Saxagliptin/metformin

Mechanism of Action

Saxagliptin: Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic control

Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance and lowers both basal and postprandial plasma glucose

Pharmacokinetics

Half-Life: saxagliptin 2.5-3.1 hr; metformin 6.2 hr (plasma) and 17.6 hr (blood)

Peak Plasma Time: metformin extended-release 4-8 hr

Peak Plasma Concentration: saxagliptin and active metabolite (24 ng/mL, 47 ng/mL)

Protein Bound: negligible for both saxagliptin and metformin

Metabolism: saxagliptin by CYP3A4/5; major active metabolite is also a DPP4 inhibitor (50% as potent); metformin is excreted unchanged in urine and does not undergo hepatic metabolism

Excretion: feces (saxagliptin 22%), urine (saxagliptin 75%; metformin 90%)  

Saxagliptin & Metformin is part of the drug class:

• Combinations of oral blood glucose lowering drugs

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone.

Tell your healthcare provider if you will be starting or stopping certain other types of medicines, such as antibiotics, or medicines that treat fungus or HIV/AIDS, because your dose of saxagliptin/metformin might need to be changed.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Serious side effects can happen in people taking saxagliptin/metformin, including:

1. Lactic Acidosis. Metformin, one of the medicines in saxagliptin/metformin, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital.

Stop taking saxagliptin/metformin and call your healthcare provider right away if you get any of the following symptoms of lactic acidosis:

• feel very weak and tired
• have unusual (not normal) muscle pain
• have trouble breathing
• have unusual sleepiness or sleep longer than usual
• have unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea
• feel cold, especially in your arms and legs
• feel dizzy or lightheaded
• have a slow or irregular heartbeat

• have kidney problems. People whose kidneys are not working properly should not take saxagliptin/metformin.
• have liver problems.
• have congestive heart failure that requires treatment with medicines.
• drink a lot of alcohol (very often or short-term “binge” drinking).
• get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids.
• have certain x-ray tests with injectable dyes or contrast agents.
• have surgery.
• have a heart attack, severe infection, or stroke.
• are 80 years of age or older and have not had your kidney function tested.

2. Inflammation of the pancreas (pancreatitis) which may be severe and lead to death. Certain medical problems make you more likely to get pancreatitis. Before you start taking saxagliptin/metformin:

• inflammation of your pancreas (pancreatitis)
• stones in your gallbladder (gallstones)
• a history of alcoholism
• high blood triglyceride levels
• a history of a serious hypersensitivity reaction to saxagliptin/metformin, such as anaphylaxis, angioedema, or exfoliative skin conditions

It is not known if having these medical problems will make you more likely to get pancreatitis with saxagliptin/metformin.

Stop taking saxagliptin/metformin and contact your healthcare provider right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

3. Low blood sugar (hypoglycemia) may become worse in people who also take another medication to treat diabetes, such as sulfonylureas or insulin. Tell your healthcare provider if you take other diabetes medicines. If you have symptoms of low blood sugar, you should check your blood sugar and treat if low, then call your healthcare provider. Symptoms of low blood sugar include:

• shaking
• sweating
• rapid heartbeat
• change in vision
• hunger
• headache
• change in mood

4. Severe and persistent joint pain. If you experience severe and persistent joint pain, contact your doctor right away. Do not stop taking your medication. Your doctor will decide if your medication is the possible cause of severe  joint pain and will discontinue the drug if appropriate.

5. Allergic (hypersensitivity) reactions, such as:

• swelling of your face, lips, throat, and other areas on your skin
• difficulty with swallowing or breathing
• raised, red areas on your skin (hives)
• skin rash, itching, flaking, or peeling

• have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in your blood or urine)
• have kidney problems
• have a history of a serious hypersensitivity reaction to saxagliptin/metformin, such as anaphylaxis, angioedema, or exfoliative skin conditions

Follow dietary (food) recommendations made by your doctor and dietitian which should include a healthy diet. Skipping meals should be avoided as this can cause problems maintaining blood sugar control. There are no specific foods to avoid while using saxagliptin/metformin.

Before you take saxagliptin/metformin, tell your healthcare provider if you:

• have type 1 diabetes. saxagliptin/metformin should not be used to treat type 1 diabetes.
• have a history or risk for diabetic ketoacidosis (high levels of certain acids, known as ketones, in the blood or urine). Saxagliptin/metformin should not be used for the treatment of diabetic ketoacidosis.
• have kidney problems.
• have liver problems.
• have heart problems, including congestive heart failure.
• are older than 80 years. If you are over 80 years old you should not take saxagliptin/metformin unless your kidneys have been checked and they are normal.
• drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking.
• are going to get an injection of dye or contrast agents for an x-ray procedure or if you are going to have surgery and will not be able to eat or drink much. In these situations, saxagliptin/metformin will need to be stopped for a short time. Talk to your healthcare provider about when you should stop saxagliptin/metformin and when you should start saxagliptin/metformin again.
• have any other medical conditions.
• are pregnant or plan to become pregnant. It is not known if saxagliptin/metformin will harm your unborn baby. If you are pregnant, talk with your healthcare provider about the best way to control your blood sugar while you are pregnant.
• are breastfeeding or plan to breastfeed. It is not known if saxagliptin/metformin passes into your breast milk. Talk with your healthcare provider about the best way to feed your baby while you take saxagliptin/metformin.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Store saxagliptin/metformin between 68°F and 77°F (20°C and 25°C).

Keep saxagliptin/metformin and all medicines out of the reach of children.