Kazano Side Effects Center

Last updated on RxList: 3/25/2022
Kazano Side Effects Center

What Is Kazano?

Kazano (alogliptin and metformin HCl) is an antidiabetic medication used to treat type 2 diabetes mellitus, along with diet and exercise.

What Are Side Effects of Kazano?

Common side effects of Kazano include:

Patients with impaired kidneys, acute or chronic metabolic acidosis, including diabetic ketoacidosis should not take Kazano. Kazano is not recommended in patients with a history of hypersensitivity reaction to alogliptin or metformin, which are components of Kazano.

Dosage for Kazano

Kazano is available in doses of 12.5 mg alogliptin and 500 mg metformin HCl; and 12.5 mg alogliptin and 1000 mg metformin HCl. Kazano should be taken twice a day with a meal. Lactic acidosis is a rare, but serious complication. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.

What Drugs, Substances, or Supplements Interact with Kazano?

Kazano may interact with cimetidine, morphine, quinine, ranitidine, topiramate, trimethoprim, vancomycin, zonisamide, acetazolamide, methazolamide, triamterene, heart or blood pressure medications, isoniazid, diuretics (water pills), steroids, phenothiazines, thyroid medicines, birth control pills and other hormones, seizure medicines, diet pills, and medicines to treat asthma, colds or allergies. Tell your doctor all medications and supplements you use.

Kazano During Pregnancy or Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant during treatment with Kazano; it is not expected to be harmful to a fetus. It is unknown if Kazano passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Kazano (alogliptin and metformin HCl) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when using this device.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Type 2 Diabetes: Signs, Symptoms, Treatments See Slideshow
Kazano Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Stop taking this medicine and call your doctor right away if you have symptoms of pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting, loss of appetite, or fast heartbeats.

Some people using metformin develop lactic acidosis, which can be fatal. Get emergency medical help if you have even mild symptoms such as:

  • unusual muscle pain;
  • feeling cold;
  • trouble breathing;
  • feeling dizzy, light-headed, tired, or very weak;
  • stomach pain, vomiting; or
  • slow or irregular heart rate.

Call your doctor at once if you have:

  • severe or ongoing pain in your joints;
  • pain or burning when you urinate;
  • liver problems--nausea, upper stomach pain, tiredness, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or
  • symptoms of heart failure--shortness of breath (even while lying down), swelling in your legs or feet, rapid weight gain.

Common side effects may include:

  • diarrhea, upset stomach;
  • increased blood pressure (severe headache, blurred vision, pounding in your neck or ears);
  • back pain, headache; or
  • cold symptoms such as stuffy nose, sinus pain, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Kazano (Alogliptin and Metformin HCl Tablets)

QUESTION

______________ is another term for type 2 diabetes. See Answer
Kazano Professional Information

SIDE EFFECTS

The following serious adverse reactions are described below or elsewhere in the prescribing information:

  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Heart Failure [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Hepatic Effects [see WARNINGS AND PRECAUTIONS]
  • Severe and Disabling Arthralgia [see WARNINGS AND PRECAUTIONS]
  • Bullous Pemphigoid [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Alogliptin And Metformin Hydrochloride

Over 2700 patients with type 2 diabetes have received alogliptin coadministered with metformin in four large, randomized, double-blind controlled clinical trials. The mean exposure to KAZANO was 58 weeks, with more than 1400 subjects treated for more than one year. These included two 26 week placebo-controlled studies, one 52 week active control study and an interim analysis of a 104 week active-controlled study. In the KAZANO arm, the mean duration of diabetes was approximately six years, the mean body mass index (BMI) was 31 kg/m² (56% of patients had a BMI ≥30 kg/m²) and the mean age was 55 years (18% of patients ≥65 years of age).

In a pooled analysis of these four controlled clinical studies, the overall incidence of adverse reactions was 74% in patients treated with KAZANO compared to 75% treated with placebo. Overall discontinuation of therapy due to adverse reactions was 6.2% with KAZANO compared to 1.9% in placebo, 6.4% in metformin and 5.0% in alogliptin.

