Dotarem (Gadoterate Meglumine) is an intravenously administered extracellular contrast agent that is used for central nervous system magnetic resonance Imaging.

Indications of Dotarem (Gadoterate Meglumine):

• CNS imaging:

  • It is used as a contrast medium for MRI in adults, adolescents,  pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity in the brain (intracranial), spine, and associated tissues.

Dotarem (Gadoterate Meglumine) dose in adults for CNS imaging:

• 0.2 mL/kg (0.1 mmol/kg) intravenously;
• may begin imaging immediately after administration.

Dotarem (Gadoterate Meglumine) dose in children:

Note:

The dose is expressed in mL/kg and mmol/kg. The parenteral solution contains 0.5 mmol/mL of gadoterate meglumine, therefore it should be used with caution.

Dotarem (Gadoterate Meglumine) Dose in the CNS Magnetic Resonance Imaging (MRI):

• Infants, Children, and Adolescents:

  • 0.2 mL/kg (0.1 mmol/kg) intravenously
  • may begin imaging immediately after administration.

Pregnancy Risk Category: C

• Contrast agents based on gadolinium can cross the placenta.
• Contrast agents containing gadolinium-based elements should not be used during pregnancy.
• A gadolinium-based contrast agent can be used with MRI if there is a significant improvement in diagnostic performance or improved fetal and maternal outcomes.
• If the information required from an MRI study cannot be obtained without a contrast agent, and cannot be delayed until after delivery, pregnant women can use gadoterate.
• It is recommended to use the lowest possible effective dose of agents that pose a low risk of developing nephrogenic fibrosis.

Gadoterate meglumine use during breastfeeding:

• Breast milk can contain gadolinium-based contrast agent excretion.
• As long as there is no excess of gadeterate in breast milk or absorption from the infant's GI tract, breastfeeding can be continued.
• Contrasting media can cause milk to have a different taste.
• If a woman wishes to stop breastfeeding temporarily, milk may be produced from both breasts for 12-24 hours following the administration of contrast media.
• Before starting the procedure, it is important to pump and store milk for future use.
• The infant's exposure and the benefits of breastfeeding to the baby during therapy will determine whether the mother decides to breastfeed.

Dotarem (Gadoterate Meglumine) dose adjustment in renal disease:

No dosage adjustment is recommended, however, use with caution. In case of worsening renal function, the risk for developing nephrogenic systemic fibrosis (NSF) is raised.

• Hemodialysis: Gadoterate meglumine is removed by hemodialysis.

Dotarem (Gadoterate Meglumine) Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Side effects of Dotarem (Gadoterate Meglumine):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Nausea

Contraindications to Dotarem (Gadoterate Meglumine):

• Hypersensitivity to gadoterate-meglumine or any other component of the formulation
• Administration of subarachnoid and epidural drugs

Warnings and precautions

• Extravasation:

  • Gadoterate may be used as a vesicant. Agents with higher osmolities or larger volumes pose higher risks.
  • Proper needle and catheter placement are essential before and during administration.
  • Monitoring of the infusion site is important.
  • Local tissue irritation is possible and extravasation should not be allowed.

• Gadolinium retention:

  • For months or even years, gadolinium can be retained in the brain, bones, skin, and other organs like kidneys, liver, and spleen. 
  • The bone has the highest concentration and longest retention.
  • The retention of linear GBCAs is higher than that of macrocyclic GBCAs, such as gadoterate meglumine and gadobutrol.
  • Gadolinium retention in the skin and other organs can have serious and pathological consequences for patients with impaired renal function. 
  • Normal renal function can lead to rare cases of skin problems.
  • It has not been shown that gadolinium retention in the brain of patients with normal renal function does have any consequences.
  • Gadolinium retention can be more dangerous in children, pregnant women, patients who require multiple lifetime doses and patients with inflammatory diseases.
  • Repetitive GBCA image studies should be avoided.

• Hypersensitivity reactions

  • Gadoterate contrast may cause anaphylactic or anaphylactoid reactions, including respiratory, cardiovascular, and dermatologic involvement. It can also lead to circulatory collapse.
  • These symptoms can appear as soon as they occur and can be treated with emergency management right away.
  • Before administering contrast media, bronchial asthma or other allergic disorders, patients should be evaluated.
  • Patients should be closely monitored during and after an infusion.
  • Hypersensitivity reactions should be treated immediately.
  • During an emergency, you should have the right equipment and trained personnel available.

