Label: CYTALUX- pafolacianine injection injection
- NDC Code(s): 81052-138-10
- Packager: On Target Laboratories, Inc.
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: New Drug Application
Updated January 31, 2022
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use CYTALUX safely and effectively. See full prescribing information for CYTALUX.
CYTALUX™ (pafolacianine) injection, for intravenous use
Initial U.S. Approval: 2021
INDICATIONS AND USAGE
CYTALUX is an optical imaging agent indicated in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions. ( 1)
DOSAGE AND ADMINISTRATION
For recommended testing, evaluations, and premedications, see Full
Prescribing Information. (2.1)
• Recommended dosage of CYTALUX is 0.025 mg/kg administered
intravenously over 60 minutes 1 hour to 9 hours prior to surgery (2.2)
• For preparation, management of infusion-related reactions, and
imaging information see Full Prescribing Information. Should only be
used by trained surgeons using FDA cleared imaging systems. ( 2.3,
DOSAGE FORMS AND STRENGTHS
Injection: 3.2 mg/1.6 mL (2 mg/mL) of pafolacianine in a single-dose
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions: Interrupt the infusion and treat as
necessary with antihistamines and/or nausea medications. ( 5.1)
• Risk of misinterpretation: Non-fluorescing tissue in the surgical field
does not rule out the presence of tumor. Fluorescence may be seen
in non-cancerous tissues. ( 5.2)
• Embryo-Fetal Toxicity: CYTALUX may cause fetal harm. Advise
females of reproductive potential of the potential risk to a fetus. ( 5.3,
• Risk of Pafolacianine Aggregation and Infusion Reactions: Use only
5% Dextrose Injection for dilution. Do not use other diluents. ( 5.4)
Most common adverse reactions (incidence ≥1%) are nausea,
vomiting, abdominal pain, flushing, dyspepsia, chest discomfort,
pruritus and hypersensitivity. ( 6)
To report SUSPECTED ADVERSE REACTIONS, contact On Target
Laboratories at 1-844-434-9333 or FDA at 1-800-FDA-1088 or
Folate Supplements: Avoid folate, folic acid, or folate-containing
supplements within 48 hours before administration of CYTALUX. (7)
See 17 for PATIENT COUNSELING INFORMATION.
Table of Contents
FULL PRESCRIBING INFORMATION: CONTENTS*
- Sections or subsections omitted from the full prescribing information are not listed.
- 1. INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Testing, Evaluations and Premedications Prior to Administration of
Obtain a pregnancy test in females of reproductive potential and verify the absence of pregnancy
prior to administration of CYTALUX [ see Warnings and Precautions (5.3) and Use in Specific
Populations ( 8.1, 8.3) ].
Discontinue folate, folic acid, or folate containing supplements 48 hours before administration of
CYTALUX [ see Drug Interactions (7)].
Consider administering antihistamines and/or anti-nausea medication for prophylaxis against infusion related
reactions [ see Warnings and Precautions (5.1)].
2.2 Recommended Dosage and Administration
The recommended dose of CYTALUX is a single intravenous infusion of 0.025 mg/kg diluted in 250
mL of 5% Dextrose Injection, administered over 60 minutes using a dedicated infusion line, 1 hour to
9 hours prior to surgery.
2.3 Preparation and Storage Instructions
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration whenever solution and container permit.
1. Use aseptic technique for the preparation of CYTALUX infusion solution.
2. Only use 5% Dextrose Injection for dilution. Do not use other diluents due to incompatibility
[see Warnings and Precautions (5.4)].
3. Thaw frozen CYTALUX vial in original carton at controlled room temperature between 20°
to 25°C (68° to 77°F) for at least 90 minutes.
4. Hand shake or vortex the thawed CYTALUX vial for 60 seconds.
5. Withdraw the calculated volume of CYTALUX for a dose of 0.025 mg/kg. Discard any
unused portion in the vial.
6. Add into a 250 mL of 5% Dextrose Injection, USP bag.
7. Gently swirl the bag by hand for 1 minute to mix the solution.
8. Visually inspect the infusion bag. The solution should be light blue/green to clear in color
and should not contain any visible particulate matter.
