OptiMARK

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

• If you have an allergy to gadolinium, versetamide, or any other part of OptiMARK.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have kidney problems.
• If you are breast-feeding. Do not breast-feed for at least 72 hours after getting this medicine.

This is not a list of all drugs or health problems that interact with OptiMARK.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

 MRI of Central Nervous System (CNS)

Optimark is indicated for use with magnetic resonance imaging (MRI) in patients with abnormal blood-brain barrier or abnormal vascularity of the brain, spine and associated tissues.

MRI of Liver

Optimark is indicated for use with MRI to provide contrast enhancement and facilitate visualization of lesions with abnormal vascularity in the liver of patients who are highly suspect for liver structural abnormalities on computed tomography.

Optimark is contraindicated in patients with:

• chronic, severe kidney disease (glomerular filtration rate, GFR <30 mL/min/1.73m2)
• acute kidney injury
• known hypersensitivity reactions to gadolinium, versetamide or any of the inert ingredients.

The following adverse reactions are discussed in greater detail in other sections of the prescribing information:

• Nephrogenic Systemic Fibrosis [see Contraindications (4), Boxed Warning and Warnings and Precautions (5.1)]
• Hypersensitivity reactions [see Contraindications (4) and Warnings and Precautions (5.3)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The adverse reactions described in this section were observed in a total of 1,309 subjects (24 healthy volunteers and 1,285 patients in clinical trials). Patients ranged in age from 12 to 85 years (mean age of 50 years) and 680 subjects (52%) were men. The ethnic distribution was 84% White, 9% Black, 3% Asian, and 4% other.

Overall, 460 subjects (35%) reported at least one adverse reaction. Most adverse reactions were mild or moderate in severity. The most commonly noted adverse reactions were: injection associated discomfort (26%), headache (9.4%), vasodilatation (6.4%), taste perversion (6.2%), dizziness (3.7%), nausea (3.2%), and paresthesia (2.2%). Table 2 lists adverse reactions reported in 1% or greater of patients.

The following adverse reactions occurred in less than 1% of the patients:

Body as a Whole:             allergic reaction, facial edema, fever, malaise, neck rigidity, neck pain, pelvic pain, increased sweating

Cardiovascular:                arrhythmia, chest pain, hypertension, hypotension, pallor, palpitation, syncope, tachycardia, vasospasm

Digestive:                        anorexia, constipation, dry mouth, dysphagia, eructation, increased salivation, thirst, vomiting

Metabolic and Nutritional: increased creatinine, edema, hypercalcemia

Musculoskeletal:              arthralgia, leg cramps, myalgia, spasm

Nervous System:              agitation, anxiety, confusion, diplopia, dystonia, hypertonia, hypesthesia, somnolence, tremor, vertigo

Respiratory System:         cough, dyspnea, laryngismus, pharyngitis, sinusitis, voice alteration

Skin and Appendages:     erythema multiforme, pruritus, rash, thrombophlebitis, urticaria

Special Senses:               parosmia, tinnitus

Urogenital:                       oliguria

Post-marketing Experience

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 (NSF)
• Hypersensitivity reactions including bronchospasm and laryngeal/pharyngeal edema
• Seizures

Nephrogenic Systemic Fibrosis

Instruct patients to inform their physician if they:

• have a history of kidney disease
• have recently received a GBCA

GBCAs increase the risk for NSF in patients with impaired elimination of the drugs. To counsel patients at risk for NSF:

• describe the clinical manifestations of NSF
• describe procedures to screen for the detection of renal impairment

Instruct the patients to contact their physician if they develop signs or symptoms of NSF following Optimark administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

Other

Instruct patients to inform their physician if they:

• are pregnant or breast feeding
• have a history of renal disease or heart disease, seizure, asthma or allergic respiratory diseases

This product is covered by U.S. Patent No. 5130120, 5137711, 5508388. The use of this product is covered by U.S. Patent No. 5130120 and 5137711.

Manufactured and Distributed by:
Liebel-Flarsheim Company LLC
Raleigh, NC 27616

Made in USA

MKR 1177Cb0816

Issued 08/16    

Sterile Solution

30 mL
NDC 0019-1177-31

Optimark™ 0.5mmol/mL
(gadoversetamide injection)

For Intravenous Injection Only

Dosage: See Package Insert.

Rx Only

MEDICATION AND FLUID PATHWAY ARE STERILE

OUTSIDE OF SYRINGE IS NOT STERILE

SINGLE DOSE UNIT, DISCARD UNUSED PORTION

PROTECT FROM LIGHT • PROTECT FROM FREEZING
Store at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature]

Manufactured by:

Liebel-Flarsheim Company LLC

8800 Durant Road

Raleigh, NC 27616

Made in USA

11630914

Applies to gadoversetamide: intravenous solution

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Change in taste.
• Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.