Usage
Glimepiride + Rosiglitazone is prescribed for type 2 diabetes mellitus in adults as an adjunct to diet and exercise to improve glycemic control. It is specifically indicated for patients who have not achieved adequate glycemic control with either glimepiride or rosiglitazone alone, or in those transitioning from separate glimepiride and rosiglitazone tablets. It is not for treating type 1 diabetes or diabetic ketoacidosis, and it’s not recommended to be used with insulin or nitrates.
This combination drug falls under the pharmacological classification of oral antidiabetic agents, comprising a thiazolidinedione (rosiglitazone) and a sulfonylurea (glimepiride).
Glimepiride stimulates the release of insulin from pancreatic beta-cells, while rosiglitazone enhances insulin sensitivity in peripheral tissues like adipose tissue, skeletal muscle, and the liver. This dual mechanism helps improve blood glucose control in patients with type 2 diabetes.
Alternate Names
Glimepiride + Rosiglitazone doesn’t have alternate names but is known under the brand name Avandaryl. The brand name Avandaryl has been discontinued in some countries like the United States.
How It Works
Pharmacodynamics: Rosiglitazone primarily acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, increasing insulin sensitivity in peripheral tissues. Glimepiride works by binding to and closing ATP-sensitive potassium channels in pancreatic beta-cells, leading to depolarization and subsequent insulin release.
Pharmacokinetics: Both drugs are administered orally. Rosiglitazone is well-absorbed and extensively metabolized in the liver, primarily by CYP2C8 and to some extent by CYP2C9. Glimepiride is also well-absorbed, extensively metabolized in the liver (primarily via CYP2C9), and excreted mainly through the kidneys.
Mode of Action: Rosiglitazone increases target cell response to insulin, while glimepiride promotes insulin secretion. This combination addresses both insulin resistance and deficient insulin production common in type 2 diabetes.
Elimination: Glimepiride is primarily eliminated through the kidneys. Rosiglitazone is mainly metabolized in the liver by CYP2C8, with some contribution from CYP2C9, and then excreted via bile and urine.
Dosage
Standard Dosage
Adults:
Initial dose: 4 mg rosiglitazone / 1 mg glimepiride or 4 mg rosiglitazone / 2 mg glimepiride once daily with the first meal.
For patients switching from separate tablets: Same dose as previously taken.
Titration: Glimepiride can be increased by a maximum of 2 mg every 1-2 weeks if needed, while rosiglitazone can be increased after 8-12 weeks if required.
Maximum dose: 8 mg rosiglitazone / 4 mg glimepiride once daily.
Children:
The use of Glimepiride + Rosiglitazone is not recommended in children under 18 years of age due to insufficient safety and efficacy data.
Special Cases:
- Elderly Patients: Start with a lower dose (4 mg/1 mg) and titrate carefully due to increased susceptibility to hypoglycemia and potential age-related kidney problems.
- Patients with Renal Impairment: For mild to moderate renal impairment (creatinine clearance 30 to 80 mL/min), careful dosing is required, and close monitoring is advised for hypoglycemia. For severe renal impairment (creatinine clearance less than 30 mL/min), this combination is contraindicated.
- Patients with Hepatic Dysfunction: Contraindicated in patients with hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure, heart disease or history of heart attack, edema, osteoporosis, and liver disease.
Clinical Use Cases
The use of Glimepiride + Rosiglitazone is not indicated in acute clinical settings like intubation, surgical procedures, mechanical ventilation, or ICU use. It’s intended for long-term management of type 2 diabetes through chronic oral administration and is not suitable for emergency situations like cardiac arrest or status epilepticus.
Dosage Adjustments
Dose modifications are based on individual glycemic response and tolerability. Renal function should be assessed, particularly in the elderly, and hepatic function should be evaluated before starting therapy. Adjust dose cautiously for patients with renal impairment.
