Rosiglitazone

Indications

Rosiglitazone is used for: Type 2 Diabetes Mellitus

Adult Dose

Type 2 Diabetes Mellitus Initial 4 mg PO qDay or divided q12hr If inadequate response afer 8-12 weeks, may increase dose to 8 mg PO qDay or divided q12hr Monitor: ALT at start of treatment, qMonth for 12 months then q3Months thereafter Dosage Modifications Active liver disease (ALT >2.5 x ULN): Do not inititate rosiglitazone

Child Dose

Renal Dose

Renal impairment: No dosage adjustments required

Administration

Contra Indications

Hypersensitivity to rosiglitazone Diabetic ketoacidosis Heart failure NYHA class III-IV Active liver disease: do not start rosiglitazone if ALT >2.5 x ULN

Precautions

Congestive heart failure risk Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients. Fluid retention, which may exacerbate or lead to heart failure, may occur; combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk of other cardiovascular effects If ALT >3 x ULN stop treatment; if 1.5-3 x normal, retest qWeek until normal or 3 x normal and need to discontinue Not for use in diabetes mellitus type 1; Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin; dose-related edema and weight gain may occur When used in combination with other hypoglycemic agents, a dose reduction of concomitant agent may be necessary to reduce risk of hypoglycemia Associated with rare cases of new onset or worsening of macular edema May result in ovulation in some premenopausal anovulatory women; ensure adequate contraception Increased risk of fractures of upper arm, hand, or foot in female patients Dose-related decreases in hemoglobin and hemocrit reported Lactation: Unsafe

Pregnancy-Lactation

Pregnancy Limited data in pregnant women are not sufficient to determine drug- associated risk for major birth defects or miscarriage; there are risks to mother and fetus associated with poorly controlled diabetes in pregnancy Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity Animal data In animal reproduction studies, no adverse developmental effects observed when drug was administered to pregnant rats and rabbits during organogenesis at exposures up to 4 times the maximum recommended human dose (MRHD) of 8 mg daily Reproductive potential of patients Discuss potential for unintended pregnancy with premenopausal women as therapy may result in ovulation in some anovulatory women Lactation There are no data on presence of rosiglitazone in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant or the underlying maternal condition

Interactions

Adverse Effects

Side effects of Rosiglitazone : >10% Increased LDL-cholesterol Increased HDL-cholesterol Increased total cholesterol 1-10% Edema Hypertension Heart failure/congestive heart failure Myocardial ischemia Diarrhea Upper respiratory tract infection Frequency Not Defined Accidental injury Anemia Back pain Fatigue Headache Hypoglycemia Myalgia Sinusitis Weight gain

Mechanism of Action

Lowers glucose by improving target cell response to insulin without increasing pancreatic cell secretion; activates nuclear peroxisome proliferator-activated receptor gamma, which influences the production of gene products involved in glucose and lipid metabolism