VERDYE 25 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Verdye 25 mg powder for solution for injection

Indocyanine green

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Verdye is and what it is used for

Verdye is a dark green powder that is mixed with water to prepare injectable solutions. The active substance of the solution is called indocyanine green, a dye. This dye is injected into one of your veins, where it mixes with the blood. Your doctor will be able to see:

• how far the dye spreads from where it was injected
• how much of it is in different parts of your body.

When Verdye is injected into the skin or subcutaneous fat tissue of patients with breast cancer, it accumulates in the lymph nodes and the lymphatic pathways are visualized.

This medicine is for diagnostic use only, to determine what medical problems you may have, for example:

• how the blood circulation works in a part of your body, for example:
  • the heart
  • the brain
  • the liver
  • a layer of the inner part of the eye called the choroid.

• how much blood is in certain parts of your body.

• how your liver works.

Verdye is also used to make lymph nodes and lymphatic pathways visible or to identify them during surgery in adult patients with breast cancer. For this purpose, the medicine is injected into the skin, subcutaneous fat tissue, or the tumor area, rather than into the veins.

The lymph nodes closest to the tumor are called sentinel lymph nodes. It is most likely that these lymph nodes and the associated lymphatic vessels are the first place where cancer cells spread. When Verdye has reached the sentinel lymph nodes, it can be checked if cancer cells are present. Verdye accumulates in the sentinel lymph nodes and can be detected by a special camera.

2. What you need to know before you use Verdye

Do not use Verdye:

• if you are allergic to indocyanine green or any of the other ingredients of this medicine (listed in section 6).
• if you have hyperthyroidism or benign tumors of the thyroid gland.
• if you have ever experienced any side effects after receiving these injections.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Verdye.

Be especially careful with Verdyeif:

• you have kidney failure.

Talk to your doctor to see if this medicine is suitable for you.

• if you are going to have a test called "radioactive iodine uptake", which evaluates thyroid function.

This test should be delayed for at least one week after receiving Verdye, because the injection could affect the result of the thyroid test.

The skin may become more sensitive to sunlight and UV radiation in patients who receive Verdye injected into the skin or subcutaneous fat tissue. Therefore, affected patients should avoid direct exposure to the sun or artificial UV radiation (e.g., tanning bed) for at least 1 week after the application of Verdye, until any green discoloration at the injection site has disappeared.

The identification of sentinel lymph nodes and the visualization of lymphatic pathways may be affected if they are located in deeper tissue layers or are covered by fatty tissue. Similarly, in patients with severe obesity (BMI > 40), the mapping of sentinel lymph nodes and the visualization of lymphatic pathways may be affected. Indocyanine green may be used in combination with radiopharmaceuticals when indicated for the detection of sentinel lymph nodes.

Patient preparation

It may be useful to administer medication to prevent nausea and vomiting to sensitive patients and to perform the injection slowly.

Patients with renal and hepatic impairment

Since adverse reactions have occurred in patients with advanced renal failure with the administration of indocyanine green, special attention should be paid to the indication for the use of Verdye in these patients.

Hepatic perfusion and/or reduced hepatic function will lead to a reduced plasma disappearance rate of indocyanine green.

Patients with cardiac insufficiency

Cardiac insufficiency may influence the extraction rate of indocyanine green due to reduced hepatic/splenic perfusion.

Children and adolescents

The use of Verdye is contraindicated in premature and newborn infants who are indicated for exchange transfusion due to hyperbilirubinemia.

Use of Verdyewith other medicines.

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines.

Tell your doctor if:

• you are taking any medicine that affects liver function, because the process of eliminating indocyanine green from the body after injection may be affected.
• you are taking, or think you may be taking, any of the medicines listed below, because some of these medicines may alter the absorption of indocyanine green, the active substance of Verdye, and may make the diagnosis inaccurate:
  • anticonvulsants (medicine to treat epilepsy)
  • cyclopropane (anesthetic)
  • enalapril maleate (medicine to treat hypertension)
  • haloperidol (medicine to treat mental illnesses and anxieties)
  • meperidine (strong pain reliever)
  • metamizole (pain reliever)
  • methadone (medicine for opioid addiction substitution treatment)
  • morphine and other opioids (strong pain relievers and/or antidiarrheal)
  • nifedipine (medicine to treat hypertension)
  • nitrofurantoin (antibiotic)
  • phenobarbital (medicine to treat epilepsy and anesthetic)
  • phenylbutazone (pain reliever)
  • progestin (contraceptive)
  • propranolol (medicine to treat hypertension and heart conditions)
  • rifampicin (antibiotic)
  • any injection containing sodium bisulfite (preservative).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

No studies have been conducted on the effects on the ability to drive and use machines.

Talk to your doctor before driving or using machines immediately after an injection.

3. How to use Verdye

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are unsure, consult your doctor again.

The injection is administered only under the supervision of a doctor.

• To dissolve indocyanine green, only water for injectable preparations is used.
• The injection solution must be inspected before administration. If it is cloudy, it will not be used.
• The doctor or nurse injects the medicine directly into a vein using a needle, catheter, or cardiac catheter.
• The vein chosen for injection depends on the type of study being performed.
• If this medicine is injected into a vein in the arm, the doctor or nurse may apply a temporary tourniquet beforehand. This facilitates the insertion of the needle into the vein.
• The dose you receive will depend on the type of test being performed and your body weight.
• Your doctor may add a product called heparin to the blood samples obtained. (It serves to prevent the samples from clotting.)
• If this medicine is injected into the skin, subcutaneous fat tissue, or the tumor area, a specially designed needle will be used.