9. Protect the infusion bag from light using a light-blocking cover during infusion and storage.
10. If not immediately used, store the diluted CYTALUX infusion solution in a refrigerator at 2°C
to 8°C (36°F to 46°F) for not more than 24 hours. Once the bag is removed from
refrigeration, infusion must be completed within 3 hours.
2.4 Management of Infusion-Related Reactions
If the patient develops an infusion reaction during administration, interrupt the infusion and treat with
antihistamines and/or anti-nausea medication as necessary, based on clinical decision. Complete the
infusion within 3 hours of the start of the initial administration [ see Warnings and Precautions (5.1)].
Clinical data demonstrates that near infrared (NIR) imaging devices which excite at 760 nm to
785 nm and detect emission at 794 nm to 796 nm are suitable for use with CYTALUX.
• CYTALUX is to be used with an NIR imaging system cleared by the FDA for specific use with
• CYTALUX should only be used by surgeons who have completed a training program on the
use of NIR imaging systems for fluorescence imaging during surgery. Training is provided by
the device manufacturer.
- 3 DOSAGE FORMS AND STRENGTHS
- 4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Infusion-Related Reactions
Adverse reactions consisting of nausea, vomiting, abdominal pain, flushing, dyspepsia, chest
discomfort, and pruritus were reported in patients receiving CYTALUX in clinical studies. 2.4 % of
patients experienced reactions during the period of administration of CYTALUX. [ see Adverse
Reactions (6.1)]. Reactions typically occurred within 15 minutes of the start of infusion. Treatment
with antihistamines and/or anti-nausea medication may be used. If an adverse reaction occurs during
administration, the infusion can be interrupted and resumed after treatment of the reaction [ see
Dosage and Administration ( 2.1, 2.4) ].
5.2 Risk of Misinterpretation
Errors may occur with the use of CYTALUX during intraoperative fluorescence imaging to detect
ovarian cancer, including false negatives and false positives. Non-fluorescing tissue in the surgical
field does not rule out the presence of ovarian cancer [ see Clinical Studies ( 14) ]. Fluorescence may
be seen in non-cancerous tissue including areas of the bowel, kidneys, lymph nodes and inflamed
5.3 Embryo-Fetal Toxicity
Based on its mechanism of action, CYTALUX may cause fetal harm when administered to a pregnant
woman. Advise females of reproductive potential of the potential risk to a fetus. Verify pregnancy
status of females of reproductive potential prior to initiating CYTALUX treatment. [ see Use in Specific
Populations ( 8.1, 8.3), Clinical Pharmacology ( 12.1) ].
5.4 Risk of Pafolacianine Aggregation and Infusion Reactions
Use of the incorrect diluent to prepare the CYTALUX infusion solution can cause the aggregation of
pafolacianine; aggregation may induce infusion reactions, such as nausea, vomiting, abdominal pain
or rash. Use only 5% Dextrose Injection to prepare the CYTALUX infusion solution. Do not use other
diluents. [see Dosage and Administration ( 2.3)].
6 ADVERSE REACTIONS
The following clinically significant adverse reaction is described elsewhere in the labeling:
• Infusion-Related Reactions [ see Warnings and Precautions ( 5.1) ]
6.1 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 safety of CYTALUX was evaluated in three open label clinical studies, two studies (N = 150 and
N = 44) in patients with ovarian cancer and one study (N = 100) in patients with cancer in the lung.
While patients with cancer in the lung were included in safety evaluation, CYTALUX is not approved
for use in patients with cancer in the lung. A total of 294 patients received 0.025 mg/kg of CYTALUX
via intravenous administration. The mean age of patients was 63.5 years; 51% were 65 years of age
or older. 89% of patients were female and 84% of patients were White.
Adverse reactions that occurred in > 1 % of patients were: nausea (15%), vomiting (5.8%), abdominal
pain (2.7%), flushing (1.7%), dyspepsia (1%), chest discomfort (1%), pruritus (1%) and
hypersensitivity (1%). In 2.4 % of patients, these adverse reactions occurred during the
administration of CYTALUX.
