Gadoteric Acid

Registered South African indications:

• Enhancement of contrast in magnetic resonance imaging (MRI)
   

Contraindications
South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to meglumine or any medicines containing gadolinium 
• Contraindications related to magnetic resonance imaging (MRI) such as patients with vascular clips and pacemakers (See additional prescribing points)

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to meglumine or any medicines containing gadolinium 

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment (GFR<30ml/min/1.73m²)
• Hepatic impairment
  - Perioperative hepatic transplantation period
• Elderly
• Porphyria
• Neonates up to 4 weeks of age and infants up to 1 year of age
• Precautions related to magnetic resonance imaging (MRI) examination (International manufacturer recommendations)
  - Patients with pacemakers, vascular clips, infusion pumps, nerve stimulators, cochlear implants
  - Suspected intracorporeal metallic foreign bodies, particularly in the eye 
• Pre-existing asthma
• Unbalanced asthma
• Presence of bronchial asthma
• History of allergy (e.g. fish and seafood allergy, hayfever, hives)
• Sensitivity to contrast media
• Low threshold for seizures
• Eating 2 hours prior to the investigation (South African manufacturer recommendations) (See additional prescribing points)
• Severe cardiovascular disease
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj, pfs, via

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Enhancement of contrast in magnetic resonance imaging (MRI)
Encephalic and spinal pathologies
- Brain tumours
- Tumours of the spine and the surrounding tissue
- Intervertebral disk prolapse
- Infectious diseases
Abdominal pathologies
- Primary and secondary liver tumours
Osteo-articular pathologies
- Bone and soft tissue tumours
- Synovial diseases

• IV: 0.1mmol/kg (0.2ml/kg)

---

Gadoteric acid is intended for intravenous administration only. In the event of extravasation, local intolerance reactions may be observed, necessitating short-term local treatment

---

Gadoteric acid must not be administered by subarachnoid (or epidural) injections

---

Gadoteric acid is for single-patient use only. Any unused solution should be discarded

---

Appropriate facilities should be readily available for coping with any complication of the procedure, as well as for emergency treatment of severe reaction to the contrast media itself (e.g. hypersensitivity, seizures)

---

International manufacturer recommendations

Enhancement of the contrast in magnetic resonance imaging (MRI) for a better visualization/delineation in
- MRI of the central nervous system including lesions of the brain, spine, and surrounding tissues 

• IV: 0.1-0.3mmol/kg (0.2-0.6ml/kg)

---

After administration of 0.1mmol/kg to patients with brain tumours, the additional dose of 0.2mmol/kg may improve tumour characterisation and facilitate therapeutic decision making

---

- Whole-body MRI including lesions of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system
- MR angiography including lesions or stenoses of the non-coronary arteries

• IV: 0.1mmol/kg (0.2ml/kg), to provide diagnostically adequate contrast

---

Angiography: In exceptional circumstances (e.g. failure to gain satisfactory images of an extensive vascular territory) administration of a second consecutive injection of 0.1mmol/kg (0.2ml/kg) may be justified. However, if the use of 2 consecutive doses of gadoteric acid is anticipated prior to commencing angiography, the use of 0.05mmol/kg (0.1ml/kg) for each dose may be of benefit, depending on the imaging equipment available

---

This medicinal agent is for diagnostic use only

---

Gadoteric acid should be used only when diagnostic information is essential and not available with unenhanced MRI

---

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 the recommended dose per kilogram of body weight

---

Method of administration: See additional prescribing points

---

Do not use by intrathecal route. Take care to maintain strictly intravenous injection: extravasation may result in local intolerance reactions, requiring the usual local care

Paed. forms avail. in SA and covered in this monograph: inj, pfs, via

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Enhancement of contrast in magnetic resonance imaging (MRI)
Encephalic and spinal pathologies
- Brain tumours
- Tumours of the spine and the surrounding tissue
- Intervertebral disk prolapse
- Infectious diseases
Abdominal pathologies
- Primary and secondary liver tumours
Osteo-articular pathologies
- Bone and soft tissue tumours
- Synovial diseases

• IV: 0.1mmol/kg (0.2ml/kg): Max: 0.1mmol/kg/dose  

---

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, at a dose not exceeding 0.1mmol/kg

---

More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadoteric acid injections should not be repeated unless the interval between injections is at least 7 days

