Dotagraf multidose

Leaflet accompanying the packaging: information for the user

Dotagraf multidose, 0.5 mmol/ml

Solution for injection

Gadoterenic acid

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should ask your doctor or radiologist.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or radiologist. See section 4.

Table of contents of the leaflet

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

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

Dotagraf multidose is a contrast agent containing gadoterenic acid. It is intended for diagnostic purposes only.
Dotagraf multidose is used to increase the contrast of images obtained during magnetic resonance imaging (MRI) examinations. This contrast enhancement improves the visibility and differentiation of the image:
Adults, children and adolescents (0-18 years)

• in MRI examinations of the central nervous system, including disorders (pathological changes) in the brain, spinal cord and surrounding tissues;
• in whole-body MRI diagnostics, including disorders (pathological changes) in the liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system.

Adults

• in MR angiography, including disorders (pathological changes) and narrowings (stenosis) of arteries, with the exception of coronary arteries.

2. Important information before using Dotagraf multidose

When not to use Dotagraf multidose

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

Warnings and precautions

Before starting treatment with Dotagraf multidose, the patient should inform their doctor or radiologist if any of the following apply:

• 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 shellfish, hives, hay fever).
• the patient is being treated with a beta-adrenergic blocker (a medicine used to treat heart disorders and high blood pressure, such as metoprolol).
• the patient has impaired kidney function.
• the patient has recently undergone or is awaiting a liver transplant.
• the patient has heart or blood vessel disease.
• the patient has a history of seizures or is being treated for epilepsy.

In all these cases, the doctor or radiologist will assess the benefit-risk ratio and decide whether the patient can be given Dotagraf multidose. If the patient is given Dotagraf multidose, the doctor or radiologist will take the necessary precautions and the administration of Dotagraf multidose will be closely monitored.
The doctor or radiologist may decide to perform a blood test to check the patient's kidney function before deciding to use Dotagraf 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, Dotagraf 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. The patient should inform the doctor or radiologist if they have:

• a pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an implant in the inner ear),
• or if there is a suspicion of the presence of any metal foreign body, especially in the eye. This is very important because it can cause serious problems, as MRI devices use very strong magnetic fields.

Dotagraf multidose and other medicines

The patient should tell their doctor or radiologist if they are taking, have recently taken or might take any other medicines. In particular, the patient should tell their doctor, radiologist or pharmacist if they are currently taking or have recently taken medicines for heart disorders or high blood pressure, such as beta-adrenergic blockers, vasoactive agents, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists.

Dotagraf multidose with food and drink

No interactions between Dotagraf multidose and food or drinks are known. However, the patient should ask their doctor, radiologist or pharmacist if it is necessary to fast before the examination.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant or plans to have a child, they should consult their doctor or radiologist before using this medicine.
Pregnancy
Gadoterenic acid may cross the placenta. It is not known whether this affects the fetus. Dotagraf multidose should not be used during pregnancy unless absolutely necessary.
Breastfeeding
The doctor or radiologist will discuss with the patient and explain whether they can continue breastfeeding or whether they should stop for 24 hours after administration of Dotagraf multidose.

Driving and using machines

There are no available data on the effect of Dotagraf multidose on the ability to drive and use machines. If the patient feels unwell after the examination, they should not drive or operate machinery.

3. How to use Dotagraf multidose

Dotagraf multidose will be administered by intravenous injection.
During the examinationthe patient will be under close supervision of the doctor or radiologist. A needle will be left in the patient's vein, so that the doctor or radiologist can quickly inject emergency medication if necessary. If the patient experiences an allergic reaction, the administration of Dotagraf multidose will be stopped.
Dotagraf multidose may be administered manually or using an automatic injector.
In newborns and infants, this medicine will be administered manually only.
This procedure may be performed in a hospital, clinic or private office. The personnel involved in performing the examination 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

Dotagraf multidose is not recommended for use in patients with severe kidney function disorders or in patients who have recently undergone or are awaiting a liver transplant. However, if the use of Dotagraf multidose is necessary during an MRI examination, the patient should receive only one dose of the medicine and should not receive another dose for at least 7 days.
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, Dotagraf multidose will only be used in these patients after careful consideration by the doctor. Newborns and infants should receive only one dose of Dotagraf multidose during the examination and should not receive another dose for at least 7 days.
Angiography is not recommended in children under 18 years of age.
Elderly patients
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 Dotagraf multidose

It is very unlikely that the patient will receive too much Dotagraf multidose. Dotagraf multidose will be administered in a medical facility by trained personnel. In the event of actual overdose, Dotagraf 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 leaflet.
If you have any further questions about the use of this medicine, you should ask your doctor or radiologist.

