Alogliptin

Name: Alogliptin

Alogliptin Precautions

Serious side effects can happen to people taking alogliptin, including inflammation of the pancreas (pancreatitis) which may be severe. Certain medical conditions make you more likely to get pancreatitis. 

Before you start taking alogliptin tell your doctor if you have ever had:

  • pancreatitis
  • stones in your gallbladder (gallstones)
  • a history of alcoholism
  • kidney problems
  • liver problems

Stop taking alogliptin and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

Alogliptin can cause other serious side effects, including:

  • Severe and persistent joint pain. If you experience severe and persistent joint pain, contact your doctor right away. Do not stop taking your medication. Your doctor will decide if your medication is the possible cause of severe  joint pain and will discontinue the drug if appropriate.
  • Allergic (hypersensitivity) reactions, such as:
    • swelling of your face, lips, throat, and other areas on your skin
    • difficulty with swallowing or breathing
    • raised, red areas on your skin (hives)
    • skin rash, itching, flaking, or peeling

If you have an allergic reaction, stop taking alogliptin and contact your doctor right away.

  • Liver problems. Call your doctor right away if you have unexplained symptoms, such as:
    • nausea or vomiting
    • stomach pain
    • unusual or unexplained tiredness
    • loss of appetite
    • dark urine
    • yellowing of your skin or the whites of your eyes
  • Low blood sugar (hypoglycemia). If you take alogliptin with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take alogliptin. If you have symptoms of low blood sugar, you should check your blood sugar and treat if low, and then call your doctor. Signs and symptoms of low blood sugar include:
    • shaking or feeling jittery
    • sweating
    • hunger
    • headache
    • change in mood
    • fast heartbeat
    • change in vision
    • confusion
    • dizziness

Do not take alogliptin if you:

Are allergic to any ingredients in alogliptin or have had a serious allergic (hypersensitivity) reaction to alogliptin. Symptoms of a serious allergic reaction to alogliptin may include:

  • swelling of your face, lips, throat, and other areas on your skin
  • difficulty with swallowing or breathing
  • raised, red areas on your skin (hives)
  • skin rash, itching, flaking, or peeling

If you have any of these symptoms, stop taking alogliptin and contact your doctor or go to the nearest hospital emergency room right away.

Other Requirements

  • Store alogliptin tablets at room temperature between 15° to 30°C (59° to 86°F).
  • Keep this and all medications out of the reach of children.

What should I avoid while taking alogliptin?

Avoid drinking alcohol.

Before Using alogliptin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For alogliptin, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to alogliptin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of alogliptin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of alogliptin in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking alogliptin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using alogliptin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Balofloxacin
  • Besifloxacin
  • Ciprofloxacin
  • Enoxacin
  • Fleroxacin
  • Flumequine
  • Gatifloxacin
  • Gemifloxacin
  • Lanreotide
  • Levofloxacin
  • Lomefloxacin
  • Moxifloxacin
  • Nadifloxacin
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Pasireotide
  • Pazufloxacin
  • Pefloxacin
  • Prulifloxacin
  • Rufloxacin
  • Sparfloxacin
  • Thioctic Acid
  • Tosufloxacin

Using alogliptin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acebutolol
  • Atenolol
  • Betaxolol
  • Bisoprolol
  • Carteolol
  • Carvedilol
  • Celiprolol
  • Esmolol
  • Labetalol
  • Levobunolol
  • Metipranolol
  • Metoprolol
  • Nadolol
  • Nebivolol
  • Oxprenolol
  • Penbutolol
  • Pindolol
  • Practolol
  • Propranolol
  • Sotalol
  • Timolol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of alogliptin. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcohol, excessive use of or
  • Gallbladder stones or
  • Pancreas problems, history of—Use with caution. May increase risk for getting pancreatitis (swelling and inflammation of the pancreas).
  • Angioedema (swelling of the face, lips, tongue, throat, arms, or legs), history with this dipeptidyl peptidase-4 (DPP-4) inhibitors—Use with caution. May increase the risk of this condition occurring again with alogliptin.
  • Diabetic ketoacidosis (high ketones and acid in the blood) or
  • Type 1 diabetes—Should not be used in patients with these conditions.
  • Heart failure, history of or
  • Kidney disease, history of—Use with caution. May increase the risk of serious side effects.
  • Kidney disease, moderate or severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Liver disease—Use with caution. May make this condition worse.

What do I need to tell my doctor BEFORE I take Alogliptin?

  • If you have an allergy to alogliptin or any other part of alogliptin.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Acidic blood problem or type 1 diabetes.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take alogliptin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How do I store and/or throw out Alogliptin?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Contraindications

History of a serious hypersensitivity reaction to Alogliptin-containing products, such as anaphylaxis, angioedema or severe cutaneous adverse reactions.

