Alogliptin-pioglitazone

Alogliptin/pioglitazone is a prescription medication used with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes. It is a combination of two prescription medications, alogliptin and pioglitazone. Alogliptin belongs to a group of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by stopping the DPP-4 enzyme from removing a hormone that is responsible for telling your body to release insulin after you eat. This allows insulin to be released, which lowers blood sugar. Pioglitazone belongs to a group of drugs called thiazolidinediones. It lowers blood sugar by helping your body use its natural insulin better.

Alogliptin/pioglitazone comes in tablet form and is usually taken once daily, with or without food. Do not break or cut alogliptin/pioglitazone tablets before swallowing.

Some of the common side effects of alogliptin/pioglitazone include stuffy or runny nose and sore throat, back pain, and cold-like symptoms.

 

Alogliptin & Pioglitazone is part of the drug class:

• Combinations of oral blood glucose lowering drugs

Alogliptin/pioglitazone can cause other serious side effects. See "Alogliptin & Pioglitazone Precautions."

The most common side effects of alogliptin/pioglitazone include:

• cold-like symptoms (upper respiratory tract infection)
• stuffy or runny nose and sore throat
• diarrhea
• increase in blood pressure
• headache
• back pain
• urinary tract infection

 Alogliptin/pioglitazone may cause low blood sugar (hypoglycemia). If you take alogliptin/pioglitazone 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/pioglitazone. 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 may include:

• shaking or feeling jittery
• sweating
• fast heartbeat
• change in vision
• hunger
• headache
• change in mood
• confusion
• dizziness

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/pioglitazone. 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.

 

Alogliptin/pioglitazone can cause serious side effects, including:

1. New or worse heart failure: Pioglitazone, one of the medicines in this medication, can cause your body to keep extra fluid (fluid retention), which leads to swelling (edema) and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. Heart failuremeans your heart does not pump blood well enough.

• Do not take alogliptin/pioglitazone if you have severe heart failure.
• If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, alogliptin/pioglitazone may not be right for you. 

​Call your doctor right away if you have any of the following:

• swelling or fluid retention, especially in the ankles or legs
• shortness of breath or trouble breathing, especially when you lie down
• an unusually fast increase in weight
• unusual tiredness

2. Inflammation of the pancreas (pancreatitis). Alogliptin, one of the medicines in alogliptin/pioglitazone, may cause pancreatitis which may be severe. Certain medical conditions make you more likely to get pancreatitis.

Before you start taking alogliptin/pioglitazone 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/pioglitazone 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.

3. Liver problems. Call your doctor right away if you have 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

4. 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.

5. Bladder cancer. There may be an increased chance of having bladder cancer when you take alogliptin/pioglitazone. You should not take alogliptin/pioglitazone 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

6. Low blood sugar (hypoglycemia). If you take alogliptin/pioglitazone 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/pioglitazone. 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 may include:

• shaking or feeling jittery
• sweating
• fast heartbeat
• change in vision
• hunger
• headache
• change in mood
• confusion
• dizziness

7. 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.

8. 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 alogliptin/pioglitazone. This can increase your chance of getting pregnant.

9. 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. Do not take alogliptin/pioglitazone if you:

• have severe heart failure
• are allergic to alogliptin, pioglitazone or any ingredient in alogliptin/pioglitazone or have had a serious allergic (hypersensitivity) reaction to alogliptin or pioglitazone. 

​Symptoms of a serious allergic reaction to alogliptin/pioglitazone 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 these symptoms, stop taking alogliptin/pioglitazone and contact your doctor or go to the nearest hospital emergency room right away.

 

The alogliptin/pioglitazone dose your doctor recommends will depend on several factors including:

• the medications you are currently taking
• other medical conditions you have
• how well alogliptin/pioglitazone works for you
• how well you tolerate the medication (side effects)

The maximum recommended daily dose is 25 mg alogliptin and 45 mg pioglitazone.

Dosage Forms & Strengths

alogliptin/pioglitazone

tablet

• 12.5mg/15mg
• 12.5mg/30mg
• 12.5mg/45mg
• 25mg/15mg
• 25mg/30mg
• 25mg/45mg

Diabetes Mellitus Type 2

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

Starting dose based on patient’s current regimen

Dosage Modifications

Limit initial dose of pioglitazone to 15 mg/day with NYHA Class 1 or II heart failure

Coadministration with strong CYP2C8 inhibitors (eg, gemfibrozil): Do not exceed 15 mg/day pioglitazone

Renal impairment

• Moderate (CrCl >30 to <60 mL/min): Not to exceed 12.5 mg/day alogliptin
• Severe (CrCl <30 mL/min or ESRD): Not recommended; coadministration of pioglitazone and alogliptin 6.25 mg qDay may be considered

Dosing Considerations

Assess renal function before initiating alogliptin and periodically thereafter

Safety and efficacy not established

Pregnancy

Limited data in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy; poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity

Lactation

There is no information regarding presence of pioglitazone or alogliptin in human milk, effects on breastfed infant, or effects on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

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.

Mechanism of Action

Alogliptin: Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner

Pioglitazone: Thiazolidinedione; improves target cell response to insulin; decreases hepatic gluconeogenesis

Absorption

Bioavailability: ~100% (alogliptin)

Duration: 24 hr (pioglitazone)

Peak plasma time: 1-2 hr (alogliptin); 2-4 hr (pioglitazone)

Distribution

Protein bound: 20% (alogliptin); >99% (pioglitazone)

Vd: 417 L (alogliptin); 0.63 L/kg (pioglitazone)

Metabolism

alogliptin

• Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine
• Active metabolite: N-demethylated (<1% of parent compound)
• Inactive metabolite: N-acetylated alogliptin (<6% of parent compound)
• Minor substrate of CYP3A4 and CYP2D6

pioglitazone

• Metabolized to active metabolites by hepatic CYP2C8 and CYP3A4
• Metabolites: metabolite II (hydroxy derivative), metabolite III (keto derivative), metabolite IV (active hydroxy derivative) (active)

Elimination

alogliptin

• Half-life: 21 hr
• Renal clearance: 9.6 L/hr
• Total body clearance: 14 L/hr
• Excretion: 76% urine; 13% feces

pioglitazone

• Half-Life: 3-7 hr
• Excretion: 15-30% urine