Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)

PROFESSIONAL INFORMATIONSCHEDULING STATUS
S4

PROPRIETARY NAME (AND DOSAGE FORM)DOTAREM® (Sterile solution for injection)
DOTAREM® PREFILLED SYRINGES (Sterile solution for injection)

COMPOSITION
Gadoteric acid (Gd-DOTA) 27,932 g/100 ml (0,5 mmol/l) corresponding to 20,246 g/100 ml DOTA
(1,4,7,10-tetra-azacyclododecane-N,N’,N”,N”’-tetra-acetic acid) and 9,062 g/100 ml gadolinium oxide.
Osmolality: 1350 mOsm/kg
Viscosity at 20 ºC: 3,2 mPa.s
Viscosity at 37 ºC: 2,0 mPa.s
pH: 6,5 – 8,0
Inactive ingredients: meglumine, water for injections

PHARMACOLOGICAL CLASSIFICATION
A28 Contrast media

PHARMACOLOGICAL ACTIONDOTAREM is a paramagnetic contrast medium for magnetic resonance imaging (MRI). Gadoteric acidis formed by complexing of the paramagnetic ion, gadolinium with 1,4,7,10-tetra-azacyclododecaneN,N’,N”,N”’-tetra-acetic acid (DOTA). The presence of 7 unpaired electrons of the gadolinium ion Gd 3+,
attributes to the string paramagnetic properties, with a shortening of the T1 longitudinal relaxation time.
This results in an increased signal intensity in T1-weighted sequences and reduced signal intensity inT2-weighted sequences in the magnetic resonance imaging.
Gadoteric acid has paramagnetic properties which increase contrast enhancement in magnetic
resonance images. It has no specific pharmacodynamic activity and is biologically inert.
Version: 14Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)
PharmacokineticsPharmacokinetic studies indicate that DOTAREM is distributed in the extracellular fluids, does notcross the blood-brain barrier, does not bind to albumin and is rapidly eliminated in an unchanged formby glomerular filtration. In patients with normal renal function, the plasma half-life is approximately 90
minutes. It is eliminated by glomerular filtration in unchanged form.
Plasma clearance is retarded in the event of renal failure. Gd-DOTA excretion in breast milk is low andcrossing of the placental barrier is low.

INDICATIONS
Enhancement of contrast in magnetic resonance imaging.
Encephalic and spinal pathologies:•Brain tumours•Tumours of the spine and the surrounding tissue•

Intervertebral disk prolapsed•

Infectious diseases

Abdominal pathologies:•Primary and secondary liver tumours

Osteo-articular pathologies:•

Bone and soft tissue tumours•

Synovial diseases

Angiography

CONTRAINDICATIONSHypersensitivity to any of the components.
Contraindications related to magnetic resonance imaging (MRI): patients with vascular clips,
pacemakers.

WARNINGS AND SPECIAL PRECAUTIONSDOTAREM should be used only when diagnostic information is essential and not available
with unenhanced magnetic resonance imaging (MRI).
Version: 14Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)

Administer only by strict intravenous injection. In the event of extravasation, local intolerance reactions
can occur, which require conventional local treatment.
DOTAREM must not be administered by subarachnoid (or epidural) injections.

Hypersensitivity-As with other gadolinium containing contrast media, hypersensitivity reactions can occur (see“Side effects”). Most of these reactions appear within at least half an hour after injection of thecontrast medium. However, as with other contrast media of this class, the occurrence ofdelayed reactions up to several days cannot be excluded.

-Patients with hypersensitivity or a previous reaction to contrast media are at increased risk of
having a severe reaction. Patients should be questioned for a history of allergy (e.g. hay fever,hives, asthma) before any contrast media is injected. In such patients, the decision to use
DOTAREM must be made after careful evaluation of the risk-benefit ratio.

-As known from the use of iodinated contrast media, hypersensitivity reactions can beaggravated in patients on beta-blockers, and particularly in the presence of bronchial asthma.
These patients may be refractory to standard treatment of hypersensitivity reactions with betaagonists.

-If hypersensitivity reactions occur, administration of the contrast media must be discontinued
immediately and, if necessary, specific therapy instituted. A venous access should thus bekept during the entire examination. To permit immediate emergency countermeasures,appropriate drugs (e.g. epinephrine and antihistamines), an endotracheal tube and arespirator should be ready at hand.

-Caution should be exercised in patients with severe renal failure or impaired renal function.

-There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use ofsome gadolinium-containing contrast agents in patients with severe renal impairment (GFR ˂30 ml/min/1,73 m2). As there is possibility that NSF may occur with DOTAREM, it should only
be used in these patients after careful consideration.

During the examination, the following are required:
Version: 14Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)- surveillance by a physician.
- maintenance of an intravenous route for emergency treatment in the event of a reaction.

