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Pharmacotherapeutic group
Dotarem is a medicinal product for diagnostic use. It belongs to the group of contrast agents used in magnetic resonance imaging (MRI).
Therapeutic indications
This medicinal product is for diagnostic use only.
Dotarem is used to enhance the contrast of the images obtained during MRI examinations, in order to improve the visualisation and delineation of certain parts of the body.
List of information necessary before taking the medicinal product
Read all the information in this section carefully.
You and your doctor should consider this information before using Dotarem.
Contraindications
DOTAREM 0.5 mmol/mL, solution for injection should not be given to you :
- if you are allergic (hypersensitive) to the active substance or any of the other ingredients in this medicine listed in section 6.
Before the examination, remove all metallic objects that you wear. Tell your doctor if you have a cardiac stimulator (pacemaker), a vascular clip, an infusion pump, a nerve stimulator, a cochlear implant (implant in the inner ear), or any other metallic foreign body, particularly in your eyes. It is a very important matter because it could cause serious disorders, since MRI machines use powerful magnetic fields.
Talk to your doctor or pharmacist before using Dotarem.
Like all MRI contrast agents and regardless of the route of administration and the dose, there is a risk of side effects, usually minor but can also be life-threatening. The possible serious reactions may occur within an hour and the minor reactions may occur up to 7 days after administration. They are unforeseeable but the risk of occurrence is increased if you have experienced a reaction during previous administration of an MRI contrast agent (see section 4 “Possible side effects”). If this is the case, you should inform the radiologist who will perform the injection.
Inform your doctor:
- if you have asthma.
- if you have a history of allergy.
- if your kidneys do not work properly.
- if you have recently had, or soon expect to have, a liver transplant.
- if you have had convulsions.
Your doctor may decide to take a blood test to check how well your kidneys are working before making the decision to use Dotarem, especially if you are 65 years of age or older.
Children
As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Dotarem will only be used in these patients after careful consideration by the doctor.
Interactions with other medicinal products
Other medicines and DOTAREM 0.5 mmol/mL, solution for injection
Tell your doctor or pharmacist if you are using, have recently used or may use any other medicine. Be particularly careful if you take medicines for high blood pressure.
Interactions with food and drink
Not applicable.
Interactions with herbal or alternative therapies
Not applicable.
Use during pregnancy or breast-feeding
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, if you think you are pregnant, or likely to be pregnant (delayed periods) ask the advice of your doctor or pharmacist before taking this medicine.
Pregnancy
You must tell your doctor if you think you are or might become pregnant, as Dotarem should not be used during pregnancy unless strictly necessary.
Breast-feeding
Tell your doctor if you are breast-feeding or about to start breast-feeding. Your doctor will discuss whether you should continue breast-feeding or interrupt breast-feeding for a period of 24 hours after you receive Dotarem.
Sportsmen
Not applicable.
Effects on the ability to drive or to use machines
Not applicable.
List of excipients with a notable effect
Not applicable.
Instructions for proper use
Not applicable.
Dosage, Method and/or route of administration, Frequency of administration, Duration of treatment
Dosage
The doctor will determine the dose that you will receive and will supervise the injection.
Method of administration
You will be administered Dotarem by intravenous injection.
Special patient groups
The use of Dotarem is not recommended in patients with severe kidney problems and patients who have recently had, or soon expect to have, a liver transplant. However if use is required you should only receive one dose of Dotarem during a scan and you should not receive a second injection for at least 7 days.
Neonates, infants, children and adolescents
As kidney function is immature in babies up to 4 weeks of age and in infants up to 1 year of age, Dotarem will only be used in these patients after careful consideration by the doctor. Neonates and infants should only receive one dose of Dotarem during a scan and should not receive a second injection for at least 7 days.
Administration of Dotarem to perform angiography is not recommended in children under the age of 18.
Elderly
It is not necessary to adjust your dose if you are 65 years of age or older but you may have a blood test to check how well your kidneys are functioning.
