Oseni Drug Description: Detailed Datasheet

Drug Description

OSENI
(alogliptin and pioglitazone) Tablets, for Oral Use

WARNING

CONGESTIVE HEART FAILURE

• Thiazolidinediones, including pioglitazone, which is a component of OSENI, cause or exacerbate congestive heart failure in some patients [see WARNINGS AND PRECAUTIONS].
• After initiation of OSENI and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in OSENI must be considered [see WARNINGS AND PRECAUTIONS].
• OSENI is not recommended in patients with symptomatic heart failure [see WARNINGS AND PRECAUTIONS].
• Initiation of OSENI in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

DESCRIPTION

OSENI tablets contain two oral antihyperglycemic drugs used in the management of type 2 diabetes: alogliptin and pioglitazone.

Alogliptin

Alogliptin is a selective, orally bioavailable inhibitor of the enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt, which is identified as 2-({6-[(3R)-3aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)benzonitrile monobenzoate. It has a molecular formula of C₁₈H₂₁N₅O₂•C₇H₆O₂ and a molecular weight of 461.51 daltons. The structural formula is:

Alogliptin benzoate is a white to off-white crystalline powder containing one asymmetric carbon in the aminopiperidine moiety. It is soluble in dimethylsulfoxide, sparingly soluble in water and methanol, slightly soluble in ethanol and very slightly soluble in octanol and isopropyl acetate.

Pioglitazone

Pioglitazone is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance. Chemically, pioglitazone is prepared as hydrochloride salt, which is identified as (±)-5-[[4-[2-(5-ethyl2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione monohydrochloride. It has a molecular formula of C₁₉H₂₀N₂O₃S•HCl and a molecular weight of 392.90 daltons. The structural formula is:

Pioglitazone hydrochloride is an odorless white crystalline powder that contains one asymmetric carbon in the thiazolidinedione moiety. The synthetic compound is a racemate and the two enantiomers of pioglitazone interconvert in vivo. It is soluble in N,N dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water and insoluble in ether.

OSENI is available as a fixed-dose combination tablet for oral administration containing 34 mg alogliptin benzoate equivalent to 25 mg alogliptin and any of the following strengths of pioglitazone hydrochloride:

• 16.53 mg pioglitazone hydrochloride equivalent to 15 mg pioglitazone (25 mg/15 mg)
• 33.06 mg pioglitazone hydrochloride equivalent to 30 mg pioglitazone (25 mg/30 mg)
• 49.59 mg pioglitazone hydrochloride equivalent to 45 mg pioglitazone (25 mg/45 mg)

OSENI is also available as a fixed-dose combination tablet for oral administration containing 17 mg alogliptin benzoate equivalent to 12.5 mg alogliptin and any of the following strengths of pioglitazone hydrochloride:

• 16.53 mg pioglitazone hydrochloride equivalent to 15 mg pioglitazone (12.5 mg/15 mg)
• 33.06 mg pioglitazone hydrochloride equivalent to 30 mg pioglitazone (12.5 mg/30 mg)
• 49.59 mg pioglitazone hydrochloride equivalent to 45 mg pioglitazone (12.5 mg/45 mg)

OSENI tablets contain the following inactive ingredients: mannitol, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate and lactose monohydrate; the tablets are film-coated with hypromellose, polyethylene glycol, titanium dioxide, talc and ferric oxide (yellow and/or red) and are marked with printing ink (Red A1 or Gray F1).

Indications

Monotherapy And Combination Therapy

OSENI is 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 pioglitazone is appropriate [see Clinical Studies].

Important Limitations Of Use

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

Dosage

DOSAGE AND ADMINISTRATION

Recommendations For All Patients

OSENI should be taken once daily and can be taken with or without food. The tablets must not be split before swallowing.

The recommended starting dose for OSENI (alogliptin and pioglitazone):

• for patients inadequately controlled on diet and exercise is 25 mg/15 mg or 25 mg/30 mg,
• for patients inadequately controlled on metformin monotherapy is 25 mg/15 mg or 25 mg/30 mg,
• for patients on alogliptin who require additional glycemic control is 25 mg/15 mg or 25 mg/30 mg,
• for patients on pioglitazone who require additional glycemic control is 25 mg/15 mg, 25 mg/30 mg or 25 mg/45 mg as appropriate based upon current therapy,
• for patients switching from alogliptin coadministered with pioglitazone, OSENI may be initiated at the dose of alogliptin and pioglitazone based upon current therapy,
• for patients with congestive heart failure (NYHA Class I or II) is 25 mg/15 mg.