Adverse reactions reported in ≥4% of patients treated with KAZANO and more frequently than in patients who received alogliptin, metformin or placebo are summarized in Table 1.

Table 1: Adverse Reactions Reported in ≥4% of Patients Treated with KAZANO and More Frequently Than in Patients Receiving Either Alogliptin, Metformin or Placebo

Number of Patients (%)
KAZANO*
N=2794
Alogliptin†
N=222
Metformin‡
N=1592
Placebo
N=106
Upper respiratory tract infection 224 (8.0) 6 (2.7) 105 (6.6) 3 (2.8)
Nasopharyngitis 191 (6.8) 7 (3.2) 93 (5.8) 2 (1.9)
Diarrhea 155 (5.5) 4 (1.8) 105 (6.6) 3 (2.8)
Hypertension 154 (5.5) 5 (2.3) 96 (6.0) 6 (5.7)
Headache 149 (5.3) 11 (5.0) 74 (4.6) 3 (2.8)
Back pain 119 (4.3) 1 (0.5) 72 (4.5) 1 (0.9)
Urinary tract infection 116 (4.2) 4 (1.8) 59 (3.7) 2 (1.9)
*KAZANO - includes data pooled for patients receiving alogliptin 25 and 12.5 mg combined with various dose of metformin
†Alogliptin - includes data pooled for patients receiving alogliptin 25 and 12.5 mg
‡Metformin - includes data pooled for patients receiving various doses of metformin

Hypoglycemia

In a 26 week, double-blind, placebo-controlled study of alogliptin in combination with metformin, the number of patients reporting hypoglycemia was 1.9% in the alogliptin 12.5 mg with metformin HCl 500 mg, 5.3% in the alogliptin 12.5 mg with metformin HCl 1000 mg, 1.8% in the metformin HCl 500 mg and 6.3% in the metformin HCl 1000 mg treatment groups.

In a 26 week placebo-controlled study of alogliptin 25 mg administered once daily as add-on to metformin regimen, the number of patients reporting hypoglycemic events was 0% in the alogliptin with metformin and 2.9% in the placebo treatment groups.

In a 52 week, active-controlled, double-blind study of alogliptin once daily as add-on therapy to the combination of pioglitazone 30 mg and metformin compared to the titration of pioglitazone 30 mg to 45 mg and metformin, the number of patients reporting hypoglycemia was 4.5% in the alogliptin 25 mg with pioglitazone 30 mg and metformin group versus 1.5% in the pioglitazone 45 mg with metformin group.

In an interim analysis conducted in a 104-week, double-blind, active-controlled study of alogliptin 25 mg in combination with metformin, the number of patients reporting hypoglycemia was 1.4% in the alogliptin 25 mg with metformin group versus 23.8% in the glipizide with metformin group.

Alogliptin

A total of 14,778 patients with type 2 diabetes participated in 14 randomized, double-blind, controlled clinical trials of whom 9052 subjects were treated with alogliptin, 3469 subjects were treated with placebo and 2257 were treated with an active comparator. The mean duration of diabetes was seven years, the mean body mass index (BMI) was 31 kg/m² (49% of patients had a BMI ≥30 kg/m²), and the mean age was 58 years (26% of patients ≥65 years of age). The mean exposure to alogliptin was 49 weeks with 3348 subjects treated for more than one year.

In a pooled analysis of these 14 controlled clinical trials, the overall incidence of adverse reactions was 73% in patients treated with alogliptin 25 mg compared to 75% with placebo and 70% with active comparator. Overall discontinuation of therapy due to adverse reactions was 6.8% with alogliptin 25 mg compared to 8.4% with placebo or 6.2% with active comparator.

Adverse reactions reported in ≥4% of patients treated with alogliptin 25 mg and more frequently than in patients who received placebo are summarized in Table 2.

