Pegulicianine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Black Box Warning
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TITLE
Serious hypersensitivity reactions, including anaphylaxis, can occur during or following administration of LUMISIGHT. Anaphylaxis occurred in 4/726 (0.6%) of patients in clinical studies. Signs and symptoms associated with other hypersensitivity reactions included pruritus, urticaria, hypotension, lip swelling, erythema, anxiety, chest pain, cyanosis, dizziness, dyspnea, headache, hypoesthesia, hyperventilation, maculopapular rash, nausea, paresthesia, visual changes, and vomiting.
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
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Overview
Pegulicianine is a diagnostic imaging agent that is FDA approved for the diagnosis of LUMISIGHT is indicated for fluorescence imaging in adults with breast cancer as an adjunct for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include *Anaphylaxis and Other Serious Hypersensitivity Reactions 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 LUMISIGHT was evaluated in 726 patients who received a single dose of 1 mg/kg of LUMISIGHT. Among these 726 patients, 703 (97%) had breast cancer and 23 (3%) had other types of cancer. The mean age of the patients was 62 years (range: 36 years to 95 years), and 98% of them were female. Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other or unreported. Distribution by ethnicity was 3% Hispanic/Latino, 93% non-Hispanic/Latino, and 4% unknown or unreported.
Adverse reactions occurring in ≥ 1% of patients receiving LUMISIGHT were hypersensitivity (1.4%, including anaphylaxis [4 out of 726]) and chromaturia (85%). Chromaturia resolved within 48 hours after administration in 93% of patients, with the longest time to resolution of 15 days.
Adverse reactions occurring in use < 1% of patients were skin discoloration after extravasation, nausea, dyspnea, pyrexia, and vomiting..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
LUMISIGHT is indicated for fluorescence imaging in adults with breast cancer as an adjunct for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pegulicianine in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pegulicianine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness of LUMISIGHT in pediatric patients have not been established.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pegulicianine in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pegulicianine in pediatric patients.
Contraindications
LUMISIGHT is contraindicated in patients with a history of hypersensitivity reaction to pegulicianine. Reactions have included anaphylaxis
Warnings
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TITLE
Serious hypersensitivity reactions, including anaphylaxis, can occur during or following administration of LUMISIGHT. Anaphylaxis occurred in 4/726 (0.6%) of patients in clinical studies. Signs and symptoms associated with other hypersensitivity reactions included pruritus, urticaria, hypotension, lip swelling, erythema, anxiety, chest pain, cyanosis, dizziness, dyspnea, headache, hypoesthesia, hyperventilation, maculopapular rash, nausea, paresthesia, visual changes, and vomiting.
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
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WARNING: ANAPHYLAXIS AND OTHER SERIOUS HYPERSENSITIVITY REACTIONS 5.1 Anaphylaxis and Other Serious Hypersensitivity Reactions Prepare for the possibility of drug hypersensitivity reactions (including anaphylaxis), which can occur during or following administration, and take the necessary precautions.
In clinical studies, 4 of 726 (0.6%) patients treated with LUMISIGHT experienced signs and symptoms consistent with anaphylaxis. The onset was during administration in three patients. Signs and symptoms associated with other hypersensitivity reactions included pruritus, urticaria, hypotension, lip swelling, erythema, anxiety, chest pain, cyanosis, dizziness, dyspnea, headache, hypoesthesia, hyperventilation, maculopapular rash, nausea, paresthesia, visual changes, and vomiting
Before LUMISIGHT administration, assess all patients for any history of hypersensitivity reaction to contrast media or products containing polyethylene glycol (PEG), as these patients may have an increased risk for hypersensitivity reaction to LUMISIGHT. In clinical studies, three out of four patients that experienced anaphylaxis did not have a history of hypersensitivity reaction to contrast media or products containing PEG.
Always have emergency resuscitation drugs, equipment, and trained personnel available. Monitor all patients for hypersensitivity reactions through symptom reporting, direct observation, and vital sign measurements. If a hypersensitivity reaction is suspected, immediately discontinue the injection and initiate appropriate therapy. LUMISIGHT is contraindicated in patients with a history of hypersensitivity reaction to pegulicianine
5.2 Risk of Misdiagnosis False positive and false negative findings may occur during use of LUMISIGHT to detect residual cancer. Absence of signal in the lumpectomy cavity does not rule out the presence of residual cancer. Additionally, positive signal has been observed in some non-cancerous tissue
5.3 Interference from Dyes Used for Sentinel Lymph Node Mapping Blue dyes used for sentinel lymph node (SLN) mapping procedures interfere with LUMISIGHT imaging. The potential of other dyes to interfere with LUMISIGHT imaging has not been evaluated. Avoid administration of dyes used for SLN mapping procedures before imaging the lumpectomy cavity in patients receiving LUMISIGHT.
