Dotarem multidose

Package Leaflet: Information for the User

DOTAREM multidose, 0.5 mmol/ml

injection solution in a vial
Gadoteric acid

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or radiologist.
• If you experience any side effects, including those not listed in this package leaflet, tell your doctor, radiologist, or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is DOTAREM multidose and what is it used for
• 2. Important information before using DOTAREM multidose
• 3. How to use DOTAREM multidose
• 4. Possible side effects
• 5. How to store DOTAREM multidose
• 6. Contents of the package and other information

1. What is DOTAREM multidose and what is it used for

DOTAREM multidose is a diagnostic agent for use in adults and children. It belongs to
the group of contrast agents used in magnetic resonance imaging (MRI).
DOTAREM multidose is used to increase the contrast of images obtained during
MRI examinations. This contrast enhancement improves the visibility and definition of:

• pathological changes in the brain, spinal cord, and surrounding tissues;
• pathological changes in the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system;
• pathological changes and stenosis in arteries, especially coronary arteries (only in adults).

This medicine is for diagnostic use only.

2. Important information before using DOTAREM multidose

When not to use DOTAREM multidose

• if the patient is allergic to the active substance or any of the other ingredients of this medicine (listed in section 6).
• if the patient is allergic to gadolinium-containing contrast agents (such as other MRI contrast agents).

Warnings and precautions

Tell your doctor or radiologist if any of the following apply to the patient:

• the patient has had a reaction to a contrast agent during an examination;
• the patient has asthma;
• the patient has had an allergic reaction (e.g., allergy to shellfish, hives, hay fever);
• the patient is being treated with a beta-adrenergic blocker (a medicine used to treat heart rhythm disorders and high blood pressure, such as metoprolol);
• the patient's kidneys do not work properly;
• the patient has recently undergone or is scheduled to undergo a liver transplant;
• the patient has a heart or blood vessel disease;
• the patient has had seizures or is being treated for epilepsy.

In all these cases, the doctor or radiologist will assess the benefit-risk ratio and decide whether to use DOTAREM multidose in the patient. If DOTAREM multidose is used, the doctor or radiologist will take the necessary precautions and monitor the administration of the medicine closely.
The doctor or radiologist may decide to perform a blood test to check the patient's kidney function before using DOTAREM multidose, especially in patients over 65 years of age.
Newborns and infants
Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, DOTAREM multidose will only be used in these patients after careful consideration by the doctor.
Before the examination, all metal objects that the patient may be wearing should be removed. Tell the doctor or radiologist if the patient has:

• a pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an implant in the inner ear),
• any suspected metal foreign body, especially in the eye. This is very important, as MRI machines use very strong magnetic fields.

DOTAREM multidose and other medicines

Tell your doctor or radiologist about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take. In particular, inform the doctor, radiologist, or pharmacist about the use of or recent use of medicines for heart rhythm disorders and high blood pressure, such as beta-adrenergic blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

DOTAREM multidose with food and drink

No interactions between DOTAREM multidose and food or drink are known. However, ask your doctor, radiologist, or pharmacist if it is necessary to avoid eating or drinking before the examination.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks she may be pregnant, or plans to have a child, she should consult her doctor or radiologist before using this medicine.
Pregnancy
Gadoteric acid may pass through the placenta. It is not known whether this affects the fetus.
DOTAREM multidose should not be used during pregnancy unless absolutely necessary.
Breastfeeding
The doctor or radiologist will discuss with the patient whether she can continue breastfeeding or should stop for 24 hours after receiving DOTAREM multidose.

Driving and using machines

There is no available data on the effect of DOTAREM multidose on the ability to drive or use machines. If the patient feels unwell after the examination, e.g., nausea (feeling sick), the patient should not drive or use machines.

3. How to use DOTAREM multidose

DOTAREM multidose will be administered by intravenous injection.
During the examinationthe patient will be closely monitored by the doctor or radiologist. A needle will be left in the patient's vein, so that if necessary, the doctor or radiologist can quickly inject life-saving medicines. If the patient has an allergic reaction, the administration of DOTAREM multidose will be stopped immediately.
DOTAREM multidose can be injected manually or using an automatic injector. In newborns and infants, the medicine is administered manually only.
The procedure can be performed in a hospital, clinic, or private office. Medical personnel know what precautions to take during the examination and are also aware of potential complications that may occur.
Dosage
The doctor or radiologist will determine the dose suitable for the patient and will supervise the administration of the medicine.

Dosage in special patient groups

It is not recommended to use DOTAREM multidose in patients with severe kidney function disorders or in patients who have recently undergone or are scheduled to undergo a liver transplant. However, if the use of DOTAREM multidose is necessary, the patient should receive only one dose of the medicine during the examination and should not receive another dose for at least 7 days.

Use in newborns, infants, children, and adolescents

Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, DOTAREM multidose will only be used in these patients after careful consideration by the doctor. Children should receive only one dose of the medicine during the examination and should not receive another dose for at least 7 days.
It is not recommended to use DOTAREM multidose for angiography in children under 18 years of age.