Symptoms and instructions in case of overdose
If you have received more DOTAREM 0,5 mmol/mL, solution for injection than you should:
In the exceptional case of an overdose, your doctor will take appropriate measures to treat any symptoms. Your doctor will monitor your renal function in this case.
Actions to be taken when one or more doses have been missed
Not applicable.
Indication of the risk of withdrawal effects
Not applicable.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist for more information.
Description of side effects
Like all medicines, DOTAREM 0.5 mmol/mL, solution for injection can cause side effects, although not everybody gets them.
The side effects of Dotarem are generally mild to moderate and are transient.
The side effects most commonly observed during administration of Dotarem are nausea, vomiting, itchiness, and allergic reactions (usually affecting the skin).
Most side effects occur during injection or during the first hour after the injection. Some side effects may appear several days after the injection of Dotarem.
There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs), usually in patients who received Dotarem together with other gadolinium-containing contrast agents.
The side effects may occur with certain frequencies, which are defined as follows:
• very common: effect reported in more than 1 in 10 patients
• common: effect reported in 1 to 10 in 100 patients
• uncommon: effect reported in 1 to 10 in 1,000 patients
• rare: effect reported in 1 to 10 in 10,000 patients
• very rare: effect reported in less than 1 in 10,000 patients
• not known: frequency cannot be estimated from the available data
The side effects reported with Dotarem are listed below:
Very common:
- headache.
- prickling sensation.
Common:
- nausea.
- vomiting.
- itching.
- skin reactions (for instance, red skin).
- warm/cold sensations.
- injection site pain
Uncommon:
- allergic reactions.
Rare:
- unusual taste in the mouth.
- urticaria (skin eruption with itching and burning sensation), excessive sweating.
Very rare:
- agitation, anxiety.
- coma, convulsions, syncope (brief loss of consciousness), faintness (dizziness and feeling of imminent loss of consciousness), dizziness, perversion of smell (often smelling unpleasant odours), tremor.
- conjunctivitis, red eye, blurred vision, increased tear secretion, swollen eyelids.
- cardiac arrest, acceleration or abnormal slowing of heart beat, irregular heartbeat, palpitations, hypotension or hypertension, increased diameter of blood vessels, pallor.
- respiratory arrest, breathing difficulties, feeling of tight throat, wheezing, feeling of blocked nose, sneezing, cough, feeling of dry throat, pulmonary oedema, pharyngeal oedema.
- diarrhoea, abdominal pain, increased salivation.
- eczema, angioneurotic oedema (angioedema), muscle contractures, muscle weakness, back pain.
- malaise, chest pain, chest discomfort, fever, rigors, swelling of the face, fatigue, coldness, injection site discomfort, injection site pain, injection site reaction, injection site swelling, diffusion of the product outside of blood vessels that can lead to inflammation (redness and local pain) or necrosis (death of the cells of the skin) at the injection site, superficial phlebitis
Unknown:
- nephrogenic systemic fibrosis.
Side effects not reported with Dotarem but reported with similar products (contrast agents for MRI administered by intravenous injection) are listed below. They may therefore occur with Dotarem:
- haemolysis (destruction of red blood cells).
- confusion.
- temporary loss of vision, pain in the eye.
- ringing in the ears, pain in the ear.
- asthma.
- dry mouth.
- skin reaction (blisters on the skin) .
- urinary incontinence (involuntary loss of urine), disorders of kidney functioning.
- abnormality of electrocardiogram, increased iron, bilirubin and ferritin in the blood, abnormality of liver function tests.
Side effects in children:
The side effects of Dotarem are uncommon in children and less severe than in adults.
If you notice any side effects, tell your doctor or pharmacist. This includes any side effects not listed in this leaflet
Keep out of the sight and reach of children.
Expiry date
Do not use this medicine after the expiry date stated on the box and the vial after "EXP". The expiry date refers to the last day of that month.
Storage conditions
No special storage conditions.
