gadoversetamide (OptiMARK)

Dosing and uses of OptiMARK (gadoversetamide)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution

• 330.9 mg/mL (0.5mmol/mL)

 

CNS or Liver MRI

Indicated for use with MRI in abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues; also indicated to enhance visualization of lesions with abnormal vascularity in the liver

0.2 mL/kg (0.1 mmol/kg) IV; infuse peripherally at rate of 1-2 mL/sec

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

OptiMARK (gadoversetamide) adverse (side) effects

1-10%

Headache (9.4%)

Vasodilation (6.4%)

Dizziness (3.7%)

Nausea (3.2%)

Paresthesia (2.2%)

Diarrhea (1.9%)

Abdominal pain (1.8%)

Rhinitis (2%)

Injection site reaction (2%)

Back pain (1%)

Dyspepsia (1%)

 

<1%

Seizures

Amblyopia

Anorexia

Cough

Diplopia

Dry skin

Dystonia

Flatulence

Hyponatremia

Neck pain

Pallor

Parosmia

Rash

Seizure

 

Postmarketing Reports

Seizures

Nephrogenic systemic fibrosis

Hypersensitivity reactions including bronchospasm and laryngeal/pharyngeal edema

 

Warnings

Black box warnings

Risk for nephrogenic systemic fibrosis (NSF) with acute or chronic renal insufficiency (GFR <30 mL/min/1.73m²), hepatorenal syndrome, or acute renal insufficiency resulting from perioperative liver transplant

NSF affects internal organs, skin, and muscle and can be fataL

Only use if essential and MRI cannot not provide appropriate diagnostic image

Screen for renal dysfunction, do not exceed recommended dosage, and allow for drug elimination before giving subsequent doses

 

Contraindications

Severe hypersensitivity reactions including anaphylaxis reported

Acute kidney disease or chronic, severe kidney disease (ie, GFR<30 mL/min/1.73m²); use associated with increased risk for nephrogenic systemic fibrosis (NSF)

 

Cautions

Screen all patients for renal dysfunction

Acute renal failure has occurred in patients with pre-existing renal insufficiency; use the lowest necessary dose and evaluate renal function

Nephrogenic systemic fibrosis (NSF) reported in patients with impaired elimination; higher than recommended dosing or repeat dosing appears to increase the risk

Anaphylactoid and other serious hypersensitivity reactions including fatal reactions reported, particularly in patients with history of allergy or drug reactions; monitor patients closely for need of emergency cardiorespiratory support

Thrombotic syndromes, anemia, hepatic/renal impairment, hemoglobinopathies (sickle cell anemia)

Risk of hypotension

Caution with hepatic impairment

History of grand mal seizure

Brain deposits

• 7/28/2015: FDA is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for MRI
• Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo ≥4 contrast MRI scans, long after the last administration
• It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects
• Early data in rat studies show that linear GBCAs are more prone to dissociation into free gadolinium and demonstrate greater brain deposition than macrocyclic GBCAs, which are less prone to dissociation

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Excreted in milk of lactating rats; official prescribing information advises women to discontinue breastfeeding and discard milk for 72 hr after receiving gadoversetamide

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of OptiMARK (gadoversetamide)

Mechanism of action

Nonionic gadolinium contrast agent; paramagnetic ion that develops a magnetic moment when placed in magnetic field that can disrupt water protons in the vicinity leading to an increase in signal intensity (brightness) of tissues

 

Pharmacokinetics

Half-Life: 103.6 minutes (elimination)

Vd: 162 mL/kg

Excretion: Urine (96%)  

Hemodialysis: 98% removed by hemodialysis over 3 sessions within 120 hr