A-Z Drug Facts > Rosiglitazone Maleate

Rosiglitazone Maleate

Pronouncation: (ROE-zi-GLI-ta-zone MAL-ee-ate)
Class: Thiazolidinedione

Trade Names:
Avandia
- Tablets 2 mg
- Tablets 4 mg
- Tablets 8 mg

Pharmacology

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

Pharmacokinetics

Absorption

Bioavailability is 99%. T _max is 1 h. When administered with food, C _max is lowered 28% with a delay in T _max by 1.75 h.

Distribution

Vd is about 17.6 L. Protein binding is 99.8%, primarily albumin.

Metabolism

Extensively metabolized by isoenzyme CYP2C8 with CYP2C9 as minor pathway.

Elimination

Eliminated in urine (64%) and feces (23%). Plasma t _½ is 103 to 158 h. Elimination t _½ is 3 to 4 h.

Special Populations

Hepatic Function Impairment

(Child-Pugh class B/C; moderate to severe) Unbound oral Cl was significantly lower, C _max and AUC were increased 2- to 3-fold, and elimination t _½ was about 2 h longer.

Gender

Mean oral Cl in women was about 6% lower.

Children

Pharmacokinetic parameters studied in children were consistent with parameter estimates in adult patients.

Race

Ethnicity had no influence on pharmacokinetics.

Renal function impairment

No dosage adjustments are needed in patients with renal function impairment.

Indications and Usage

Improves glycemic control of type 2 diabetes mellitus as monotherapy and as an adjunct to diet and exercise; in combination with metformin, insulin, or a sulfonylurea when diet, exercise, and a single agent does not result in adequate glycemic control in patients with type 2 diabetes mellitus; in combination with a sulfonylurea plus metformin when diet, exercise, and both agents do not result in adequate glycemic control of type 2 diabetes.

Unlabeled Uses

Increased ovulation frequency in women with polycystic ovary syndrome; reduced in-stent restenosis in patients with diabetes; reduced risk of adverse CV events and improved clinical outcomes in nondiabetic patients with metabolic syndrome after coronary stent implantation.

Contraindications

Established New York Heart Association class III or IV heart failure; hypersensitivity to any component of the product.

Dosage and Administration

Monotherapy
Adults

PO Initiate therapy at 4 mg/day, administered as a single dose or 2 divided doses. For patients not responding adequately, the dose may be increased to 8 mg/day after 8 to 12 wk of therapy.

Metformin
Combination Therapy Adults

PO In combination with metformin, initiate therapy with rosiglitazone 4 mg as a single dose or 2 divided doses.

Sulfonylureas
Combination Therapy Adults

PO In combination with sulfonylureas, the recommended dose of rosiglitazone is 4 mg as a single dose or 2 divided doses. If patient reports hypoglycemia, decrease the sulfonylurea dose.

Sulfonylureas and Metformin
Combination Therapy Adults

PO In combination with a sulfonylurea and metformin, initiate therapy with rosiglitazone 4 mg as single dose or 2 divided doses. If patient develops hypoglycemia, decrease the sulfonylurea dose.

Insulin
Combination Therapy Adults

PO In combination with insulin, initiate therapy with rosiglitazone 4 mg (max dose) as single dose or 2 divided doses. If patient reports hypoglycemia or if fasting blood glucose concentrations decrease to less than 100 mg/dL, it is recommended that the insulin dose be decreased 10% to 25%. Individualize further adjustments based on glucose-lowering response.

Hepatic Function Impairment Adults

PO Treatment should not be initiated in patients exhibiting evidence of active liver disease or increased serum transaminase levels (ALT greater then 2.5 × ULN at the start of therapy).

General Advice

• Administer without regard to meals. Administer with food if GI upset occurs. Max dose is 8 mg/day (4 mg/day in combination with insulin).

Storage/Stability

Store at 59° to 86°F. Dispense in light-resistent containers.

Drug Interactions

CYP2C8 inducers (eg, rifampin)

May decrease rosiglitazone AUC; changes in diabetes treatment may be needed when the CYP2C8 inducer is started or stopped.

CYP2C8 inhibitors (eg, azole antifungal agents [ketoconazole], fluvoxamine, gemfibrozil, trimethoprim)

May elevate rosiglitazone plasma levels, increasing the pharmacologic effects and adverse reactions.

Insulin

Risk of edema may be increased, even after several months of therapy.