If applicable, warnings against certain visible signs of deterioration
Do not discard any medicine in the drains or with household waste. Ask your pharmacist to discard medicines you no longer use. These measures will help protect the environment.
The active substance is :
Gadoteric acid: 100 mL of solution contains 27.932 g (equivalent to DOTA (20.246 g) and to gadolinium oxide (9.062 g))
The other ingredients are :
Meglumine, water for injections.
Marketing Authorisation Holder
GUERBET
BP 57400
95943 ROISSY CHARLES DE GAULLE CEDEX
Distributor
GUERBET
BP 57400
95943 ROISSY CHARLES DE GAULLE CEDEX
Manufacturer
GUERBET
BP 57400
95943 ROISSY CHARLES DE GAULLE CEDEX
NA
NA
NA
NA
NA
NA
NA
NA
This medicinal product is for diagnostic use only.
Magnetic resonance imaging for:
- cerebral and spinal disease,
- diseases of the vertebral column,
- and other whole body pathologies (including angiography).
Posology
The recommended dose is 0.1 mmol/kg, i.e. 0.2 mL/kg, in adults, children and infants.
In angiography, depending on the results of the examination being performed, a second injection may be administered during the same session if necessary.
In some exceptional cases, as when confirming isolated metastasis or detecting leptomeningeal tumours, a second injection of 0.2 mmol/kg can be administered.
Special populations
Impaired renal function
Dotarem should only be used in patients with severe renal impairment (GFR < 30 mL/min/1.73m2) and in patients in the perioperative liver transplantation period after careful benefit/risk assessment and if the diagnostic information is essential and not available with non-enhanced MRI (see section 4.4).
If it is necessary to use Dotarem, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Dotarem injections should not be repeated unless the interval between injections is at least 7 days.
Paediatric population
Neonates up to 4 weeks of age and infants up to 1 year of age
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Dotarem should only be used in these patients after careful consideration, at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Dotarem injections should not be repeated unless the interval between injections is at least 7 days.
Dotarem is not recommended for angiography in children under the age of 18 because of insufficient data on efficacy and safety in this indication.
Elderly (65 years of age and above)
No dosage adjustment is considered necessary. Caution should be exercised in elderly patients (see section 4.4).
Method of administration
The product must be administered by strict intravenous injection.
Administer only by intravenous injection.
Gadoteric acid must not be injected via the subarachnoid (or epidural) route.
There is always a risk of hypersensitivity regardless of the dose injected.
4.4.1 Warnings
All MRI contrast agents can cause minor or major hypersensitivity reactions that may be life-threatening. These hypersensitivity reactions may be either allergic (described as anaphylactic reactions when serious) or non-allergic. They may be immediate (within 60 minutes) or delayed (up to 7 days). Anaphylactic reactions occur immediately and can be fatal. They are independent of the dose, can occur after even the first dose of the product, and are often unpredictable.
There is a risk of hypersensitivity whatever the dose injected.
Emergency resuscitation equipment must be immediately available due to the risk of a major reaction.
Patients who already experienced a reaction during previous administration of a gadolinium-containing MRI contrast agent are at higher risk for another reaction to the same or even a different contrast agent, and consequently they are considered to be subjects at risk.
Injection of gadoteric acid may exacerbate pre-existing asthma. In patients with uncontrolled asthma, the decision to administer gadoteric acid must be made after a careful assessment of the benefit-to-risk ratio.
As with iodinated contrast agents, hypersensitivity reactions may be more difficult to treat in patients taking beta blockers, particularly if they are asthmatic. These patients may be refractory to standard treatments for hypersensitivity reactions using beta-stimulants.
4.4.2 Precautions for use
4.4.2.1. Hypersensitivity to MRI contrast agents
Before the examination:
- identify subjects at risk in a precise interview on their history. Corticosteroids and H1 antihistamines have been proposed as premedication in patients at greatest risk for hypersensitivity reactions (patients with known hypersensitivity to a contrast agent). However, they do not prevent the occurrence of serious or fatal anaphylactic shock.
