Gadoversetamide (OptiMARK) is a Gadolinium-based contrast agent that is used in brain, spine, and liver imaging. It should be avoided in patients with renal dysfunction because of the risk of nephrogenic systemic fibrosis.

Gadoversetamide Uses:

• CNS imaging:

  • For use with MRI in patients with an abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues.

• Liver imaging:

  • For use with MRI to provide contrast enhancement and facilitate visualization of lesions with abnormal vascularity in the liver of patients who are highly suspect for liver structural abnormalities on computed tomography.

• Off Label Use of Gadoversetamide in Adults:

  • Magnetic resonance angiography (MRA)

Gadoversetamide Dose in Adults

Dose in the CNS or liver imaging:

• IV: 0.1 mmol/kg (0.2 mL/kg)

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• An agent that uses gadolinium as a contrast agent could cross the placenta
• Contrast agents containing gadolinium-based elements in pregnancy should not be used.
• Gadolinium-based contrast agents with MRI may be considered for pregnant women if it is expected that it will significantly improve diagnostic performance and improve fetal or maternal outcomes.
• It is also important to consider only using a contrast agent if it is necessary to obtain the required information from an MRI study. This should not be delayed after delivery.
• Low-risk agents for nephrogenic Fibrosis should only be given at the lowest dose.

Use gadoversetamide in lactation

• Breast milk may contain gadolinium-based, contrast agents.
• Breastfeeding may be continued after use due to the low expected excretion of breast milk and the low absorption by infants' GI tract.
• Contrast media can theoretically alter milk's taste. It can also be given to mothers who have temporarily stopped breastfeeding. 
• They can then breastfeed and then discard breast milk from either one or both breasts for between 12-24 hours.
• They are able to store and pump milk prior to the procedure, then bottle-feed any milk that was stored.
• The manufacturer recommends that you stop breastfeeding immediately and throw away breast milk for at least 72 hours after administration.

Dose in Kidney Disease:

• GFR ≥30 mL/minute/1.73 m²:

  • The manufacturer's labeling does not include any dosage adjustments.
  • This has not been tested. As renal function declines, the risk of developing NSF increases.

• GFR <30 mL/minute/1.73 m²:

  • Contraindicated.

  • Hemodialysis

    • Patients already on hemodialysis should be given prompt hemodialysis (eg within three hours) if they are exposed. The data shows that hemodialysis increases gadolinium elimination, with gadolinium excretory rate averages of 78%, 96%, and 99%, respectively.

  • Peritoneal dialysis

    • It is possible to clear gadolinium less efficiently.

Dose in Liver disease:

The manufacturer's labeling does not contain any dosage adjustments; the pharmacokinetics of the drug is not significantly modified.

Common Side Effects of Gadoversetamide Include:

• Local:

  • Discomfort at the injection site
  • Injection site reaction

• Cardiovascular:

  • Vasodilatation

• Central Nervous System:

  • Headache
  • Dizziness
  • Paresthesia
  • Pain

• Gastrointestinal:

  • Dysgeusia
  • Nausea
  • Abdominal Pain
  • Diarrhea
  • Dyspepsia

• Neuromuscular & Skeletal:

  • Asthenia
  • Back Pain

• Respiratory:

  • Rhinitis

Contraindications to Gadoversetamide (OptiMARK):

• Chronic, severe kidney disease (GFR >30 mL/minute/1.73m2);
• acute kidney injury;
• hypersensitivity gadolinium, versetamide or any other component of the formulation.

Canadian labeling: Additional contraindications that are not found in the US labeling 

• Preterm neonates as young as 4 weeks due to impaired renal function

Warnings and precautions

• Gadolinium retention:

  • Gadolinium can be stored in the brain, skin, brain and other organs for months to years (kidneys liver, spleen). 
  • The longest retention and highest concentration of gadolinium is found in bone.
  • Linear GBCs such as gadodiamide and gadoversetamide, and gadoxetate dimeglumine have a higher retention than macrocyclic ones like gadoterate and gadobutrol.
  • Patients with impaired renal function have had their lives made more difficult by the pathologic and clinical consequences of gadolinium accumulation in their skin and other parts. 
  • However, they have rarely experienced skin problems not associated with renal impairment.
  • Gadolinium retention in the brain and in patients with normal renal function has not been shown to have any adverse effects.
  • Gadolinium retention may be more common in patients with normal renal function. 
  • Patients who need multiple lifetime doses, pregnant patients or children, as well as patients with inflammatory conditions, are at greater risk.
  • Reducing repetition in GBCA imaging studies.

• Hypersensitivity reactions

  • Hypersensitivity (rarely) can occur. It is possible to develop hypersensitivity (rare) during use.
  • Sometimes, delayed reactions can occur within hours after administration.
  • Hypersensitivity reactions may occur in patients who have suffered from bronchial asthma, allergic reactions or other symptoms in the past. Be careful.

• Nephrogenic systemic Fibrosis: [US Boxed Warn]

  • Gadolinium-based contrast agent may pose a greater risk to patients with impaired renal function. GBCA enhanced image should not be used unless absolutely necessary to diagnose.
  • Patients with severe, acute renal disease or acute kidney injury (GFR 30mL/minute/1.73m2) are not recommended.
  • Patients with moderate or chronic renal disease have a lower risk (GFR 30 to 60 mL/minute/1.73m2) than patients with milder chronic renal disease (GFR 60 mL/minute/1.73m2).
  • NSF can be fatal and affects skin, muscles, internal organs, and skin.
  • All patients must be tested for kidney disease before administering medication.
  • Patients at high risk of NSF should not exceed the recommended dose. They should also allow sufficient time (ie, several half-lives) for elimination before re-administration. It is better to avoid re-administration.
  • Consider prompt hemodialysis for patients on hemodialysis.

• Renal impairment

  • Patients with severe kidney impairment should be cautious.
  • Patients with renal impairment have experienced a dose-dependent worsening or acute renal failure, usually within 48 hours of administration.
  • Assess the renal function in patients with severe kidney disease before using. Consider following-up monitoring.

Monitoring parameters:

• Hypersensitivity signs (during and after the procedure);
• renal function (prior and/or long-term monitoring) of signs and symptoms (eg., burning, itching and swelling, hardening and/or tightening skin, joint stiffness and deep hip or rib-bone pain, muscle weakness and limited range of motion, and/or yellowed/raised areas on the whites of the eyes).

How to administer Gadoversetamide (OptiMARK)?

IV:

• Give a rapid bolus injection of 1 to 2 milliliters per second. 
• To ensure full injection of the medium, flush the line with NS 5mL. 
• Within 60 minutes after injection, imaging should be complete.

Mechanism of action of Gadoversetamide (OptiMARK):

• Gadoversetamide, a paramagnetic compound, is formed through the chelation gadolinium/versetamide.
• An external magnetic field can induce a strong local magnetic field in the tissues.
• The local magnetism causes water protons to be disrupted in the area, resulting in a change of proton density and spin characteristics that can be detected using the imaging device.

Distribution:

• V: 162 +-25 mL/kg. It does not cross the intact blood-brain barrier. Distribution half-life: 13.3 +-6.8 minutes

Half-life elimination:

• 103.6 +- 19.5 mins; extended in renal impairment

Excretion

• Urine (96% in 24 hours)

International Brand Names of Gadoversetamide:

• OptiMARK
• Gadamide
• OptiMark
• Optimark

Gadoversetamide Brand Names in Pakistan:

No Brands Available in Pakistan.