Adverse Reactions
Clinical Trials Experience
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 LUMISIGHT was evaluated in 726 patients who received a single dose of 1 mg/kg of LUMISIGHT. Among these 726 patients, 703 (97%) had breast cancer and 23 (3%) had other types of cancer. The mean age of the patients was 62 years (range: 36 years to 95 years), and 98% of them were female. Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other or unreported. Distribution by ethnicity was 3% Hispanic/Latino, 93% non-Hispanic/Latino, and 4% unknown or unreported.
Adverse reactions occurring in ≥ 1% of patients receiving LUMISIGHT were hypersensitivity (1.4%, including anaphylaxis [4 out of 726]) and chromaturia (85%). Chromaturia resolved within 48 hours after administration in 93% of patients, with the longest time to resolution of 15 days.
Adverse reactions occurring in use < 1% of patients were skin discoloration after extravasation, nausea, dyspnea, pyrexia, and vomiting.
Postmarketing Experience
There is limited information regarding Pegulicianine Postmarketing Experience in the drug label.
Drug Interactions
Blue dyes used for SLN mapping procedures generate a fluorescent signal that interferes with the signal from LUMISIGHT when injected into the breast prior to imaging with LUMISIGHT. The potential of other dyes to interfere with LUMISIGHT imaging has not been evaluated. Avoid administration of dyes used for SLN mapping procedure before imaging the lumpectomy cavity in patients receiving LUMISIGHT.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): There are no available data on pegulicianine use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction studies were not conducted with pegulicianine.
The 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 risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pegulicianine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Pegulicianine during labor and delivery.
Nursing Mothers
There are no data on the presence of pegulicianine or its metabolites 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 LUMISIGHT and any potential adverse effects on the breastfed infant from LUMISIGHT or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness of LUMISIGHT in pediatric patients have not been established.
Geriatic Use
Of 703 patients in clinical studies of LUMISIGHT for breast cancer who received the recommended dose of 1 mg/kg, 44% were 65 years of age and over, while 8% were 75 and over. No overall differences in safety or effectiveness have been observed between these patients and younger adult patients.
Gender
There is no FDA guidance on the use of Pegulicianine with respect to specific gender populations.
Race
There is no FDA guidance on the use of Pegulicianine with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Pegulicianine in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Pegulicianine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pegulicianine in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Pegulicianine in patients who are immunocompromised.
Administration and Monitoring
Administration
- Withdraw the calculated volume from the appropriate number of vials into one syringe for administration of one single dose of 1 mg/kg. *Verify that the syringe contains the intended volume.
- Prior to administration of LUMISIGHT, flush the peripheral intravenous (IV) line with 10 mL to 20 mL of 0.9% Sodium Chloride Injection, USP.
- Administer LUMISIGHT as an IV injection over 3 minutes beginning 2 hours to 6 hours prior to imaging with the Lumicell DVS.
- After administration of LUMISIGHT, flush the IV line with 10 mL to 20 mL of 0.9% Sodium Chloride Injection, USP.
Monitoring
There is limited information regarding Pegulicianine Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Pegulicianine and IV administrations.
Overdosage
There is limited information regarding Pegulicianine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Pegulicianine Pharmacology in the drug label.
Mechanism of Action
Pegulicianine is a prodrug that is optically inactive when intact and produces a fluorescent signal after its peptide chain is cleaved by cathepsins and matrix metalloproteases (MMPs). The levels of these enzymes are higher in and around tumor and tumor-associated cells than normal cells.
This enzymatic cleavage results in “fragment 2” and “fragment 3”, which are optically active metabolites that emit fluorescence, as well as “fragment 1” containing the fluorescence quencher that keeps the intact molecule optically inactive. “Fragment 2” and “fragment 3” absorb light in the visible light region with a peak absorption at 650 nm and fluoresce with a peak emission at 675 nm.
Structure
There is limited information regarding Pegulicianine Structure in the drug label.
