Adult Dosing
Type II diabetes mellitus (NIDDM)
- Initial dose
- 1 mg/4 mg PO qd with the first meal
- For adults already treated with a sulfonylurea or a thiazolidinedione: 2 mg/4 mg PO qd may be considered
- Notes:
- Start the rosiglitazone component of the drug at the lowest recommended dose
- Carefully monitor for adverse events related to fluid retention before increasing the dose of rosiglitazone
- When switching from combination therapy of rosiglitazone plus glimepiride as separate tablets, the usual starting dose of (glimepiride/rosiglitazone) is the dose of rosiglitazone and glimepiride already being taken
- Titration of dose
- Dose increases should be individualized based on the patient’s glycemic response. Patients sensitive to glimepiride (elderly, debilitated, or malnourished, and those with renal, hepatic, or adrenal insufficiency) should be carefully titrated to avoid hypoglycemia. If hypoglycemia occurs during titration or maintenance of treatment, a dose reduction in the glimepiride component may be considered. Increases in the rosiglitazone dosage should be accompanied by careful monitoring for adverse effects related to fluid retention
- For switching to combination therapy in patients currently treated with rosiglitazone: Increase the dose of the glimepiride component of the combination drug if adequate control is not achieved after 1 to 2 wks; the glimepiride dose may be titrated in no >2 mg increments. After increasing the glimiperide dose, titration of the combination drug is recommended if there is inadequate control after 1 to 2 wks
- For switching to combination therapy in patients currently treated with sulfonylurea: Increase the dose of the rosiglitazone component of the combination drug if patients are not adequately controlled after 8-12 wks. After an increase in the dosage of the rosiglitazone component, dose titration of the combination drug is recommended if patients are not adequately controlled after 2-3 months. Observe carefully for hypoglycemia when being transferred from longer half-life sulfonylureas to combination drug because of potential overlapping of drug effect
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
See Supplemental Patient Information
- Based on the study conducted by the University Group Diabetes Program (UGDP), oral hypoglycemic drugs are associated with an increased risk of cardiovascular mortality as compared to treatment with diet alone or diet plus insulin
- Potential risks and advantages of glimepiride-containing tablets and alternate mode of therapy should be informed to the patients
- Thiazolidinediones, including rosiglitazone, alone or in combination with other hypoglycemic agents, can cause fluid retention leading to or exacerbating heart failure. Use cautiously in patients with edema; monitor for signs and symptoms of heart failure and manage according to current standards of care [US Black Box Warning]
- Contraindicated in patients with established NYHA Class III or IV heart failure and symptomatic heart failure [US Black Box Warning]
- Not recommended in patients experiencing an acute coronary event; consider discontinuing during this acute phase
- Coadministration of rosiglitazone with insulin is not recommended as it increases the risk of congestive heart failure
- A meta-analysis of 52 clinical trials, most of which compared rosiglitazone to placebo, showed that rosiglitazone is associated with an increased risk of myocardial infarction. Three other trials, comparing rosiglitazone to some other approved oral antidiabetic agents or placebo, showed a statistically non-significant increased risk of myocardial infarction, and a statistically non-significant decreased risk of death. There have been no clinical trials conducted to directly compare the cardiovascular risk of rosiglitazone and pioglitazone (another thiazolidinedione). But in a separate trial, pioglitazone, compared with placebo, did not show an increased risk of myocardial infarction or death [US Black Box Warning]
- Because of the potential increased risk of MI, prescribers must discuss the risks and benefits of taking this combination drug with the patients
- Severe hypoglycemia can occur. Elderly, debilitated or malnourished patients, and those with adrenal, pituitary, renal or hepatic insufficiency are at a higher risk. Reduction in the glimepiride dose may be required
- Rosiglitazone, alone or in combination with other hypoglycemic agents, may cause weight gain probably due to fluid retention and fat accumulation
- Do not initiate therapy in case of active liver disease or elevated serum ALT levels >2.5 x ULN
- Evaluate serum ALT levels prior to, and periodically during treatment. If ALT levels remain >3x ULN or if jaundice is observed, discontinue therapy. IF symptoms suggesting hepatic dysfunction occur, the decision whether to continue treatment should be guided by clinical judgment pending laboratory evaluations
- As per postmarketing experience, macular edema has been reported in some diabetic patients taking rosiglitazone or another thiazolidinedione. Perform routine ophthalmologic examination in these patients
- Risk of fracture should be considered in patients treated with rosiglitazone, particularly in females; assess and maintain bone health according to current standards of care
- Rosiglitazone may decrease hemoglobin and hematocrit levels
- Use of sulfonylurea agents can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Use cautiously in patients with G6PD deficiency or consider a non-sulfonylurea alternative
- A temporary loss of glycemic control can occur in patients stabilized on any antidiabetic regimen when exposed to stress such as fever, trauma, infection, or surgery. Temporarily withhold therapy and administer insulin
- Thiazolidinediones may cause ovulation in some premenopausal anovulatory women. Advice patients to use adequate contraception
Cautions: Use cautiously in
- Hepatic impairment
- Hypersensitivity to sulfonamides
Supplemental Patient Information
- Advise patients to avoid excessive use of alcohol while receiving treatment
- Instruct premenopausal women to take adequate contraception because of the increased risk for pregnancy while taking rosiglitazone
- Advise patients to promptly report their physicians if unexplained symptoms of abdominal pain, nausea, vomiting, anorexia, fatigue, or dark urine develop
Pregnancy Category:C
Breastfeeding: Information not available on glimepiride/rosiglitazone use during breastfeeding, use an alternate drug especially while nursing a newborn or preterm infant. Monitor blood glucose levels of the breastfed infant during maternal treatment with hypoglycemic agents. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 20 May 2011). As per manufacturer's data, glimepiride/rosiglitazone should not be administered to nursing women.
US Trade Name(s)
US Availability
Avandaryl (glimepiride/rosiglitazone)
- TABS:
- 1 mg/4 mg
- 2 mg/4 mg
- 4 mg/4 mg
- 2 mg/8 mg
- 4 mg/8 mg
Canadian Trade Name(s)
Canadian Availability
Avandaryl (glimepiride/rosiglitazone )
- TABS:
- 1 mg/4 mg
- 2 mg/4 mg
- 4 mg/4 mg
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
Pricing data from www.DrugStore.com in U.S.A.
- Avandaryl 4-1 MG TABS [Bottle] (GLAXO SMITH KLINE)
30 mg = $155.31
90 mg = $434.86 - Avandaryl 4-4 MG TABS [Bottle] (GLAXO SMITH KLINE)
30 mg = $155.31
90 mg = $434.86 - Avandaryl 4-2 MG TABS [Bottle] (GLAXO SMITH KLINE)
30 mg = $156
90 mg = $447.65
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.