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DOTAREM® (gadoterate meglumine) Injection


  

For more information about DOTAREM®, please see the Full Prescribing Information and Medication Guide (also available: Spanish Version Medication Guide)

Dear Health Care Provider Letter- Gadolinium Retention. 

Dotarem® (gadoterate meglumine) Injection, is the first macrocyclic and ionic gadolinium-based contrast agent in the USA.

 

IMPORTANT SAFETY INFORMATION

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

  • The risk for NSF appears highest among patients with:
    • Chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or
    • Acute kidney injury.
  • Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age > 60 years, hypertension, diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.
  • For patients at highest risk for NSF, do not exceed the recommended DOTAREM dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.--------------------------------------------------------------

Indications and Usage

DOTAREM® (gadoterate meglumine) injection is a prescription gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

Contraindications

History of clinically important hypersensitivity reactions to DOTAREM.

Warnings and Precautions

  • Hypersensitivity Reactions: Anaphylactic and anaphylactoid reactions have been reported with DOTAREM, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died. In most cases, initial symptoms occurred within minutes of DOTAREM administration and resolved with prompt emergency treatment.
  • Before DOTAREM administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to DOTAREM.
  • Administer DOTAREM only in situations where trained personnel  and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation.
  • Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by brain, skin, kidney, liver and spleen. The duration of retention also varies by tissue, and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs.
  • Consequences of gadolinium retention in the brain have not been established. Adverse events involving multiple organ systems have been reported in patients with normal renal function without an established causal link to gadolinium retention.
  • Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging.
  • Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of DOTAREM. Extravasation into tissues during DOTAREM administration may result in tissue irritation.

Adverse Reactions

  • The most common adverse reactions associated with DOTAREM in clinical trials were nausea, headache, injection site pain, injection site coldness and rash.
  • Serious adverse reactions in the Postmarketing experience have been reported with DOTAREM. These serious adverse reactions include but are not limited to: arrhythmia, cardiac arrest, respiratory arrest, pharyngeal edema, laryngospasm, bronchospasm, coma and convulsion.

Use in Specific Populations

  • Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive. Advise pregnant women of the potential risk of fetal exposure to GBCAs.
  • Lactation: There are no data on the presence of gadoterate in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk. 
  • Pediatric Use: The safety and efficacy of DOTAREM at a single dose of 0.1 mmol/kg has been established in pediatric patients from birth (term neonates ≥ 37 weeks gestational age) to 17 years of age based on clinical data. The safety of DOTAREM has not been established in preterm neonates. No cases of NSF associated with DOTAREM or any other GBCA have been identified in pediatric patients age 6 years and younger.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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OPTIMARK® (gadoversetamide) Injection


For more information about OPTIMARK®, please see the Full Prescribing Information and Medication Guide.

Dear Health Care Provider Letter - Gadolinium Retention.


 IMPORTANT SAFETY INFORMATION

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

  • Do not administer Optimark to patients with:
    • chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or
    • Acute kidney injury
  • Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age > 60 years, hypertension, diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.

Do not exceed the recommended Optimark dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.------------------------------------------------

Indications and Usage

Optimark® (gadoversetamide) injection is a prescription gadolinium-based paramagnetic contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in patients with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. It is also indicated for use with MRI to provide contrast enhancement and facilitate visualization of lesions with abnormal vascularity in the liver in patients who are highly suspect for liver structural abnormalities on computed tomography.

Contraindications

Optimark is also contraindicated in patients with:

  • Known hypersensitivity reactions to gadolinium, versetamide or any of the inert ingredients.

Warnings and Precautions

  •  Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs (<30 mL/min/1.73m2) and patients with acute kidney injury. Do not administer Optimark to these patients.
  • Screen patients for acute kidney injury and other conditions that may reduce renal function. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronic kidney disease (e.g., age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing.
  • When administering Optimark, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug prior to any re-administration. Record the specific GBCA and the dose administered to a patient.
  • Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by brain, skin, kidney, liver and spleen. The duration of retention also varies by tissue, and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs.
  • Consequences of gadolinium retention in the brain have not been established. Adverse events involving multiple organ systems have been reported in patients with normal renal function without an established causal link to gadolinium retention.
  • Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging.
  • Severe hypersensitivity reactions including anaphylaxis have been observed with administration of gadolinium products including Optimark. Patients with a history of allergy, drug reactions or other hypersensitivity-like disorders may be at greater risk and should be closely observed during the procedure and for several hours after drug administration.
  • Interference by Optimark in the measurements of serum iron, copper and zinc has been observed.
  • In the presence of Optimark, the Ortho-cresophthalin complexone (OCP) produces an erroneous, low value for serum calcium. The magnitude of this artifact is proportional to the concentration of Optimark in the blood, and accurate values can be obtained approximately 90 minutes following injection. In patients with renal insufficiency, clearance of Optimark is slowed and the interference with calcium determination by OCP is prolonged.

Adverse Reactions

  • The following adverse reactions have been identified during post-approval use of Optimark. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Optimark.
    • Nephrogenic Systemic Fibrosis
    • Hypersensitivity reactions including bronchospasm and laryngeal/pharyngeal edema
    • Seizures
  • Common adverse reactions were injection associated discomfort, headache, vasodilatation, taste perversion, dizziness, nausea, and paresthesia.