7 DRUG INTERACTIONS
Use of folate, folic acid, or folate-containing supplements may reduce binding of pafolacianine to
folate receptors overexpressed on ovarian cancer cells and could reduce the detection of malignant
lesions with CYTALUX. Avoid administration of folate, folic acid, or folate-containing supplements
within 48 hours before administration of CYTALUX [see Dosage and Administration (2.1) and Clinical
8 USE IN SPECIFIC POPULATIONS
Based on its mechanism of action, pafolacianine may cause fetal harm when administered to a
pregnant woman [ see Clinical Pharmacology ( 12.1) ]. There are no available human data to evaluate
for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal
No adverse developmental effects were observed in rats and rabbits with intravenous administration
of pafolacianine during organogenesis (embryofetal development) at doses up to 158-fold (rat) and
570-fold (rabbit) the recommended human dose of 0.025 mg/kg based on AUC, otherwise 9.6 and
38.4 fold based on human equivalent dose (HED) ( see Data).
The estimated background risk of major birth defects and miscarriage for the indicated populations
are unknown. All pregnancies have a background risk of birth defects, loss or other adverse
outcomes. In the U.S. general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In the definitive embryo-fetal development (EFD) studies, pafolacianine was intravenously
administered at doses of, during the period of organogenesis namely, 0.015, 0.15, and 1.5 mg/kg/day
from gestational day (GD) 6 to GD17 in rats (HEDs of 0.002, 0.024 and 0.242 mg/kg/day) and 0.3, 1,
and 3 mg/kg/day from GD7 to GD20 in rabbits (HEDs of 0.097, 0.323 and 0.968 mg/kg/day). No
significant drug-related maternal toxicity and embryo-fetal development toxicity were observed.
NOAELs were 1.5 mg/kg/day in rats and 3 mg/kg/day in rabbits. Estimated systemic exposures were
158 times (rat) and 570 times (rabbit) the human exposure at a human dose of 0.025 mg/kg based on
plasma AUC comparison.
There are no data on the presence of pafolacianine in either human or animal milk, the effects on the
breastfed infant, or the effects on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for CYTALUX and any
potential adverse effects on the breastfed infant from CYTALUX or from the underlying maternal
8.3 Females and Males of Reproductive Potential
CYTALUX may cause fetal harm if administered to a pregnant woman [ see Warnings And
Precautions ( 5.3) and Use In Specific Populations ( 8.1)] .
Obtain a pregnancy test in females of reproductive potential and verify the absence of
pregnancy prior to administration of CYTALUX [ see Dosage And Administration ( 2.1) ].
8.4 Pediatric Use
Safety and effectiveness of CYTALUX in pediatric patients have not been established.
CYTALUX contains pafolacianine, an optical imaging agent, as a tetrasodium salt referred to as
pafolacianine sodium. Chemically, pafolacianine sodium is (S)-2-(4-(((2-amino-4-oxo-3,4-
Tetrasodium. Pafolacianine sodium has a molecular formula of C 61H 63N 9Na 4O 17S 4, a molecular mass
of 1414.42 g/mol and has the following structure:
CYTALUX (pafolacianine) injection is a sterile, non-pyrogenic, dark bluish green, clear aqueous
solution for intravenous use. Each vial contains 3.2 mg (2 mg/mL) pafolacianine (equivalent to 3.4 mg
pafolacianine sodium),14.4 mg sodium chloride, 0.23 mg potassium phosphate monobasic, 1.27 mg
sodium phosphate dibasic heptahydrate in 1.6 mL volume. The pH is adjusted with sodium hydroxide
and/or hydrochloric acid and is between 7.1 to 7.8.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
CYTALUX is a fluorescent drug that targets folate receptor (FR) which may be overexpressed in
ovarian cancer. Pafolacianine binds to FR-expressing cancer cells with ~1 nM affinity, internalizes via
receptor mediated endocytosis, and concentrates in FR-positive cancer tissues. Pafolacianine
absorbs light in the near-infrared (NIR) region within a range of 760 nm to 785 nm with peak
absorption of 776 nm and emits fluorescence within a range of 790 nm to 815 nm with a peak
emission of 796 nm.