The OSENI dose can be titrated up to a maximum of 25 mg/45 mg once daily based on glycemic response as determined by hemoglobin A1c (A1C).

After initiation of OSENI or with dose increase, monitor patients carefully for adverse reactions related to fluid retention as has been seen with pioglitazone (e.g., weight gain, edema and signs and symptoms of congestive heart failure) [see BOXED WARNING and WARNINGS AND PRECAUTIONS].

Patients With Renal Impairment

No dose adjustment of OSENI is necessary for patients with mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min).

The dose of OSENI is 12.5 mg/15 mg, 12.5 mg/30 mg or 12.5 mg/45 mg once daily for patients with moderate renal impairment (CrCl ≥30 to <60 mL/min).

OSENI is not recommended for patients with severe renal impairment or ESRD [see Use In Specific Populations and CLINICAL PHARMACOLOGY]. Coadministration of pioglitazone and alogliptin 6.25 mg once daily based on individual requirements may be considered in these patients.

Because there is a need for dose adjustment based upon renal function, assessment of renal function is recommended prior to initiation of OSENI therapy and periodically thereafter.

Coadministration With Strong CYP2C8 Inhibitors

Coadministration of pioglitazone and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately three-fold. Therefore, the maximum recommended dose of OSENI is 25 mg/15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

• 25 mg/15 mg tablets are yellow, round, biconvex, and film-coated, with both “A/P” and “25/15” printed on one side.
• 25 mg/30 mg tablets are peach, round, biconvex, and film-coated, with both “A/P” and “25/30” printed on one side.
• 25 mg/45 mg tablets are red, round, biconvex, and film-coated, with both “A/P” and “25/45” printed on one side.
• 12.5 mg/15 mg tablets are pale yellow, round, biconvex, and film-coated, with both “A/P” and “12.5/15” printed on one side.
• 12.5 mg/30 mg tablets are pale peach, round, biconvex, and film-coated, with both “A/P” and “12.5/30” printed on one side.
• 12.5 mg/45 mg tablets are pale red, round, biconvex, and film-coated, with both “A/P” and “12.5/45” printed on one side.

Storage And Handling

OSENI tablets are available in the following strengths and packages:

25 mg/15 mg tablet: yellow, round, biconvex and film-coated with both “A/P” and “25/15” printed on one side, available in:

NDC 64764-251-03 Bottles of 30 tablets
NDC 64764-251-04 Bottles of 90 tablets
NDC 64764-251-05 Bottles of 500 tablets

25 mg/30 mg tablet: peach, round, biconvex and film-coated with both “A/P” and “25/30” printed on one side, available in:

NDC 64764-253-03 Bottles of 30 tablets
NDC 64764-253-04 Bottles of 90 tablets
NDC 64764-253-05 Bottles of 500 tablets

25 mg/45 mg tablet: red, round, biconvex, film-coated and with both “A/P” and “25/45” printed on one side, available in:

NDC 64764-254-03 Bottles of 30 tablets
NDC 64764-254-04 Bottles of 90 tablets
NDC 64764-254-05 Bottles of 500 tablets

12.5 mg/15 mg tablet: pale yellow, round, biconvex and film-coated with both “A/P” and “12.5/15” printed on one side, available in:

NDC 64764-121-03 Bottles of 30 tablets
NDC 64764-121-04 Bottles of 90 tablets
NDC 64764-121-05 Bottles of 500 tablets

12.5 mg/30 mg tablet: pale peach, round, biconvex and film-coated with both “A/P” and “12.5/30” printed on one side, available in:

NDC 64764-123-03 Bottles of 30 tablets
NDC 64764-123-04 Bottles of 90 tablets
NDC 64764-123-05 Bottles of 500 tablets

12.5 mg/45 mg tablet: pale red, round, biconvex and film-coated with both “A/P” and “12.5/45” printed on one side, available in:

NDC 64764-124-03 Bottles of 30 tablets
NDC 64764-124-04 Bottles of 90 tablets
NDC 64764-124-05 Bottles of 500 tablets

Storage

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed and protect from moisture and humidity.

Distributed by Takeda Pharmaceuticals America, Inc. Deerfield, IL 60015. Revised: Dec 2017

Side Effects

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

• have other medical conditions
• are pregnant or plan to become pregnant. It is not known if OSENI can harm your unborn baby. Talk to your doctor about the best way to control your blood sugar while you are pregnant or if you plan to become pregnant.
• are a premenopausal woman who does not have periods regularly or at all. OSENI may increase your chance of becoming pregnant. Talk to your doctor about birth control choices while taking OSENI. Tell your doctor right away if you become pregnant while taking OSENI.
• are breastfeeding or plan to breastfeed. It is not known whether OSENI passes into your breast milk and if it can harm your baby. Talk with your doctor about the best way to control your blood glucose levels while breastfeeding.

