Kazano

What is Kazano?

Kazano contains 2 prescription diabetes medicines, alogliptin (NESINA) and metformin hydrochloride. Kazano is a prescription medicine used along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.

Kazano is not for people with type 1 diabetes. It is not known if Kazano is safe and effective in children under the age of 18.

Description

KAZANO tablets contain two oral antihyperglycemic drugs used in the management of type 2 diabetes: alogliptin and metformin hydrochloride.

 

Metformin Hydrochloride

Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5∙HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown:

KAZANO is available as a tablet for oral administration containing 17 mg alogliptin benzoate equivalent to 12.5 mg alogliptin and:

• 500 mg metformin hydrochloride which is equivalent to 389.93 mg metformin base (12.5 mg/500 mg) or
• 1000 mg metformin hydrochloride which is equivalent to 779.86 mg metformin base (12.5 mg/1000 mg).

KAZANO tablets contain the following inactive ingredients: mannitol, microcrystalline cellulose, povidone, crospovidone, and magnesium stearate; the tablets are film-coated with hypromellose 2910, talc, titanium dioxide and ferric oxide yellow.

Mechanism of Action

 

Alogliptin and Metformin Hydrochloride

KAZANO combines two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes: alogliptin, a selective inhibitor of DPP-4, and metformin HCl, a member of the biguanide class.

 

Alogliptin

Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

 

Metformin Hydrochloride

Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may actually decrease.

What is the most important information I should know about Kazano?

Kazano can cause serious side effects, including:

1. Lactic Acidosis. Metformin, one of the medicines in Kazano, can cause a rare but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital.
Call your doctor right away if you have any of the following symptoms, which could be signs of lactic acidosis:

• you feel cold in your hands or feet
• you feel dizzy or lightheaded
• you have a slow or irregular heartbeat
• you feel very weak or tired
• you have unusual (not normal) muscle pain
• you have trouble breathing
• you feel sleepy or drowsy
• you have stomach pains, nausea or vomiting

Most people who have had lactic acidosis with metformin have other things that, combined with metformin, led to the lactic acidosis. Tell your doctor if you have any of the following, because you have a higher chance for getting lactic acidosis with Kazano if you:

• have severe kidney problems or your kidneys are affected by certain x-ray tests that use injectable dye
• have liver problems
• drink alcohol very often, or drink a lot of alcohol in 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 surgery
• have a heart attack, severe infection, or stroke

The best way to keep from having a problem with lactic acidosis from metformin is to tell your doctor if you have any of the problems listed above. You doctor may decide to stop Kazano for a while if you have any of these things.

Kazano can have other serious side effects. See “What are the possible side effects of Kazano?”

2. Inflammation of the pancreas (pancreatitis). Alogliptin, one of the medicines in Kazano, may cause pancreatitis, which may be severe. Certain medical conditions make you more likely to get pancreatitis.

Before you start taking Kazano:
Tell your doctor if you have ever had:

• pancreatitis
• high blood triglyceride levels
• kidney problems
• stones in your gallbladder (gall stones)
• liver problems
• history of alcoholism

Stop taking Kazano and call your doctor 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. Heart failure: Heart failure means your heart does not pump blood well enough.

Before you start taking Kazano:
Tell your healthcare provider if you have ever had heart failure or have problems with your kidneys.
Contact your healthcare provider right away if you have any of the following symptoms:

• increasing shortness of breath or trouble breathing especially when lying down
• an unusually fast increase in weight
• unusual tiredness
• swelling of feet, ankles, or legs

These may be symptoms of heart failure.

Who should not take Kazano?

Do not take Kazano if you:

• have severe kidney problems
• have a condition called metabolic acidosis or have had diabetic ketoacidosis (increased ketones in your blood or urine)
• are going to get an injection of dye or contrast agents for an x-ray procedure, Kazano may need to be stopped for a short time. Talk to your doctor about when you should stop Kazano and when you should start Kazano again
• are allergic to alogliptin (NESINA) or metformin or any of the ingredients in Kazano or have had a serious allergic (hypersensitivity) reaction to alogliptin or metformin. See the end of this Medication Guide for a complete list of the ingredients in Kazano

Symptoms of a serious allergic reaction to Kazano may include:

• 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

If you have any of these symptoms, stop taking Kazano and contact your doctor or go to the nearest hospital emergency room right away.

What should I tell my healthcare provider before taking Kazano?

Before you take Kazano, tell your doctor if you:

• have or have had inflammation of your pancreas (pancreatitis)
• have severe kidney or liver problems
• have heart problems, including congestive heart failure
• are going to get an injection of dye or contrast agents for an x-ray procedure, Kazano may need to be stopped for a short time. Talk to your doctor about when you should stop Kazano and when you should start Kazano again
• drink alcohol very often or drink a lot of alcohol in short-term “binge” drinking
• have other medical conditions
• are pregnant or plan to become pregnant. It is not known if Kazano will harm your unborn baby. Talk with your doctor about the best way to control your blood sugar while you are pregnant or if you plan to become pregnant
• are breastfeeding or plan to breastfeed. It is not known if Kazano passes into your breast milk. Talk with your doctor about the best way to feed your baby if you are taking Kazano

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist before you start any new medicine.