Tumor to background ratios changed with different mass doses studied. High tumor to background
ratio was observed with 0.025 mg/kg dose. CYTALUX exposure-response relationships and the time
course of pharmacodynamic responses are unknown.
The mean C max of pafolacianine was 59.1 ± 5.94 ng/mL and AUC inf was 63.6 ± 12.6 ng.hr/mL.
The mean volume of distribution (V z) is 17.1 ± 5.99 L, indicating distribution into tissues.
Plasma protein binding of pafolacianine is 93.7%. No notable partitioning into red blood cells has
The elimination half-life of pafolacianine is 0.44 ± 0.23 hours and mean plasma clearance is 28.6 ±
Pafolacianine sodium is not metabolized by cytochrome P450 (CYP) enzymes.
Following a single IV infusion of radiolabeled pafolacianine sodium, approximately 35% of the dose
was recovered in urine (19.1%) and in feces (15.8%) after approximately 3-5 weeks.
No clinically significant differences in pharmacokinetics of pafolacianine were identified based on age
18 – 89 years, weight 41.6 – 133.6 kg, mild to moderate renal impairment (CLcr 30 to 89 mL/min),
mild to moderate hepatic impairment (total bilirubin < 3 ULN and AST > ULN). The effect of severe
renal impairment (CLcr < 30 mL/min) and severe hepatic impairment (total bilirubin > 3 ULN and any
AST value) on the pharmacokinetics of pafolacianine have not been studied.
Drug Interaction Studies
No clinical studies evaluating the drug interaction potential of pafolacianine have been conducted.
In Vitro Studies
CYP Enzymes: Pafolacianine is not an inhibitor of CYPs 1A2, 2B6, 2C8, 2C9, 2C19 2D6, 3A4/5.
UDP-glucuronosyltransferase (UGT) Enzymes: Pafolacianine is not an inhibitor of UGT1A1.
Transporter Systems: Pafolacianine is a substrate for OATP1B1, OATP1B3, and OAT1. Pafolacianine
is not an inhibitor of OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, MATE2-K, P-gp, or BCRP
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity studies of pafolacianine have been conducted.
No genotoxic hazards were identified when pafolacianine was evaluated in a standard testing battery
consisting of a bacterial reverse mutation assay, an in vitro micronucleus study conducted in Chinese
Hamster Ovary (CHO) cells, and a rat bone marrow micronucleus study.
Impairment of Fertility
Reproductive and developmental toxicity (fertility and embryonic development, pre- and postnatal
development) studies in animals have not been performed to evaluate the effects of pafolacianine on
14 CLINICAL STUDIES
The safety and efficacy of CYTALUX was evaluated in a randomized, multicenter, open-label study
(NCT03180307). The study enrolled 178 women diagnosed with ovarian cancer or with high clinical
suspicion of ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking,
or recurrent ovarian cancer surgery. One hundred and fifty women highly suspicious for or with
confirmed ovarian cancer received CYTALUX (dosed at 0.025 mg/kg at least 1 hour before initiation
of fluorescence imaging). Among them, 134 women with mean age 60 (range 33 to 81) years
received both normal light imaging evaluation and fluorescence imaging evaluation (the Intent to
The study assessed the proportion of patients with at least one evaluable ovarian cancer lesion
confirmed by central pathology that was detected with CYTALUX under fluorescent light but not under
normal light or palpation and not otherwise identified for resection prior to surgery. The detection
proportion was estimated in women who underwent both normal light and fluorescent light (Intent-to-
Image Set), see Table 1. The detection performance for the Intent to Image set met the pre-specified
Table 1: Detection Proportion with CYTALUX Under Fluorescent Light but Not Under Normal
Light or Palpation In the Intent-To-Image Set
(N=134) Patients with at least one confirmed ovarian cancer evaluable lesion Number (n) 36 Proportion (%) 0.269 (26.9%) 95% Cl (proportion) (0.196*, 0.352)
*The lower bound of the 95% confidence interval based on exact binomial exceeds the prespecified proportion of 0.10.
