FDA Label for Isosulfan Blue

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.

2.1 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.

Other

1% aqueous solution (isosulfan blue)

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

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

5.1 Hypersensitivity Reactions

Life threatening anaphylactic reactions (respiratory distress, shock, angioedema) 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, co-oximetry may be needed to verify methemoglobin level.

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.

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:

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Isosulfan blue injection 1% is a sterile aqueous solution for subcutaneous administration. Phosphate buffer in sterile, pyrogen free water is added in sufficient quantity to yield a final pH of 6.8 to 7.4. Each mL of solution contains 10 mg isosulfan blue, 6.6 mg sodium monohydrogen phosphate and 2.7 mg potassium dihydrogen phosphate. The solution contains no preservative. Isosulfan blue injection 1% is a contrast agent for the delineation of lymphatic vessels.

12.2 Pharmacodynamics

Following subcutaneous administration, isosulfan blue injection 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye.

12.3 Pharmacokinetics

Up to 10% of the subcutaneously administered dose of isosulfan blue injection 1% is excreted unchanged in the urine in 24 hours in humans.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of isosulfan blue injection 1%. Reproduction studies in animals have not been conducted and, therefore, it is unknown if a problem concerning mutagenesis or impairment of fertility in either males or females exists.

13.3 Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with isosulfan blue injection 1%. It is not known whether isosulfan blue injection 1% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Isosulfan blue injection 1% should be given to a pregnant woman only if clearly needed.

16 How Supplied/Storage And Handling

Isosulfan blue injection 1% is supplied as a 5 mL single-dose vial, 1% aqueous solution in a phosphate buffer prepared by appropriate manufacturing to be sterile and pyrogen-free.

NDC 70069-221-06

carton containing 6 x 5 mL single-dose vials

STORAGE: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Avoid excessive heat.

17 Patient Counseling Information

Inform patients that urine color may be blue for 24 hours following administration of isosulfan blue injection 1%.

Manufactured By:                                                                           

Wintac Limited                                                                                  

Bangalore 562123                                                                              

India

Code No.: KR/DRUGS/KTK/28/289/97

Manufactured for:

Somerset Therapeutics, LLC

Somerset, NJ 08873

ST-ISB11/P/00

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