Throughout the examination, maintain:
- medical monitoring
•
an indwelling intravenous catheter.
After the examination:
- After contrast agent administration, the patient must be kept under observation for at least 30 minutes, as most serious adverse reactions occur within this time period.
- The patient must be warned of the possibility of delayed reactions (for up to 7 days) (see section 4.8).
4.4.2.2 Impaired renal function
Prior to administration of gadoteric acid, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.
There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30 ml/min/1.73m2). Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with gadoteric acid, it should therefore only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI.
Haemodialysis shortly after gadoteric acid administration may be useful at removing gadoteric acid from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.
4.4.2.3 Neonates and infants
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, gadoteric acid should only be used in these patients after careful consideration.
In neonates and infants, the required dose must be administered manually.
Depending on the amount of gadoteric acid to be administered to the child, it is preferable to use vials of gadoteric acid and a disposable syringe of appropriate volume to obtain a more precise injection volume.
4.4.2.4 Elderly
As the renal clearance of gadoteric acid may be impaired in the elderly, it is particularly important to screen patients 65 years of age and older for an eventual renal dysfunction.
4.4.2.5 Central nervous system disorders
Patients with a history of seizures are at higher risk for seizures.
Combinations requiring caution
Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists: these medicinal products decrease the efficacy of the mechanisms of cardiovascular compensation for blood pressure disorders. The physician must be informed before injection of gadolinium complexes and resuscitation equipment must be on hand.
Interactions with other medicinal products have not been reported. No formal studies on interactions have been carried out.
Pregnancy
There are no data on the use of gadoteric acid in pregnant women. Preclinical studies have not provided direct or indirect evidence of deleterious effects with respect to reproductive toxicity (see section 5.3.). Gadoteric acid should not be used during pregnancy unless the patient's clinical situation requires administration of the product.
Breast-feeding
Gadolinium containing contrast agents are excreted into breast milk in very small amounts (see section 5.3). At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk and poor absorption from the gut. The physician and breast-feeding mother should decide whether to continue breast-feeding or to interrupt it for 24 hours following administration of gadoteric acid.
No studies on the effects on the ability to drive and use machines have been performed.
During clinical studies on 1,941 patients, 3.6% of them experienced an adverse reaction related to administration of gadoteric acid, the most common being pain and sensations of heat or cold at the injection site and nausea.
Adverse reactions related to the use of gadoteric acid are generally mild to moderate and are transient.
During clinical trials, headache and paresthesia were the very commonly observed (> 1/10), and nausea, vomiting and skin reactions such as eruptions and pruritus were common (> 1/100 to < 1/10).
The adverse reactions most commonly reported during the administration of gadoteric acid since it has been marketed are nausea, vomiting, pruritus and hypersensitivity reactions.
The effects most commonly observed during hypersensitivity reactions are skin rashes, which can be localized, extensive or generalized. These reactions are usually immediate (during the injection or over the hour following the start of the injection) or sometimes delayed (one hour to several days after the injection), and then appear in the form of adverse skin reactions.
Immediate reactions comprise one or several, successive or concomitant effects, usually including skin reactions, respiratory and/or cardiovascular disorders, which may be the first signs of shock, which can rarely be fatal.
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with gadoteric acid, most of which were in patients co-administered other gadolinium-containing contrast agents (see section 4.4).
Adverse reactions are presented in the following table according to system organ class and frequency, using the following categories: very common (≥1/10), common (≥1/100 to 1<1/10), uncommon (≥1/1,000 to 1<1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), undetermined frequency (cannot be estimated on the basis of available data). The frequencies presented were obtained from the data of an observational study on 82,103 patients.