Overdosage

The highest doses of Alogliptin tablets administered in clinical trials were single doses of 800 mg to healthy subjects and doses of 400 mg once daily for 14 days to patients with type 2 diabetes (equivalent to 32 times and 16 times the maximum recommended clinical dose of 25 mg, respectively). No serious adverse reactions were observed at these doses.

In the event of an overdose, it is reasonable to institute the necessary clinical monitoring and supportive therapy as dictated by the patient's clinical status. Per clinical judgment, it may be reasonable to initiate removal of unabsorbed material from the gastrointestinal tract.

Alogliptin is minimally dialyzable; over a three-hour hemodialysis session, approximately 7% of the drug was removed. Therefore, hemodialysis is unlikely to be beneficial in an overdose situation. It is not known if Alogliptin tablets are dialyzable by peritoneal dialysis.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Inform patients of the potential risks and benefits of Alogliptin tablets.

Patients should be informed that acute pancreatitis has been reported during use of Alogliptin tablets. Patients should be informed that persistent, severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue Alogliptin tablets and contact their physician if persistent severe abdominal pain occurs.

Patients should be informed of the signs and symptoms of heart failure. Before initiating Alogliptin tablets, patients should be asked about a history of heart failure or other risk factors for heart failure including moderate to severe renal impairment. Patients should be instructed to contact their healthcare providers as soon as possible if they experience symptoms of heart failure, including increasing shortness of breath, rapid increase in weight, or swelling of the feet.

Patients should be informed that allergic reactions have been reported during use of Alogliptin tablets. If symptoms of allergic reactions (including skin rash, hives and swelling of the face, lips, tongue and throat that may cause difficulty in breathing or swallowing) occur, patients should be instructed to discontinue Alogliptin tablets and seek medical advice promptly.

Patients should be informed that postmarketing reports of liver injury, sometimes fatal, have been reported during use of Alogliptin tablets. If signs or symptoms of liver injury occur, patients should be instructed to discontinue Alogliptin tablets and seek medical advice promptly.

Inform patients that hypoglycemia can occur, particularly when an insulin secretagogue or insulin is used in combination with Alogliptin tablets. Explain the risks, symptoms and appropriate management of hypoglycemia.

Inform patients that severe and disabling joint pain may occur with this class of drugs. The time to onset of symptoms can range from one day to years. Instruct patients to seek medical advice if severe joint pain occurs.

Inform patients that bullous pemphigoid may occur with this class of drugs. Instruct patients to seek medical advice if blisters or erosions occur [see Warnings and Precautions (5.7)].

Instruct patients to take Alogliptin tablets only as prescribed. If a dose is missed, advise patients not to double their next dose.

Instruct patients to read the Medication Guide before starting Alogliptin tablets therapy and to reread each time the prescription is refilled. Instruct patients to inform their healthcare provider if an unusual symptom develops or if a symptom persists or worsens.

ALO332 R4

Pharmacology

Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-4 enzyme.

Absorption

Extensive (~100%) regardless of food intake

Distribution

417 L

Metabolism

Not extensively metabolized; minor metabolism via CYP2D6 and CYP3A4 suggested by in vitro studies (<7% of parent compound is transformed to active and inactive metabolites)

Excretion

Urine 76% (60% to 71% as unchanged drug); feces 13%

Time to Peak

~1 to 2 hours

Half-Life Elimination

~21 hours

Protein Binding

20%

Dosing Adult

Diabetes mellitus, type 2: Oral: 25 mg once daily

Concomitant use with insulin and/or insulin secretagogues (eg, sulfonylureas): Reduced dose of insulin and/or insulin secretagogues may be needed.

Drug Interactions

ACE Inhibitors: DPP-IV Inhibitors may enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulin: DPP-IV Inhibitors may enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sulfonylureas: DPP-IV Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: Cardiac failure (4%)

Central nervous system: Headache (4%)

Genitourinary: Decreased estimated GFR (5%)

Hepatic: Increased serum ALT (>3 times ULN: 1%)

Renal: Renal function abnormality (3%; patients with high cardiovascular risk: 23%), renal disease (patients with high cardiovascular risk: 17%), renal insufficiency (patients with high cardiovascular risk: 8%)

Respiratory: Nasopharyngitis (5%), upper respiratory tract infection (5%)

<1% (Limited to important or life-threatening): Anaphylaxis, hepatic failure, hypersensitivity reaction, pancreatitis, severe arthralgia (FDA Safety Alert, Aug 28, 2015), Stevens-Johnson syndrome

Adverse Effects

>10%

Hypoglycemia (1.5-35%); higher when added to insulin

1-10%

Nasopharyngitis (4.4%)

Headache (4.2%)

Upper respiratory tract infection (4.2%)

<1%

Hypersensitivity (0.6%)

Pancreatitis (0.2%)

Postmarketing reports

Severe and disabling arthralgia

Bullous pemphigoid

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