---

Use for whole-body MRI is not recommended in children <6 months of age

---

In neonates and infants, the required dose should be administered by hand

---

Gadoteric acid is intended for intravenous administration only. In the event of extravasation, local intolerance reactions may be observed, necessitating short-term local treatment

---

Gadoteric acid must not be administered by subarachnoid (or epidural) injections

---

Gadoteric acid is for single-patient use only. Any unused solution should be discarded

---

Appropriate facilities should be readily available for coping with any complication of the procedure, as well as for emergency treatment of severe reaction to the contrast media itself (e.g. hypersensitivity, seizures)

---

International manufacturer recommendations

Enhancement of the contrast in magnetic resonance imaging (MRI) for a better visualization/delineation in
- MRI of the central nervous system including lesions of the brain, spine, and surrounding tissues
- Whole-body MRI including lesions of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system

• IV: 0.1mmol/kg (0.2ml/kg): Max: 0.1mmol/kg/dose

---

More than one dose should not be used during a scan

---

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 after careful consideration at a dose not exceeding 0.1 mmol/kg. Because of the lack of information on repeated administration, gadoteric acid injections should not be repeated unless the interval between injections is at least 7 days

---

This medicinal agent is for diagnostic use only

---

Gadoteric acid should be used only when diagnostic information is essential and not available with unenhanced MRI

---

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 the recommended dose per kilogram of body weight

---

Method of administration: See additional prescribing points

---

Do not use by intrathecal route. Take care to maintain strictly intravenous injection: extravasation may result in local intolerance reactions, requiring the usual local care

---

Angiography: Not established for use in children below 18 years

Pregnancy
South African manufacturer recommendations

• Caution; not recommended
• There are no data from the use of gadoteric acid in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• Gadoteric acid should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid

International manufacturer recommendations

• Caution; not recommended
• There are no data from the use of gadoteric acid in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
• Gadoteric acid crosses the placenta slowly. Gadoteric acid should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid

Breastfeeding

• Caution 
• Gadolinium-containing contrast media are excreted into breast milk in very small amounts
• At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk and poor absorption from the gut
• Continuing or discontinuing breastfeeding for a period of 24 hours after administration of gadoteric acid should be at the discretion of the doctor and breastfeeding mother

Fertility 
South African manufacturer recommendations

• There are no clinical data available with regard to effects on fertility

International manufacturer recommendations

• No information available

Renal Impairment

• Mild to moderate (GFR≥30ml/min/1.73m²): No dose adjustment recommended 
• Severe (GFR<30ml/min/1.73m²): Caution; no dose adjustment recommended 
  Gadoteric acid should only be used in patients with severe renal impairment after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast-enhanced MRI. If it is necessary to use gadoteric acid, the dose should not exceed 0.1mmol/kg body weight
  More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadoteric acid injections should not be repeated unless the interval between injections is at least 7 days

Hepatic Impairment

• Caution; no dose adjustment recommended 
  The adult dose applies. Caution is recommended, especially in the case of perioperative liver transplantation period
  Gadoteric acid should only be used 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. If it is necessary to use gadoteric acid, the dose should not exceed 0.1mmol/kg body weight
  More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadoteric acid injections should not be repeated unless the interval between injections is at least 7 days  

Elderly 

• Caution; no dose adjustment recommended 
  As the renal clearance of gadoteric acid may be impaired in elderly patients, it is particularly important to screen patients aged 65 years and older for renal dysfunction

Porphyria Information 

• Not yet classified (NC) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety 
• Agitation
• Headache
• Dizziness
• Somnolence
• Paraesthesia
  - Burning sensation 
• Syncope
  - Presyncope
• Coma
• Seizure
• Tremor
• Parosmia
• Asthenia

Cardiovascular Disorders 

• Palpitations 
• Cardiac arrest
• Arrhythmia
  - Dysrhythmia
• Bradycardia
• Tachycardia
• Hypotension
• Hypertension 
• Vasodilatation

Respiratory Disorders

• Sneezing
• Cough
• Dyspnoea
• Nasal congestion
• Respiratory arrest
• Bronchospasm
• Laryngospasm
• Pharyngeal oedema
• Dry throat
• Pulmonary oedema
• Chest pain
• Chest discomfort

Gastrointestinal Disorders 

• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Salivary hypersecretion

Musculoskeletal Disorders

• Muscle cramps
• Muscular weakness
• Back pain 
• Muscle contracture
• Thoracic pain 