Table 2: Adverse Reactions Reported in ≥4% Patients Treated with Alogliptin 25 mg and More Frequently Than in Patients Given Placebo in Pooled Studies

Number of Patients (%)
Alogliptin 25 mg
N=6447
Placebo
N=3469
Active Comparator
N=2257
Nasopharyngitis 309 (4.8) 152 (4.4) 113 (5.0)
Upper Respiratory Tract Infection 287 (4.5) 121 (3.5) 113 (5.0)
Headache 278 (4.3) 101 (2.9) 121 (5.4)

Hypoglycemia

Hypoglycemic events were documented based upon a blood glucose value and/or clinical signs and symptoms of hypoglycemia.

In the monotherapy study, the incidence of hypoglycemia was 1.5% in patients treated with alogliptin compared to 1.6% with placebo. The use of alogliptin as add-on therapy to glyburide or insulin did not increase the incidence of hypoglycemia compared to placebo. In a monotherapy study comparing alogliptin to a sulfonylurea in elderly patients, the incidence of hypoglycemia was 5.4% with alogliptin compared to 26% with glipizide.

In the EXAMINE trial, the incidence of investigator reported hypoglycemia was 6.7% in patients receiving alogliptin and 6.5% in patients receiving placebo. Serious adverse reactions of hypoglycemia were reported in 0.8% of patients treated with alogliptin and in 0.6% of patients treated with placebo.

Metformin Hydrochloride

Table 3: Most Common Adverse Reactions (≥5%) in a Placebo-Controlled Clinical Study of Metformin Monotherapy*

Adverse Reaction Metformin Monotherapy
(n=141)
Placebo
(n=145)
% of Patients
Diarrhea 53.2 11.7
Nausea/vomiting 25.5 8.3
Flatulence 12.1 5.5
Asthenia 9.2 5.5
Indigestion 7.1 4.1
Abdominal discomfort 6.4 4.8
Headache 5.7 4.8
*Reactions that were more common in metformin than placebo-treated patients

Laboratory Abnormalities

Alogliptin And Metformin Hydrochloride

No clinically meaningful differences were observed among treatment groups regarding hematology, serum chemistry or urinalysis results.

Metformin Hydrochloride

In metformin clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Alogliptin

Gastrointestinal disorders: acute pancreatitis, diarrhea, constipation, nausea, ileus

Hepatobiliary disorders: fulminant hepatic failure

Immune system disorders: hypersensitivity reactions including anaphylaxis

Investigations: hepatic enzyme elevations

Musculoskeletal and Connective Tissue Disorders: severe and disabling arthralgia, rhabdomyolysis

Renal and urinary disorders: tubulointerstitial nephritis

Skin and subcutaneous tissue disorders: angioedema, rash, urticaria and severe cutaneous adverse reactions including Stevens-Johnson syndrome, bullous pemphigoid

Metformin

Hepatobiliary disorders: Cholestatic, hepatocellular, mixed hepatocellular liver injury

DRUG INTERACTIONS

Metformin Hydrochloride

Carbonic Anhydrase Inhibitors
Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with KAZANO may increase the risk of lactic acidosis.
Intervention: Consider more frequent monitoring of these patients.
Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide
Drugs that Reduce Metformin Clearance
Clinical Impact: 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) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see CLINICAL PHARMACOLOGY].
Intervention: Consider the benefits and risks of concomitant use.
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine
Alcohol
Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism.
Intervention: Warn patients against excessive alcohol intake while receiving KAZANO.
Insulin Secretagogues and Insulin
Clinical Impact: Coadministration of KAZANO with an insulin secretagogue (e.g., sulfonylurea) or with insulin may increase the risk of hypoglycemia.
Intervention: Patients may require a lower dose of the insulin secretagogue or insulin.
Drugs Affecting Glycemic Control
Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control.
Intervention: When such drugs are administered to a patient receiving KAZANO, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving KAZANO, the patient should be observed closely for hypoglycemia.
Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and isoniazid
Alogliptin
Cytochrome (CYP) P450, CYP-Substrates or Inhibitors
Clinical Impact: Alogliptin is primarily renally excreted. Cytochrome (CYP) P450-related metabolism is negligible. No significant drug-drug interactions were observed with the CYP-substrates or inhibitors tested or with renally excreted drugs [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Kazano (Alogliptin and Metformin HCl Tablets)

© Kazano Patient Information is supplied by Cerner Multum, Inc. and Kazano Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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