FDA Label for Isosulfan Blue

The following document was submitted to the FDA by the labeler of this product Auromedics Pharma Llc. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.

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.

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.

5.1 Hypersensitivity Reactions

Life-threatening anaphylactic reactions (respiratory distress, shock, angioedema) have occurred after isosulfan blue 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 1%. Trained personnel should be available to administer emergency care including resuscitation.

5.2 Precipitation Of Isosulfan Blue 1% By Lidocaine

The admixture of isosulfan blue 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 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 four hours after administration. Arterial blood gas analysis may be needed to verify decreased arterial partial pressure of oxygen.

Isosulfan blue 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 Postmarketing 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 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 1%.

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 1% is administered to a nursing mother.

8.4 Pediatric Use

Safety and effectiveness of isosulfan blue 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 1%.

11 Description

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

Isosulfan Blue Chemical structure - isosulfan str

Isosulfan blue injection 1% is a sterile, non-pyrogenic, aqueous dark blue color solution for subcutaneous administration. Phosphate buffer in water for injection 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 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 1% is excreted unchanged in the urine in 24 hours in human.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of isosulfan blue 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.

13.2 Teratogenic Effects

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

16 How Supplied/Storage And Handling

Isosulfan blue injection 1% is a sterile, non-pyrogenic, aqueous dark blue color solution and is supplied as follows:

Isosulfan blue injection 1%

50 mg per 5 mL (10 mg / mL):
5 mL Single Dose Vials
in a Carton of 6                                                                      NDC 55150-240-05

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

Discard Unused Portion.

The vial stoppers are not made with natural rubber latex.

17 Patient Counseling Information

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

Distributed by:
AuroMedics Pharma LLC
279 Princeton-Hightstown Rd.
E. Windsor, NJ 08520

Manufactured by:
Aurobindo Pharma Limited
Hyderabad - 500038
India

Package Label-Principal Display Panel - 1% [50 Mg Per 5 Ml (10 Mg / Ml)] - Container Label

Rx only                 NDC 55150-240-05
Isosulfan Blue
Injection 1%
50 mg per 5 mL
(10 mg / mL)
For Lymphography
For Subcutaneous Use Only
5 mL                        Single Dose Vial

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 1% [50 mg per 5 mL (10 mg / mL)] - Container Label - isosulfan fig1

Package Label-Principal Display Panel - 1% [50 Mg Per 5 Ml (10 Mg / Ml)] - Container-Carton (6 Vials)

Rx only                        NDC 55150-240-05
Isosulfan Blue
Injection 1%
50 mg per 5 mL
(10 mg / mL)
For Lymphography
For Subcutaneous Use Only
Sterile                                            6 X 5 mL
Non-Pyrogenic                Single Dose Vials
AUROMEDICS

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 1% [50 mg per 5 mL (10 mg / mL)] - Container-Carton (6 Vials) - isosulfan fig2

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