rosiglitazone

Action and Spectrum

Actions: 

• Increases insulin sensitivity in muscle, liver, and adipose tissue 

• Improves glucose uptake and utilization in muscle and liver 

• Reduces glucose production by the liver 

• Increases glucose uptake and storage in adipose tissue 

• Reduces inflammation in adipose tissue 

• Modulates lipid metabolism, leading to reductions in triglycerides and increases in high-density lipoprotein (HDL) cholesterol 

Spectrum: 

• rosiglitazone is indicated for the treatment of type 2 diabetes, either as monotherapy or in combination with other antidiabetic agents such as metformin, sulfonylureas, or insulin. 

• It is not recommended for the treatment of type 1 diabetes or diabetic ketoacidosis. 

• rosiglitazone has been shown to improve glycemic control and reduce HbA1c levels in patients with type 2 diabetes. 

• It may also have beneficial effects on lipid levels, blood pressure, and cardiovascular risk factors in some patients. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Increased LDL 

Increased HDL 

Increased total cholesterol 

1-10% 

Edema 

Hypertension 

Myocardial ischemia 

Diarrhea 

Upper respiratory tract infection 

Frequency not defined 

Accidental injury 

Anemia 

Back pain 

Fatigue 

Headache 

Hypoglycemia 

Myalgia 

Sinusitis 

Weight gain 

Black Box Warning

Black Box Warning: 

Risk of congestive heart failure 

Not recommended for patients with symptomatic heart failure 

Contraindication / Caution

Contraindication/Caution 

Contraindications 

• Patients with heart failure 

• Patients with a history of liver disease 

• Patients with active bladder cancer or a history of bladder cancer 

Cautions 

• Patients with a history of heart disease 

• Patients with a history of angina (chest pain) 

• Patients with a history of stroke 

• Patients with a history of liver disease or abnormal liver function tests 

• Patients with a history of macular edema (swelling in the back of the eye) 

• Patients with a history of fractures or osteoporosis 

• Patients taking insulin or other diabetes medications 

• Patients with a history of allergy to rosiglitazone or any of its components 

Pregnancy / Lactation

Pregnancy consideration:  

rosiglitazone crosses the placenta; hence dose should be considered accordingly. 

Breastfeeding warnings:  

No data is available about the excretion of rosiglitazone in breastmilk. 

Pregnancy category: 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 

• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 

• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 

• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 

• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 

• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

rosiglitazone is an oral medication used to treat type 2 diabetes mellitus. It belongs to the thiazolidinedione class of drugs and works by increasing the body’s sensitivity to insulin, a hormone that regulates blood sugar levels. 

The pharmacology of rosiglitazone involves its activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) which is a transcription factor that regulates glucose and lipid metabolism. Rosiglitazone binds to PPAR-γ, which causes an increase in the transcription of genes involved in glucose uptake, storage, and utilization in muscle and adipose tissue. 

Furthermore, rosiglitazone also reduces hepatic glucose output by decreasing gluconeogenesis and glycogenolysis in the liver. The overall effect of rosiglitazone is to decrease blood glucose levels by improving insulin sensitivity and glucose utilization. 

Pharmacodynamics: 

The pharmacodynamics of rosiglitazone involves its interaction with peroxisome proliferator-activated receptor gamma (PPAR-γ), which is a nuclear receptor that regulates glucose and lipid metabolism. rosiglitazone binds to PPAR-γ, resulting in conformational changes that allow the receptor to form a heterodimer with another nuclear receptor, the retinoid X receptor (RXR). 

The PPAR-γ/RXR heterodimer complex then binds to specific DNA sequences in the promoter regions of target genes, leading to increased transcription of genes involved in glucose and lipid metabolism, such as those for glucose transporter 4 (GLUT4) and adiponectin. The activation of these genes results in increased glucose uptake and utilization in adipose tissue and muscle and decreased hepatic glucose output by decreasing gluconeogenesis and glycogenolysis in the liver. 

In addition to its effects on glucose and lipid metabolism, rosiglitazone has also been shown to have anti-inflammatory and anti-proliferative effects. It decreases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and inhibits the growth of vascular smooth muscle cells, which may contribute to its beneficial effects on cardiovascular health. 

Pharmacokinetics: 

Absorption 

Bioavailability is 99% 

Onset of takes place Initial effect delayed; maximum effect may take up to 12 weeks 

Distribution  

Peak Plasma concentration is achieved in 1 hours 

Protein Bound is more than 99% 

The half-life is achieved in 3-4 hours  

The volume of distribution is 17.6 L 

Metabolism 

The drug is metabolized by hepatic CYP2C8 & CYP2C9 (towards minor extent) 

Elimination and Excretion 

The drug is excreted 64% in urine and 22% in feces 

Adminstartion

Administration: 

rosiglitazone is available as an oral tablet and is usually taken once or twice daily, with or without food. The recommended starting dose for most patients is 4 milligrams per day, which may be increased to a maximum of 8 milligrams per day, based on the patient’s response and tolerability. 

It is important to note that rosiglitazone should not be used as a first-line therapy for type 2 diabetes mellitus and should only be used in patients who have not achieved adequate glycemic control with other antidiabetic medications. 

Furthermore, rosiglitazone should be used with caution in patients with a history of cardiovascular disease, as it has been associated with an increased risk of cardiovascular events, such as myocardial infarction and stroke. Regular monitoring of blood glucose levels, liver function tests, and lipid levels may also be necessary during rosiglitazone therapy. 

rosiglitazone should not be used during pregnancy or in patients with severe hepatic impairment. It may also interact with other medications, such as rifampin, ketoconazole, and gemfibrozil, and should be used with caution in patients taking these medications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: rosiglitazone 

Pronounced: ro-si-glit-a-zone 

Why do we use rosiglitazone? 

rosiglitazone is used to treat type 2 diabetes mellitus, a condition in which the body is unable to use insulin properly, leading to high blood sugar levels. It is typically used in combination with other antidiabetic medications, such as metformin, sulfonylureas, or insulin, to help control blood sugar levels in patients who have not achieved adequate glycemic control with other treatments. 

rosiglitazone works by increasing the body’s sensitivity to insulin, a hormone that regulates blood sugar levels. It does this by activating peroxisome proliferator-activated receptor gamma (PPAR-γ), a transcription factor that regulates glucose and lipid metabolism. This results in increased glucose uptake and utilization in adipose tissue and muscle and decreased hepatic glucose output by decreasing gluconeogenesis and glycogenolysis in the liver. 

rosiglitazone may also have additional beneficial effects on cardiovascular health, such as anti-inflammatory and anti-proliferative effects, although its use has been associated with an increased risk of cardiovascular events, such as myocardial infarction and stroke.