DRUG INTERACTIONS

Aromatic L-amino acid decarboxylase (AADC) inhibitors

Prior to Fluorodopa F 18 Injection administration, use of AADC inhibitors (e.g. carbidopa, benserazide etc.) may increase Fluorodopa F 18 bioavailability to the brain by inhibiting peripheral decarboxylase activity and restricting peripheral Fluorodopa F 18 metabolism 

Dopamine agonists, dopamine reuptake inhibitors, dopamine releasing agents (DRAs), peripheral catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors Therapy for Parkinson’s syndromes includes dopamine agonists, dopamine reuptake inhibitors, dopamine releasing agents (DRAs) such as psychostimulants of the amphetamine class, peripheral catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors.

Whether discontinuation of these drugs prior to Fluorodopa F 18 administration may minimize the interference with a Fluorodopa F 18 image is not fully known; however, if use of these drugs can be safely suspended, discontinue use 12 hours before administration of Fluorodopa F18 Injection

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

FLUORODOPA F 18 Injection safely and effectively.

See full prescribing information for FLUORODOPA F 18 Injection. FLUORODOPA F 18 Injection, for intravenous use

Initial U.S. Approval: 2019

INDICATIONS AND USAGE

 Fluorodopa F 18 Injection is a radioactive diagnostic agent indicated for use in positron emission tomography (PET) to visualize dopaminergic nerve terminals in the striatum for the evaluation of adult patients with suspected Parkinsonian syndromes (PS). Fluorodopa F 18 PET is an adjunct to other diagnostic evaluations.

INDICATIONS AND USAGE

 Fluorodopa F 18 Injection is a radioactive diagnostic agent indicated for use in positron emission tomography (PET) to visualize dopaminergic nerve terminals in the striatum for the evaluation of adult patients with suspected Parkinsonian syndromes (PS). Fluorodopa F 18 PET is an adjunct to other diagnostic evaluations.

DOSAGE AND ADMINISTRATION

• The recommended adult dose is 185 megabecquerels (MBq) [5 millicuries (mCi)] by intravenous injection infused over 1 minute. 

• Use aseptic techniques and radiation shielding to maintain sterility during all operations involved in the manipulation and administration of Fluorodopa F 18 Injection. 

• Instruct patients to void immediately before imaging and start imaging at approximately 80 minutes post administration (with a 9 second CT scan for attenuation correction) followed by 3D PET scan from 80 to 100 minutes post administration. 

• See full prescribing information for additional preparation, administration, imaging and radiation dosimetry information. 

DOSAGE FORMS AND STRENGTHS

Injection: clear, colorless solution in a multiple-dose glass vial containing 15.5 MBq/mL to 308.2 MBq/mL (0.42 mCi/mL to 8.33 mCi/mL) of Fluorodopa F 18 Injection. 

17 PATIENT COUNSELING INFORMATION

Patient Preparation Instruct patients to:

• Drink water in the 4 hours before their PET study and continue hydration with water or other fluids (as tolerated) after the study.

• Void 70 minutes after the administration of Fluorodopa F 18, before the start of the imaging study, and as frequently as possible after the study is complete for a total of 12 hours 

Lactation

To decrease radiation exposure to a nursing infant, advise a lactating woman to pump and discard breastmilk for at least 24 hours (12 half-lives) after administration of Fluorodopa F 18 Injection. (8.2).

Manufactured & Distributed by:

The Feinstein Institutes for Medical Research Cyclotron/Radiochemistry Facility 350 Community Drive Manhasset, New York, 11030

 CLINICAL PHARMACOLOGY

1. Mechanism of Action

In dopaminergic nerve terminals in the brain, Fluorodopa (FDOPA) F 18 is decarboxylated by amino acid decarboxylase to Fluorodopamine (FDA) F 18 and stored in presynaptic vesicles in the brain.

The accumulation of F 18 FDA in the striatum is visually detected in the PET scan.

2. Pharmacodynamics

Optimal PET imaging is achieved between 75 to 90 minutes after administration of Fluorodopa F 18 Injection based on its pharmacokinetics. The relationship between Fluorodopa F 18 dose and plasma concentration is not fully characterized.

3. Pharmacokinetics

Distribution

Following the intravenous administration, Fluorodopa F 18 is cleared from the blood with a biologic half-life of about 1 to 3 hours.

The time course of “background” brain radioactivity after Fluorodopa F 18 was evaluated. F 18 activity in the cerebellum was greater than the parietal or occipital cortex during the first 30 minutes after Fluorodopa F 18 suggesting regional differences in amino acid transport.

Elimination

Fluorodopa F 18 is cleared from the blood and tissue within 24 hours.

Metabolism:

Fluorodopa F 18 is decarboxylated by aromatic amino acid decarboxylase in the striatum to Fluorodopamine F 18. Fluorodopamine F 18 is also metabolized via monoamine oxidase to yield [18F] 6-fluoro-3,4-dihydroxyphenylacetic acid (18FDOPAC) and subsequently by COMT to yield [18F]6-fluorohomovanillic acid (18FHVA). 

Elimination:

80% of the radioactivity is eliminated through the urine. Urine radioactivity peaks at about 30 minutes post-injection. The radiation absorbed dose to the bladder wall is reduced by emptying the bladder just before scanning.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no available data on Fluorodopa F 18 Injection use in pregnant women. Additionally, animal reproductive and developmental toxicity studies have not been conducted with Fluorodopa F 18 Injection.

However, all radiopharmaceuticals, including Fluorodopa F 18 Injection, have a potential to cause fetal harm depending on the stage of fetal development, and the magnitude of the radiation dose.

If considering Fluorodopa F 18 Injection administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from the drug and the gestational timing of exposure.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively, regardless of drug exposure.

2. Lactation

Risk Summary No data are available regarding the presence of Fluorodopa F 18 Injection in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production.

Exposure of Fluorodopa F 18 Injection to a breast fed infant can be minimized by temporary discontinuation of breastfeeding 

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fluorodopa F 18 Injection and any potential adverse effects on the breastfed child from Fluorodopa F 18 Injection or from the underlying maternal condition.

The body of scientific information related to radioactivity decay, drug tissue distribution and drug elimination shows that less than 0.01% of the radioactivity administered remains in the body after 24 hours.

Clinical Considerations

To decrease radiation exposure to a nursing infant, advise a lactating woman to pump and discard breastmilk for at least 24 hours (12 half-lives) after administration of Fluorodopa F 18 Injection.

3.Pediatric Use

The safety and effectiveness of Fluorodopa F 18 Injection for visualization of dopaminergic neurons in the striatum has not been established in pediatric patients.