AVANDAMET

AVANDAMET — rosiglitazone maleate and metformin hydrochloride tablet, film coated
Physicians Total Care, Inc.

WARNINGS

Rosiglitazone maleate: CONGESTIVE HEART FAILURE AND MYOCARDIAL INFARCTION

  • Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.2)]. After initiation of AVANDAMET, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of AVANDAMET must be considered.
  • AVANDAMET is not recommended in patients with symptomatic heart failure. Initiation of AVANDAMET in patients with established NYHA Class III or IV heart failure is contraindicated. [See Contraindications (4) and Warnings and Precautions (5.2).]
  • A meta-analysis of 52 clinical trials (mean duration 6 months; 16,995 total patients), most of which compared rosiglitazone to placebo, showed rosiglitazone to be associated with an increased risk of myocardial infarction. Three other trials (mean duration 46 months; 14,067 total patients), 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 directly comparing cardiovascular risk of rosiglitazone and ACTOS® (pioglitazone, another thiazolidinedione), but in a separate trial, pioglitazone (when compared to placebo) did not show an increased risk of myocardial infarction or death. [See Warnings and Precautions (5.3).]

Metformin hydrochloride: LACTIC ACIDOSIS

  • Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure. [See Warnings and Precautions (5.1).]
  • Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. [See Warnings and Precautions (5.1).]
  • If acidosis is suspected, discontinue AVANDAMET and hospitalize the patient immediately [see Warnings and Precautions (5.1)].

1 INDICATIONS AND USAGE

After consultation with a healthcare professional who has considered and advised the patient of the risks and benefits of rosiglitazone, AVANDAMET® is indicated as an adjunct to diet and exercise to improve glycemic control when treatment with both rosiglitazone and metformin is appropriate in adults with type 2 diabetes mellitus who either are:

  • already taking rosiglitazone, or
  • not already taking rosiglitazone and unable to achieve glycemic control on other diabetes medications and, in consultation with their healthcare provider, have decided not to take pioglitazone (ACTOS®) or pioglitazone-containing products (ACTOPLUS MET® , ACTOPLUS MET XR® , DUETACT®) for medical reasons.
Other Important Limitations of Use:
  • Due to its mechanism of action, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDAMET should not be used in patients with type 1 diabetes.
  • Coadministration of AVANDAMET with insulin is not recommended [see Warnings and Precautions (5.2, 5.3)].

2 DOSAGE AND ADMINISTRATION

Prior to prescribing AVANDAMET, refer to Indications and Usage (1) for appropriate patient selection.

2.1 Starting Dose

AVANDAMET is generally given in divided doses with meals.

All patients should start the rosiglitazone component of AVANDAMET at the lowest recommended dose. Further increases in the dose of rosiglitazone should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning and Warnings and Precautions (5.4)].

If therapy with a combination tablet containing rosiglitazone and metformin is considered appropriate for a patient with type 2 diabetes mellitus, then the selection of the dose of AVANDAMET should be based on the patient’s current doses of rosiglitazone and/or metformin.

To switch to AVANDAMET for patients currently treated with metformin, the usual starting dose of AVANDAMET is 4 mg rosiglitazone (total daily dose) plus the dose of metformin already being taken (see Table 1).

To switch to AVANDAMET for patients currently treated with rosiglitazone, the usual starting dose of AVANDAMET is 1,000 mg metformin (total daily dose) plus the dose of rosiglitazone already being taken (see Table 1).

When switching from combination therapy of rosiglitazone plus metformin as separate tablets, the usual starting dose of AVANDAMET is the dose of rosiglitazone and metformin already being taken.

Table 1. AVANDAMET Starting Dose for Patients Treated with Metformin and/or Rosiglitazone
PRIOR THERAPY Usual AVANDAMET Starting Dose
Total daily dose Tablet strength Number of tablets
Metformina
1,000 mg/day 2 mg/500 mg 1 tablet twice a day
2,000 mg/day 2 mg/1,000 mg 1 tablet twice a day
Rosiglitazone
4 mg/day 2 mg/500 mg 1 tablet twice a day
8 mg/day 4 mg/500 mg 1 tablet twice a day

a For patients on doses of metformin between 1,000 and 2,000 mg/day, initiation of AVANDAMET requires individualization of therapy.

2.2 Dose Titration

AVANDAMET is generally given in divided doses with meals, with gradual dose escalation. This reduces gastrointestinal side effects (largely due to metformin) and permits determination of the minimum effective dose for the individual patient.

Sufficient time should be given to assess adequacy of therapeutic response. FPG should be used initially to determine the therapeutic response to AVANDAMET. If additional glycemic control is needed, the daily dose of AVANDAMET may be increased by increments of 4 mg rosiglitazone and/or 500 mg metformin.

After an increase in metformin dosage, dose titration is recommended if patients are not adequately controlled after 1 to 2 weeks. After an increase in rosiglitazone dosage, dose titration is recommended if patients are not adequately controlled after 8 to 12 weeks.

2.3 Maximum Dose

The maximum recommended total daily dose of AVANDAMET is 8 mg rosiglitazone (taken as 4 mg twice daily) and 2,000 mg metformin (taken as 1,000 mg twice daily).

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