Omniscan

OMNISCAN (gadodiamide) Injection is the formulation of the gadolinium complex of diethylenetriamine pentaacetic acid bismethylamide, and is an injectable, nonionic extracellular enhancing agent for magnetic resonance imaging. OMNISCAN is administered by intravenous injection.

OMNISCAN is provided as a sterile, clear, colorless to slightly yellow, aqueous solution. Each 1 mL contains 287 mg gadodiamide and 12 mg caldiamide sodium in Water for Injection. The pH is adjusted between 5.5 and 7.0 with hydrochloric acid and/or sodium hydroxide. OMNISCAN contains no antimicrobial preservative. OMNISCAN is a 0.5 mol/L solution of aqua[5,8-bis(carboxymethyl)11-[2-(methylamino)-2-oxoethyl]-3-oxo-2,5,8,11-tetraazatridecan-13-oato (3-)-N5, N8, N11, O3, O5, O8, O11, O13] gadolinium hydrate, with a molecular weight of 573.66 (anhydrous), an empirical formula of C16H28GdN5O9•xH2O, and the following structural formula:

Pertinent physicochemical data for OMNISCAN are noted below:

PARAMETER

OMNISCAN has an osmolality approximately 2.8 times that of plasma at 37°C and is hypertonic under conditions of use.

Gadodiamide is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRI.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

Gadodiamide can cause unusual results with certain medical for 12 to 24 hours after your MRI. Tell any doctor who treats you that you have received gadodiamide.

Since gadodiamide is used only during your MRI, you will not be on a dosing schedule.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

This medication can harm the kidneys in certain people, and this effect may be increased if you also use other medicines harmful to the kidneys. Many other drugs (including some over-the-counter medicines) can harm your kidneys. You may need dose adjustments or special tests if you have recently used any of these medications, such as:

• lithium (Eskalith, Lithobid);

• methotrexate (Rheumatrex, Trexall);

• pain or arthritis medicines such as aspirin (Anacin, Excedrin), acetaminophen (Tylenol), ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;

• medicines used to treat ulcerative colitis, such as mesalamine (Pentasa) or sulfasalazine (Azulfidine);

• medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune) or tacrolimus (Prograf);

• IV antibiotics such as amphotericin B (Amphotec, AmBisome, Abelcet), amikacin (Amikin), bacitracin (Baci IM), capreomycin (Capastat), gentamicin (Garamycin), kanamycin (Kantrex), streptomycin, or vancomycin (Vancocin, Vancoled);

• antiviral medicines such as acyclovir (Zovirax), adefovir (Hepsera), cidofovir (Vistide), foscarnet (Foscavir), ganciclovir (Cytovene), valacyclovir (Valtrex), or valganciclovir (Valcyte); or

• cancer medicine such as aldesleukin (Proleukin), carmustine (BiCNU, Gliadel), cisplatin (Platinol), ifosfamide (Ifex), oxaliplatin (Eloxatin), streptozocin (Zanosar), or tretinoin (Vesanoid).

There may be other drugs that can affect gadodiamide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

In the U.S.

• Omniscan

Available Dosage Forms:

• Solution

Therapeutic Class: Radiological Non-Ionic Contrast Media

Hypersensitivity Reactions

Anaphylactoid and anaphylactic reactions, with cardiovascular, respiratory and/or cutaneous manifestations, resulting in death have occurred. If such a reaction occurs, stop Omniscan Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after Omniscan Injection.

Nephrogenic Systemic Fibrosis

[see BOXED WARNING]

Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m2) and in patients with acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced MRI. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a gadolinium-based contrast agent in order to enhance the contrast agent's elimination. The usefulness of hemodialysis in the prevention of NSF is unknown.

Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a gadolinium-based contrast agent and the degree of renal function impairment at the time of exposure.

Post-marketing reports have identified the development of NSF following single and multiple administrations of gadolinium-based contrast agents. These reports have not always identified a specific agent. Where a specific agent was identified, the most commonly reported agent was gadodiamide (Omniscan™), followed by gadopentetate dimeglumine (Magnevist®) and gadoversetamide (OptiMARK®). NSF has also developed following sequential administrations of gadodiamide with gadobenate dimeglumine (MultiHance®) or gadoteridol (ProHance®). The number of post-marketing reports is subject to change over time and may not reflect the true proportion of cases associated with any specific gadolinium-based contrast agent.

The extent of risk for NSF following exposure to any specific gadolinium-based contrast agent is unknown and may vary among the agents. Published reports are limited and predominantly estimate NSF risks with gadodiamide. In one retrospective study of 370 patients with severe renal insufficiency who received gadodiamide, the estimated risk for development of NSF was 4% (J Am Soc Nephrol 2006;17:2359). The risk, if any, for the development of NSF among patients with mild to moderate renal insufficiency or normal renal function is unknown.

Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent prior to any readministration. [See Clinical Pharmacology (12.2) and Dosage and Administration (2)].

Acute Renal Failure

In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred, mostly within 48 hours of Omniscan Injection. The risk of renal failure may increase with increasing dose of gadolinium contrast. Use the lowest necessary dose of contrast and evaluate renal function in patients with renal insufficiency. Acute renal failure was observed in <1% of patients in Omniscan clinical studies [see Adverse Reactions (6.0)].

Omniscan is cleared by glomerular filtration. Hemodialysis also enhances Omniscan clearance [see Use in Specific Populations (8.5), (8.6)].

Not for Intrathecal Use

Inadvertent intrathecal use of Omniscan has occurred and caused convulsions, coma, sensory and motor neurologic deficits.

Impaired Visualization of Lesions Detectable with Noncontrast MRI

Paramagnetic contrast agents such as Omniscan might impair the visualization of lesions which are seen on the noncontrast MRI. This may be due to effects of the paramagnetic contrast agent, or imaging parameters. Exercise caution when Omniscan MRI scans are interpreted in the absence of a companion noncontrast MRI.

Laboratory Test Findings

Asymptomatic, transitory changes in serum iron have been observed. The clinical significance is unknown.

Omniscan interferes with serum calcium measurements with some colorimetric (complexometric) methods commonly used in hospitals, resulting in serum calcium concentrations lower than the true values. In patients with normal renal function, this effect lasts for 12-24 hours. In patients with decreased renal function, the interference with calcium measurements is expected to last during the prolonged elimination of Omniscan. After patients receive Omniscan, careful attention should be used in selecting the type of method used to measure calcium.

Specific drug interaction studies have not been conducted.

1. Patients receiving Omniscan should be instructed to inform their physician if they:
   • are pregnant or breast feeding, or
   • have a history of renal disease, convulsions, asthma or allergic respiratory disorders, or recent administration of gadolinium-based contrast.
2. Patients with impaired renal function who receive repetitive administrations of a gadolinium-containing contrast agent may have an increased risk for the development of nephrogenic systemic fibrosis if the time interval between the administrations precludes clearance of the contrast agent from the body. In these situations, patients should contact their physician if they develop 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 deep in the hip bones or ribs; or muscle weakness.

Distributed by GE Healthcare Inc.
Princeton, NJ

Manufactured by GE Healthcare Ireland
Cork, Ireland

Omniscan is a trademark of GE Healthcare.

GE and the GE Monogram are trademarks of General Electric Company.

OptiMARK® is a registered trademark of Mallinckrodt Inc.
Magnevist® is a registered trademark of Verlex Laboratories, Inc.
MultiHance® is a registered trademark of Bracco International B.V.
ProHance® is a registered trademark of Bracco Diagnostics Inc.