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.

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

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Assess renal function prior to initiation of KAZANO and periodically thereafter.

KAZANO is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m².

KAZANO is not recommended in patients with an eGFR between 30 and 60 mL/min/1.73 m² because these patients require a lower daily dosage of alogliptin than what is available in the fixed combination KAZANO product.

Discontinue KAZANO at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m²; in patients with a history of liver disease, alcoholism or heart failure, or in patients who will be administered intra-arterial iodinated contrast.

KAZANO is contraindicated in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin.

After initiation of KAZANO, patients should be observed for signs and symptoms of pancreatitis. If pancreatitis is suspected, alogliptin should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using KAZANO.

If abnormal liver tests persist or worsen, KAZANO should be interrupted and investigation done to establish the probable cause.

Consider the risks and benefits of KAZANO prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy.

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin. These reactions include anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome.

Decrease to subnormal levels of previously normal serum vitamin B12 levels.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors.

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP inhibitor.

Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving KAZANO.

Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with KAZANO.

Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce nonanion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with KAZANO may increase the risk of lactic acidosis. Consider more frequent monitoring of these patients.

Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis.

Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and isoniazid. When such drugs are administered to a patient receiving KAZANO, the patient should be closely observed for loss of blood glucose control.

There is the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some premenopausal anovulatory women.

Limited available data with KAZANO or alogliptin in pregnant women are not sufficient to inform a 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.

There is no information regarding the presence of KAZANO or alogliptin in human milk, the effects on the breastfed infant, or the effects on milk production. Alogliptin is present in rat milk. Limited published studies report that metformin is present in human milk.

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• Use in patients under the age of 18. GoToSource

Worsening heart failure. GoToSource

Kidney injury. GoToSource

Liver injury and hypoglycemia (low blood sugar). GoToSource

Pancreatitis (inflammation of the pancreas). GoToSource

Severe joint pain. GoToSource

Anaphylaxis (life-threatening allergic reaction), angioedema (swelling in the deep layers of skin) and cutaneous reactions including bullous pemphigoid (skin blistering disorder). GoToSource

Vitamin B12 deficiency. GoToSource

Lactic acidosis (too much acid in the body). GoToSource

Lawsuits filed for heart failure, pancreatitis, pancreatic cancer and rhabdomyolysis.