Patients over 65 years of age

There is no need to adjust the dose in patients over 65 years of age, but it may be necessary to perform a blood test to check kidney function.

Overdose of DOTAREM multidose

It is very unlikely that the patient will receive too much of the medicine. DOTAREM multidose will be administered in a medical facility by properly trained personnel.
In the event of an overdose, DOTAREM multidose can be removed from the body by hemodialysis (blood purification).
Additional information on the use and handling of this medicine by medical personnel is provided at the end of this package leaflet.
If you have any further questions about the use of this medicine, ask your doctor or radiologist.

4. Possible side effects

Like all medicines, DOTAREM multidose can cause side effects, although not everybody gets them.
After administrationthe patient will be monitored for at least half an hour. Most side effects occur immediately or with some delay. Some side effects may occur even up to seven days after the injection of DOTAREM multidose.
There is a small risk of an allergic reaction to DOTAREM multidose. Such
reactions can be severe and cause shock(a life-threatening allergic reaction). The following symptoms may be the first signs of shock. If the patient notices any of the following symptoms, they should immediately inform the doctor, radiologist, or other medical personnel:

• swelling of the face, lips, and/or throat, which may cause difficulty swallowing or breathing
• swelling of the hands or feet
• feeling of dizziness (low blood pressure)
• breathing difficulties
• wheezing
• coughing
• itching of the skin
• runny nose
• sneezing
• eye irritation
• hives
• rash

Uncommon side effects (may affect up to 1 in 100 people)

• hypersensitivity
• headache
• unusual taste in the mouth
• dizziness
• drowsiness
• feeling of tingling, heat, or cold and/or pain
• increased or decreased blood pressure
• nausea (feeling sick)
• abdominal pain
• rash
• feeling of heat, feeling of cold
• weakness
• discomfort at the injection site, reaction at the injection site, feeling of cold at the injection site, swelling at the injection site, extravasation of the product, which may lead to inflammation (redness and local pain)

Rare side effects (may affect up to 1 in 1,000 people)

• anxiety, fainting (dizziness and loss of consciousness)
• swelling of the eyelids
• palpitations
• sneezing
• vomiting
• diarrhea
• increased salivation
• hives, itching, sweating
• chest pain, chills

Very rare side effects (may affect up to 1 in 10,000 people)

• anaphylactic and anaphylactoid reactions
• agitation
• coma, seizures, fainting (short-term loss of consciousness), disorders of smell (perception of often unpleasant odors), convulsions
• conjunctivitis, blurred vision, increased tearing
• sudden cardiac arrest, rapid or slow heart rate, arrhythmia, vasodilation, pallor
• respiratory arrest, pulmonary edema, breathing difficulties, wheezing, stuffy nose, coughing, dry throat, choking sensation, bronchospasm, throat swelling
• flushing, redness of the skin, swelling of the lips, local swelling in the mouth
• muscle spasms, muscle weakness, back pain
• weakness, discomfort in the chest, fever, swelling of the face, extravasation of the product, which may lead to tissue necrosis at the injection site, phlebitis
• decreased oxygen content in the blood.

There have been reports of nephrogenic systemic fibrosis (NSF), which causes skin hardening and may also affect soft tissues and internal organs, mainly in patients who received DOTAREM multidose with other gadolinium-containing contrast agents. If the patient notices any changes in skin color and/or thickness anywhere on the body within weeks after the MRI examination, they should inform the radiologist who performed the examination.

Reporting side effects

If side effects occur, including those not listed in this package leaflet, tell your doctor or radiologist.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products – Al. Jerozolimskie 181 C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store DOTAREM multidose

Keep the medicine out of the sight and reach of children.
There are no special precautions for storage.
Do not use this medicine after the expiry date stated on the vial and carton after "EXP". The expiry date refers to the last day of the month.
It is very unlikely that the patient will be asked to dispose of any leftover DOTAREM multidose.

6. Contents of the package and other information

What DOTAREM multidose contains

• The active substance of the medicine is gadoteric acid. One milliliter of the injection solution contains 279.32 mg of gadoteric acid (as meglumine salt), which corresponds to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other ingredients of the medicine are meglumine and water for injections.

