ZYOGREEN

e. 5 mg/mL solution). 5 mg/kg.

Method of administration In oncology:

Subcutaneous route. The injection is given intraoperatively via the subcutaneous route in the periareolar or peritumoral zone. The injection is given approximately 10 minutes before the start of surgery. The breast is massaged for a few minutes after the injection.

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, Zyogreen is intended for intravenous injection via an injection needle, a central or peripheral catheter or cardiac catheter.

The administration and site of Zyogreen are of critical importance for the quality of the measurements. In principle, for obtaining optimal quality first pass indicator dilution curves, the injection should be as close as possible to the vascular bed, organ or tissue of interest.

On peripheral intravenous injection, venipuncture should be done after application of a tourniquet. After release of the tourniquet, Zyogreen should be injected immediately and the arm should be raised. This ensures rapid transport of the dye from the site of injection and peripheral injection is then practically equivalent to central venous injection.

Areas under the first pass curve, transit time, half-life, plasma disappearance rate and retention rate of Zyogreen can be determined: a. non-invasively by pulse dye densitometry or near infrared spectroscopy b. invasively by fibre optic probes/catheters in suitable vessels c.

conventionally by determination of the concentration either by continuous withdrawal of heparinised blood through a cuvette densitometer or by collection of blood samples and measurement of the plasma concentration in a photometer Evaluation of fundus perfusion in ophthalmic angiography The perfusion of the fundus of the eye can be determined and quantified by ophthalmic fluorescence angiography.

Measurement of tissue perfusion Tissue perfusion of the superficial tissue layers can be made visible and quantified by near infrared fluorescence video angiography.

Immediate hypersensitivity reactions may occur. These reactions may include one or more of the following effects, occurring concomitantly or successively: cutaneous (urticaria, pruritus, facial oedema), respiratory (bronchospasm, laryngospasm, shortness of breath), gastrointestinal (nausea) and/or cardiovascular reactions (acceleration of heart rate, fall in blood pressure, cardiac arrest).

Any of these effects may be a warning sign of an anaphylactic reaction. Adverse reactions are listed in the following table by system organ class and frequency, according to the following categories: Very common (≥ 1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000, <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

System organ class Undesirable effects Frequency of undesirable effects Anaphylactic reaction* Very rareImmune system disorders Hypersensitivity Not known Vascular disorders Hot flushes Rare Vomiting UncommonGastrointestinal disorders Nausea Uncommon Rash Rare Urticaria Rare Skin reaction Rare Pruritus Rare Hyperhidrosis Rare Angioedema Very rare Skin and subcutaneous tissue disorders Alteration of skin colour** Not known Dizziness RareGeneral disorders and abnormalities at the administration site Staining at the injection site Not known *Anaphylactic reaction after administration of indocyanine green alone or after concomitant administration of indocyanine green and fluorescein.

**Temporary discolouration of the integuments observed in the event of accidental para-venous injection. g. 9 % saline intravenously (repeat after 10 minutes if necessary)” Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

• There is a risk of hypersensitivity reactions with Zyogreen irrespective of the route of administration and the dose administered. • Serious allergic reactions (such as Quincke's oedema or anaphylactic reaction) have been reported very rarely after administration of indocyanine green alone or after concomitant administration of indocyanine green and fluorescein.

This risk means that the patient must be monitored during and after the injection of these products. Zyogreen should only be administered under the 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. • The iodine content of Zyogreen 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 Zyogreen. • When Zyogreen is administered 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.

• Heparin preparations containing sodium bisulphite may reduce the absorption peak of indocyanine green in plasma and blood. Therefore heparin should not be used as an anticoagulant for the collection of samples for analysis.

1. Other contraindications include: • patients with hyperthyroidism, patients with autonomic thyroid adenomas. • in-vitro experiments have shown that indocyanine green displaces bilirubin from its protein binding. Zyogreen should not be used in premature infants or neonates in whom an exchange transfusion is indicated due to hyperbilirubinemia, • if injection of Zyogreen was poorly tolerated in the past it must not be used again, since severe anaphylactic reactions might occur.

• patients with hypersensitivity to iodine.