Adults

Dosing by measurement

Cardiac, circulatory, and microcirculatory diagnosis:

0.1 to 0.3 mg/kg body weight as a bolus injection

Diagnosis of liver function:

0.25 to 0.5 mg/kg body weight as a bolus injection

Ophthalmic angiography:

0.1 to 0.3 mg/kg body weight as a bolus injection

Imaging of sentinel lymph nodes and visualization of lymphatic pathways, regardless of body weight:

1 to 10 mg per injection. The volume per injection should not exceed 2 mL, and the concentration of indocyanine green should not exceed 5 mg/mL. Larger volumes may also be administered per injection if dilutions below 5 mg/mL are used. A lower dose (1 to 5 mg per injection) may be advantageous if administration is in the skin or subcutaneous fat tissue. A higher dose (5 to 10 mg) may be advantageous in deeper tissue areas.

Total daily dose:

The total daily dose of Verdye should be less than 5 mg/kg body weight.

For the detection of sentinel lymph nodes and visualization of lymphatic pathways, the total daily dose should not exceed 10 mg.

Elderly

Dosing by measurement

Cardiac, circulatory, and microcirculatory diagnosis:

0.1 to 0.3 mg/kg body weight as a bolus injection

Diagnosis of liver function:

0.25 to 0.5 mg/kg body weight as a bolus injection

Ophthalmic angiography:

0.1 to 0.3 mg/kg body weight as a bolus injection

Imaging of sentinel lymph nodes and visualization of lymphatic pathways, regardless of body weight:

1 to 10 mg per injection. The volume per injection should not exceed 2 mL, and the concentration of indocyanine green should not exceed 5 mg/mL. Larger volumes may also be administered per injection if dilutions below 5 mg/mL are used. A lower dose (1 to 5 mg per injection) may be advantageous if administration is in the skin or subcutaneous fat tissue. A higher dose (5 to 10 mg) may be advantageous in deeper tissue areas.

Total daily dose:

The total daily dose of Verdye should be less than 5 mg/kg body weight.

For the detection of sentinel lymph nodes and visualization of lymphatic pathways, the total daily dose should not exceed 10 mg.

Patients with renal insufficiency

In patients with terminal renal insufficiency, the incidence of anaphylactic reactions appears to increase.

Patients with hepatic insufficiency

For patients with impaired liver function, there is a low plasma elimination rate.

Patients with cardiac insufficiency

Cardiac insufficiency may influence the extraction rate of indocyanine green due to reduced hepatic/splenic perfusion.

Use in children and adolescents

Dosing by measurement

Cardiac, circulatory, and microcirculatory diagnosis:

0.1 to 0.3 mg/kg body weight as a bolus injection

Diagnosis of liver function:

Not recommended due to lack of data

Ophthalmic angiography:

0.1 to 0.3 mg/kg body weight as a bolus injection

Imaging of sentinel lymph nodes and visualization of lymphatic pathways:

Not recommended due to lack of data.

Total daily dose:

Children from 0 to 2years:

The total daily dose of Verdye should be less than 1.25 mg/kg body weight.

Children from 2 to 11 years:

The total daily dose of Verdye should be less than 2.5 mg/kg body weight.

Children from 11 to 18 years:

The total daily dose of Verdye should be less than 5 mg/kg body weight.

If you use more Verdyethan you should

Tell your doctor if you think you have been given too much medicine.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Severe allergic reactions:Very rare (affect less than 1 in 10,000 patients).

The symptoms are:

• constriction of the throat
• itching
• spotted skin
• hives
• coronary artery spasm
• swelling of the face (facial edema)
• breathing difficulties
• chest pain or tightness
• rapid heartbeat
• low blood pressure and shortness of breath
• heart failure (cardiac arrest)
• restlessness
• nausea
• feeling of heat
• hot flashes.

The possibility of an allergic reaction is higher in patients with extremely severe kidney failure. Additionally, reversible green discoloration of the skin at the injection site has been reported after the application of indocyanine green in the skin or subcutaneous fat tissue.

In case of symptoms of severe allergic reaction, you may need to receive emergency treatmentsuch as:

• injections of adrenaline, hydrocortisone, and antihistamines
• artificial blood or electrolyte solutions (by drip)
• oxygen to facilitate breathing.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Verdye

Keep this medicine out of the sight and reach of children.

Do not store above 30°C.

The glass vials should be kept in their outer packaging to protect the medicine from light.

Once the injection solution is prepared, it should be protected from light and used immediately. Only use solutions that are free of visible particles.

Do not useVerdye after the expiry date stated on the packaging and on the label of the vial. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Verdye

The active substance is indocyanine green.

Each amber glass vial contains:

25 mg of indocyanine green powder (to be reconstituted with 5 mL of water for injectable preparations).

Appearance and packaging of the product

Verdye powder for solution for injection is available in the following presentation: 5 vials containing 25 mg of the active substance, indocyanine green.

The container is hermetically sealed with a gray rubber stopper and fixed with an aluminum cap covered by a blue polypropylene cap.

Marketing authorization holder:

Diagnostic Green Limited,

Athlone Business and Technology Park,

Garrycastle, Athlone, Westmeath

N37 F786, Ireland

www.diagnosticgreen.com

T: +353 90 646 5499

Date of last revision of this leaflet:December 2023.

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This information is intended only for healthcare professionals:

The complete summary of product characteristics of Verdye 25 mg powder for solution for injection is included as a separate document in the product packaging, in order to provide healthcare professionals with additional scientific and practical information on the administration and use of this medicine.

Please consult the summary of product characteristics.