Verdye

Package leaflet: Information for the user

VERDYE 5 mg/ml powder for injectable solution

Indocyanine green
Please read all of this leaflet carefully before you use this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What VERDYE is and what it is used for
2. What you need to know before using VERDYE
3. How to use VERDYE
4. Possible side effects
5. How to store VERDYE
6. Contents of the pack and other information

1. What VERDYE is and what it is used for

What VERDYE is
VERDYE is a dark green powder that is mixed with water for injectable preparations. The active substance in the solution is called indocyanine green, a dye. This solution is injected into one of your veins, where it mixes with your blood. The doctor will then be able to see:

• how far the dye travels from where it was injected.
• how much is present in various parts of your body.

When VERDYE is injected into the skin or into subcutaneous fatty tissue, it accumulates in the lymph nodes and allows visualization of the lymphatic pathways.

What VERDYE is used for
It is for diagnostic use only, to help identify health conditions, for example:
a) how well blood flows through a part of the body, such as through:

• your heart
• your brain
• your liver
• a layer of the inner part of your eye called the choroid.

b) how much blood is present in certain parts of the body.
c) how well the liver is functioning.

VERDYE is also used to make sentinel lymph nodes and lymphatic pathways visible or to identify them during surgical procedures in adult patients with breast cancer. For this purpose, the dye must be injected into the skin, into the fatty tissue beneath the skin, or into the area of the tumour, rather than into veins.

The lymph nodes located closest to the tumour are called sentinel lymph nodes. These lymph nodes and their associated lymphatic vessels are most likely the first sites to which tumour cells spread.

Once VERDYE has reached the sentinel lymph nodes, they can be examined to check for the presence of tumour cells. VERDYE accumulates in the sentinel lymph nodes and can be detected using a special video camera.

2. What you need to know before using VERDYE

Do not use VERDYE

• if you are allergic to indocyanine green, sodium iodide, or iodine.
• if you have hyperfunction of the thyroid gland or a benign thyroid tumour.
• if you have ever experienced any adverse reactions after receiving these injections.
• in these specific patient groups: Premature infants and newborns suffering from hyperbilirubinemia (a condition in which there is an abnormally high amount of bilirubin in the blood) must not receive VERDYE.

Warnings and precautions
Talk to your doctor or pharmacist before using VERDYE,

• if you suffer from renal insufficiency. Consult your doctor to determine whether this medicine is suitable for you.
• if you need to undergo a test called "radioactive iodine uptake test", a test that evaluates how well your thyroid is functioning. This test must be delayed for at least one week after administration of VERDYE, because the injection may affect the outcome of the thyroid test.
• because the skin of patients receiving an injection of VERDYE into the skin or underlying fatty tissue may become more sensitive to sunlight or UV rays. These patients should therefore avoid direct exposure to sunlight or artificial UV radiation (e.g. sunlamps) for at least 1 week after administration of VERDYE or until any greenish discoloration at the injection site has disappeared.

Other medicines and VERDYE
Inform your doctor or pharmacist if you are taking/using, have recently taken/used, or might take/use any other medicines.
This is particularly important

• if you are taking any medicine that affects your liver function, as the process of eliminating indocyanine green from your body after injection may be influenced.
• if you are taking/using, or think you might take/use, any of the following medicines listed below, as some of these may alter the way indocyanine green, the active substance in VERDYE, is absorbed by the body and may make diagnosis inaccurate:
  • -

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding with breast milk, consult your doctor before using this medicine. Your doctor will decide whether it is appropriate to administer this medicine to you.
Driving and using machines
No studies have been conducted on the effects on the ability to drive vehicles or operate machinery.
Please consult your doctor before driving or operating machinery immediately after an injection.

3. How to use VERDYE

The injection is performed only under the supervision of a physician.

• Only water for injections must be used to dissolve indocyanine green.
• The injectable solution should be inspected before administration. If it is cloudy,

it must not be used.

• The doctor or nurse will inject the medicine directly into a vein using a needle, catheter, or cardiac catheter (heart).
• The vein chosen for injection will depend on the type of investigation to be performed.
• If this medicine is injected into a vein in the arm, the doctor or nurse may need to

apply a tourniquet first. This makes it easier to insert the needle into the vein.

• The dose you receive will depend on both the type of test being performed and your body weight.
• The doctor may need to add a substance called heparin to the blood samples taken. This is to prevent the samples from clotting.
• If this medicine is injected into the skin, subcutaneous fatty tissue, or into the tumor area, a special needle will be used.

Recommended dosages (mg/kg = milligrams of medicine per kilogram of body weight):
Single doses
Adults (18 - 64 years), elderly (65 years or older), adolescents and children (11 - 18 years):

• For assessments of blood flow through the heart, brain, general circulation, and microcirculation (e.g., blood flow through parts of the eye, the choroid), the recommended dose is 0.1 - 0.3 mg/kg body weight.
• For liver function assessment, the recommended dose is 0.25 - 0.5 mg/kg body weight.
• For sentinel lymph node imaging and visualization of lymphatic pathways, regardless of body weight: 5 to 10 mg per injection. This corresponds to 1-2 ml of reconstituted solution at 5 mg/ml. The injection volume must not exceed 2 ml. Larger volumes may be administered if higher dilutions are used.

