Pioglitazone/glimepiride 30-2mg Tab

Pioglitazone is a thiazolidinedione that acts as a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma receptors are found in adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma nuclear receptors modulates the transcription of insulin-responsive genes involved in the control of glucose and lipid metabolism, thereby improving insulin sensitivity in target tissues. Glimepiride is a sulfonylurea that lowers blood glucose by stimulating the release of insulin from functioning pancreatic beta cells. It also has extrapancreatic effects, including increasing peripheral glucose uptake and utilization.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Changes in eyesight
Painful urination or blood in urine
Frequent urination
Bone pain
Feeling extremely tired or weak
Severe dizziness or fainting
Low blood sugar (hypoglycemia), which can be more likely when taking this medication with other diabetes drugs. Symptoms may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience any of these symptoms, call your doctor right away and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.

Severe Skin Reaction and Liver Problems

A severe skin reaction called Stevens-Johnson syndrome/toxic epidermal necrolysis can occur, which may cause permanent health problems or even death. Seek medical help immediately if you experience:

Red, swollen, blistered, or peeling skin (with or without fever)
Red or irritated eyes
Sores in your mouth, throat, nose, or eyes

Liver problems, which can be fatal, have rarely occurred with this medication. Contact your doctor right away if you notice:

Dark urine
Tiredness
Decreased appetite
Upset stomach or stomach pain
Light-colored stools
Vomiting
Yellow skin or eyes

Other Possible Side Effects

Most people do not experience severe side effects, but some may occur. If you notice any of the following side effects or if they bother you or do not go away, contact your doctor or seek medical attention:

Headache
Diarrhea
Upset stomach
Muscle pain
Signs of a common cold
Sinus pain
Sore throat
Weight gain
Pain in arms or legs

Reporting Side Effects

This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Acidic blood problems
+ Bladder cancer
+ Type 1 diabetes (note: this medication is not intended to treat type 1 diabetes)
* If the patient is a child, as this medication is not suitable for pediatric use

This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine whether it is safe to take this medication in combination with your other medications and health conditions. Never start, stop, or adjust the dose of any medication without consulting your doctor first.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

If you experience low blood sugar, do not drive, as this can significantly increase your risk of being involved in a crash.

There is a potential increased risk of developing bladder cancer associated with the use of this drug. Discuss this with your doctor to understand the implications.

Be aware that this medication can cause low blood sugar, which, if severe, can lead to seizures, loss of consciousness, permanent brain damage, and even death. Consult your doctor about how to manage this risk.

Follow your doctor's instructions for monitoring your blood sugar levels regularly.

Additionally, have your blood work checked as directed by your doctor and discuss the results with them.

If you have a deficiency of the enzyme G6PD (glucose-6-phosphate dehydrogenase), use this medication with caution, as it may increase the risk of anemia. Individuals of African, South Asian, Middle Eastern, and Mediterranean descent are more likely to have low G6PD levels.

Before consuming alcohol, consult your doctor to understand any potential risks or interactions.

Adhere to the diet and exercise plan recommended by your doctor to ensure optimal management of your condition.

If you are also taking colesevelam, administer it at least 4 hours after taking this medication to avoid any potential interactions.

Be aware that this drug may increase the risk of death from heart disease. Discuss this risk with your doctor to understand the implications and how to mitigate them.

During periods of stress, such as fever, infection, injury, or surgery, your blood sugar levels may become more difficult to control. Changes in physical activity, exercise, or diet can also affect your blood sugar levels.

This medication may increase the risk of fractures, particularly in females. The risk of broken bones may be higher after taking this drug for a year or more, with most fractures occurring in the upper arm, hand, or foot. Consult your doctor about strategies to maintain bone health and address any concerns you may have.

If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.

For individuals of childbearing age who have not been ovulating, there is a potential risk of pregnancy. If you wish to avoid pregnancy, use effective birth control measures while taking this drug.

If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. It is crucial to discuss the benefits and risks of this medication to both you and your baby to make an informed decision.

• Gemfibrozil (significant increase in pioglitazone exposure)
• Bosentan (significant decrease in pioglitazone exposure)
• Miconazole (oral, may potentiate glimepiride effect)

• Insulin and other antidiabetic agents (increased risk of hypoglycemia)
• CYP2C8 inhibitors (e.g., trimethoprim, clopidogrel) - may increase pioglitazone levels
• CYP2C8 inducers (e.g., rifampin) - may decrease pioglitazone levels
• CYP2C9 inhibitors (e.g., fluconazole, amiodarone) - may increase glimepiride levels
• CYP2C9 inducers (e.g., rifampin) - may decrease glimepiride levels
• Beta-blockers (may mask symptoms of hypoglycemia)
• NSAIDs, salicylates, sulfonamides, chloramphenicol, coumarin derivatives, probenecid, MAO inhibitors, anabolic steroids, disopyramide, fenfluramine, fibrates, fluoxetine, guanethidine, ifosfamide, pentoxifylline, phenylbutazone, phosphodiesterase-5 inhibitors, quinolones, reserpine, somatostatin analogs, tetracyclines, tritoqualine (may potentiate hypoglycemic effect of glimepiride)
• Corticosteroids, diuretics, thyroid hormones, estrogens, oral contraceptives, phenothiazines, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid (may decrease hypoglycemic effect of glimepiride)

• Alcohol (may potentiate or attenuate glimepiride effect, increased risk of lactic acidosis with pioglitazone)
• Colesevelam (may reduce absorption of glimepiride; administer glimepiride at least 4 hours before colesevelam)
• Topiramate (increased risk of fluid retention with pioglitazone)

• Not available

• Symptoms of hypoglycemia (e.g., sweating, tremor, dizziness, confusion, hunger, rapid heartbeat)
• Symptoms of heart failure (e.g., unusual weight gain, swelling of ankles/feet, shortness of breath, fatigue)
• Symptoms of liver dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, dark urine, jaundice, anorexia)
• Symptoms of bladder cancer (e.g., hematuria, dysuria, urinary urgency)
• Visual disturbances (macular edema)

Category C. Not recommended during pregnancy. Insulin is generally preferred for glycemic control in pregnant women with diabetes.

Not recommended during breastfeeding. Both pioglitazone and glimepiride are likely excreted into breast milk and could cause adverse effects in the infant (e.g., hypoglycemia with glimepiride).

Safety and effectiveness have not been established in pediatric patients. Not recommended for use in children.

Use with caution in elderly patients. Increased risk of hypoglycemia with glimepiride, especially in those with impaired renal function. Increased risk of fluid retention, heart failure, and bone fractures with pioglitazone. Start with lower doses and titrate slowly, monitoring closely for adverse effects.

• This combination drug should be taken once daily with the first main meal to minimize the risk of hypoglycemia from glimepiride.
• Patients should be educated on the signs and symptoms of hypoglycemia and how to manage them.
• Closely monitor patients for signs and symptoms of heart failure (e.g., rapid weight gain, edema, dyspnea) due to the pioglitazone component. Discontinue if heart failure develops or worsens.
• Regular monitoring of liver function tests (ALT) is crucial due to the risk of idiosyncratic liver injury with pioglitazone.
• Inform patients about the potential increased risk of bladder cancer with pioglitazone and advise them to report any blood in urine or other urinary symptoms.
• Bone fractures, particularly in women, are a known risk with pioglitazone. Consider bone health assessment.
• Macular edema has been reported with pioglitazone; patients reporting visual disturbances should be referred for ophthalmologic evaluation.

• Metformin (first-line for most T2DM patients)
• Other sulfonylureas (e.g., glipizide, glyburide)
• Other thiazolidinediones (e.g., rosiglitazone - limited use due to cardiovascular concerns)
• DPP-4 inhibitors (e.g., sitagliptin, saxagliptin)
• SGLT2 inhibitors (e.g., empagliflozin, canagliflozin)
• GLP-1 receptor agonists (e.g., liraglutide, semaglutide)
• Insulin therapy

If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication.

This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for guidance.

In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.