• Nephrogenic systemic Fibrosis: [US Boxed Warn]

  • Patients who have difficulty eliminating contrast agents are at greater risk of developing nephrogenic fibrosis.
  • Therefore, it is important to avoid GBCA enhanced imaging unless it is absolutely necessary for diagnostic purposes.
  • High risk patients with severe, acute kidney disease or acute kidney injury (GFR 30mL/minute/1.73m2) are at highest risk.
  • Nephrogenic systemic Fibrosis can cause life-threatening systemic fibrosis, which can affect the skin, muscles, and internal organs.
  • Before administering medication, patients should be checked for signs of acute kidney injury and other conditions that could affect renal function. 
  • Patients at high risk of chronic declines in kidney function (e.g., patients over 60, chronic hypertension, diabetes) should have their glomerular filtration rate monitored.
  • Patients at high risk for nephrogenic syndromeic fibrosis should not exceed the recommended dose and should allow sufficient time between administrations.
  • Patients with chronic mild or moderate renal disease (GFR 30 - 59 mL/minute/1.73m2) and chronic moderate renal disease are at low risk for nephrogenic fibrosis.
  • Patients who are dialysis-dependent should immediately begin hemolysis.
  • NSF should be reported to the manufacturer or Food and Drug Administration.

• Renal impairment

  • Gadolinium agents may cause acute kidney injury in patients with chronic renal impairment.
  • The lowest dose is required to achieve adequate imaging.
  • All patients should have their renal function assessed.
  • Patients with a history renal dysfunction should be followed-up.

Monitoring parameters:

• RFTs before administration
• Signs of hypersensitivity (during and after administration)
• Signs and symptoms of extravasation at the injection site
• Signs and symptoms of nephrogenic systemic fibrosis (eg, burning, itching, swelling, skin hardening and/or tightening, stiffness of joints, deep hip or rib bone pain, muscle weakness, limited range of motion, and/or yellowed/raised spots on the white part of eyes.

How to administer Dotarem (Gadoterate Meglumine)?

• An IV bolus injection should be given by manual injection or power injector.
• The infusion should be given at a rate of approximately 2 mL/second.
• The line should be flushed with normal saline after administration for complete injection of contrast agent.
• Gadoterate can act as a vesicant. Higher risks are associated with agents with higher osmolarity or higher volumes.
• Before and during administration, proper needle or catheter placement is necessary. Extravasation should be avoided.

Extravasation management:

• The infusion should be stopped immediately and disconnected in case of extravasation.
• The cannula should be removed and extremity should be elevated. It is not recommended to aspirate extravasated contrast media.
• Hyaluronidase use in the management of contrast media extravasation is not recommended by the American College of Radiology due to conflicting information.
• Its utility in extravasation management is suggested by some other sources.

If using hyaluronidase: Intradermal or SubQ:

• A total of 1 to 1.7 mL (15 units/mL) should be given as five separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into the area of extravasation at the leading edge in a clockwise manner or
• injection of a total of 5 mL (150 units/mL) as five separate 1 mL injections around the extravasation site can be given.

Mechanism of action of Dotarem (Gadoterate Meglumine):

• Gadoterate meglumine is a gadolinium-containing paramagnetic macrocyclic ionic contrast agent.
• Exposure to an external magnetic field can induce a local magnetic moment in the tissues.
• This local magnetic effect increases signal intensity in tissues by increasing the water proton relaxation.
• Contrast cannot cross the blood-brain border so brain lesions can only be increased if the blood-brain barriers are broken or there is abnormal blood flow.

The onset of action:

• Imaging may begin immediately after administration.

Distribution:

• 179 ± 26 mL/kg (female);
• 211 ± 35 mL/kg (male);
• does not cross intact blood-brain barrier.

Protein binding:

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• None.

Metabolism:

• Not metabolized.

Half-life elimination:

• 1.4 ± 0.2 hours (female);
• 2 ± 0.7 hours (male).

Excretion:

• Urine (72.9% ± 17% female; 85.4 ± 9.7% male).

International Brands of Gadoterate meglumine:

• Dotarem

Gadoterate meglumine Brand Names in Pakistan:

No Brands Available in Pakistan.