Kazano

Instructions

Metformin must be taken with food

Swallow whole, do not chew, split, or crush

Kazano is part of the drug class:

• Combinations of oral blood glucose lowering drugs

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known whether Kazano passes into your breast milk. Talk with your doctor about the best way to feed your baby if you are taking 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 schedule. Do not take 2 doses of Kazano at the same time.
• If you take too much Kazano, call your doctor or go to the nearest hospital emergency room right away.
• 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.

The dose your doctor recommends will depend on several factors including:

• the medications you are currently taking
• other medical conditions you have
• how well Kazano works for you
• how well you tolerate the medication (side effects)

The maximum recommended daily dose is 25 mg alogliptin and 2000 mg metformin.

WARNING: LACTIC ACIDOSIS

• Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.
• The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. 
• If acidosis is suspected, Kazano should be discontinued and the patient hospitalized immediately.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Monotherapy and Combination Therapy

Kazano is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both alogliptin and metformin is appropriate [see Clinical Studies (14)].

Important Limitations of Use

Kazano is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Alogliptin and Metformin Hydrochloride

No carcinogenicity, mutagenicity or impairment of fertility studies have been conducted with Kazano. The following data are based on findings in studies performed with alogliptin or metformin individually.

Alogliptin

Rats were administered oral doses of 75, 400 and 800 mg/kg alogliptin for two years. No drug-related tumors were observed up to 75 mg/kg or approximately 32 times the maximum recommended clinical dose of 25 mg, based on area under the plasma concentration curve (AUC) exposure. At higher doses (approximately 308 times the maximum recommended clinical dose of 25 mg), a combination of thyroid C-cell adenomas and carcinomas increased in male but not female rats. No drug-related tumors were observed in mice after administration of 50, 150 or 300 mg/kg alogliptin for two years, or up to approximately 51 times the maximum recommended clinical dose of 25 mg, based on AUC exposure.

Alogliptin was not mutagenic or clastogenic, with and without metabolic activation, in the Ames test with S. typhimurium and E. coli or the cytogenetic assay in mouse lymphoma cells. Alogliptin was negative in the in vivo mouse micronucleus study.

In a fertility study in rats, alogliptin had no adverse effects on early embryonic development, mating or fertility, at doses up to 500 mg/kg, or approximately 172 times the clinical dose based on plasma drug exposure (AUC).

Metformin Hydrochloride

Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg and 1500 mg/kg, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin in male rats. There was an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg.

There was no evidence of a mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells) or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.

Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons.

Kazano tablets are available in the following strengths and packages:

12.5 mg/500 mg tablet: pale yellow, oblong, film-coated tablets with "12.5/500" debossed on one side and "322M" debossed on the other side, available in:

12.5 mg/1000 mg tablet: pale yellow, oblong, film-coated tablets with "12.5/1000" debossed on one side and "322M" debossed on the other side, available in:

Storage

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed.

Kazano contains a combination of alogliptin and metformin. Alogliptin and metformin are oral diabetes medicines that help control blood sugar levels.

Metformin works by decreasing glucose (sugar) production in the liver and decreasing absorption of glucose by the intestines. Alogliptin works by regulating the levels of insulin your body produces after eating.

Kazano is used with diet and exercise to improve blood sugar control in adults with type 2 diabetes.

Kazano is not for treating type 1 diabetes.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You may have signs of low blood sugar, such as extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

Avoid drinking alcohol. It lowers blood sugar and may increase your risk of lactic acidosis.

Common side effects of Kazano include: lactic acidosis, nausea, vomiting, and hypoglycemia. Other side effects include: upper respiratory tract infection, abdominal distress, headache, and nasopharyngitis. See below for a comprehensive list of adverse effects.