglitazone) increases risk for peripheral edema
• Inactive tablet ingredients (i.e., ghost tablet) may be eliminated in the feces as a soft, hydrated mass
• Pancreatitis reported with saxagliptin; monitor for signs and symptoms and discontinue if pancreatitis suspected
• Serious hypersensitivity reactions with saxagliptin reported (typically within the first 3 months of therapy)
• Caution with history of angioedema
• Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
• Iodinated contrast imaging procedures
  • Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
  • Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
• Hypoglycemia
  • Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol
  • Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects
  • Insulin secretagogues, such as sulfonylureas, cause hypoglycemia; therefore, when used in combination with saxagliptin, a lower dose of the insulin secretagogue may be required to reduce the risk of hypoglycemia
• Congestive heart failure (CHF) risks
  • In the SAVOR-TIMI 53 trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) 16,492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo
  • A higher incidence of hospitalization for CHF was observed in patients treated with saxagliptin compared with those treated with placebo (3.5% vs 2.8%; P=0.007); this increased risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease
  • Circulation. 2014 Oct 28;130(18):1579-88

Pregnancy and Lactation

• Limited available data in pregnant women are not sufficient to determine drug-associated risk for major birth defects and miscarriage; published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk
• No adverse developmental effects independent of maternal toxicity observed when saxagliptin and metformin were administered separately or in combination to pregnant rats and rabbits during period of organogenesis
• Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes increases fetal risk for major malformations, still birth, and macrosomia related morbidity
• Lactation
  • There is no information regarding presence of metformin or alogliptin in human milk, effects on breastfed infant, or effects on milk production; limited published studies report that metformin is present in human milk; however, there is insufficient information to determine effects of metformin on breastfed infant and no available information on effects of metformin on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition