Dotarem

Package leaflet: Information for the user

DOTAREM, 0.5 mmol/ml
solution for injection in pre-filled syringe
Acidum gadotericum
Please read all of this leaflet carefully before the medicine is administered because it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or radiologist.
• If you experience 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. Important information before using DOTAREM
3. How to use DOTAREM
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 delineation of:

• pathological lesions in the brain, spinal cord and surrounding tissues;
• pathological lesions in the liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system;
• pathological lesions and narrowing in arteries, especially in the coronary arteries (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 components of this medicine (listed in section 6.).
• if the patient is allergic to gadolinium-containing medicines (such as other contrast agents used in magnetic resonance imaging).

Warnings and precautions
You should 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 previously had an allergic reaction (e.g. to seafood, hives, hay fever);
• the patient is being treated with beta-blockers (medicines used to treat heart disorders and high blood pressure, such as metoprolol);
• the patient’s kidneys are not functioning properly;
• the patient has recently undergone or is scheduled to undergo a liver transplant;
• the patient has a disease affecting the heart or blood vessels;
• the patient has experienced seizures or is being treated for epilepsy.

In all such cases, the doctor or radiologist will assess the benefit-risk ratio and determine whether DOTAREM can be administered to the patient. If DOTAREM is to be used, the doctor or radiologist will take necessary precautions, and administration of DOTAREM will be closely monitored.
The doctor or radiologist may decide to perform a blood test 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 administered to such patients only after careful consideration by the doctor.

Before the examination, all metallic objects the patient may be wearing should be removed. Please 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 magnetic resonance imaging equipment uses very strong magnetic fields, which may cause serious problems.

DOTAREM with other medicines
You should tell your 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 disorders and high blood pressure, such as beta-blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

DOTAREM with food and drink
There are no known interactions between DOTAREM and food or drink. However, you should ask your doctor, radiologist, or pharmacist whether fasting or avoiding fluids is required 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 explain whether she can continue breastfeeding or should interrupt it for 24 hours after administration of DOTAREM.

Driving and operating machinery
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 experiencing nausea (feeling sick), the patient should not drive or operate machinery.

3. How to use DOTAREM

The DOTAREM medicine will be administered as an intravenous injection.
During the examination, the patient will be closely monitored by a doctor or radiologist. An intravenous
catheter will remain in place so that, if necessary, the doctor or radiologist can quickly administer life-saving
medicines. 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 newborns and infants, this medicine will be administered only manually.
The procedure may be performed in a hospital, outpatient clinic, or private office. Medical staff are aware of
the precautions to be taken during the examination and are familiar with potential complications that may
occur.

Dosage
The doctor 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 impairment or for patients who have recently
undergone or are scheduled to undergo liver transplantation. However, if use of DOTAREM is necessary,
the patient should receive only a single dose during the examination and should not receive another dose for
at least 7 days.

Use in newborns, infants, children, and adolescents
Due to immature 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 physician. Children should receive only
a single dose during the examination and should not receive another injection for at least 7 days.
Its use in angiography is not recommended in children under 18 years of age.

Elderly patients
There is no need to adjust the dose in patients aged 65 years and older; however, blood tests may be necessary
to assess kidney function.

Administration of a higher than recommended dose of DOTAREM
It is very unlikely that a patient would receive an excessive dose of the medicine. DOTAREM will be
administered in a medical facility by appropriately trained personnel. In the event of actual overdose,
DOTAREM may 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 leaflet.
If you have any further questions regarding the use of this medicine, please consult your doctor or radiologist.

4. Possible adverse reactions

Like all medicines, 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 that the patient may experience an allergic reaction to DOTAREM. Such reactions can be severe and may lead to anaphylactic shock (a severe allergic reaction that may be life-threatening). The following symptoms may be early 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 swallowing or breathing,
• swelling of hands or feet,
• feeling of dizziness (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
• tingling sensation, feeling of heat or cold and/or pain
• increased or decreased blood pressure
• nausea
• abdominal pain
• rash
• feeling of warmth, feeling of cold
• discomfort at injection site, reaction at injection site, feeling of cold at injection site, swelling at injection site, extravasation of the product (leakage outside blood vessels), which may lead to inflammation (redness and local pain)

Rare adverse reactions (may occur in up to 1 in 1000 people)

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

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

• anaphylactic or anaphylactoid reactions
• agitation
• coma, seizures, syncope (transient loss of consciousness), disturbances of smell (perception of often unpleasant odors), convulsions
• conjunctivitis, blurred vision, excessive tearing
• sudden cardiac arrest, rapid or slow heartbeat, cardiac arrhythmias, vasodilation, pallor
• respiratory arrest, pulmonary edema, breathing difficulties, wheezing, nasal congestion, cough, dry throat, throat tightness with sensation of suffocation, respiratory muscle spasms, throat swelling
• rash, skin redness, swelling of lips and 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 levels in the blood.

There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs), which usually occurred in patients who received DOTAREM together with other contrast agents containing gadolinium. If, within weeks after an MRI examination, the patient notices changes in color 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 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 at the 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 sight and reach of children.
Do not freeze.
Do not use this medicine after the expiry date stated on the ampoule-syringe and on the 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 package 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).
• Other components of the medicine are meglumine and water for injections.

What DOTAREM looks like and contents of the pack
DOTAREM is a clear, colourless or yellow solution for intravenous injection.
The DOTAREM pack contains:

• one plastic syringe prefilled with 10, 15 or 20 ml of injection solution, graduated every 1 ml, without needle;
• or 10 plastic syringes prefilled with 10, 15 or 20 ml of injection solution, graduated every 1 ml, without needles.

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: In neurological 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 administration of 0.1 mmol/kg body weight in patients with brain tumours, 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 contrast for diagnosis 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 consecutive 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 beneficial to administer 0.05 mmol/kg body weight (i.e. 0.1 ml/kg body weight) per 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 scan. Due to immature renal function in neonates 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 procedure. Due to lack of data on repeated administration, DOTAREM injections should not be repeated unless the interval between consecutive injections 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 renal impairment: In patients with mild to moderate renal impairment (GFR ≥30 ml/min/1.73 m²), the adult dose should be used. See section “Renal impairment” below.
• Patients with hepatic impairment: 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 for intravenous use only. DOTAREM must not be administered by intrathecal or epidural injection.
Infusion rate: 3–5 ml/min (in angiographic studies, a higher infusion rate up to 120 ml/min, i.e. 2 ml/sec, may be used).
Optimal imaging: 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 supine position. After administration, the patient should be monitored for at least 30 minutes, as experience shows that most adverse reactions occur during this period.
Screw the plunger rod onto the rubber plunger and inject the volume of product required for the examination intravenously.
For single use only; any unused portions must be discarded.
The injection solution should be inspected visually before use. Only clear, particle-free solutions 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 neonates and infants, the required dose should be administered manually.
Renal impairment
It is recommended that all patients undergo laboratory tests to assess renal function prior to 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 assessment of benefit versus risk 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 procedure. Due to lack of data on repeated administration, DOTAREM injections should not be repeated unless the interval between consecutive injections is at least 7 days.
Haemodialysis shortly after administration of DOTAREM may facilitate elimination of DOTAREM from the body. There is no evidence supporting initiation of haemodialysis for prophylaxis or treatment of NSF in patients 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.
Neonates and infants
See section “Dosage and method of administration, use in children”.
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 left to the discretion of the physician and the breastfeeding mother.
Instructions for use
Removable identification labels from the syringes 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.