CNS disorders
Like with other gadolinium containing contrast agents, special precaution is necessary in patients witha low threshold for seizures. Precautionary measures should be taken, e.g. close monitoring. All
equipment and drugs necessary to counter convulsions, which may occur, must be made ready foruse beforehand.

It is of decisive importance for prompt action in the event of contrast medium incidents to be familiar
with the practice of emergency measures. To permit immediate counter-measures to be taken in
emergencies, appropriate medicines and instruments (e.g. endotracheal tube and ventilator) should bereadily available.

INTERACTIONS
No interactions have been reported.

PREGNANCY AND LACTATION
Although no teratogenic effects have been observed in animals to date, the safety of DOTAREM in
human pregnancy and lactating women has not been demonstrated.

DOSAGE AND DIRECTIONS FOR USE
The lowest dose that provides sufficient enhancement for diagnostic purposes should be used. The
dose should be calculated based on the patient’s body weight, and should not exceed therecommended dose per kilogram of body weight detailed in this section.
The recommended dose is 0,2 ml/kg in adults and in children.
In angiography, depending on the results of the examination performed, a second injection of 0,2
ml/kg in adults may be administered during the same session if necessary.
The product is intended for intravenous administration only.

Version: 14Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)
SIDE EFFECTS
Side effects in association with the use of DOTAREM are usually mild to moderate in intensity andtransient in nature. A sensation of heat, cold and/or pain at the injection site is the most frequently
observed reaction.

During clinica l trials headache and paraesthesia were very commonly observed (> 10 %) and nausea,
vomiting and skin reactions such as erythematous rash and pruritus were commonly observed (< 1/10- > 1 %)However, rare anaphylactoid reactions have been reported that may be very rarely severe, lifethreatening or have a fatal outcome, particularly in patients with a history of allergy. These allergoid
reactions can occur irrespective of the amount administered and the mode of administration and may
take the form of one or more of the following symptoms: angioedema, anaphylactic shock, circulatory
and cardiac arrest, hypotension, larynx oedema, bronchospasm, laryngospasm, pulmonary oedema,
dyspnoea, stridor, coughing, pruritus, rhinitis, sneezing, conjunctivitis, urticaria and rash. Some of these
symptoms may be the first signs of incipient state of anaphylactic shock. Delayed contrast medium
reactions are possible.

Since post-marketing, the following adverse reactions have been reported:

General disorders and administration site conditions:
Very rarely (< 0,01 %): chest pain, back pain, malaise, fever, sweating increased, coldness, pallor andsyncope.

While injecting DOTAREM into veins with a small lumen, there is the possibility of adverse effects suchas redness and swelling. In case of extra vascular injection local tissue pain may occur. Cases ofsuperficial phlebitis, possibly related to the injection technique, have been rarely reported.

Respiratory, thoracic and mediastinal disorders:
Very rarely (< 0,01 %): respiratory disorders.
Version: 14
Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)

Gastrointestinal disorders:
Very rarely (< 0,01 %): abdominal pain.

Skin and subcutaneous tissue disorders:
Very rarely (< 0,01 %): eczema, erythema, urticaria, pruritus and rash.

Nervous system disorders:
Very rarely (< 0,01 %): dizziness, generalized convulsions, tremor, fatigue and somnolence.

Musculoskeletal, connective tissue and bone disorders:
Very rarely (< 0,01 %): muscle cramps, muscle weakness.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See “Side effects”. Treatment is symptomatic and supportive.

IDENTIFICATIONA clear colourless to yellow solution.

PRESENTATIONDOTAREM sterile solution for injection is available in clear glass vials containing 5 ml, 10 ml, 15ml, 20 ml, 60 ml and 100 ml and DOTAREM PREFILLED SYRINGES in 10 ml, 15 ml and 20 ml
plastic prefilled syringes.
DOTAREM sterile solution for injection and DOTAREM PREFILLED SYRINGES are sold as single
units or as 10 units per pack.
Not all pack sizes are marketed at any one time.

STORAGE INSTRUCTIONSStore at or below 30 ºC. Protect from light.
Do not freeze prefilled syringes.
Version: 14Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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Guerbet South Africa (Pty) Ltd
Dotarem and Dotarem Prefilled Syringes (Solution for Injection)
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERSDOTAREM: 31/28/0550
DOTAREM PREFILLED SYRINGES: 31/28/0551

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Guerbet South Africa (Pty) Ltd

Hertford Office Park, Building I
90 Bekker Road, Vorna Valley
Midrand, Gauteng, 1682

DATE OF PUBLICATION OF THIS PACKAGE INSERT
Date of registration: 1 September 1997
Date of revision: ---Version: 14
Submission date: 14 November 2022
Approved/Implemented: 20 January 2023

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