ProHance

PROHANCE- gadoteridol injection, solution
BRACCO DIAGNOSTICS INC

1  INDICATIONS AND USAGE

1.1 MRI of the Central Nervous System (CNS)

ProHance is indicated for magnetic resonance imaging (MRI) in adults and pediatric patients including term neonates to visualize lesions with disrupted blood brain barrier and/or abnormal vascularity in the brain (intracranial lesions), spine and associated tissues.

1.2 MRI of Extracranial/Extraspinal Head and Neck

ProHance is indicated for MRI in adults to visualize lesions in the head and neck.

2  DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

The recommended dose for adult and pediatric patients, including term neonates, is 0.2 mL/kg (0.1 mmol/kg) administered as a rapid intravenous infusion (10 mL/min to 60 mL/min) or bolus (greater than 60 mL/min). Table 1 provides weight-adjusted recommended dose volumes.

Table 1: Recommended Volume of ProHance Injection by Body Weight
Body Weight (kg)	Volume to be Administered (mL)
2.5	0.5
5	1
10	2
20	4
30	6
40	8
50	10
60	12
70	14
80	16
90	18
100	20
110	22
120	24
130	26
140	28
150	30

MRI of the CNS in Adults:

• A supplementary dose of 0.4 mL/kg (0.2 mmol/kg) may be given up to 30 minutes after the first dose in adult patients with normal renal function suspected of having poorly visualized CNS lesions, in the presence of negative or equivocal scans
• The safety and efficacy of supplementary dosing have not been established in pediatric patients

2.2 Administration

• Visually inspect ProHance for particulate matter and discoloration prior to use
• 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 intravenous line because of the potential for chemical incompatibility
• Inject at least a 5 mL normal saline flush immediately after ProHance injection to ensure complete administration
• Imaging procedures should be completed within 1 hour
• ProHance vials are intended only for single-dose administration. Administer immediately after opening and discard any unused product

2.3 Directions for Use

Vials

• Draw ProHance into the syringe immediately before use. Do not pierce the rubber stopper more than once. Discard any unused vial contents.

ProHance single dose syringe*

• Screw the threaded tip of the plunger rod clockwise into the cartridge plunger and push forward a few millimeters to break any friction between the cartridge plunger and syringe barrel

• Holding syringe erect, unscrew the plastic tip cap from the tip of the syringe and attach either a sterile, disposable needle or tubing with a compatible Luer lock using a push-twist action (slip tip)
• Hold the syringe erect and push plunger forward until all of the air is evacuated and fluid either appears at the tip of the needle or the tubing is filled
• Following the usual aspiration procedure, complete the injection
• Inject at least a 5 mL normal saline flush immediately after ProHance injection to ensure complete administration
• Properly dispose of the syringe and any other materials used

*The syringe assembly is a HYPAK SCF® single dose syringe supplied by Becton Dickinson

3  DOSAGE FORMS AND STRENGTHS

ProHance is supplied as a sterile, non-pyrogenic, and colorless to slightly yellow solution available in single-dose vials or prefilled syringes. Each mL contains 279.3 mg (0.5 mmol/mL) of gadoteridol for injection.

4  CONTRAINDICATIONS

ProHance is contraindicated in patients with known allergic or hypersensitivity reactions to ProHance [see Warnings and Precautions (5.2)].

5  WARNINGS AND PRECAUTIONS

5.1 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 among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR less than 30 mL/min/1.73m²) as well as patients with acute kidney injury. 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 ProHance administration to Bracco Diagnostics (1-800-257-5181) 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 chronically reduced renal function (for example, age greater than 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. For patients at highest risk for NSF, do not exceed the recommended ProHance dose and allow a sufficient period of time for elimination of the drug prior to re-administration. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent’s elimination. The usefulness of hemodialysis in the prevention of NSF is unknown. [see Clinical Pharmacology (12)].