Kazano may affect the way other medicines work, and other medicines may affect how Kazano works. Contact your doctor before you start or stop other types of medicines.

How should I take Kazano?

• Take Kazano exactly as your doctor tells you to take it.
• Take Kazano 2 times each day.
• Take Kazano with food to lower your chances of having an upset stomach.
• Do not break or cut Kazano tablets before swallowing.
• Your doctor may need to change your dose of Kazano to control your blood glucose. Do not change your dose unless told to do so by your doctor.
• If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose, and take the next dose at your regular time. Do not take 2 doses of Kazano at the same time.
• If you take too much Kazano, call your doctor or your poison control center right away at 1-800-222-1222.
• If your body is under stress, such as from fever, infection, accident or surgery, the dose of your diabetes medicines may need to be changed. Call your doctor right away.
• Stay on your diet and exercise programs and check your blood sugar as your doctor tells you to.
• Your doctor may do certain blood tests before you start Kazano and during treatment as needed. Your doctor may ask you to stop taking Kazano based on the results of your blood tests due to how well your kidneys are working.
• Your doctor will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C.

What are the possible side effects of Kazano?

Kazano can cause serious side effects, including:

• See “What is the most important information I should know about Kazano?”
• Serious allergic (hypersensitivity) reactions, such as:
  • swelling of your face, lips, throat and other areas on your skin
  • difficulty swallowing or breathing
  • raised, red areas on your skin (hives)
  • skin rash, itching, flaking or peeling

If you have these symptoms, stop taking Kazano and contact your doctor right away or go to the nearest hospital emergency room.

• Liver problems. Call your doctor right away or go to the nearest hospital emergency room if you have unexplained symptoms, such as:
  • nausea or vomiting
  • stomach pain
  • unusual or unexplained tiredness
  • loss of appetite
  • dark urine
  • yellowing of your skin or the whites of your eyes
• Low Vitamin B12 levels. Some people taking metformin one of the medicines in Kazano had low levels of Vitamin B12. Your doctor should do blood tests every year and check your Vitamin B12 levels every 2 to 3 years while you are taking Kazano.
• Low blood sugar (hypoglycemia). If you take Kazano with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take Kazano. If you have symptoms of low blood sugar, you should check your blood sugar and treat if low, and then call your doctor. Signs and symptoms of low blood sugar may include:
  • shaking or feeling jittery
  • fast heartbeat
  • hunger
  • change in mood
  • dizziness
  • sweating
  • change in vision
  • headache
  • confusion
• Joint pain. Some people who take medicines called DPP-4 inhibitors, one of the medicines in Kazano, may develop joint pain that can be severe. Call your doctor if you have severe joint pain.
• Skin reaction. Some people who take medicines called DPP-4 inhibitors, one of the medicines in Kazano, may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your doctor right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your doctor may tell you to stop taking Kazano.

The most common side effects of Kazano include:

• cold-like symptoms (upper respiratory tract infection)
• stuffy or runny nose and sore throat
• diarrhea
• increase in blood pressure
• headache
• back pain
• urinary tract infection

Taking Kazano with food can help lessen the common stomach side effects of metformin that usually happen at the beginning of treatment. If you have unexplained stomach problems, tell your doctor. Stomach problems that start later, during treatment, may be a sign of something more serious.

Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Kazano. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Kazano

Medicines are sometimes prescribed for purposes other than those listed in the Medication Guide. Do not take Kazano for a condition for which it was not prescribed. Do not give Kazano to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Kazano. If you would like to know more information, talk with your doctor. You can ask your doctor or pharmacist for information about Kazano that is written for health professionals.

For more information go to www.kazano.com or call 1-877-TAKEDA-7 (1-877-825-3327).

How should I store Kazano?

• Store Kazano at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep the container of Kazano tightly closed.

Keep Kazano and all medicines out of the reach of children.

What are the ingredients in Kazano?

Active ingredients: alogliptin and metformin hydrochloride

Inactive ingredients: mannitol, microcrystalline cellulose, povidone, crospovidone and magnesium stearate; the tablets are film-coated with hypromellose 2910, talc, titanium dioxide and ferric oxide yellow.

Label

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PRINCIPAL DISPLAY PANEL – 12.5 MG/500 MG BOTTLE LABEL

• NDC 64764-335-60
• Kazano
• (alogliptin and
  metformin HCl) tablets
• 12.5* mg/500 mg
• Dispense with
  Medication Guide
• 60 Tablets
• Takeda
  Rx Only

PRINCIPAL DISPLAY PANEL – 12.5 MG/1000 MG BOTTLE LABEL