System Organ Class | Frequency: adverse reactions |
Immune system disorders | Uncommon: hypersensitivity, anaphylactic reactions, anaphylactoid reactions |
Psychiatric disorders | Very rare: agitation, anxiety |
Nervous system disorders | Very common: paresthesia, headache Rare: dysgeusia Very rare: coma, seizures, syncope, faintness, dizziness, parosmia, tremor |
Eye disorders | Very rare: conjunctivitis, ocular hyperaemia, blurred vision, increased lacrimal secretion, eyelid oedema |
Cardiac disorders | Very rare: cardiac arrest, bradycardia, tachycardia, arrhythmia, palpitations |
Vascular disorders | Very rare: hypotension, hypertension, vasodilatation, pallor |
Respiratory, thoracic and mediastinal disorders: | Very rare: respiratory arrest, pulmonary oedema, bronchospasm, laryngospasm, pharyngeal oedema, dyspnoea, nasal congestion, sneezing, cough, dry throat |
Gastrointestinal disorders | Common: nausea, vomiting, Very rare: diarrhoea, abdominal pain, excessive salivation |
Skin and subcutaneous tissue disorders | Common: pruritus, erythema, eruptions Rare: urticaria, hyperhidrosis, Very rare: eczema, angioneurotic oedema (angioedema) |
The following adverse reactions have been reported with other intravenous MRI contrast agents. Consequently, they may also occur during treatment with Dotarem:
System Organ Class | Adverse reaction |
Blood and lymphatic system disorders | Haemolysis |
Psychiatric disorders | Confusion |
Eye disorders | Transient blindness, eye pain |
Ear and labyrinth disorders | Tinnitus, ear pain |
Respiratory, thoracic and mediastinal disorders: | Asthma |
Gastrointestinal disorders | Dry mouth |
Skin and subcutaneous tissue disorders | Bullous dermatitis |
Renal and urinary disorders | Urinary incontinence, renal tubular necrosis, acute renal failure |
Investigations | Prolonged PR on electrocardiogram, elevated serum iron, elevated serum bilirubin, elevated serum ferritin, abnormal liver function tests |
Adverse reactions in children
Adverse reactions related to gadoteric acid are uncommon in children. The expected types of reaction are identical to those reported in adults. When they occur, the reactions are less severe than in adults.
No overdose has been reported.
In the event of a very high dose, water and electrolyte loss must be compensated by suitable rehydration. Renal function must be monitored for at least three days.
Gadoteric acid can be removed from the body by haemodialysis. However, there is no evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).
Pharmacotherapeutic group: paramagnetic contrast media for MRI, ATC code: V08 CA02.
Gadoteric acid has paramagnetic properties allowing MRI contrast enhancement. It has no specific pharmacodynamic activity and is biologically very inert.
Following intravenous injection, gadoteric acid is mainly distributed in the extracellular fluid. It is not bound to plasma albumin and does not cross the healthy blood-brain barrier.
In patients with normal renal function, the plasma half-life is about 90 minutes. Gadoteric acid is eliminated in unchanged form by glomerular filtration.
Plasma clearance is delayed in patients with impaired renal function.
A small amount of gadoteric acid is excreted in breast milk and crosses the placenta
Non-clinical data reveal no special hazard for humans, based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, or toxicity to reproduction.
In acute toxicity studies of intravenous gadoteric acid in mice and rats, adverse effects (seizures, transient respiratory disorders) were only reported at doses much higher than those used in man.
Administration of gadoteric acid at daily doses of up to 15 times the recommended dose in clinical practice and for 28 days did not induce any marked effect apart from reversible vacuolization of renal proximal tubule cells.
Animal studies showed negligible (less than 1% of the administered dose) secretion of gadoteric acid in maternal milk.
No teratogenic effect was demonstrated in rats and rabbits.
No mutagenic effect was demonstrated on the reagent systems used.
Meglumine, water for injections.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
No special precautions for storage.
Type II glass vials containing 5, 10, 15 and 20 mL, closed with a rubber stopper.
Not all pack sizes may be marketed.
The peel-off tracking label on the vials should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.
Prepare a syringe with a needle. Remove the plastic disk. After cleaning the stopper with a pad soaked in alcohol, puncture the stopper with the needle. Withdraw the quantity of product required for the examination and inject it intravenously.
Any unused product or waste material should be disposed of in accordance with local requirements