Patient-level false positive rate of CYTALUX with NIR fluorescent light with respect to the detection of
ovarian cancer lesions confirmed by central pathology was 20.2% with 95% confidence interval
16 HOW SUPPLIED/STORAGE AND HANDLING
CYTALUX (pafolacianine) injection, 3.2 mg /1.6 mL (2 mg/mL), is a dark bluish green, clear aqueous
solution packaged in a sealed amber glass single-dose vial. It is supplied in a carton containing 10
vials (NDC 81052-138-10), vials are individually packaged.
Storage and Handling
Store frozen between -25° to -15°C (-13° to 5°F). Store in original carton to protect from light.
17 PATIENT COUNSELING INFORMATION
Advise females of reproductive potential of the potential risk to a fetus and to contact their healthcare
provider with a known or suspected pregnancy
[ see Warnings and Precautions ( 5.3) and Use In Specific Populations ( 8.1) ].
Folate Supplements Usage
Inform patients that folic acid may reduce the detection of cancer tissue with CYTALUX. Advise the
patient to stop taking folate, folic acid, or folate-containing supplements 48 hours before
administration of CYTALUX [ see Dosage and Administration ( 2.1) and Drug Interactions ( 7) ].
Grand River Aseptic Manufacturing
140 Front Ave SW
Grand Rapids, MI 49506
Thermofisher Allentown Packaging Facility
Or Patheon Logistics
100 Berkeley Dr.
Swedesboro, NJ 08085
Fisher Clinical Services Inc.
7554 Schantz Rd.
Allentown, PA 18100-9032
PACKAGING - PRINCIPAL DISPLAY PANEL
3.2 mg / 1.6 mL
10 x 1.6 mL Single-Dose Vials. Discard Unused Portion
For Intravenous Infusion After Dilution
Store at -25° to -15°C ( -13° to 5°F)
Store in original carton to protect from light.
ON TARGET LABORATORIES
3.2 mg pafolacianine (equivalent to 3.4 mg
14.4 mg sodium chloride, USP
0.23 mg potassium phosphate monobasic
1.27 mg potassium phosphate dibasic heptahydrate
Thaw at room temperature, 20° to 25°C (68° to 77°F),
for at least 90 minutes in the carton prior to preparation.
Must dilute with 5% dextrose injection, USP only
before use. Store diluted solution in dark in refrigerator
and use within 24 hrs. of preparation.
Recommended Dosage: See Prescribing Information
On Target Laboratories
West Lafayette, IN 47906
For more information, visit www.CYTALUX.com
or call 1.844.434.9333.
Single Vial carton Label
3.2 mg / 1.6 mL
For Intravenous Infusion After Dilution
Store in freezer at -25° to -15°C (-13° to 5°F)
Store in original carton to
protect from light.
ON TARGET LABORATORIES
3.2 mg pafolacianine (equivalent
to 3.4 mg pafolacianine sodium)
14.4 mg sodium chloride, USP
0.23 mg potassium phosphate
1.27 mg potassium phosphate
Thaw at room temperature, 20° to 25°C
(68° to 77°F), for at least 90 minutes
in the carton prior to preparation.
Must dilute with 5% dextrose
injection, USP only before use.
Store diluted solution in dark in
refrigerator and use within 24 hrs.
See Prescribing Information
On Target Laboratories
West Lafayette, IN 47906
For more information,
or call 1.844.434.9333.
INGREDIENTS AND APPEARANCE
pafolacianine injection injection
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:81052-138 Route of Administration INTRAVENOUS Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PAFOLACIANINE SODIUM (UNII: 4HUF3V875C) (PAFOLACIANINE - UNII:F7BD3Z4X8L) PAFOLACIANINE 3.2 mg in 1.6 mL Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R) SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE (UNII: 70WT22SF4B) SODIUM CHLORIDE (UNII: 451W47IQ8X) HYDROCHLORIC ACID (UNII: QTT17582CB) POTASSIUM PHOSPHATE, MONOBASIC (UNII: 4J9FJ0HL51) SODIUM HYDROXIDE (UNII: 55X04QC32I) Product Characteristics Color green (Dark Bluish) Score Shape Size Flavor Imprint Code Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:81052-138-10 10 in 1 CARTON 11/29/2021 1 1 in 1 CARTON 1 1.6 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA214907 11/29/2021 Labeler - On Target Laboratories, Inc. (968729181)