ROSIGLITAZONE MALEATE

Clinical safety rating: safe

Strong CYP2C8 inhibitors may increase levels Can cause or exacerbate congestive heart failure and myocardial ischemia.

How it works

Rosiglitazone is a thiazolidinedione that acts as a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ). Activation of PPARγ increases insulin sensitivity in adipose tissue, skeletal muscle, and liver, leading to reduced hepatic gluconeogenesis and increased glucose uptake.

What the body does with it

Metabolism	Extensively metabolized by CYP2C8 and to a lesser extent by CYP2C9. No significant metabolism by CYP3A4.
Excretion	Primarily hepatic metabolism via CYP2C8, with less than 1% excreted unchanged in urine. Fecal excretion of metabolites accounts for approximately 64% and renal excretion for 23% of the dose.
Half-life	Terminal elimination half-life is 3-4 hours; clinically relevant as dosing is twice daily to maintain steady-state concentrations.
Protein binding	Highly protein bound (99.8%), primarily to albumin.
Volume of Distribution	Apparent volume of distribution is approximately 0.25 L/kg, indicating distribution primarily into extracellular fluid.
Bioavailability	Oral bioavailability is 99% (highly absorbed) with no significant food effect.
Onset of Action	Oral: Onset of glycemic effect occurs within 1-2 hours after a single dose, with maximal effect on insulin sensitivity developing over 6-8 weeks.
Duration of Action	Duration of action is approximately 24 hours following a single oral dose; however, full therapeutic benefit on glycemic control requires several weeks of continued therapy.

Classification & Brands

Dosing & administration

4 mg orally once daily; may increase to 8 mg once daily after 12 weeks if inadequate glycemic response.

Dosage form	TABLET
Renal impairment	No dose adjustment required for renal impairment; not dialyzable.
Liver impairment	Contraindicated in Child-Pugh class B and C. No adjustment needed for Child-Pugh class A.
Pediatric use	Not approved for use in pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 4 mg once daily; monitor for fluid retention and cardiovascular events.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP2C8 inhibitors may increase levels Can cause or exacerbate congestive heart failure and myocardial ischemia.

FDA category	Animal
Breastfeeding	Unknown if rosiglitazone is excreted in human milk. Animal studies suggest presence in milk. M/P ratio not established. Due to potential for adverse effects on breastfed infant (e.g., altered glucose metabolism), breastfeeding is not recommended during therapy.
Teratogenic Risk	Rosiglitazone is classified as FDA Pregnancy Category C. In animal studies, it was associated with fetal growth restriction at doses 2-4 times the human AUC. Human data: Limited. Risk cannot be excluded. First trimester: Potential for embryotoxicity based on animal data. Second/Third trimesters: May cause fetal adipose tissue accumulation, but no specific human malformations documented. Avoid use unless benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: CONGESTIVE HEART FAILURE. Rosiglitazone can cause or exacerbate congestive heart failure. It is contraindicated in patients with New York Heart Association (NYHA) Class III or IV heart failure. Monitor for signs and symptoms of heart failure. Discontinue if heart failure develops.

Side Effect Profile

Common Effects	Weight gain
Serious Effects

Absolute Contraindications

["NYHA Class III or IV heart failure","Type 1 diabetes mellitus","Diabetic ketoacidosis","Active liver disease or ALT > 2.5 times upper limit of normal","Hypersensitivity to rosiglitazone or any excipient"]

Clinical Precautions

Precautions

["May cause fluid retention and edema, leading to or worsening heart failure","Increased risk of cardiovascular events, especially myocardial infarction","Hepatotoxicity, monitor liver enzymes","Bone fractures, particularly in female patients","Macular edema","Weight gain"]

Clinical Tips & Counseling

Drug interactions

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ROSIGLITAZONE MALEATE

Clinical safety rating: safe

Strong CYP2C8 inhibitors may increase levels Can cause or exacerbate congestive heart failure and myocardial ischemia.

How it works

What the body does with it

Metabolism	Extensively metabolized by CYP2C8 and to a lesser extent by CYP2C9. No significant metabolism by CYP3A4.
Excretion	Primarily hepatic metabolism via CYP2C8, with less than 1% excreted unchanged in urine. Fecal excretion of metabolites accounts for approximately 64% and renal excretion for 23% of the dose.
Half-life	Terminal elimination half-life is 3-4 hours; clinically relevant as dosing is twice daily to maintain steady-state concentrations.
Protein binding	Highly protein bound (99.8%), primarily to albumin.
Volume of Distribution	Apparent volume of distribution is approximately 0.25 L/kg, indicating distribution primarily into extracellular fluid.
Bioavailability	Oral bioavailability is 99% (highly absorbed) with no significant food effect.
Onset of Action	Oral: Onset of glycemic effect occurs within 1-2 hours after a single dose, with maximal effect on insulin sensitivity developing over 6-8 weeks.
Duration of Action	Duration of action is approximately 24 hours following a single oral dose; however, full therapeutic benefit on glycemic control requires several weeks of continued therapy.

Classification & Brands

Dosing & administration

4 mg orally once daily; may increase to 8 mg once daily after 12 weeks if inadequate glycemic response.

Dosage form	TABLET
Renal impairment	No dose adjustment required for renal impairment; not dialyzable.
Liver impairment	Contraindicated in Child-Pugh class B and C. No adjustment needed for Child-Pugh class A.
Pediatric use	Not approved for use in pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 4 mg once daily; monitor for fluid retention and cardiovascular events.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP2C8 inhibitors may increase levels Can cause or exacerbate congestive heart failure and myocardial ischemia.

FDA category	Animal
Breastfeeding	Unknown if rosiglitazone is excreted in human milk. Animal studies suggest presence in milk. M/P ratio not established. Due to potential for adverse effects on breastfed infant (e.g., altered glucose metabolism), breastfeeding is not recommended during therapy.
Teratogenic Risk	Rosiglitazone is classified as FDA Pregnancy Category C. In animal studies, it was associated with fetal growth restriction at doses 2-4 times the human AUC. Human data: Limited. Risk cannot be excluded. First trimester: Potential for embryotoxicity based on animal data. Second/Third trimesters: May cause fetal adipose tissue accumulation, but no specific human malformations documented. Avoid use unless benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Common Effects	Weight gain
Serious Effects