Alogliptin and pioglitazone

What is Alogliptin and pioglitazone?

• Alogliptin and pioglitazone (OSENI) is a dipeptidyl peptidase-4 inhibitor and thiazolidinedione combination product used along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.

What are the uses of this medicine?

• This medicine contains 2 prescription diabetes medicines, alogliptin (NESINA) and pioglitazone (ACTOS).
• OSENI is a prescription medicine used along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes.

• Limitations of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis.

How does this medicine work?

• Alogliptin (al" oh glip' tin) is an inhibitor of dipeptidyl peptidase-4, which is the major enzyme responsible for the degradation of glucagon-like peptide-1 (GLP-1), an important gastrointestinal hormone (incretin) that increases glucose dependent insulin secretion by the pancreas. By prolonging the effect of GLP-1, alogliptin increases insulin levels and lowers blood glucose and helps in glycemic control in patients with type 2 diabetes.

• Pharmacologic studies indicate that pioglitazone improves insulin sensitivity in muscle and adipose tissue while inhibiting hepatic gluconeogenesis. Unlike sulfonylureas, pioglitazone is not an insulin secretagogue.
• Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ).
• PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle and liver.
• Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin- responsive genes involved in the control of glucose and lipid metabolism.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• History of a serious hypersensitivity reaction to alogliptin or pioglitazone, components of OSENI, such as anaphylaxis, angioedema or severe cutaneous adverse reactions.
• NYHA Class III or IV heart failure.

What drug interactions can this medicine cause?

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. Limit the pioglitazone dose to 15 mg daily.
• CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone concentrations.
• Topiramate may decrease pioglitazone concentrations. when OSENI and topiramate are used concomitantly, monitor patients for adequate glycemic control.

Is this medicine FDA approved?

• Initial U.S. Approval: 2013

How should this medicine be used?

Recommended Dosage: 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).

Coadministration with Strong CYP2C8 Inhibitors

• The maximum recommended dose of pioglitazone is 15 mg once daily in patients taking strong CYP2C8 inhibitors (e.g., gemfibrozil).

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.

Administration

• 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 dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form: As Tablets:

• 25 mg alogliptin and 15 mg pioglitazone, 25 mg alogliptin and 30 mg pioglitazone, 25 mg alogliptin and 45 mg pioglitazone.
• 12.5 mg alogliptin and 15 mg pioglitazone, 12.5 mg alogliptin and 30 mg pioglitazone, 12.5 mg alogliptin and 45 mg pioglitazone.

This medicine is available in fallowing brand namesː

• OSENI

What side effects can this medication cause?

The most common side effects of this medicine include:

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

OSENI can cause serious side effects, including:

• Heart failure
• Inflammation of the pancreas (pancreatitis)
• Allergic (hypersensitivity) reactions
• Liver problems
• Broken bones (fractures)
• Bladder cancer
• Low blood sugar (hypoglycemia)
• Diabetic eye disease with swelling in the back of the eye (macular edema)
• Release of an egg from an ovary in a woman (ovulation) leading to pregnancy
• Joint pain
• Skin reaction

What special precautions should I follow?

• Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of congestive heart failure. Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure. Monitor patients at risk for heart failure for signs and symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of OSENI.
• There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue OSENI.
• There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome. In such cases, promptly discontinue OSENI, assess for other potential causes, institute appropriate monitoring and treatment and initiate alternative treatment for diabetes.
• Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt OSENI and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart OSENI if liver injury is confirmed and no alternative etiology can be found. Use with caution in patients with liver disease.
• In controlled clinical trials, edema was reported more frequently in patients treated with pioglitazone.
• Increased incidence of fractures in female patients. Apply current standards of care for assessing and maintaining bone health.
• OSENI may increase the risk of bladder cancer. Do not use in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer.
• When an insulin secretagogue (e.g., sulfonylurea) or insulin is used in combination with OSENI, a lower dose of insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia.
• Macular edema has been reported. Recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes.
• Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue if appropriate.
• There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue OSENI.
• There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with OSENI.

What to do in case of emergency/overdose?

• No serious adverse reactions have been reported.

Management of overdosage:

• In the event of overdosage, appropriate supportive treatment should be initiated according to patient's clinical signs and symptoms.
• 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 is dialyzable by peritoneal dialysis.

Can this medicine be used in pregnancy?

• Limited data with OSENI in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage.

Can this medicine be used in children?

• Safety and effectiveness of OSENI in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• 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.

Who manufactures and distributes this medicine?

Distributed by Takeda Pharmaceuticals America, Inc. Lexington

What should I know about storage and disposal of this medication?

• Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Keep container tightly closed and protect from moisture and humidity.

• Dailymed label info on Alogliptin and pioglitazone
• FDA Alogliptin and pioglitazone

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