Maximum daily dose – for blood circulation studies and liver function assessment
Adults and elderly:
The total daily dose should remain below 5 mg/kg body weight.
Adolescents and children:

• (11 - 18 years): The total daily dose should remain below 5 mg/kg body weight.
• (2 - 11 years): The total daily dose should remain below 2.5 mg/kg body weight.
• (0 months - 2 years): The total daily dose should remain below 1.25 mg/kg body weight.

Use in children and adolescents
The single doses to be used in children and adolescents for blood circulation studies and liver function assessment are the same as those for adults, but the total daily dose must be kept below 2.5 mg/kg body weight in children aged 2 to 11 years and below 1.25 mg/kg body weight in children aged 0 to 2 years.
Use in patients with renal or hepatic impairment
VERDYE must be administered with caution in cases of severe renal or hepatic impairment.
Maximum daily dose – for sentinel lymph node imaging and visualization of lymphatic pathways
Adults and elderly
For sentinel lymph node identification and visualization of lymphatic pathways, the total daily dose must not exceed 10 mg.
Use in children and adolescents
The use of VERDYE in children and adolescents for sentinel lymph node imaging and visualization of lymphatic pathways is not recommended due to insufficient data on safety and efficacy.
Measurements after injection
After injection, the doctor may measure the concentration of dye relative to blood volume.
Measurements are generally taken from an artery, a finger, or an earlobe. You may ask your doctor to explain the techniques associated with this procedure.
If you use more VERDYE than you should
Inform your doctor if you think you have been given too much medicine.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Severe allergic reaction: Very rare (may affect up to 1 in 10,000 people)
Symptoms include:

• tightness in the throat
• skin itching
• skin spots
• hives
• facial swelling (facial edema)
• difficulty breathing
• chest tightness and/or pain
• rapid heartbeat
• drop in blood pressure and shortness of breath
• heart failure (cardiac arrest)
• restlessness
• feeling sick (nausea)
• sensation of warmth
• flushing

Along with symptoms of allergic reaction, an increase in certain white blood cells associated with allergic reactions (eosinophilia) may occur. The risk of an allergic reaction is higher in patients with extremely severe renal failure. In case of a severe allergic reaction, you may require emergency treatment such as:

• injection of adrenaline (epinephrine), hydrocortisone, or antihistamines,
• artificial blood or electrolyte solutions (intravenous infusion),
• oxygen, to help you breathe.

Other side effects
Additionally, after administration of indocyanine green into the skin or subcutaneous fatty tissue, a reversible greenish discoloration of the skin at the injection site has been reported (frequency not known – frequency cannot be estimated from the available data).
In very rare cases (may affect up to 1 in 10,000 people), nausea, hives, or coronary artery spasm have also been reported.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store VERDYE

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
The glass vials must be kept in the cardboard box to protect the medicine from light.
Once the injectable solution has been prepared, it must be protected from light and used immediately.
Use only solutions that are free from visible particles.
Do not use this medicine after the expiry date stated on the carton and on the label of the vial. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What VERDYE contains
The active substance is indocyanine green.
Each vial contains:
• 25 mg of indocyanine green as powder (to be reconstituted with 5 ml of water for injectable preparations)
• 50 mg of indocyanine green as powder (to be reconstituted with 10 ml of water for injectable preparations)

Description of the appearance of VERDYE and package contents
VERDYE is a dark green powder for injectable solution in an amber glass vial sealed with a grey rubber stopper and secured with an aluminium cap covered by a blue polypropylene flip-off seal.
It is available in two pack sizes:
• 5 vials containing 25 mg of indocyanine green
• 5 vials containing 50 mg of indocyanine green
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Diagnostic Green Limited
Athlone Business and Technology Park
Garrycastle, Athlone, Co. Westmeath
N37 F786, Ireland
Tel.: +353 90 646 5499
Email: [email protected]

Manufacturer
Renew Pharmaceuticals Ltd.
Athlone Business and Technology Park
Garrycastle, Athlone, Co. Westmeath
N37 F680
Ireland

Distributor
A.P.M. Srl
(Azienda Prodotti Medicali)
Via Tolstoi n.7
20090 Trezzano sul Naviglio (MI)
Italy

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Greece, Italy, Czech Republic, Netherlands, Poland, Slovenia: VERDYE
Croatia, Denmark, Finland, Ireland, Portugal, United Kingdom (Northern Ireland), Romania, Sweden, Hungary: Verdye

The following information is intended for healthcare professionals only:

Instructions for handling
This medicinal product must be reconstituted immediately before use.
Reconstitute this medicinal product by adding 5 ml of water for injections to the vial containing 25 mg of active substance, or 10 ml of water for injections to the vial containing 50 mg of active substance, to obtain in both cases a dark green injectable solution with a concentration of 5 mg/ml (0.5% weight/volume).
Visually inspect the reconstituted solution. If incompatibility is observed in the form of a non-clear solution, then the reconstituted solution must be discarded.
Use only clear solutions without visible particles.
This medicinal product is for single use only.
If sentinel lymph nodes and lymphatic vessels are located in deeper tissue layers or are covered by adipose tissue, their identification and visualization may be impaired. Consequently, sentinel lymph node mapping and lymphatic vessel visualization may be compromised even in patients with marked obesity (BMI >40).