gadoteridol (Rx)

1-10%

Nausea (1.4%)

<1%

Dysgeusia (0.9%)

Headache (0.7%)

Dizziness (0.4%)

Urticaria (0.4%)

<0.4%

• General disorders and administration site conditions: Asthenia, chest discomfort, facial edema, feeling hot, injection site coldness, injection site erythema, injection site pain, injection site warmth, pain, pyrexia
• Cardiac: Angina pectoris, palpitations, atrioventricular block first degree
• Ear and labyrinth disorders: Ear discomfort, tinnitus
• Eye disorders: Eye pruritus, lacrimation increased
• Gastrointestinal disorders: Abdominal discomfort, abdominal pain, diarrhea, dry mouth, gingival pain, oral pruritus, swollen tongue, vomiting
• Infections and infestations: Gingivitis, rhinitis
• Investigations: Alanine aminotransferase increased, aspartate aminotransferase increased, blood chloride increased, blood pressure immeasurable, blood urea decreased, hemoglobin decreased, heart rate increased
• Metabolism and nutrition disorders: Decreased appetite, hypoglycemia
• Musculoskeletal and connective tissue disorders: Back pain, musculoskeletal stiffness
• Nervous system disorders: Formication, hypoesthesia, hypokinesia, lethargy, loss of consciousness, migraine, paresthesia, presyncope, seizure, syncope, taste disorder
• Psychiatric disorders: Anxiety, mental status changes
• Respiratory, thoracic, and mediastinal disorders: Cough, dry throat, dyspnea, nasal discomfort, throat irritation
• Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritus, rash, rash morbilliform
• Vascular disorders: Flushing, hypotension, peripheral coldness, vascular rupture, vasodilatation, vasospasm

Postmarketing Reports

General disorders and administration site conditions: Fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems

Cardiac disorders: Cardiac arrest, bradycardia, hypertension

Immune system disorders: Hypersensitivity/anaphylactoid reactions including cardiac arrest, cyanosis, pharyngeal edema, laryngospasm, bronchospasm, angioedema, cough, sneezing, conjunctivitis, eyelid edema, hyperhidrosis, urticaria

Nervous system disorders: Coma, loss of consciousness, vasovagal reaction, tremor

Respiratory, thoracic and mediastinal disorders: Respiratory arrest, pulmonary edema

Renal and urinary system disorders: Acute renal failure

Contraindications

Hypersensitivity

Cautions

Caution in hyperthyroidism, pheochromocytoma, renal/hepatic impairment

Therapy in patients with sickle cell anemia not studied

Screen patients for kidney disease before use and monitor renal function afterward; nephrogenic systemic fibrosis (NSF) associated with use of gadolinium contrast media in patients with kidney disease; do not exceed recommended dose (see Black Box Warnings)

Gadolinium retention

• Gadolinium is retained for months or years in several organs
• Highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (eg, brain, skin, kidney, liver, and spleen)
• Duration of retention also varies by tissue and is longest in bone
• Patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions are at higher risk of gadolinium retention

• Brain deposits

  • FDA investigated the risk of brain deposits following repeated use of GBCAs for MRI in 2015
  • 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
  • As of 2017, the FDA review had not identified adverse health effects from gadolinium retained in the brain after the use of GBCAs MRI; all GBCAs may be associated with some gadolinium retention in the brain and other body tissues
  • 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

Hypersensitivity reactions

• Anaphylactic and anaphylactoid reactions reported, involving cardiovascular, respiratory, and/or cutaneous manifestations
• Some patients experienced circulatory collapse and died; in most cases, initial symptoms occurred within minutes of administration and resolved with prompt emergency treatment
• Prior to administration, ensure availability of trained personnel and medications to treat hypersensitivity reactions
• Consider risk for hypersensitivity reactions, especially in patients with a history of hypersensitivity reactions or a history of asthma or other allergic disorders; if such a reaction occurs, stop drug and immediately begin appropriate therapy
• Observe patients for signs and symptoms of a hypersensitivity reaction during and for up to 2 hours after therapy administration

Pregnancy

GBCAs cross the placenta and result in fetal exposure and gadolinium retention

Human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive

Estimated background risk of major birth defects and miscarriage for the indicated population is unknown

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes

Animal data

• In animal reproduction studies in rats, drug doubled the incidence of post-implantation loss at up to 16 times recommended human dose (RHD); there were no adverse developmental effects observed in rabbits with intravenous administration of gadoteridol during organogenesis at doses up to 19 times the recommended human dose of 0.1 mmol/kg

Lactation

There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production; however, published lactation data on other GBCAs indicate that 0.01 to 0.04% of maternal gadolinium dose is present in breast milk and there is limited GBCA gastrointestinal absorption in breast-fed infant; drug is present in rat milk

Developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant or from underlying maternal condition

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.

Mechanism of Action

Paramagnetic agent; exposure to external magnetic field in gadopentetate may induce a large magnetic field. The local magnetism may change proton density and spin characteristics, which it is then detected by the imaging device

Pharmacokinetics

Half-Life: 1.5 hr

Vd: 204 mL/kg

Excretion: Urine (~94%)

IV Administration

Do not administer the solution if it is discolored or particulate matter is present Concurrent medications or parenteral nutrition should not be physically mixed with contrast agents and should not be administered in the same IV line because of the potential for chemical incompatibility

Flush IV line with at least 5 mL 0.9% NaCl immediately after gadoteridol injection to ensure complete administration

Imaging procedures should be completed within 1 hr

Vials are intended only for single-dose administration

Administer immediately after opening and discard any unused product

Administer by IV bolus or rapid infusion