Pioglitazone/glimepiride 30-4mg Tab

Pioglitazone is a thiazolidinedione that acts as a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ receptors are found in adipose tissue, skeletal muscle, and liver. Activation of PPARγ leads to increased insulin sensitivity in these tissues, reducing insulin resistance and improving glucose uptake and utilization. It also suppresses hepatic glucose production. Glimepiride is a sulfonylurea that lowers blood glucose by stimulating the release of insulin from the pancreatic beta cells. It binds to the sulfonylurea receptor on the beta-cell membrane, leading to closure of ATP-sensitive potassium channels, depolarization of the membrane, and opening of voltage-gated calcium channels. The resulting influx of calcium triggers insulin secretion.

Serious Side Effects: Seek Medical Attention Immediately

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 help right away:

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
Pain or blood while urinating
Frequent urination
Bone pain
Feeling extremely tired or weak
Severe dizziness or fainting
Low blood sugar (hypoglycemia), which can occur, especially when used with other diabetes medications. Symptoms may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience any of these symptoms, contact your doctor immediately and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or certain fruit juices.

Rare but Serious Skin Reaction

A severe skin reaction, known as Stevens-Johnson syndrome or toxic epidermal necrolysis, can occur. This condition can cause serious health problems and may be life-threatening. 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

In rare cases, this medication can cause liver problems, which can be life-threatening. 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 Side Effects

Most people do not experience serious side effects, but some may occur. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:

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

If you have questions about side effects or want to report any 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. Describe the symptoms you experienced with the allergy.
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 children

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 if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change 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.

Long-term use of this drug may increase your risk of developing bladder cancer. Be sure to discuss this potential risk with your doctor.

One of the possible side effects of this medication is low blood sugar, which can be severe. If left untreated, very low blood sugar can lead to seizures, loss of consciousness, permanent brain damage, and even death. It is crucial to talk to your doctor about how to manage low blood sugar.

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

Your doctor may also recommend regular blood tests to check for any potential side effects. Be sure to discuss any concerns or questions you have with your doctor.

If you have a deficiency of the enzyme G6PD, you may be at a higher risk of developing anemia. This deficiency is more common in individuals of African, South Asian, Middle Eastern, and Mediterranean descent. Be cautious and discuss this with your doctor.

Before consuming alcohol, consult with 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, take it at least 4 hours after taking this medication to minimize any potential interactions.

There is evidence suggesting that this drug may increase the risk of death from heart disease. Discuss this risk with your doctor to understand the potential implications.

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

This medication may increase your risk of fractures, particularly in females. Most fractures reported in clinical studies occurred in the upper arm, hand, or foot after taking the drug for at least 1 year. Talk to your doctor about ways to maintain bone health and address any concerns you may have.

If you are 65 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 possibility of pregnancy while taking this drug. If you wish to avoid pregnancy, use birth control measures while on this medication.

If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor. It is essential to discuss the potential benefits and risks of this medication to both you and your baby.

• Bosentan (increased risk of liver enzyme elevations with pioglitazone)
• Miconazole (oral) (increased glimepiride levels, severe hypoglycemia)

• Gemfibrozil (increases pioglitazone exposure, increased risk of adverse effects)
• Rifampin (decreases pioglitazone exposure, reduced efficacy)
• Beta-blockers (mask symptoms of hypoglycemia, may prolong hypoglycemia)
• Alcohol (potentiates hypoglycemic effect of glimepiride)
• NSAIDs (may increase glimepiride levels and risk of hypoglycemia)
• Sulfonamides (may increase glimepiride levels and risk of hypoglycemia)
• Chloramphenicol (may increase glimepiride levels and risk of hypoglycemia)
• Coumarin derivatives (may potentiate or weaken glimepiride's effect)
• Corticosteroids, Thiazide diuretics, Thyroid hormones, Sympathomimetics (may decrease hypoglycemic effect of glimepiride)
• Insulin or other insulin secretagogues (increased risk of hypoglycemia)

• CYP2C8 inhibitors (e.g., Trimethoprim, Clopidogrel) may increase pioglitazone levels.
• CYP2C8 inducers (e.g., Phenytoin, Carbamazepine) may decrease pioglitazone levels.
• CYP2C9 inhibitors (e.g., Fluconazole, Amiodarone) may increase glimepiride levels.
• CYP2C9 inducers (e.g., Rifampin, Barbiturates) may decrease glimepiride levels.
• Colesevelam (may reduce glimepiride absorption, administer glimepiride at least 4 hours before colesevelam).

• Not available

• Symptoms of hypoglycemia (e.g., sweating, tremor, dizziness, confusion, hunger, irritability)
• Symptoms of heart failure (e.g., unusual rapid weight gain, shortness of breath, swelling of ankles or feet, unusual fatigue)
• Symptoms of liver dysfunction (e.g., nausea, vomiting, abdominal pain, dark urine, jaundice, unexplained fatigue)
• Symptoms of bladder cancer (e.g., hematuria, dysuria, urinary urgency)
• Symptoms of macular edema (e.g., blurred vision, decreased visual acuity)

Generally not recommended during pregnancy. Both pioglitazone and glimepiride are Pregnancy Category C. Poorly controlled diabetes during pregnancy increases the risk of birth defects, miscarriage, preeclampsia, and other complications. Insulin is generally preferred for glycemic control during pregnancy.

Not recommended during breastfeeding. Both pioglitazone and glimepiride are excreted in breast milk in animal studies. Glimepiride can cause hypoglycemia in the breastfed infant. Pioglitazone's effects on the infant are unknown but potential for adverse effects exists.

Safety and effectiveness have not been established in pediatric patients. Use is not recommended.

Use with caution in elderly patients. They may be at increased risk for hypoglycemia (due to glimepiride) and heart failure (due to pioglitazone). Start with lower doses and titrate slowly. Monitor renal function closely.

• Pioglitazone/glimepiride is a fixed-dose combination, which may limit dose flexibility for individual components. Consider separate agents if precise titration of each is needed.
• Always assess for signs and symptoms of heart failure before initiating and during therapy with pioglitazone, especially in patients with risk factors.
• Educate patients thoroughly on the symptoms and management of hypoglycemia due to the glimepiride component.
• Monitor liver enzymes periodically, especially if symptoms of liver injury develop. Discontinue if ALT > 3x ULN.
• Inform patients about the potential increased risk of bladder cancer with pioglitazone, especially with long-term use (>1 year). Advise them to report any hematuria or urinary symptoms.
• Pioglitazone can cause dose-related fluid retention and edema, which may lead to or worsen heart failure. This risk is higher when used with insulin.
• Pioglitazone has been associated with an increased risk of bone fractures in women. Counsel patients on bone health.
• This combination is not for type 1 diabetes or diabetic ketoacidosis.

• Metformin
• DPP-4 inhibitors (e.g., Sitagliptin, Saxagliptin)
• SGLT2 inhibitors (e.g., Canagliflozin, Dapagliflozin)
• GLP-1 receptor agonists (e.g., Liraglutide, Semaglutide)
• Insulin
• Other sulfonylureas (e.g., Glipizide, Glyburide)
• Other thiazolidinediones (e.g., Rosiglitazone - limited use due to cardiovascular concerns)

If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. 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, which provides crucial information about its safe use. It is essential 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 clarification.

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