What DOTAREM multidose looks like and contents of the package

DOTAREM multidose is a clear, colorless solution for intravenous injection, colorless or in various shades of yellow.
The package of DOTAREM multidose contains one vial containing 60 or 100 ml of the injection solution.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer:

GUERBET
BP 57400
95943 Roissy CdG cedex
France

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

DOTAREM multidose

Date of last revision of the package leaflet: 08.05.2024

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Information intended for healthcare professionals only:

Dosage

Adults:

• MRI of the brain and spinal cord: In studies of the nervous system, doses range from 0.1 to 0.3 mmol/kg body weight, which corresponds to 0.2 to 0.6 ml/kg body weight. After administration of 0.1 mmol/kg body weight to patients with brain tumors, administration of an additional dose of 0.2 mmol/kg body weight may improve tumor visibility and facilitate treatment decisions.
• MRI of the whole body and angiography: The recommended dose for intravenous injection, providing contrast suitable for diagnosis, is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight).
• Angiography: In exceptional circumstances (e.g., when images of satisfactory quality covering an extensive vascular area are not obtained) a second, subsequent dose of 0.1 mmol/kg body weight (corresponding to 0.2 ml/kg body weight) may be justified. However, if two consecutive doses of DOTAREM multidose are planned before the start of angiography, it may be beneficial to administer 0.05 mmol/kg body weight (i.e., 0.1 ml/kg body weight) in each dose, depending on the available imaging equipment.

Children and adolescents (0-18 years):

• MRI of the brain and spinal cord / whole-body MRI: The recommended dose of DOTAREM multidose is 0.1 mmol/kg body weight. Do not administer more than one dose during scanning. Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, DOTAREM multidose should only be used in these patients after careful consideration by the doctor. The dose should not exceed 0.1 mmol/kg body weight. Do not administer more than one dose during the imaging examination. Due to the lack of information on repeated administration, do not repeat injections of DOTAREM multidose unless the interval between injections is at least 7 days.

Angiography:
DOTAREM multidose is not recommended for use in angiography in children under 18 years of age.

Special patient groups:

• Patient with kidney function disorders: In patients with mild to moderate kidney function disorders (GFR ≥30 ml/min/1.73 m), the doses recommended for adults are used. See "Kidney function disorders" below.
• Patient with liver function disorders: In these patients, the doses recommended for adults are used. Caution is advised, especially in the perioperative period of liver transplantation.

Method of administration

DOTAREM multidose is indicated for intravenous administration only.
DOTAREM multidose should not be administered by subarachnoid or intrathecal injection.
Infusion rate: 3-5 ml/min (at angiographic examinations, a higher infusion rate of up to 120 ml/min, i.e., 2 ml/sec, can be used).
Optimal imaging: within 45 minutes of injection
Optimal imaging sequence: T1-weighted images
Whenever possible, the contrast agent should be administered intravenously to the patient in a supine position. After administration, the patient should be monitored for at least half an hour, as experience shows that most side effects occur during this period.
The rubber stopper must be pierced only once using a suitable spike adapter for solution withdrawal.
Generally, the solution withdrawal adapter must contain the following elements: a trocar, a sterile air filter, a Luer connector, and a tight protective cap.
A single-dose syringe (sterile) can be used for single administration of the product or for injection of a second dose of contrast agent in a bolus, if clinically justified.
An automatic injection system can only be used for a single patient for multiple administrations of the product.
The product volumes remaining in the vial and the single-dose product after completion of the examination must be discarded within 24 hours of piercing the rubber stopper. The manufacturer's instructions must be strictly followed.
The injection solution should be visually inspected before use. Only a clear solution without visible particles is suitable for use.
Children and adolescents (0-18 years)
Depending on the amount of DOTAREM multidose to be administered to the child, it is recommended to use vials of DOTAREM multidose in combination with a single-dose syringe with a capacity adapted to this amount, in order to maintain higher precision of the injected dose.
In newborns and infants, the required dose should be administered manually.

Kidney function disorders

It is recommended that all patients undergo laboratory tests to check kidney function before administration of DOTAREM multidose.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of gadolinium-containing contrast agents in patients with acute or chronic kidney function disorders (GFR <30 ml min 1.73 m). patients who have undergone liver transplantation are particularly at risk, due to the high frequency of acute kidney failure in this group. risk nsf associated with use dotarem multidose, product should only be used severe function disorders and perioperative period after careful benefit-risk assessment when diagnostic information is essential cannot obtained using mri without contrast enhancement. if multidose necessary, dose not exceed 0.1 mmol kg body weight. do administer more than one during imaging examination. lack on repeated administration, repeat injections unless interval between least 7 days.
Hemodialysis performed shortly after administration of DOTAREM multidose may facilitate the elimination of DOTAREM multidose from the body. There is no evidence to support the initiation of hemodialysis as a prophylactic or therapeutic measure for NSF in patients who are not currently receiving hemodialysis.

Patients over 65 years of age

As kidney clearance of gadoteric acid may be decreased in patients over 65 years of age, it is particularly important to check kidney function before administration of DOTAREM multidose in patients over 65 years of age.

Newborns and infants

See "Dosage and method of administration, use in children".

Pregnancy and breastfeeding

DOTAREM multidose should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoteric acid.
Continuation or discontinuation of breastfeeding for 24 hours after administration of DOTAREM multidose should be left to the discretion of the doctor and the breastfeeding mother.

Instructions for use of the product

The detachable labels on the vials should be attached to the patient's file to allow for accurate identification of the contrast agent used. The administered dose should also be recorded. If an electronic patient card is used, the product name, batch number, and administered dose should be entered.