Isosulfan Blue

Mylan Institutional LLC

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use isosulfan blue injection 1% safely and effectively. See full prescribing information for isosulfan blue injection 1%. Isosulfan Blue Injection 1%Initial U.S. Approval: 1981RECENT MAJOR CHANGESWarnings and Precautions, Interference with Oxygen Saturation and Methemoglobin Measurements (5.3). 10/2007INDICATIONS AND USAGEIsosulfan blue injection 1% upon subcutaneous administration, delineates the lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; lymph node response to therapeutic modalities (1.1).DOSAGE AND ADMINISTRATIONIsosulfan blue injection 1% is to be administered subcutaneously, one-half (1/2) mL into three (3) interdigital spaces of each extremity per study. A maximum dose of 3 mL (30 mg) isosulfan blue is, therefore, injected (2.1).DOSAGE FORMS AND STRENGTHS1% aqueous solution (isosulfan blue)CONTRAINDICATIONSHypersensitivity to triphenylmethane or related compounds (4).WARNINGS AND PRECAUTIONS •Life threatening anaphylactic reactions have occurred after isosulfan blue injection 1% administration. Monitor patients closely for at least 60 minutes after administration of isosulfan blue injection 1% (5.1). •The admixture of isosulfan blue injection 1% with local anesthetics results in an immediate precipitation of 4% to 9% drug complex. Use a separate syringe for anesthetics (5.2). •Isosulfan blue injection 1% interferes with measurements in peripheral blood pulse oximetry. Arterial blood gas analysis may be needed (5.3). Side Effects Hypersensitivity Reactions: Hypersensitivity reactions occur in approximately 2% of patients and include life threatening anaphylactic reactions with respiratory distress, shock, angioedema, urticaria, pruritus. A death has been reported following IV administration of a similar compound (6). To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONSNo drug interactions have been identified for isosulfan blue injection 1% (7).USE IN SPECIFIC POPULATIONS •Caution should be exercised when isosulfan blue injection 1% is administered to nursing mothers (8.3). •Safety and effectiveness of isosulfan blue injection 1% in children has not been established (8.4).

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 ISOSULFAN BLUE INDICATIONS AND USAGE
  • 1.1 Lymphatic Vessel Delineation
• 2 ISOSULFAN BLUE DOSAGE AND ADMINISTRATION
  • 2.1 Subcutaneous administration
• 3 DOSAGE FORMS AND STRENGTHS
• 4 ISOSULFAN BLUE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Hypersensitivity Reactions
  • 5.2 Precipitation of Isosulfan Blue Injection 1% by Lidocaine
  • 5.3 Interference with Oxygen Saturation and Methemoglobin Measurements
• 6 ISOSULFAN BLUE ADVERSE REACTIONS
  • 6.1 Post-Marketing Experience
• 7 DRUG INTERACTIONS
• 8 USE IN SPECIFIC POPULATIONS
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
• 10 OVERDOSAGE
• 11 ISOSULFAN BLUE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 13.2 Teratogenic Effects
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Lymphatic Vessel Delineation

Isosulfan blue injection 1% upon subcutaneous administration, delineates lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; and lymph node response to therapeutic modalities.

2 DOSAGE AND ADMINISTRATION

2.1 Subcutaneous administration

Isosulfan blue injection 1% is to be administered subcutaneously, one-half (1/2) mL into three (3) interdigital spaces of each extremity per study. A maximum dose of 3 mL (30 mg) isosulfan blue is, therefore, injected.

3 DOSAGE FORMS AND STRENGTHS

1% aqueous solution (isosulfan blue)

4 CONTRAINDICATIONS

Isosulfan blue injection 1% is contraindicated in those individuals with known hypersensitivity to triphenylmethane or related compounds.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Life threatening anaphylactic reactions (respiratory distress, shock, angio-edema) have occurred after isosulfan blue injection 1% administration. Reactions are more likely to occur in patients with a history of bronchial asthma, allergies, drug reactions or previous reactions to triphenylmethane dyes. Monitor patients closely for at least 60 minutes after administration of isosulfan blue injection 1%. Trained personnel should be available to administer emergency care including resuscitation.

5.2 Precipitation of Isosulfan Blue Injection 1% by Lidocaine

The admixture of isosulfan blue injection 1% (with local anesthetics (i.e. lidocaine)) in the same syringe results in an immediate precipitation of 4% to 9% drug complex. Use a separate syringe to administer a local anesthetic.

5.3 Interference with Oxygen Saturation and Methemoglobin Measurements

Isosulfan blue injection 1% interferes with measurements of oxygen saturation in peripheral blood by pulse oximetry and can cause falsely low readings. The interference effect is maximal at 30 minutes and minimal generally by 4 hours after administration. Arterial blood gas analysis may be needed to verify decreased arterial partial pressure of oxygen.

Isosulfan blue injection 1% may also cause falsely elevated readings of methemoglobin by arterial blood gas analyzer. Therefore, cooximetry may be needed to verify methemoglobin level.

6 ADVERSE REACTIONS

6.1 Post-Marketing Experience

Hypersensitivity Reactions: Case series report an overall incidence of hypersensitivity reactions in approximately 2% of patients. Life threatening anaphylactic reactions have occurred. Manifestations include respiratory distress, shock, angioedema, urticaria, pruritus. A death has been reported following administration of a similar compound employed to estimate the depth of a severe burn. Reactions are more likely to occur in patients with a personal or family history of bronchial asthma, significant allergies, drug reactions or previous reactions to triphenylmethane dyes [see Warnings and Precautions (5)].

Laboratory Tests: Isosulfan blue injection 1% interferes with measurements of oxygen saturation by pulse oximetry and of methemoglobin by gas analyzer [see Warnings and Precautions (5)].

Skin: transient or long-term (tattooing) blue coloration.

7 DRUG INTERACTIONS

No drug interactions have been identified with isosulfan blue injection 1%.

8 USE IN SPECIFIC POPULATIONS

8.3 Nursing Mothers

It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when isosulfan blue injection 1% is administered to a nursing mother.

8.4 Pediatric Use

Safety and effectiveness of isosulfan blue injection 1% in children have not been established.

10 OVERDOSAGE

Do not exceed indicated recommended dosage as overdosage levels have not been identified for isosulfan blue injection 1%.

11 DESCRIPTION

The chemical name of isosulfan blue injection 1% is N-[4- [[4-(diethylamino)phenyl] (2,5-disulfophenyl) methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium hydroxide, inner salt, sodium salt. Its structural formula is:

ISOSULFAN BLUE