Avandia

The management of antidiabetic therapy should be individualized. All patients should start AVANDIA at the lowest recommended dose. Further increases in the dose of AVANDIA should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning and Warnings and Precautions (5.1)].

AVANDIA may be administered at a starting dose of 4 mg either as a single daily dose or in 2 divided doses. For patients who respond inadequately following 8 to 12 weeks of treatment, as determined by reduction in fasting plasma glucose (FPG), the dose may be increased to 8 mg daily as monotherapy or in combination with metformin, sulfonylurea, or sulfonylurea plus metformin. Reductions in glycemic parameters by dose and regimen are described under Clinical Studies (14.1). AVANDIA may be taken with or without food.

The total daily dose of AVANDIA should not exceed 8 mg.

2.1 Monotherapy

The usual starting dose of AVANDIA is 4 mg administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4-mg twice-daily regimen resulted in the greatest reduction in FPG and hemoglobin A1c (HbA1c).

2.2 Combination With Sulfonylurea or Metformin

When AVANDIA is added to existing therapy, the current dose(s) of the agent(s) can be continued upon initiation of therapy with AVANDIA.

Sulfonylurea

When used in combination with sulfonylurea, the usual starting dose of AVANDIA is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin

The usual starting dose of AVANDIA in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with AVANDIA.

2.3 Combination With Sulfonylurea Plus Metformin

The usual starting dose of AVANDIA in combination with a sulfonylurea plus metformin is 4 mg administered as either a single dose once daily or divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

2.4 Specific Patient Populations

Renal Impairment

No dosage adjustment is necessary when AVANDIA is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and AVANDIA is also contraindicated in patients with renal impairment.

Hepatic Impairment

Liver enzymes should be measured prior to initiating treatment with AVANDIA. Therapy with AVANDIA should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of AVANDIA, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6) and Clinical Pharmacology (12.3).]

Pediatric

Data are insufficient to recommend pediatric use of AVANDIA [see Use in Specific Populations (8.4)].

The management of antidiabetic therapy should be individualized. All patients should start AVANDIA at the lowest recommended dose. Further increases in the dose of AVANDIA should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning and Warnings and Precautions (5.1)].

AVANDIA may be administered at a starting dose of 4 mg either as a single daily dose or in 2 divided doses. For patients who respond inadequately following 8 to 12 weeks of treatment, as determined by reduction in fasting plasma glucose (FPG), the dose may be increased to 8 mg daily as monotherapy or in combination with metformin, sulfonylurea, or sulfonylurea plus metformin. Reductions in glycemic parameters by dose and regimen are described under Clinical Studies (14.1). AVANDIA may be taken with or without food.

The total daily dose of AVANDIA should not exceed 8 mg.

2.1 Monotherapy

The usual starting dose of AVANDIA is 4 mg administered either as a single dose once daily or in divided doses twice daily. In clinical trials, the 4-mg twice-daily regimen resulted in the greatest reduction in FPG and hemoglobin A1c (HbA1c).

2.2 Combination With Sulfonylurea or Metformin

When AVANDIA is added to existing therapy, the current dose(s) of the agent(s) can be continued upon initiation of therapy with AVANDIA.

Sulfonylurea

When used in combination with sulfonylurea, the usual starting dose of AVANDIA is 4 mg administered as either a single dose once daily or in divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin

The usual starting dose of AVANDIA in combination with metformin is 4 mg administered as either a single dose once daily or in divided doses twice daily. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with AVANDIA.

2.3 Combination With Sulfonylurea Plus Metformin

The usual starting dose of AVANDIA in combination with a sulfonylurea plus metformin is 4 mg administered as either a single dose once daily or divided doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

2.4 Specific Patient Populations

Renal Impairment

No dosage adjustment is necessary when AVANDIA is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and AVANDIA is also contraindicated in patients with renal impairment.

Hepatic Impairment

Liver enzymes should be measured prior to initiating treatment with AVANDIA. Therapy with AVANDIA should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of AVANDIA, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6) and Clinical Pharmacology (12.3).]

Pediatric

Data are insufficient to recommend pediatric use of AVANDIA [see Use in Specific Populations (8.4)].

2.1  Recommended Dosing

The recommended dose of KALBITOR is 30 mg (3 mL), administered subcutaneously in three 10 mg (1 mL) injections. If the attack persists, an additional dose of 30 mg may be administered within a 24 hour period.

2.2  Administration Instructions

KALBITOR should only be administered by a healthcare professional with appropriate medical support to manage anaphylaxis and hereditary angioedema.

KALBITOR should be refrigerated and protected from the light.  KALBITOR is a clear, colorless liquid; visually inspect each vial for particulate matter and discoloration prior to administration.  If there is particulate matter or discoloration, the vial should not be used.

Using aseptic technique, withdraw 1 mL (10 mg) of KALBITOR from the vial using a large bore needle.  Change the needle on the syringe to a needle suitable for subcutaneous injection.  The recommended needle size is 27 gauge.  Inject KALBITOR into the skin of the abdomen, thigh, or upper arm.  Repeat the procedure for each of the 3 vials comprising the KALBITOR dose.  The injection site for each of the injections may be in the same or in different anatomic locations (abdomen, thigh, upper arm).  There is no need for site rotation.  Injection sites should be separated by at least 2 inches (5 cm) and away from the anatomical site of attack.

The same instructions apply to an additional dose administered within 24 hours.  Different injection sites or the same anatomical location (as used for the first administration) may be used.