VERDYE

3 mg/kg body weight as intravenous bolus injection Identification of sentinel lymph nodes and visualization of lymphatic pathways regardless of body weight: 5 to 10 mg per injection (intradermal, subcutaneous or peritumoral). This corresponds to 1 to 2 ml of the reconstituted 5 mg/ml solution.

The volume per injection should not exceed 2 ml. g. 5 mg/ml, the reconstituted solution can be further diluted with 5 ml or 10 ml water for injections depending on the vial size).

Total daily dose in adults, elderly, adolescents, children:

Adults, elderly, adolescents 11 - 18 years: The total daily dose of Verdye should be kept below 5 mg/kg body weight. 5 mg/kg body weight. 25 mg/kg body weight. 25 mg/kg body weight in children 0 - 2 years. Patients with renal impairment Verdye has not formally been studied in patients with renal impairment.

No specific dose recommendations for this patient population are available. 4). Patients with hepatic impairment Verdye has not formally been studied in patients with hepatic impairment. No specific dose recommendations for this patient population are available.

g. alcoholic or biliary cirrhosis), plasma clearance of indocyanine green may be reduced. Identification of sentinel lymph nodes and visualization of lymphatic pathways For the identification of sentinel lymph nodes and visualization of lymphatic pathways, the total daily dose of Verdye should not exceed 10 mg; the use in children and adolescents is not recommended due to insufficient data on safety and efficacy.

Method of administration Before administration the powder must be reconstituted with water for injections. 6. The reconstituted solution is clear and free from visible particles. Verdye is administered by intravenous, intradermal, subcutaneous or peritumoral injection.

Methods of measurement The absorption and emission maximum of indocyanine green are both in the near infrared range, the absorption maximum at 800 nm and the emission maximum for fluorescence measurement at 830 nm. In in-vitro-tests indocyanine green remains stable in human serum for several days.

Dissolved in water, indocyanine green shows no detectable decomposition at least for a few hours. Diagnostic procedures with Verdye should be performed under the supervision of a physician. Measurement of cardiac, circulatory and cerebral blood flow as well as liver function diagnostics and ophthalmologic angiography For cardiac, circulatory, microcirculatory and liver function diagnostics, as well as for ophthalmologic angiography, Verdye is intended for intravenous injection via an injection needle, a central or peripheral catheter or cardiac catheter.

The evaluation of undesirable effects is based on the following frequency definitions: Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1 000 to <1/100) Rare (≥1/10 000 to <1/1 000) Very rare (<1/10 000) Not known (cannot be estimated from the available data) Anaphylactic or urticarial reactions have been reported in patients with or without history of allergy to iodides.

Also, in very rare cases coronary artery spasm has been described. Furthermore, greenish reversible skin discoloration at the injection site following paravasal (intradermal, subcutaneous) application of indocyanine green has been reported.

It is known that injection of indocyanine green preparations can in very rare cases cause nausea and anaphylactoid or anaphylactic reactions (<1/10 000). In patients with terminal renal insufficiency the possibility of an anaphylactic reaction seems to be increased.

Symptoms which should be mentioned are: unrest, feeling of warmth, pruritus, urticaria, acceleration of heart rate, fall in blood pressure and shortness of breath, bronchospasm, flush, cardiac arrest, laryngospasm, facial oedema, nausea.

Together with the anaphylactoid reaction, hypereosinophilia may occur. g. 9 % saline intravenously (repeat after 10 minutes if necessary) Urticarial reactions of the skin occurred very rarely (<1/10 000). Tabulated list of undesirable reactions System Organ Class Frequency Undesirable reaction Immune system disorders Very rare Anaphylactoid reaction, Anaphylactic reaction Cardiac disorders Very rare Coronary arteriospasm Gastrointestinal disorders Very rare Nausea Skin and subcutaneous tissue disorders Very rare Urticaria General disorders and administration site conditions Not known Injection site discoloration Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

• Since severe anaphylactic reactions might occur after application of Verdye, it must only be applied under supervision of a physician and emergency resuscitation facilities should be available for immediate use. Patients should be monitored for at least an hour after administration of indocyanine green for the occurrence of hypersensitivity reactions.

• Due to an increased incidence of adverse reactions in patients with severe renal insufficiency, Verdye must only be applied after a careful benefit/risk assessment. • Heparin preparations containing sodium bisulphite reduce the absorption peak of indocyanine green in plasma and blood and, therefore, should not be used as an anticoagulant for the collection of samples for analysis.

• Indocyanine green is stable in plasma and whole blood so that samples obtained in discontinuous sampling techniques may be read hours later. Sterile techniques have to be used in handling the dye solution. • The iodine content of Verdye can interfere with thyroid tests performed before or after administration of the dye.

Therefore, radio-active iodine uptake studies should not be performed for at least a week following the use of Verdye. • When Verdye is applied intradermally or subcutaneously, patients should be advised to avoid direct sun or UV radiation for at least 1 week or until any greenish discoloration at the injection site has disappeared.

• The identification of sentinel lymph nodes and visualization of lymphatic pathways may be impaired if they are located in deeper tissue layers or are covered by fatty tissue. Similarly, in patients with pronounced obesity (BMI >40), the mapping of sentinel lymph nodes and visualization of lymphatic pathways may be impaired.

Verdye is contraindicated for safety reasons: • in patients with hypersensitivity to indocyanine green or to sodium iodide unless special precautions are taken, • in patients with hypersensitivity to iodine, • in patients with hyper-thyroidism, patients with autonomic thyroid adenomas, • as in-vitro experiments have shown that indocyanine green displaces bilirubin from its protein binding, Verdye must not be used in premature infants or neonates in whom an exchange transfusion is indicated due to hyperbilirubinemia, • if injection of Verdye was poorly tolerated in the past it must not be used again, since severe anaphylactic reactions might occur.