Alogliptin

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take this medicine with or without food. Follow your doctor's instructions.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, pale skin, irritability, dizziness, feeling shaky, or trouble concentrating.

Keep a source of sugar with you in case you have low blood sugar. Sugar sources include fruit juice, hard candy, crackers, raisins, and non-diet soda. Be sure your family and close friends know how to help you in an emergency. If you have severe hypoglycemia and cannot eat or drink, use a glucagon injection. Your doctor can prescribe a glucagon emergency injection kit and tell you how to use it.

Check your blood sugar carefully during times of stress, travel, illness, surgery or medical emergency, vigorous exercise, or if you drink alcohol or skip meals. These things can affect your glucose levels and your dose needs may also change. Do not change your medication dose or schedule without your doctor's advice.

Alogliptin is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light.

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).

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

The most common side effects of alogliptin include:

• stuffy or runny nose and sore throat
• headache
• cold-like symptoms (upper respiratory tract infection)

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 alogliptin. For more information, ask your doctor or pharmacist.

Serious side effects have been reported with alogliptin. See "Drug Precautions" section.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

No significant drug interactions have been identified, however, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Before you take alogliptin, tell your doctor if you:

• have or have had inflammation of your pancreas (pancreatitis)
• have kidney or liver problems
• have other medical conditions
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

In the U.S.

• Nesina

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidiabetic

Pharmacologic Class: Alogliptin

Use alogliptin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about alogliptin, please talk with the doctor, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about alogliptin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using alogliptin.

Review Date: October 4, 2017

Alogliptin tablets are 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 (12.3)].

Alogliptin tablets are available as film-coated tablets containing 25 mg, 12.5 mg or 6.25 mg of Alogliptin as follows:

25 mg tablet: light red, oval, biconvex, film-coated, with "TAK ALG-25" printed on one side, available in:

12.5 mg tablet: yellow, oval, biconvex, film-coated, with "TAK ALG-12.5" printed on one side, available in:

6.25 mg tablet: light pink, oval, biconvex, film-coated, with "TAK ALG-6.25" printed on one 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].

• Alogliptin Benzoate

Diabetes mellitus, type 2: Management of adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise as monotherapy or in combination therapy

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl ≥30 to <60 mL/minute: 12.5 mg once daily

CrCl ≥15 to <30 mL/minute: 6.25 mg once daily

ESRD (CrCl <15 mL/minute or requiring hemodialysis): 6.25 mg once daily; administered without regard to timing of hemodialysis

Peritoneal dialysis: There is no dosage adjustment provided in the manufacturer’s labeling (has not been studied).

May be taken with or without food.

Dosage Forms & Strengths

tablet

• 6.25mg
• 12.5mg
• 25mg

Diabetes Mellitus Type 2

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

25 mg PO qDay

Dosage Modifications

Renal impairment

• Mild (CrCl ≥60mL/min): No dosage adjustment required
• Moderate (CrCl ≥30 to <60 mL/min): Decrease dose to 12.5 mg PO qDay
• Severe (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min) or requiring hemodialysis: 6.25 mg PO qDay
• May administer without regard to the timing of dialysis
• Peritoneal dialysis: Not studied

Hepatic impairment

• Mild-to-moderate (Child-Pugh A and B): No dosage adjustment required
• Severe (Child-Pugh C): Not studied

Dosing Considerations

Limitations of use: Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings

Assess renal function before initiating alogliptin and periodically thereafter

Safety and efficacy not established

Pregnancy Category: B

Lactation: Unknown whether distributed in breast milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Applies to alogliptin: oral tablet

General

The most frequently reported side effects included nasopharyngitis, headache, and upper respiratory tract infection.[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal pain, gastroesophageal reflux disease
Uncommon (0.1% to 1%): Pancreatitis
Postmarketing reports: Acute pancreatitis, diarrhea, constipation, nausea, ileus[Ref]

During clinical trials, acute pancreatitis was reported in 6 (0.2%) patients receiving 25 mg and 2 patients (less than 0.1%) who were treated with active comparators or placebo. In a cardiovascular outcome trial of patient with high cardiovascular risk, acute pancreatitis was reported in 10 patients receiving this drug and 7 patients receiving placebo (0.4% vs 0.3%).[Ref]

Musculoskeletal

Frequency not reported: Arthralgia[Ref]

Between October 2006 and December 2013, thirty-three cases of severe arthralgia have been reported to the FDA Adverse Event Reporting System Database. Each case involved the use of 1 or more dipeptidyl peptidase-4 (DPP-4) inhibitor. In all cases, substantial reduction in prior activity level was reported, 10 patients were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of starting therapy, in 23 cases symptoms resolved less than 1 month after discontinuation. A positive rechallenge was reported in 8 cases, with 6 cases involving use of a different DPP-4 inhibitor. Sitagliptin had the greatest number of cases reported (n=28) followed by saxagliptin (n=5), linagliptin (n=2), alogliptin (n=1), and vildagliptin (n=2).[Ref]

Hepatic

Postmarketing reports: Hepatic enzyme elevations, fulminant hepatic failure[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reactions (0.6%)
Postmarketing reports: Anaphylaxis, angioedema, rash, urticaria, severe cutaneous adverse reactions (Stevens-Johnson syndrome)[Ref]

Nervous system

Common (1% to 10%): Headache[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, upper respiratory tract infection[Ref]

Dermatologic

Postmarketing reports of bullous pemphigoid requiring hospitalization have been reported with dipeptidyl peptidase-4 (DPP-4) inhibitors use. These case typically recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor.[Ref]

Common (1% to 10%): Pruritus, rash
Postmarketing reports: Exfoliative skin conditions including Stevens-Johnson syndrome, erythema multiforme, angioedema, urticaria

Dipeptidyl peptidase-4 inhibitors:
Postmarketing reports: Bullous pemphigoid[Ref]

Metabolic

Common (1% to 10%): Hypoglycemia

Based on a pooled analysis the hypoglycemic risk of this drug was considered neutral.

Cardiovascular

Frequency not reported: Heart failure[Ref]

In a clinical trial in patients with recent acute coronary syndrome, a greater proportion of patients receiving this drug were hospitalized for congestive heart failure compared with placebo (3.9% [n=106] vs 3.3% [n=89]),[Ref]

Some side effects of alogliptin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Administration advice:
-Take orally once a day
-May take with or without food

If a dose is missed take as soon as remembered; but if it is time for your next dose, skip the missed dose

General:
-May be used as monotherapy or in combination therapy in adults with type 2 diabetes mellitus.
-Not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis as it would not be effective in these settings.

Monitoring:
-Cardiovascular: Signs and symptoms of heart failure
-Renal: Assess renal function at baseline and periodically during therapy
-Hepatic: Signs and symptoms of hepatotoxicity
-Monitor for signs and symptoms of pancreatitis
-Monitor glycemic control

Patient advice:
-Patients should be informed that acute pancreatitis, heart failure, allergic reactions, and liver injury have occurred with use of this drug; they should understand the importance of reporting signs and symptoms of these conditions and when to promptly seek medical attention.
-Patients should understand the importance of adhering to dietary instructions and regular physical activity; they should be able to recognize the signs and symptoms of high and low blood sugar and how to treat.
-During periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.
-Instruct patients to contact their health care provider if they develop severe and persistent joint pain or if blisters or erosions occur on skin.