SPL UNCLASSIFIED SECTION.

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.

TERATOGENIC EFFECTS SECTION.

13.2 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 pregnant woman or can affect reproduction capacity. Isosulfan blue injection 1% should be given to pregnant woman only if clearly needed.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 50 mg/5 mLNDC 67457-220-05Isosulfan Blue Injection 1%50 mg/5 mL (10 mg/mL)For LymphographyFor Subcutaneous Use OnlyRx only x mL Single-Dose VialsSterile. Non-Pyrogenic. Single-Dose Container.Contains no preservatives.Not for Multiple-Use.Discard Unused Portion.Each mL contains:Isosulfan Blue . . . . . . . . . . . . 10 mgSodium monohydrogen phosphate. . . . 6.6 mgPotassium dihydrogen phosphate . . . . 2.7 mgConsult Accompanying Prescribing Information Before Administering Drug.Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.]Avoid excessive heat.Manufactured for: Mylan Institutional LLC Morgantown, WV 26505 U.S.A.Manufactured by:Mylan InstitutionalGalway, IrelandMI:220:6C:R5Mylan.com. Isosulfan Blue Injection 1% Carton Label.

PEDIATRIC USE SECTION.

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

PHARMACODYNAMICS SECTION.

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.

PHARMACOKINETICS SECTION.

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.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Hypersensitivity Reactions: Hypersensitivity reactions occur in approximately 2% of patients and include life threatening anaphylactic reactions with respiratory distress, shock, angioedema, urticaria, pruritus. death has been reported following IV administration of similar compound (6). To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 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. death has been reported following administration of similar compound employed to estimate the depth of severe burn. Reactions are more likely to occur in patients with 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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 problem concerning mutagenesis or impairment of fertility in either males or females exists.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 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.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Isosulfan blue injection 1% is contraindicated in those individuals with known hypersensitivity to triphenylmethane or related compounds.. Hypersensitivity to triphenylmethane or related compounds (4).

DESCRIPTION SECTION.

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 BLUEIsosulfan blue injection 1% is sterile aqueous solution for subcutaneous administration. Phosphate buffer in sterile, pyrogen free water is added in sufficient quantity to yield 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 contrast agent for the delineation of lymphatic vessels.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND 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. maximum dose of mL (30 mg) isosulfan blue is, therefore, injected (2.1).. 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. maximum dose of mL (30 mg) isosulfan blue is, therefore, injected.Discard unused portion.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. 1% aqueous solution (isosulfan blue). 1% aqueous solution (isosulfan blue).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. No drug interactions have been identified with isosulfan blue injection 1%.. No drug interactions have been identified for isosulfan blue injection 1% (7).

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Isosulfan Blue Injection 1% is supplied as 5 mL single-dose vial, 1% aqueous solution in phosphate buffer prepared by appropriate manufacturing to be sterile and pyrogen-free.NDC 67457-220-05carton containing x mL single-dose vialsStorage: Vials should be stored at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.] Avoid excessive heat.Discard unused portion.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Isosulfan 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).. 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.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Inform patients that urine color may be blue for 24 hours following administration of isosulfan blue injection 1%.Manufactured for: Mylan Institutional LLC Morgantown, WV 26505 U.S.A.Manufactured by: Mylan Institutional Galway, Ireland0874L102Revised: 9/2020MI:ISOSIJ:R5.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 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 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 injection 1%. It is not known whether isosulfan blue injection 1% can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Isosulfan blue injection 1% should be given to pregnant woman only if clearly needed.

NURSING MOTHERS SECTION.

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 nursing mother.

OVERDOSAGE SECTION.

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

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. oCaution should be exercised when isosulfan blue injection 1% is administered to nursing mothers (8.3).oSafety and effectiveness of isosulfan blue injection 1% in children has not been established (8.4).. oCaution should be exercised when isosulfan blue injection 1% is administered to nursing mothers (8.3).. oSafety and effectiveness of isosulfan blue injection 1% in children has not been established (8.4).. 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 nursing mother.. 8.4 Pediatric Use. Safety and effectiveness of isosulfan blue injection 1% in children have not been established.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oLife 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).oThe admixture of isosulfan blue injection 1% with local anesthetics results in an immediate precipitation of 4% to 9% drug complex. Use separate syringe for anesthetics (5.2).oIsosulfan blue injection 1% interferes with measurements in peripheral blood pulse oximetry. Arterial blood gas analysis may be needed (5.3).. oLife 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).. oThe admixture of isosulfan blue injection 1% with local anesthetics results in an immediate precipitation of 4% to 9% drug complex. Use separate syringe for anesthetics (5.2).. oIsosulfan blue injection 1% interferes with measurements in peripheral blood pulse oximetry. Arterial blood gas analysis may be needed (5.3).. 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 history of bronchial asthma, allergies, drug reactions or previous reactions to tri-phenylmethane 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 separate syringe to administer 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 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.