Use in Specific Populations

  • Pregnancy: GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive. Instruct patients to inform their physician if they are pregnant.
  • Nursing Mothers: Women should discontinue nursing and discard breast milk up to 72 hours after Optimark injection. Instruct patients to inform their physician if they are breast feeding.
  • Pediatric Use: The safety and effectiveness of Optimark injection in pediatric patients have not been established. Pediatric patients may be particularly vulnerable to adverse GBCA reactions due to renal immaturity and/or unrecognized renal insufficiency.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.fda.gov/metwatch or call 1-800-FDA-1088.

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LIPIODOL® (ethiodized oil) Injection


For more information about LIPIODOL®, please see the Full Prescribing Information.

Dear Health Care Provider Letter - Temporary Importation.

Lipiodol® (ethiodized oil) Injection is approved in the US for selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC), lymphography in adult and pediatric patients, and hysterosalpingography in adults and is the only oil-based contrast agent in the USA.


IMPORTANT SAFETY INFORMATION

WARNING: FOR INTRALYMPHATIC, INTRAUTERINE AND SELECTIVE HEPATIC INTRA-ARTERIAL USE ONLY
Pulmonary and cerebral embolism can result from inadvertent intravascular injection or intravasation of Lipiodol. Inject Lipiodol slowly with radiologic monitoring; do not exceed recommended dose.

Indication and Usage

LIPIODOL® (ethiodized oil) injection is a prescription oil-based radio-opaque contrast agent indicated for:

  • hysterosalpingography in adults
  • lymphography in adult and pediatric patients
  • selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma (HCC)

LIPIODOL® is contraindicated in patients with hypersensitivity to LIPIODOL®, hyperthyroidism, traumatic injuries, recent hemorrhage or bleeding.

  • LIPIODOL® Hysterosalpingography is contraindicated in pregnancy, acute pelvic inflammatory disease, marked cervical erosion, endocervicitis and intrauterine bleeding, in the immediate pre-or postmenstrual phase, or within 30 days of curettage or conization.
  • LIPIODOL® Lymphography is contraindicated in patients with a right to left cardiac shunt, advanced pulmonary disease, tissue trauma or hemorrhage advanced neoplastic disease with expected lymphatic obstruction, previous surgery interrupting the lymphatic system, radiation therapy to the examined area.
  • LIPIODOL® Selective Hepatic Intra-arterial Injection is contraindicated in the presence of dilated bile ducts unless external biliary drainage was performed before injection.

Warnings and Precautions

  • Pulmonary and cerebral embolism may occur immediately or after a few hours to days from inadvertent systemic vascular injection or intravasation of LIPIODOL®. Avoid use in patients with severely impaired lung function, cardiorespiratory failure or right-sided cardiac overload.
  • Anaphylactoid and anaphylactic reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following LIPIODOL® administration. Avoid use in patients with a history of sensitivity to other iodinated contrast agents, bronchial asthma or allergic disorders because of an increased risk of a hypersensitivity reaction to LIPIODOL®.
  • LIPIODOL® hepatic intra-arterial administration can exacerbate chronic liver disease.
  • Iodinated contrast media can affect thyroid function because of the free iodine content and can cause hyperthyroidism or hypothyroidism in predisposed patients.

Adverse Reactions

  • Hysterosalpingography - Abdominal pain, foreign body reactions, exacerbation of pelvic inflammatory disease.
  • Lymphography - Cardiovascular collapse, lymphangitis, thrombophlebitis, edema or exacerbation of preexisting lymphedema, delayed healing at the site of incision.
  • Selective Hepatic Intra-arterial Injection - Fever, abdominal pain, nausea, and vomiting are the most common reactions; other reactions include hepatic ischemia, liver enzymes abnormalities, transitory decrease in liver function, liver decompensation and renal insufficiency. Procedural risks include vascular complications and infections.

Use in Specific Populations

  • Pregnancy: There are no adequate and well-controlled studies of LIPIODOL® (ethiodized oil) injection effects in pregnant women. It is not known whether LIPIODOL® can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. The use of LIPIODOL® during pregnancy causes iodine transfer which may interfere with the thyroid function of the fetus and result in brain damage and permanent hypothyroidism.
  • Lactation: LIPIODOL® is excreted in human milk. Avoid use of LIPIODOL® in a nursing woman because of risk of hypothyroidism in nursing infants. If breast feeding is continued the neonate's thyroid function should be monitored. 
  • Pediatric: For lymphography use a dose of minimum of 1 mL to a maximum of 6 mL according to the anatomical area to be visualized. Do not exceed 0.25 mL/kg. Administer the smallest possible amount of LIPIODOL® according to the anatomical area to be visualized.
  • Geriatric: There are no studies conducted in geriatric patients.
  • Renal Impairment: Prior to an intra-arterial administration of LIPIODOL® screen all patients for renal dysfunction by obtaining history and/or laboratory tests. Consider follow-up renal function assessments for patients with a history of renal dysfunction.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.fda.gov/medwatch or call 1-800-FDA-1088.