Adult Dosing
Type II diabetes mellitus (NIDDM)
Adult patients inadequately controlled with diet and exercise
- Initial dose: 500 mg/2 mg PO (metformin/rosiglitazone) bid
- Titration: May increase 500 mg/day metformin q1-2 wks and 4 mg/day rosiglitazone q8-12 wks, if patients are not adequately controlled [Max: (metformin/rosiglitazone) 2000 mg/8 mg/day]
Adult patients inadequately controlled with metformin monotherapy
- If on 1,000 mg/day metformin: Start 500 mg/2 mg (1 tablet) PO bid; may increase 500 mg/day metformin q1-2wk [Max: (metformin/rosiglitazone) 2000 mg/8 mg/day]
- If on 2,000 mg/day metformin: Start 1000 mg/2 mg (1 tablet) PO bid; may increase 500 mg/day metformin q1-2wk [Max: (metformin/rosiglitazone) 2000 mg/8 mg/day]
Adult patients inadequately controlled with rosiglitazone monotherapy
- If on 4 mg/day rosiglitazone: Start 500 mg/2 mg (1 tablet) PO bid; may increase by 4 mg/day rosiglitazone q8-12wk [Max: (metformin/rosiglitazone) 2000 mg/8 mg/day]
- If 8 on mg/day rosiglitazone: Start 500 mg/4 mg (1 tablet) PO bid; may increase 4 mg/day rosiglitazone q8-12wk [Max: (metformin/rosiglitazone) 2000 mg/8 mg/day]
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Rosiglitazone maleate:Congestive heart failure and myocardial infarction
- Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients. Observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema) after initiation and titration. If signs and symptoms of heart failure develop, manage according to current standards of care (discontinuation of treatment/dose reduction)
- Metformin/rosiglitazone is contraindicated in patients with established NYHA Class III or IV heart failure
- A meta-analysis of 52 clinical trials showed that rosiglitazone (as compared to placebo) is associated with an increased risk of myocardial infarction. Three other trials comparing rosiglitazone to other approved oral antidiabetic agents or placebo, showed statistically non-significant increased risk of myocardial infarction and statistically non-significant decreased risk of death. No studies directly compare cardiovascular risk of rosiglitazone and other thiazolidinediones, but in separate study, pioglitazone did not show an increased risk of myocardial infarction or death
- Due to potential risk of myocardial infarction, this drug is available through a restricted distribution program called the AVANDIA-Rosiglitazone Medicines Access Program into which both prescribers and patients need to enroll
Metformin hydrochloride: Lactic acidosis
- Lactic acidosis can occur due to metformin use. Most cases of metformin induced lactic acidosis in diabetic patients occurs in those with significant renal insufficiency. Risk further increases with sepsis, dehydration, hepatic insufficiency, renal impairment excess alcohol intake, and acute congestive heart failure
- Onset may be subtle with nonspecific symptoms like malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Lab findings include low pH, increased anion gap and elevated blood lactate
- Discontinue administration of this drug if acidosis is suspected and hospitalize the patient immediately
See Supplemental Patient Information
- Lactic acidosis, a rare metabolic complication but fatal occurs with metformin accumulation during rosigliatzone/metformin therapy [US Black Box Warning]
- Thiazolidinediones cause or exacerbate congestive heart failure in some patients, due to fluid retention [US Black Box Warning]
- Coadministration of rosiglitazone and insulin is not recommended as it increases the risk of congestive heart failure
- Rosiglitazone as compared to placebo is associated with an increased risk of myocardial infarction, according to a meta-analysis of 52 clinical trials [US Black Box Warning]
- Rosiglitazone can cause fluid retention, which can exacerbate or lead to congestive heart failure. Use cautiously in patients with edema and monitor the patient for the signs and symptoms of heart failure
