Dotarem

Package leaflet: Information for the user

DOTAREM, 0.5 mmol/ml
solution for injection in vial
Gadoteric acid
Please read all of this leaflet carefully before this medicine is administered, 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 or radiologist.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, radiologist, or pharmacist. See section 4.

Leaflet contents

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

1. What DOTAREM is and what it is used for

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

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

This medicine is intended for diagnostic use only.

2. Important information before using DOTAREM

When NOT to use DOTAREM

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

Warnings and precautions
You must inform your doctor or radiologist if any of the following apply to the patient:

• the patient has previously experienced a reaction to a contrast agent during an examination;
• the patient has asthma;
• the patient has a history of allergies (e.g. allergy to seafood, hives, hay fever);
• the patient is being treated with beta-blockers (medicines used to treat heart conditions and high blood pressure, such as metoprolol);
• the patient's kidneys are not functioning properly;
• the patient has recently undergone or is scheduled for a liver transplant;
• the patient has a disease affecting the heart or blood vessels;
• the patient has had seizures or is being treated for epilepsy.

In all such cases, the doctor or radiologist will evaluate the benefit-risk ratio and determine whether DOTAREM can be administered to the patient. If DOTAREM is administered, the doctor or radiologist will take necessary precautions and the administration of DOTAREM will be closely monitored.
The doctor or radiologist may decide to perform blood tests to check the patient's kidney function before administering DOTAREM, especially in patients aged 65 years and older.

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 will be used in such patients only after careful consideration by the doctor.

Before the examination, all metallic objects the patient may be wearing should be removed. You must inform the doctor or radiologist if the patient has any of the following implanted:

• cardiac pacemaker,
• vascular clip,
• infusion pump,
• nerve stimulator,
• cochlear implant (inner ear implant),
• any suspected metallic foreign body, especially in the eye. This is very important, as serious problems may occur due to the use of very strong magnetic fields in magnetic resonance imaging equipment.

DOTAREM and other medicines
You must tell the doctor or radiologist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. In particular, inform the treating physician, radiologist, or pharmacist if the patient is taking or has recently taken medicines for heart conditions and high blood pressure, such as beta-blockers, vasoactive agents, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor antagonists.

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

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or radiologist before using this medicine.

Pregnancy
Gadoteric acid may cross the placenta. It is not known whether this may affect the unborn child.
DOTAREM must not be used during pregnancy unless absolutely necessary.

Breastfeeding
The doctor or radiologist will discuss with the patient and advise whether she may continue breastfeeding or should interrupt it for 24 hours after administration of DOTAREM.

Driving and using machines
There are no available data on the effects of DOTAREM on the ability to drive. If the patient feels unwell after the examination, for example nausea (feeling sick), the patient should not drive or operate machinery.

3. How to use DOTAREM

DOTAREM will be administered as an intravenous injection.
During the examination, the patient will be closely monitored by a physician or radiologist. An intravenous catheter will remain in place in the patient's vein so that, if necessary, the physician or radiologist can rapidly administer life-saving medications. If the patient experiences an allergic reaction, administration of DOTAREM will be immediately discontinued.
DOTAREM may be injected manually or using an automated injector.
In neonates and infants, this medicine is administered exclusively by manual injection.
The procedure may be performed in a hospital, outpatient clinic, or private office. Medical personnel are aware of the precautions to be taken during the examination and are familiar with potential complications that may occur.

Dosage
The physician or radiologist will determine the appropriate dose for the patient and will supervise the injection of the medicine.

Dosage in special patient groups
DOTAREM is not recommended for patients with severe renal function impairment or for patients who have recently undergone or are scheduled to undergo liver transplantation. However, if administration of DOTAREM is considered necessary, the patient should receive only a single dose during the examination and should not receive another dose within at least 7 days.

Use in neonates, infants, children, and adolescents
Due to immature kidney function in neonates up to 4 weeks of age and infants up to 1 year of age, DOTAREM will be used in such patients only after careful physician evaluation. Children should receive only a single dose during the examination and should not receive another injection within at least 7 days.
Use in angiography is not recommended in children under 18 years of age.

Elderly patients
Dosage adjustment is not required for patients aged 65 years and older; however, blood tests to assess kidney function may be necessary.

Administration of a higher than recommended dose of DOTAREM
It is highly unlikely that a patient would receive an overdose of the medicine. DOTAREM is administered in a medical facility by appropriately trained personnel. In the event of an actual overdose, DOTAREM can be removed from the body by hemodialysis (blood cleansing).

Additional information on the use and handling of this medicine by medical personnel is provided at the end of this leaflet.
If you have any further questions about the use of this medicine, consult your physician or radiologist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
After administration, the patient will be monitored for at least half an hour. Most adverse
reactions occur immediately or with some delay. Some adverse reactions may occur even up to seven days after injection of DOTAREM.
There is a small risk of an allergic reaction to DOTAREM in the patient. Such reactions may be
severe and may cause shock (an allergic reaction that may be life-threatening). The following symptoms may be the first signs of shock. If the patient notices any of the symptoms listed below, they should immediately inform the doctor, radiologist, or another healthcare professional:

• swelling of the face, lips and (or) throat, which may cause difficulty in swallowing or breathing
• swelling of the hands or feet
• feeling dizzy (hypotension)
• difficulty breathing
• wheezing
• cough
• skin itching
• watery nasal discharge
• sneezing
• eye irritation
• urticaria
• rash

Uncommon adverse reactions (may occur in up to 1 in 100 people)

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

Rare adverse reactions (may occur in up to 1 in 1,000 people)

• anxiety, fainting (dizziness and risk of loss of consciousness)
• eyelid swelling
• palpitations
• sneezing
• vomiting
• diarrhoea
• increased salivation
• urticaria, itching, sweating
• chest pain, chills

Very rare adverse reactions (may occur in up to 1 in 10,000 people)

• anaphylactic and anaphylactoid reactions
• agitation
• coma, seizures, syncope (brief loss of consciousness), disturbances in smell (perception of often unpleasant odours), convulsions
• conjunctivitis, blurred vision, excessive tearing
• sudden cardiac arrest, rapid or slow heartbeat, arrhythmia, vasodilation, pallor
• respiratory arrest, pulmonary oedema, breathing difficulties, wheezing, nasal congestion, cough, dry throat, throat tightness with a feeling of suffocation, respiratory muscle spasms, throat oedema
• rash, skin redness, lip oedema, local swelling in the oral cavity
• muscle spasms, muscle weakness, back pain
• weakness, chest discomfort, fever, facial swelling, extravasation of the drug outside blood vessels, which may lead to tissue necrosis at the injection site, phlebitis
• decreased oxygen level in blood.

There have been reports of nephrogenic systemic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs), which generally occurred in patients who received DOTAREM together with other contrast agents containing gadolinium. If, in the weeks following an MRI examination, the patient notices changes in the colour and (or) thickness of the skin anywhere on the body, they should inform the radiologist who performed the examination.
Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, the patient should inform their doctor or radiologist.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products – Al. Jerozolimskie 181 C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, e-mail: [email protected]
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store DOTAREM

Keep this medicine out of the sight and reach of children.
No special storage conditions are required.
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 stated month.
It is highly unlikely that a patient will be asked to dispose of any leftover DOTAREM medicine.

6. Contents of the pack and other information

What DOTAREM contains

• The active substance is gadoteric acid. One millilitre of the injection solution contains 279.32 mg of gadoteric acid (as meglumine salt), corresponding to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other components are: meglumine and water for injections.

What DOTAREM looks like and contents of the pack
DOTAREM is a clear, colourless solution for intravenous injection, colourless or with various shades of yellow.
The DOTAREM pack contains one vial containing 5, 10, 15, 20 or 60 ml of injection solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer:
GUERBET
BP 57400
95943 Roissy CdG cedex
France
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
DOTAREM

Information intended exclusively for medical professionals or healthcare personnel:
Dosage

Adults:

• Brain and spinal MRI: For neurological system imaging, doses range from 0.1 to 0.3 mmol/kg body weight, corresponding to 0.2 to 0.6 ml/kg body weight. After administering 0.1 mmol/kg body weight to patients with brain tumours, administration of an additional dose of 0.2 mmol/kg body weight may improve tumour visibility and facilitate treatment decisions.
• Whole-body MRI and angiography: The recommended intravenous dose providing adequate diagnostic contrast is 0.1 mmol/kg body weight (i.e. 0.2 ml/kg body weight).
• Angiography: In exceptional circumstances (e.g. when satisfactory image quality covering a large vascular area has not been achieved), administration of 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 are anticipated before starting angiography, it may be preferable to administer 0.05 mmol/kg body weight (i.e. 0.1 ml/kg body weight) for each dose, depending on the available imaging equipment.

Children and adolescents (0–18 years):

• Brain and spinal MRI / Whole-body MRI: The recommended and maximum dose of DOTAREM is 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging session. Due to the immaturity of renal function in newborns up to 4 weeks of age and infants up to 1 year of age, DOTAREM should be used in these patients only after careful consideration and at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging session. Due to lack of data on repeated administration, repeat injections of DOTAREM should not be given unless the interval between doses is at least 7 days.

• Angiography: The use of DOTAREM is not recommended for angiography in children under 18 years of age due to insufficient data on efficacy and safety for this indication.

Special patient groups:

• Patients with impaired renal function: In patients with mild to moderate renal impairment (GFR ≥30 ml/min/1.73 m²), the adult dose should be used. See section "Renal function impairment" below.
• Patients with impaired liver function: In such patients, the adult dose should be used. Caution is recommended, especially in the perioperative period related to liver transplantation.

Method of administration
DOTAREM is indicated exclusively for intravenous administration. DOTAREM must not be administered intrathecally or epidurally.
Infusion rate: 3–5 ml/min (in angiographic procedures, a higher infusion rate up to 120 ml/min, i.e. 2 ml/sec, may be used).
Optimal imaging window: within 45 minutes after injection.
Optimal imaging sequence: T1-weighted images.
Whenever possible, the contrast agent should be administered intravenously to the patient in a lying position. After administration, the patient should be monitored for at least 30 minutes, as experience shows that most adverse reactions occur during this period.
Prepare a syringe with a needle. Remove the plastic disk. Clean the stopper with an alcohol swab and/or gauze, then pierce the stopper with the needle. Withdraw the volume of product required for the examination and administer it intravenously to the patient.
For single use only; any unused portions must be discarded.
The injection solution should be inspected visually prior to use. Only clear solutions free from visible particles should be used.

Children and adolescents (0–18 years)
Depending on the amount of DOTAREM to be administered to a child, it is recommended to use vials of DOTAREM in combination with a single-use syringe of appropriate capacity to ensure higher precision of the administered dose.
In newborns and infants, the required dose should be administered manually.

Renal function impairment
It is recommended that all patients undergo laboratory tests to assess renal function before administration of DOTAREM.
There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of gadolinium-containing contrast agents in patients with acute or chronic renal impairment (GFR <30 ml/min/1.73 m²). Patients undergoing liver transplantation are at particular risk due to the high frequency of acute renal failure in this group. Because of the risk of NSF associated with the use of DOTAREM, this product should be used in patients with severe renal impairment and in patients in the perioperative period of liver transplantation only after careful benefit-risk assessment and only when diagnostic information is essential and cannot be obtained by non-contrast MRI. If DOTAREM must be used, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging session. Due to lack of data on repeated administration, repeat injections of DOTAREM should not be given unless the interval between doses is at least 7 days.
Haemodialysis shortly after administration of DOTAREM may facilitate elimination of DOTAREM from the body. There is no evidence to support initiating haemodialysis for prevention or treatment of NSF in patients who are not currently undergoing haemodialysis.

Elderly patients
Since renal clearance of gadoteric acid may be reduced in elderly patients, it is particularly important to assess renal function in patients aged 65 years and older prior to administration.

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

Effect on pregnancy and breastfeeding
DOTAREM should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoteric acid.
Continuation or interruption of breastfeeding for 24 hours after administration of DOTAREM should be decided by the physician and the breastfeeding mother.

Instructions for use
The peel-off identification labels from the vials should be attached to the patient's records to allow accurate identification of the gadolinium-containing contrast agent used. The administered dose should also be recorded. When using an electronic patient record, the product name, batch number, and administered dose should be entered.