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

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist before you start a new medicine.

OSENI may affect the way other medicines work, and other medicines may affect how OSENI works. Contact your doctor before you start or stop other types of medicines.

How should I take OSENI?

• Take OSENI exactly as your doctor tells you to take it.
• Take OSENI 1 time each day with or without food.
• Do not break or cut OSENI tablets before swallowing.
• Your doctor may need to change your dose of OSENI to control your blood glucose. Do not change your dose unless told to do so by your doctor.
• If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take 2 doses of OSENI at the same time.
• If you take too much OSENI, call your doctor or go to the nearest hospital emergency room right away.
• If your body is under stress, such as from fever, infection, accident or surgery, the dose of your diabetes medicines may need to be changed. Call your doctor right away.
• Stay on your diet and exercise programs and check your blood sugar as your doctor tells you to.
• Your doctor may do certain blood tests before you start OSENI and during treatment as needed. Your doctor may change your dose of OSENI based on the results of your blood tests due to how well your kidneys are working.
• Your doctor will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C.
• Your doctor should check your eyes regularly while you take OSENI.

What are the possible side effects of OSENI?

• OSENI can cause serious side effects, including:
• See “What is the most important information I should know about OSENI?”
• Allergic (hypersensitivity) reactions, such as:
  • swelling of your face, lips, throat and other areas on your skin
  • difficulty swallowing or breathing
  • raised, red areas on your skin (hives)
  • skin rash, itching, flaking or peeling

If you have these symptoms, stop taking OSENI 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
• Broken bones (fractures). Usually in the hand, upper arm or foot in women. Talk to your doctor for advice on how to keep your bones healthy.
• Bladder cancer. There may be an increased chance of having bladder cancer when you take OSENI. You should not take OSENI if you are receiving treatment for bladder cancer. Tell your doctor right away if you have any of the following symptoms of bladder cancer:
  • blood or a red color in your urine
  • an increased need to urinate
  • pain while you urinate
• Low blood sugar (hypoglycemia). If you take OSENI 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 OSENI. If you have symptoms of low blood sugar, you should check your blood sugar and treat if low, then call your doctor. Signs and symptoms of low blood sugar may include:
  • shaking or feeling jittery
  • sweating
  • fast heartbeat
  • change in vision
  • hunger
  • headache
  • change in mood
  • confusion
  • dizziness
• Diabetic eye disease with swelling in the back of the eye (macular edema). Tell your doctor right away if you have any changes in your vision. Your doctor should check your eyes regularly.
• Release of an egg from an ovary in a woman (ovulation) leading to pregnancy. Ovulation may happen when premenopausal women who do not have regular monthly periods take OSENI. This can increase your chance of getting pregnant.
• Joint pain. Some people who take medicines called DPP-4 inhibitors, one of the medicines in OSENI, may develop joint pain that can be severe. Call your doctor if you have severe joint pain.
• Skin reaction. Some people who take medicines called DPP-4 inhibitors, one of the medicines in OSENI, may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your doctor right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your doctor may tell you to stop taking OSENI.

The most common side effects of OSENI include stuffy or runny nose and sore throat, back pain, 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 OSENI. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store OSENI?

• Store OSENI at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep container tightly closed and protect from moisture and humidity.

Keep OSENI and all medicines out of the reach of children.

General information about the safe and effective use of OSENI

Medicines are sometimes prescribed for purposes other than those listed in the Medication Guide. Do not take OSENI for a condition for which it was not prescribed. Do not give OSENI to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about OSENI. If you would like to know more information, talk with your doctor. You can ask your doctor or pharmacist for information about OSENI that is written for health professionals.

For more information, go to www.oseni.com or call 1-877-TAKEDA-7 (1-877-825-3327).

What are the ingredients in OSENI?

Active ingredients: alogliptin and pioglitazone.

Inactive ingredients: mannitol, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate, and lactose monohydrate; the tablets are film-coated with hypromellose, polyethylene glycol, titanium dioxide, talc and ferric oxide (yellow and/or red) and are marked with red A1 or gray F1 printing ink.

This Medication Guide has been approved by the U.S. Food and Drug Administration.