Nevirapine

Nevirapine plasma concentrations may be reduced, decreasing efficacy.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

CHF (postmarketing).

CNS

Headache (6%); fatigue (4%).

Dermatologic

Pruritus; rash; Stevens-Johnson syndrome; urticaria (postmarketing)

EENT

Sinusitis (3%); macula edema (postmarketing).

GI

Diarrhea (2%).

Hematologic-Lymphatic

Anemia (2%); decreased WBC; dose-related decreases in Hgb and Hct.

Hepatic

Hepatic enzyme elevation 3 or more times ULN; hepatitis (postmarketing).

Lab Tests

Decreases in free fatty acids; increase in HDL, LDL, and total cholesterol.

Metabolic-Nutritional

Hyperglycemia (4%); hypoglycemia (1%).

Musculoskeletal

Back pain (4%).

Respiratory

Upper respiratory tract infection (10%); pleural effusion, pulmonary edema (postmarketing).

Miscellaneous

Injury (8%); edema (5%); anaphylactic reactions; angioedema (postmarketing).

Precautions

Warnings CHF May occur or be exacerbated. Observe patients for signs and symptoms of heart failure after starting therapy or increasing the dose. Manage heart failure according to current standards of care. Consider discontinuation or dose reduction. Use of drug is not recommended in patients with symptomatic heart failure.

Monitor Obtain periodic fasting blood glucose and hemoglobin A 1c (HbA 1c )concentrations to monitor therapeutic response. Assess liver enzymes prior to initiation of therapy and periodically thereafter.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Use with caution. Do not initiate therapy in patients with clinical evidence of active liver disease or baseline ALT more than 2.5 × ULN. Discontinue therapy if ALT increases to more than 3 × ULN and persists.

Bone fractures

Increased incidence of bone fractures noted in women but not in men.

Diabetic ketoacidosis

Not recommended.

Edema

Use with caution; can cause fluid retention.

Hematologic

Decreases in Hgb (1 g/dL or less) and Hct (3.3% or less) have been reported; may be related to dose-related increases in plasma volume associated with rosiglitazone therapy.

Hypoglycemia

May increase risk of hypoglycemia when used in combination with other hypoglycemic agents; may need dose reduction of concomitant agent.

Ovulation

May result in resumption of ovulation in premenopausal anovulatory women with insulin resistance.

Type 1 diabetes

Not recommended.

Weight gain

Dose-related weight gain has been seen alone and in combination with other hypoglycemic agents. Unusually rapid increases in weight may be caused by fluid accumulation; assess such patients for fluid accumulation and volume-related events.

Overdosage

Symptoms

Limited data are available.

Patient Information

• Advise patient to review the patient information leaflet carefully before starting therapy and to reread and check for new information each time the medication is refilled.
• Advise patient to take once or twice daily as prescribed.
• Advise patient that medication can be taken without regard to meals but to take with food if stomach upset occurs.
• Advise patient that it may take 2 wk before a reduction in blood glucose is noted and that it may take 2 to 3 mo before the full effect is seen.
• Instruct patient that this drug is not a substitute for diet and exercise and that patient should continue to follow prescribed regimens.
• Educate patient regarding type 2 diabetes and its management.
• Emphasize the importance of regular daily blood glucose monitoring and periodic HbA _1c tests. Ensure that patient knows their target values for both.
• Educate patient regarding potential long-term complications of diabetes and need for regular general physical and eye examinations.
• Advise patient to carry medical identification (eg, card, bracelet) of diabetes.
• Advise patient to report any of the following to health care provider immediately: abdominal pain, anorexia, dark urine, edema or swelling, fatigue, unexplained nausea and/or vomiting, unexplained shortness of breath, unusually rapid increase in weight, yellowing of the skin or eyes.
• Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event either occurs.
• Advise patient to discuss a plan with health care provider for managing each of the following situations: accidental administration of too little or too much rosiglitazone, change in physical activity, dosing during intercurrent conditions (eg, infection, sick days, stress, trauma, vomiting), inadequate food intake or a skipped meal, missed rosiglitazone dose, travel across time zones.
• Instruct patient to notify health care provider if experiencing hypoglycemic or hyperglycemic episodes.
• Advise patient that blood will be drawn to check liver function prior to starting therapy and periodically thereafter.
• Caution women that drug can cause resumption of ovulation in premenopausal anovulatory women with insulin resistance. Advise such women to discuss adequate contraceptive measures with health care provider.

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