4. Possible side effects

Like all medicines, Dotagraf 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 shortly after administration of the medicine. Some side effects may occur up to seven days after injection of Dotagraf multidose.

There is a small risk of an allergic reaction to Dotagraf multidose. Such

reactions can be severe and can 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 their doctor, radiologist or other medical staff:

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

Uncommon side effects (may occur in up to 1 in 100 patients)

• hypersensitivity (allergic reaction),
• headache,
• unusual taste in the mouth,
• dizziness,
• drowsiness,
• feeling of tingling, heat/burning, cold and/or pain,
• low or high blood pressure,
• nausea (vomiting),
• abdominal pain,
• rash,
• feeling of heat, feeling of cold,
• asthenia (loss of energy, weakness),
• discomfort at the injection site, reactions at the injection site, feeling of coolness at the injection site, swelling at the injection site, extravasation of the medicine, which can lead to inflammation (redness and local pain).

Rare side effects (may occur in up to 1 in 1,000 patients)

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

Very rare side effects (may occur in up to 1 in 10,000 patients)

• anaphylactic or anaphylactoid reactions (a severe, potentially life-threatening allergic reaction),
• agitation,
• coma, seizures, fainting (brief loss of consciousness), disorders of smell (perception of often unpleasant odors), muscle tremors,
• conjunctivitis, redness of the eyes, blurred vision, increased tearing,
• cardiac arrest, accelerated or slowed heart rate, irregular heartbeat, vasodilation, pallor,
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, feeling of nasal congestion, coughing, dry throat, throat constriction with a feeling of suffocation, bronchospasm, throat swelling,
• skin rash, redness of the skin, swelling of the lips and inside the mouth,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation of the medicine, which can lead to tissue necrosis at the injection site, phlebitis,
• decreased oxygen levels in the blood.

There have been reports of nephrogenic systemic fibrosis (a condition that causes skin hardening and may also affect soft tissues and internal organs), which mostly occurred in patients receiving Dotagraf multidose together with other gadolinium-containing contrast agents. If, in the weeks following the MRI examination, the patient notices changes in skin color and/or thickness at any site on the body, they should inform their radiologist.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should tell their doctor or radiologist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dotagraf multidose

The medicine should be stored out of the sight and reach of children.
There are no special precautions for storage.
The chemical and physical stability of the medicine after preparation has been demonstrated for at least 72 hours at room temperature. From a microbiological point of view, the medicine should be used immediately. If the medicine is not used immediately, the user is responsible for ensuring the appropriate storage conditions and storage time before administration, which should not exceed 24 hours at 2°C – 8°C, unless the medicine has been opened in controlled and validated aseptic conditions.
The medicine should not be used after the expiry date stated on the vial and carton, after the term "Exp". The expiry date refers to the last day of the month stated.

6. Contents of the packaging and other information

What Dotagraf multidose contains

• The active substance is gadoterenic acid. One milliliter of the solution for injection contains 279.32 mg of gadoterenic acid (as meglumine salt), which corresponds to 0.5 mmol of gadoterenic acid (as meglumine salt).
• The other ingredients are meglumine, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and water for injections.

What Dotagraf multidose looks like and contents of the pack

Dotagraf multidose is a colorless to yellowish, clear solution for intravenous injection.
The packaging of Dotagraf multidose contains one or ten vials with 60 ml or 100 ml of solution for injection.
Not all pack sizes may be marketed.

Marketing authorization holder

Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany

Manufacturer

Sanochemia Pharmazeutika GmbH
Landegger Straße 7
2491 Neufeld/Leitha
Austria

This medicinal product is authorized in the Member States of the EEA under the following names:

Date of last revision of the leaflet:November 2024
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Information intended for healthcare professionals only:

Dosage

The smallest dose that provides sufficient contrast enhancement for diagnostic purposes should be used. The dose should be calculated based on the patient's body weight and should not exceed the recommended dose per kilogram of body weight specified in this section.

