Gadobenate dimeglumine (MultiHance) is a gadolinium-based magnetic resonance contrast agent that is used during MR imaging of the central nervous system and renal angiography.

Gadobenate dimeglumine Uses:

• CNS imaging:

  • Magnetic resonance imaging (MRI) agent to visualize CNS lesions in adults and pediatric patients with an abnormal blood-brain barrier or abnormal vascularity in the spine, brain, and associated tissues

• Renal and aorto-ilio-femoral vasculature imaging:

  • Magnetic resonance angiography (MRA) agent to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease

Gadobenate dimeglumine Dose in Adults

Gadobenate dimeglumine Dose in the CNS imaging:

• IV: 0.1 mmol per kg (0.2 mL per kg)

Gadobenate dimeglumine Dose in Renal and aorto-ilio-femoral vasculature imaging:

• IV: 0.1 mmol per kg (0.2 mL per kg);
• calculate scan delay with test bolus (1 to 2 mL) or with automatic detection technique

Gadobenate dimeglumine Dose in Childrens

Note: Dosing presented in mL per kg and mmol per kg; use caution.

Gadobenate dimeglumine Dose in CNS magnetic resonance imaging:

• Infants and Children <2 years of age:

  • IV: 0.1 to 0.2 mL per kg (0.05 to 0.1 mmol per kg); may begin imaging immediately after administration.

• Children ≥2 years and Adolescents:

  • IV: 0.2 mL per kg (0.1 mmol per kg); may begin imaging immediately after administration.

Gadobenate dimeglumine Pregnancy Cateogry: C

• Contrast agents containing gadolinium may cross the placenta.
• Contrast agents containing gadolinium-based elements in pregnancy should not be used.
• Additionally, it is important to only consider using a contrast agent if the information required from an MRI study can't be obtained without it. This cannot be delayed until after delivery.
• If it is proven to significantly improve diagnostic performance, and is expected that it will improve fetal and maternal outcomes, a gadolinium-based contrast agents with MRI might be considered for pregnancy.
• Agents that pose a low risk of developing nephrogenic fibrosis are recommended to be administered at the lowest possible dose.

Gadobenate dimeglumine use during breastfeeding:

• Breast milk may contain gadolinium-based, contrast agents.
• Theoretically speaking, milk's taste could be affected if it contains contrast media.
• Women who choose to temporarily stop breastfeeding can express breast milk or discard it from one breast for 12-24 hours after administration of contrast media.
• They can store and pump milk before the procedure, then bottle-feed the milk stored during that time.
• Breastfeeding may continue after discontinuation due to the low expected excretion of breast milk and low absorption by infants' GI tract.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Gadobenate dimeglumine Dose in Kidney Disease:

Manufacturer's labeling doesn't provide any dosage adjustments; use with caution. The risk for NSF development increases as renal function decreases.

• Hemodialysis:

  • If administered to patients already receiving hemodialysis, consider prompt hemodialysis following exposure (eg, within 3 hours).
  • Data has shown hemodialysis enhances gadolinium elimination with average gadolinium excretory rates of 78 percent, 96 percent, and 99 percent in the first, second, and third hemodialysis sessions, respectively.

• Peritoneal dialysis:

  • Likely to be less efficient at clearing gadolinium. If unable to perform hemodialysis after the procedure, more frequent peritoneal dialysis cycles are suggested.

Dose in Liver disease:

The manufacturer's labeling doesn't provide any dosage adjustments.

Side Effects of Gadobenate dimeglumine:

• Central nervous system:

  • Feeling hot
  • Headache

• Gastrointestinal:

  • Nausea
  • Vomiting

• Local:

  • Injection site reaction

Contraindications to Gadobenate dimeglumine:

Hypersensitivity to gadobenate dimeglumine, any gadolinium based contrast agent or any component in the formulation

Warnings and precautions

• Arrhythmias:

  • Cardiac arrhythmias were observed. Patients with predisposing proarrhythmic conditions and concurrent proarrhythmic drug treatment should be cautious.
  • While QT changes compared with placebo were small (less than 5msec) and patients did not experience malignant arrhythmias in any way, numerically more patients experienced QT prolongation of 30-60msecs and >=61msecs in clinical trials compared to placebo.

• Extravasation:

  • Monitor infusion site.
  • Avoid extravasation.
  • Use Vesicant to ensure the proper placement of needles or catheters before and during administration.
  • Injection site reactions may include swelling, blistering and local pain.

• Gadolinium retention:

  • Gadolinium can be retained in bone, skin, and other organs for many months to years (kidneys, liver, spleen). The bone has the highest concentration and longest retention.
  • Linear GBCAs, such as gadodiamide, gadoversetamide, gadoxetate dimeglumine and gadobenate dimeglumine, have a higher retention rate than macrocyclic ones (gadoterate, gadobutrol and gadoteridol).
  • Patients with impaired renal function have had to deal with the clinical and pathologic consequences of gadolinium storage in their skin and other organs.
  • Rarely, however, have they experienced skin problems that were not related to renal impairment.
  • Patients with normal renal function may be more at risk of gadolinium retention.
  • These include patients who require multiple lifetime doses, pregnant or pediatric patients, as well as patients with inflammatory conditions.
  • Gadolinium retention in the brain and in patients with normal renal function has not been shown to have any adverse effects.
  • Minimize repetitive GBCA imaging studies.