Side Effects
Common Side Effects
- Upper respiratory tract infection
- Headache
- Peripheral edema
- Weight gain
- Hypoglycemia
Rare but Serious Side Effects
- Congestive heart failure
- Myocardial ischemia
- Hepatotoxicity
- Severe hypoglycemia
- Fractures (especially in women)
- Macular edema
Long-Term Effects
- Increased risk of cardiovascular events with rosiglitazone
- Weight gain
- Fluid retention
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Angioedema
- Hepatic failure
- Severe hypoglycemia
Contraindications
- Hypersensitivity to rosiglitazone, glimepiride, sulfonylureas, or sulphonamides.
- Type 1 diabetes.
- Diabetic ketoacidosis.
- Severe renal impairment.
- Hepatic impairment.
- NYHA Class III or IV heart failure.
- History of heart attack.
Drug Interactions
- Gemfibrozil: Increases the risk of hypoglycemia with glimepiride.
- Rifampin: May decrease rosiglitazone concentration.
- Fluconazole: May increase rosiglitazone concentration.
- Beta-blockers: Can mask symptoms of hypoglycemia.
Pregnancy and Breastfeeding
Glimepiride + Rosiglitazone should not be used during pregnancy or breastfeeding. Insulin is the preferred treatment for diabetes during pregnancy.
Drug Profile Summary
- Mechanism of Action: Rosiglitazone: PPARγ agonist improving insulin sensitivity. Glimepiride: Sulfonylurea stimulating insulin release.
- Side Effects: Hypoglycemia, edema, weight gain, upper respiratory infections, headache.
- Contraindications: Heart failure, hepatic impairment, severe renal impairment, type 1 diabetes.
- Drug Interactions: Gemfibrozil, rifampin, fluconazole, beta-blockers.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Initial: 4mg/1mg or 4mg/2mg once daily. Maximum: 8mg/4mg once daily.
- Monitoring Parameters: HbA1c, fasting blood glucose, liver enzymes, weight, signs of heart failure.
Popular Combinations
Not applicable. Glimepiride + Rosiglitazone is a fixed-dose combination and is typically not prescribed along with other anti-diabetic medications.
Precautions
- Monitor for signs and symptoms of heart failure.
- Monitor liver function tests, especially in the first year.
- Monitor for hypoglycemia, especially in the elderly and those with renal impairment.
- Patients should follow a diet and exercise program.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Glimepiride + Rosiglitazone?
A: Initial: 4 mg rosiglitazone / 1 mg glimepiride or 4 mg rosiglitazone / 2 mg glimepiride taken once daily with the first meal. Maximum: 8 mg rosiglitazone / 4 mg glimepiride daily.
Q2: What is the mechanism of action of Glimepiride + Rosiglitazone?
A: Glimepiride stimulates insulin release, while rosiglitazone improves insulin sensitivity.
Q3: What are the common side effects of Glimepiride + Rosiglitazone?
A: Hypoglycemia, edema, weight gain, upper respiratory infections, headache.
Q4: What are the contraindications for using Glimepiride + Rosiglitazone?
A: Heart failure, hepatic impairment, severe renal impairment, type 1 diabetes.
Q5: Can Glimepiride + Rosiglitazone be used during pregnancy?
A: No, it is contraindicated during pregnancy and breastfeeding.
Q6: What are the potential drug interactions with Glimepiride + Rosiglitazone?
A: Gemfibrozil, rifampin, fluconazole, beta-blockers.
Q7: How should I monitor patients on Glimepiride + Rosiglitazone?
A: Monitor HbA1c, fasting blood glucose, liver enzymes, weight, and signs of heart failure.
Q8: What are some important patient counseling points for Glimepiride + Rosiglitazone?
A: Adherence to diet and exercise, recognition of hypoglycemia symptoms, regular monitoring of blood glucose, and reporting any signs of edema or heart failure.
Q9: In what patient population is Glimepiride + Rosiglitazone contraindicated?
A: Patients with NYHA Class III or IV heart failure, hepatic impairment, severe renal impairment, or type 1 diabetes.