• MRI of the brain and spinal cord: In central nervous system studies, 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 facilitate the determination of the nature of the tumor and the decision on treatment.
• MRI of the whole body and angiography: The recommended dose for intravenous injection, providing sufficient contrast for diagnosis, is 0.1 mmol/kg body weight (i.e. 0.2 ml/kg body weight). Angiography: In exceptional cases (e.g. when images of satisfactory quality covering an extensive vascular area are not obtained), it may be justified to administer a second, subsequent dose of 0.1 mmol/kg body weight (i.e. 0.2 ml/kg body weight). However, if two consecutive doses of Dotagraf 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: MRI of the brain and spinal cord/whole-body MRI: the recommended and maximum dose of Dotagraf multidose is 0.1 mmol/kg body weight. No more than one dose should be administered during the examination. Due to the lack of data on repeated administration, Dotagraf multidose should not be readministered at intervals of less than 7 days. Dotagraf multidose is not recommended for use in angiography in children under 18 years of age due to insufficient data on efficacy and safety in this indication.
  • 1. Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Dotagraf multidose should only be used in these patients after careful consideration, at a dose not exceeding 0.1 mmol/kg body weight. During one examination, no more than one dose should be administered. Due to the lack of data on repeated administration, Dotagraf multidose should not be readministered at intervals of less than 7 days.

The dose should not exceed the recommended dose per kilogram of body weight specified in this section.

• Patients with kidney disorders: In patients with mild to moderate kidney impairment (GFR ≥30 ml/min/1.73 m), the doses recommended for adults should be used. See also "Kidney disorders" below.
• Patients with liver disorders: In these patients, the doses recommended for adults should be used. Caution is recommended, especially in the perioperative period related to liver transplantation.

Method of administration

Dotagraf multidose is intended for intravenous administration only. It should not be administered intraperitoneally. It should only be administered intravenously: extravasation may cause local intolerance reactions, requiring local treatment.
Infusion rate: 3-5 ml/min (during angiographic studies, a higher infusion rate of up to 120 ml/min, i.e. 2 ml/s, may 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 remain under observation 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.
Generally, the spike should have the following elements: a trocar, a sterile air filter, a luer-type connector and a tight protective cap.
A single-use syringe (sterile) may be used for single administration of the medicinal product or for injection of a second dose of the contrast agent in a bolus, if clinically justified.
An automatic injection system may only be used for a single patient for multiple administrations of the medicinal product.
The volume of the medicinal product remaining in the vial and the single-use device after completion of the examination must be discarded within 24 hours of piercing the rubber stopper. The instructions of the device manufacturer must be strictly followed.
The solution for injection should be inspected visually before use. Only clear solutions free from visible particles should be used.
Children and adolescents
Depending on the amount of Dotagraf multidose to be administered to the child, it is recommended to use vials of Dotagraf multidose with a single-use syringe of a capacity adapted to this amount in order to maintain greater accuracy of the administered volume.
In newborns and infants, the required dose should be administered manually.

Kidney disorders

It is recommended that all patients undergo screening laboratory tests for kidney disorders before administration of Dotagraf multidose:

There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of some gadolinium-containing contrast agents in patients with acute or chronic severe kidney impairment (GFR <30 ml min 1.73 m). patients undergoing liver transplantation are particularly at risk of this complication, as group is high developing acute kidney impairment. since there a nsf after administration dotagraf multidose, it should only be used in with severe impairment and the perioperative period related to careful assessment benefit-risk ratio when diagnostic information essential cannot obtained using mri without contrast enhancement. if use multidose necessary, dose not exceed 0.1 mmol kg body weight. during one examination, no more than administered. due lack data on repeated administration, readministered intervals less 7 days.
Hemodialysis performed shortly after administration of Dotagraf multidose may facilitate its removal from the body. There is no evidence to justify the initiation of hemodialysis to prevent NSF or to treat it in patients not already undergoing hemodialysis.

Elderly patients

Since kidney clearance of gadoterenic acid may be impaired in elderly patients, it is particularly important to check kidney function before administration of Dotagraf multidose in patients over 65 years of age.

Newborns and infants

See Dosage and Method of administration, Children and adolescents.

Pregnancy and breastfeeding

Dotagraf multidose should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoterenic acid.
The decision to continue breastfeeding or to stop it for 24 hours after administration of Dotagraf multidose should be made by the doctor and the breastfeeding mother.

Instructions for handling Dotagraf multidose

The removable label from the vial should be attached to the patient's file to allow accurate recording of the contrast agent used. The administered dose should also be recorded. If the patient's file is kept electronically, the name of the medicinal product, batch number and administered dose should be entered into the file.