• Hypersensitivity

  • Ensure that patients are monitored closely throughout and up to two hours after an infusion.
  • Begin immediate treatment if hypersensitivity develops
  • When needed, appropriate equipment (eg ventilator) as well as emergency medication (eg epinephrine), should be readily available.
  • Sometimes, delayed reactions can occur within hours after administration.
  • Anaphylactic and anaphylactic reactions (some fatal) can occur (with cardiovascular, respiratory or dermatologic involvement); symptoms usually occurred within minutes.
  • Patients who have had bronchial asthma or allergic reactions in the past may be at higher risk of developing hypersensitivity reactions. Be careful.

• Nephrogenic systemic Fibrosis: [US Boxed Warn]

  • Gadolinium-based contrast agent (GBCAs), increases the risk of nephrogenic fibrosis in patients with kidney impairment.
  • Avoid use unless GBCA enhanced imagery is absolutely necessary for diagnostic purposes.
  • Patients with severe, acute kidney disease or acute kidney injury are at greatest risk (glomerular filter rate [GFR] 30mL/minute/1.73m2).
  • NSF can cause fatal or debilitating systemic fibrosis. It affects the skin, muscles, and internal organs.
  • Screen all patients for acute kidney damage or other conditions that could affect renal function before administering medication.
  • GFR estimates should be done for patients at high risk of chronic declines in renal function (eg., patients over 60, chronic hypertension, and diabetes).
  • Patients at high risk of NSF should not be given more than the recommended dose. Allow for a sufficient time between administrations.
  • Patients with moderate or chronic renal disease have a lower risk of NSF (GFR 30 to 60 mL/minute per 1.73m2), and patients with milder chronic renal disease have a much lower GFR (GFR 60 mL/minute per 1.73m2).
  • Consider prompt initiation for patients on hemodialysis.
  • NSF should be reported to the manufacturer or Food and Drug Administration (FDA)

• Metabolic disorders

  • May prolong systemic exposure with some drugs (eg, anthracyclines, cisplatin ) due to competition for certain multispecific organic anion transporters (MOAT) especially in patients with decreased MOAT activity (eg, Dubin Johnson syndrome).

• Renal impairment

  • Patients with impaired renal function should be cautious.
  • Before using, evaluate the renal function of patients with kidney impairment; consider following-up monitoring.
  • Patients with acute renal impairment have experienced a dose-dependent worsening or acute renal failure after the administration of gadolinium agents. This usually occurs within 48 hours.

Gadobenate dimeglumine: Drug Interaction

Monitoring parameters:

• Signs of hypersensitivity (during and for several hours after the procedure);
• renal function (prior to administration);
• short- and long-term monitoring of signs and symptoms of nephrogenic systemic fibrosis (NSF) eg, itching, swelling, burning, hardening, and/or tightening of the skin, joint stiffness, deep hip or rib bone pain, muscle weakness, limited range of motion, and/or yellowed/raised spots on whites of the eye.
• Monitor infusion site.

How to administer Gadobenate dimeglumine?

IV:

• Administer a rapid IV bolus injection.
• To ensure complete injection of medium, flush line with NS after administration using at least 5 mL (for CNS imaging) or at least 20 mL (for renal or aorto-ilio-femoral vasculature imaging).
• Do not administer other medications in the same IV line.
• May begin imaging immediately after administration.
• It is a vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management:

• If extravasation occurs, stop infusion immediately and disconnect; remove needle/cannula; elevate extremity.
• Aspiration of extravasated contrast media is not recommended.
• Information conflicts regarding the use of hyaluronidase; other sources suggest its utility in extravasation management; the American College of Radiology (ACR) Manual on Contrast Media does not recommend hyaluronidase in the management of contrast media extravasation.
• If using hyaluronidase: Intradermal or SubQ:
  • Inject a total of 1 to 1.7 mL (15 units/mL) as 5 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 5 separate 1 mL injections around the extravasation site has also been used successfully.

Mechanism of action of Gadobenate dimeglumine:

• Gadobenate dimeglumine is a gadolinium-containing paramagnetic agent.
• Exposed tissues are subject to a strong local magnetic field when exposed to an external magnetic force.
• The local magnetism causes water protons to be disrupted in the area, which results in a change of proton density and spin characteristics that can be detected using an imaging device.

Metabolism:

• After injection, dimeglumine and gadobenate dissociate.
• Pharmacokinetics are based upon gadobenate.
• There is no biotransformation of gadobenate.

Half-life elimination:

• Distribution half-life:
  • Children 2 to 5 years: 0.13 ± 0.08 hours (Pirovano 2015)
  • Adults: 0.084 ± 0.012 to 0.605 ± 0.072 hours (Spinazzi 1999)
• Elimination half-life:
  • Normal renal function:
    • Children 2 to 5 years: 1.22 ± 0.24 hours (Pirovano 2015)
    • Adults: 1.2 ± 0.09 to 1.96 ± 0.16 hours (Spinazzi 1999)
  • CrCl 30 to less than 60 mL/minute: 6.1 ± 3 hours
  • CrCl 10 to less than 30 mL/minute: 9.5 ± 3.1 hours
  • End-stage renal disease (ESRD) (without dialysis): 42.4 ± 24.4 hours

Excretion:

• Urine (78 percent  to 96 percent );
• feces (0.6 percent  to 4 percent )

International Brand Names of Gadobenate dimeglumine:

• mr-lux
• Multihance
• MultiHance

Gadobenate dimeglumine Brand Names in Pakistan:

There is no brand available in Pakistan.