Skin and Subcutaneous Tissue Disorders 

• Rash
• Urticaria
• Pruritus
• Erythema
• Hyperhidrosis
• Angioedema
• Eczema
• Nephrogenic systemic fibrosis
• Injection site reactions
  - Extravasation
  - Pain
  - Discomfort
  - Oedema
  - Inflammation (in case of extravasation)
  - Coldness
  - Heat
• Injection site necrosis (in case of extravasation)
• Superficial phlebitis
• Pallor
• Face oedema

Immune, Blood and Lymphatic System Disorders 

• Hypersensitivity
• Anaphylactic reaction 
• Anaphylactoid reaction
• Chills
• Pyrexia
• Decreased oxygen saturation

Sensory Disorders 

• Eyelid oedema 
• Conjunctivitis
• Ocular hyperaemia
• Blurred vision
• Increased lacrimation
• Dysgeusia 
• Parosmia

Others

• Feeling hot
• Feeling cold

• Beta-blockers
• Vasoactive substances
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor antagonists

• Renal function (prior to administration)

Additional observations

• Signs of hypersensitivity (during and post-administration)
• Signs/symptoms of nephrogenic systemic fibrosis (NSF)
  - Burning
  - Itching
  - Swelling, hardening and/or tightening of skin
  - Joint stiffness
  - Deep hip or rib bone pain
  - Muscle weakness
  - Limited range of motion
  - Yellowed/raised spots on whites of eye
• Signs/symptoms of extravasation at injection site

Method of administration (International manufacturer recommendations)

• Indicated for intravenous administration only
• Infusion rate: 3-5ml/min (higher infusion rates up to 120ml/min, i.e. 2ml/sec, may be used for angiographic procedures)
• Optimal imaging: within 45 minutes after injection
• Optimal image sequence: T1-weighted
• Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the administration, the patient should be kept under observation for at least half an hour, since experience shows that the majority of undesirable effects occur within this time
• 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
• For single use only, any unused solution should be discarded
• The solution for injection should be inspected visually prior to use. Only clear solutions free of visible particles should be used

Patient preparation (South African manufacturer recommendations)

• Nausea and vomiting are known possible undesirable effects when using MRI contrast media. The patient should therefore refrain from eating for 2 hours prior to the investigation

Hypersensitivity

• Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g. seafood allergy, hay fever, hives), sensitivity to contrast media and bronchial asthma as the reported incidence of adverse reactions to contrast media is higher in patients with these conditions and premedication with antihistamines and/or glucocorticoids may be considered
• During the examination, supervision by a physician is necessary. If hypersensitivity reactions occur, administration of the contrast medium must be discontinued immediately and - if necessary - specific therapy instituted. A venous access should thus be kept during the entire examination. To permit immediate emergency countermeasures, appropriate drugs (e.g. epinephrine and antihistamines), an endotracheal tube and a respirator should be ready at hand

Coadministration with medications 

• Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists: these medicinal products decrease the efficacy of the mechanisms of cardiovascular compensation for blood pressure disorders. The application of contrast media may increase the incidence of hypersensitivity reactions in patients taking beta-blockers. The radiologist must be informed before injection of gadolinium complexes, and resuscitation equipment must be at hand

MRI examination

• The usual precautions for MRI examination should be taken, such as exclusion of patients with pacemakers, vascular clips, infusion pumps, nerve stimulators, cochlear implants, or suspected intracorporeal metallic foreign bodies, particularly in the eye

Gadoteric acid has no specific pharmacodynamic activity. Gadoteric acid is a paramagnetic contrast medium for magnetic resonance imaging (MRI). The contrast-enhancing effect is mediated by gadoteric acid which is an ionic gadolinium complex composed out of gadolinium oxide and 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid (DOTA), and present as meglumine salt.

Injection (per 100ml) 27.932g 

• Dotarem Prefilled Syringes (Guerbet South Africa) originator 

Injection (per 100ml) 27.899g

• Dotarem 10Ml (Guerbet South Africa) originator 
• Dotarem 15Ml (Guerbet South Africa) originator 
• Dotarem 20Ml (Guerbet South Africa) originator  

Pre-filled syringe (per ml) 0.5mmol

• Clariscan (GE Healthcare) 

Pre-filled syringe (per 100ml) 27.932g  

• Dotarem Prefilled Syringes (Guerbet South Africa) originator 

Vial (per ml) 0.5mmol

• Clariscan (GE Healthcare)