- Rosiglitazone, alone or in combination with other hypoglycemic agents, cause weight gain, probably due to fluid retention and fat accumulation
- Rosiglitazone causes hepatitis and elevates liver enzyme levels. Evaluate serum ALT levels before starting rosiglitazone/metformin therapy and periodically during the treatment. If ALT levels >3 x ULN or any signs of hepatic dysfunction appear, discontinue therapy
- Consider risk of fracture in patients treated with rosiglitazone, especially females. Provide attention to and assess and maintain bone health according to current standards of care
- As per postmarketing experience, macular edema has been reported in some diabetic patients who were taking rosiglitazone or another thiazolidinedione. Perform routine ophthalmologic examination in these patients
- Decline in mean hemoglobin values can occur with rosiglitazone. Vitamin B12 deficiency may contribute to the observed reductions in hemoglobin. Monitor hematological parameters at baseline and periodically on an annual basis
- Metformin therapy can cause a decrease to subnormal levels of previously normal serum vitamin B12 levels; measure hematological parameters annually
- A temporary loss of glycemic control can occur in patients stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, temporary withhold the therapy and administer insulin
- Rosiglitazone in combination with other hypoglycemic agents cause hypoglycemia. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly at higher risk, dose reduction of the concomitant agent can be considered
- Thiazolidinediones cause ovulation in some premenopausal anovulatory women. Advise patient to use adequate contraception
Cautions: Use cautiously in
- Cardiac disease
- Risk of CHF
- NYHA Class I-II heart failure
- Elderly or debilitated patients
- Risk of hypoglycemia
- Female patients
- Premenopausal anovulatory women
- Edema
- Alcohol abuse
Supplemental Patient Information
- Patients should be instructed to avoid excessive use of alcohol while receiving treatment
Pregnancy Category:C
Breastfeeding: Safety unknown for combination drug. Metformin is detectable in low levels in the serum of breastfed infants. Milk metformin levels are relatively constant and infants receive <0.5% of the maternal weight-adjusted dosage. No adverse effects were found in breastfed infants in one prospective study. Use with caution while nursing newborn/premature infants and those with renal impairment. It is not known weather rosiglitazone is excreted in breast milk; an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Monitor blood glucose level of infant during maternal therapy with hypoglycemic agents. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 9 February 2011). As per manufacturer's data both rosiglitazone and metformin are excreted in rat milk, whether excreted in human milk is not known, but as many drugs are excreted in human milk, it should not be administered to a nursing woman.
US Trade Name(s)
US Availability
Avandamet (metformin/rosiglitazone)
- TABS
- 500 mg/2 mg
- 500 mg/4 mg
- 1000 mg/2 mg
- 1000 mg/4 mg
Canadian Trade Name(s)
Canadian Availability
Avandamet (metformin/rosiglitazone)
- TABS
- 500 mg/1 mg
- 500 mg/2 mg
- 500 mg/4 mg
- 1000 mg/2 mg
- 1000 mg/4 mg
UK Trade Name(s)
UK Availability
Avandamet (metformin/rosiglitazone)
- TABS
- 500 mg/2 mg
- 1000 mg/2 mg
- 1000 mg/4 mg
Australian Trade Name(s)
Australian Availability
Avandamet (metformin/rosiglitazone)
- TABS
- 500 mg/1 mg
- 500 mg/2 mg
- 500 mg/4 mg
- 1000 mg/2 mg
- 1000 mg/4 mg
[Outline]
Pricing data from www.DrugStore.com in U.S.A.
- Avandamet 4-1000 MG TABS [Bottle] (GLAXO SMITH KLINE)
60 mg = $279.99
180 mg = $808.28 - Avandamet 4-500 MG TABS [Bottle] (GLAXO SMITH KLINE)
60 mg = $279.99
180 mg = $785.93 - Avandamet 2-500 MG TABS [Bottle] (GLAXO SMITH KLINE)
60 mg = $174.07
180 mg = $472.47 - Avandamet 2-1000 MG TABS [Bottle] (GLAXO SMITH KLINE)
60 mg = $161.64
180 mg = $455.07
Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.