June 25, 2016
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Kazano

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Kazano




Kazano Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 10/06/2015

Kazano (alogliptin and metformin HCl) is an antidiabetic medication used to treat type 2 diabetes mellitus, along with diet and exercise. Common side effects of Kazano include upper respiratory tract infection, diarrhea, high blood pressure, headache, back pain, urinary tract infection, and cold symptoms (stuffy nose, sinus pain, sore throat). 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.

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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Kazano in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Some people develop lactic acidosis while taking alogliptin and metformin. Early symptoms may get worse over time and this condition can be fatal. Stop taking this medicine and get emergency medical help if you have even mild symptoms such as:

  • muscle pain or weakness;
  • numb or cold feeling in your arms and legs;
  • trouble breathing;
  • feeling dizzy, light-headed, tired, or very weak;
  • stomach pain, nausea with vomiting; or
  • slow or uneven heart rate.

Stop using alogliptin and call your doctor at once if you have:

  • severe pain in your upper stomach spreading to your back;
  • nausea and vomiting, loss of appetite, fast heart rate;
  • pain or burning when you urinate;
  • itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • increased blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath);
  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • diarrhea;
  • 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)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Kazano FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

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

  1. Pancreatitis [see WARNINGS AND PRECAUTIONS]
  2. Heart Failure [see WARNINGS AND PRECAUTIONS]
  3. Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  4. Hepatic Effects [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 v arious 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

Metformin may lower serum vitamin B12 concentrations. Measurement of hematologic parameters on an annual basis is advised in patients on KAZANO, and any apparent abnormalities should be appropriately investigated and managed [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

Alogliptin

The following adverse reactions have been identified during the postmarketing use of alogliptin. 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.

Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria and severe cutaneous adverse reactions, including Stevens-Johnson syndrome, hepatic enzyme elevations, fulminant hepatic failure, severe and disabling arthralgia, acute pancreatitis, diarrhea, constipation, nausea, and ileus [see WARNINGS AND PRECAUTIONS]

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

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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