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Optimark

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OptiMARK

WARNINGS

Nephrogenic Systemic Fibrosis (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m²) as well as patients with acute kidney injury. Do not administer OptiMARK™ to these patients. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30 -59 mL/min/1.73m²) and little, if any, for patients with chronic, mild kidney disease (GFR 60 -89 mL/min/1.73m²). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following OptiMARK™ administration to Mallinckrodt Inc. (1-800-778-7898) or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).

Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. 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.

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. 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 (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Acute Kidney Injury (AKI)

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.

Hypersensitivity Reactions

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. If a reaction occurs, stop OptiMARK™ and immediately begin appropriate therapy including resuscitation. Patients with a history of allergy, drug reactions or other hypersensitivity-like disorders should be closely observed during the procedure and for several hours after drug administration (see PRECAUTIONS, General).

Deoxygenated sickle erythrocytes have been shown in vitro studies to align perpendicular to a magnetic field; this may result in vaso-occlusive complications in vivo. The enhancement of magnetic moment by gadoversetamide may potentiate sickle erythrocyte alignment. OptiMARK™ Injection in patients with sickle cell anemia and other hemoglobinopathies has not been studied.

The potential risk of hemolysis after injection of OptiMARK™ Injection in patients with other hemolytic anemias has not been studied.

Patients with history of allergy, renal insufficiency or drug reaction should be observed for several hours after drug administration (see PRECAUTIONS).

PRECAUTIONS

General

Diagnostic procedures that involve the use of contrast agents should be carried out under direction of a physician with the prerequisite training and a thorough knowledge of the procedure to be performed.

Personnel trained in resuscitation techniques and resuscitation equipment should be available.

The possibility of a reaction, including serious, life threatening, fatal, anaphylactoid or cardiovascular reactions or other idiosyncratic reactions should always be considered especially in those patients with a known clinical hypersensitivity, a history of asthma, or other respiratory disorders (see ADVERSE REACTIONS).

Some paramagnetic contrast agents may impair the visualization of existing lesions, which are seen on the unenhanced, non-contrast MRI. This may be due to effects of the paramagnetic contrast agent, imaging parameters, misregistration, etc. CAUTION SHOULD BE EXERCISED WHEN A CONTRAST ENHANCED INTERPRETATION IS MADE IN THE ABSENCE OF A COMPANION UNENHANCED MRI.

Since gadoversetamide is cleared from the body by glomerular filtration, caution should be exercised in patients with impaired renal function (GFR ≥ 30 and < 90 mL/min/1.73m²). Dose adjustments in renal impairment have not been studied. OptiMARK™ Injection has been shown to be removed from the body by hemodialysis (see CLINICAL PHARMACOLOGY, Elimination and Special Populations, Renal Insufficiency).

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of gadoversetamide. The results of the following genotoxicity assays were negative: Salmonella/E. Coli reverse mutation (Ames) assay, mouse lymphoma mutagenesis assay, and the in vivo mammalian micronucleus assay. The in vitro CHO chromosome aberration assay without metabolic activation was positive.

OptiMARK™ Injection administered to rats in a fertility study was shown to have irreversible reduction and degeneration of spermatocytes in testes and epididymides, and impaired male fertility, following intravenous doses of 2.0 mmol/kg/day (4 times the human dose based on body surface area) for 7 weeks. These effects were not observed at 0.5 mmol/kg/day (1 times the human dose based on a body surface area).

In a separate 28-day repeat dose study in rats, OptiMARK™Injection was shown to have irreversible reduction of male reproductive organ weights, degeneration of the germinal epithelium of the testes, presence of germ cells in the epididymides, and reduced sperm count following daily intravenous doses of 3.0 mmol/kg/day (6 times the human dose based on body surface area). These effects were not observed at 0.6 mmol/kg/day (1 times the human dose based on surface area). These effects were not observed in similar studies conducted in dogs.

In a single dose study in rats, OptiMARK™ Injection did not produce adverse effects on the male reproductive system 24 hours and 14 days after intravenous administration of 0.5 to 15 mmol/kg (1 to 25 times the human dose based on body surface area).

Pregnancy Category C

OptiMARK™ Injection reduced neonatal weights from birth through weaning at maternal doses of 0.5 mmol/kg/day (1 times the human dose based on body surface area) for 5 weeks (including gestation) and paternal doses of 0.5 mmol/kg/day for 12 weeks. This effect was not observed at 0.1 mmol/kg (0.2 times the human dose based on a body surface area). Maternal toxicity was not observed at any dose.

OptiMARK™ Injection caused a reduced mean fetal weight, abnormal liver lobation, delayed ossification of sternebrae, and delayed behavioral development (startle reflex and air rights reflex) in fetuses from female rats dosed with 4.9 mmol/kg/day (10 times the human dose based on body surface area) on days 7 through 17 of gestation. These effects were not observed at 0.7 mmol/kg/day (1 times the human dose based on body surface area). Maternal toxicity was observed at 4.9 mmol/kg/day.

OptiMARK™ Injection caused forelimb flexures and cardiovascular changes in fetuses from female rabbits dosed with 0.4 and 1.6 mmol/kg/day (respectively, 1 and 4 times the human dose based on body surface area) on gestation days 6 through 18. The cardiovascular changes were malformed thoracic arteries, a septal defect, and abnormal ventricle. These effects were not observed at 0.1 mmol/kg/day (0.3 times the human dose based on body surface area). Maternal toxicity was not observed at any dose.

Adequate and well-controlled studies were not conducted in pregnant women. OptiMARK™ Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

153Gd-labeled OptiMARK™ Injection was excreted in the milk of lactating rats receiving a single intravenous dose of 0.1 mmol/kg. Women should discontinue nursing and discard breast milk up to 72 hours after OptiMARK™ Injection administration (see CLINICAL PHARMACOLOGY, Distribution).

Pediatric Use

The safety and effectiveness of OptiMARK™ Injection in pediatric patients has not been established. Pediatric patients may be particularly vulnerable to adverse GBCA reactions due to renal immaturity and/or unrecognized renal insufficiency.

Last reviewed on RxList: 9/9/2013
This monograph has been modified to include the generic and brand name in many instances.

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