Pharmacodynamics
The relationships between the plasma concentrations of the optically active metabolites and the time course of pharmacodynamic response have not been fully characterized.
Pharmacokinetics
Elimination
Metabolism
Pegulicianine is cleaved by cathepsins and matrix metalloproteases to the active metabolites “fragment 2” and “fragment 3.” Pegulicianine undergoes minimal hepatic metabolism in vitro.
Excretion
Pegulicianine excretion pathway in humans is unknown. Observed blue/green discoloration of urine (chromaturia) in subjects receiving pegulicianine suggests that pegulicianine and/or its metabolites may be excreted renally.
Specific Populations
Patients with Renal Impairment
Mild renal impairment (RI) does not appear to have a clinically meaningful effect on the pharmacokinetics, safety, and efficacy of pegulicianine and fragment 3; fragment 2 data are not available. The effect of moderate or severe RI on the pharmacokinetics, safety, and efficacy of pegulicianine, fragment 2, and fragment 3 has not been evaluated.
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies in animals have been conducted to evaluate the carcinogenic potential of pegulicianine.
The nonfluorescent major metabolite of pegulicianine was not mutagenic in nonclinical tests, i.e., in vitro reverse mutation test in bacteria (Ames test), in vitro chromosomal aberration test in human peripheral blood lymphocytes, and in vivo (mice) micronucleus test after intravenous doses up to 11.24 mg/kg (225 times the pegulicianine clinical dose of 1 mg/kg).
No reproductive and developmental toxicity studies in animals have been performed to evaluate the effects of pegulicianine on fertility.
Clinical Studies
The efficacy and safety of LUMISIGHT for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery in patients with breast cancer were evaluated in a randomized, multicenter, intra-patient controlled clinical trial NCT03686215. A total of 406 adult patients with confirmed invasive breast cancer, ductal carcinoma in situ (DCIS), or both received 1 mg/kg LUMISIGHT by intravenous injection 2 hours to 6 hours prior to imaging with the Lumicell DVS. Among them, 357 patients underwent LUMISIGHT-guided imaging after completion of the standard of care lumpectomy procedure. Patients who received neoadjuvant chemotherapy or radiotherapy prior to surgery were excluded from study. After the standard of care (SOC) lumpectomy was completed, the lumpectomy cavity was divided into six regions based on anatomic orientation and each region was imaged with the Lumicell DVS. When positive fluorescence signal was detected, the tissue was resected with a cavity shave procedure and the region was re-imaged. A maximum of two LUMISIGHT-guided shaves were obtained from a single region. Histopathology analysis of excised tissue served as the reference standard. Cavity regions that did not have a LUMISIGHT-guided cavity shave or tissue from a second surgery for a reference standard were assigned the margin status of the corresponding outermost surface of the lumpectomy specimen or SOC cavity shave, with a positive margin defined as tumor on ink for invasive cancers (with or without DCIS) or within 2 mm of the inked margin for DCIS alone.
The mean age of patients was 62 years (range: 36 years to 83 years). Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other. Distribution by ethnicity was 3% Hispanic/Latino, 94% non-Hispanic/Latino, and 3% unknown or unreported. In the study group, 70% of patients had invasive ductal carcinoma (with or without DCIS), 20% had DCIS only, 10% had invasive lobular carcinoma (with or without DCIS), and <1% had both invasive ductal and invasive lobular carcinoma.
The study assessed the proportion of patients receiving LUMISIGHT who had residual cancer detected and removed using the Lumicell DVS after completion of SOC lumpectomy. One hundred and sixty-six (166) of 357 (46%) patients had at least one LUMISIGHT-guided shave. A total of 27 of 357 patients had residual cancer confirmed by histopathology in at least one LUMISIGHT-guided shave (7.6%; 95% CI: 5.0%, 10.8%).
Table 1 shows sensitivity and specificity of LUMISIGHT for residual breast cancer after completion of SOC lumpectomy calculated from the 2,346 evaluable images in the study. Regions of the lumpectomy cavity from which LUMISIGHT-guided shaves were taken contributed more than one image to the analysis.
A total of 155 of 357 (43%) patients had at least one false positive image, and 28 of 357 (8%) patients had at least one false negative image. Among the 166 patients with at least one LUMISIGHT-guided shave, the mean total LUMISIGHT-guided shave volume was 22 cm3 ± 20 cm3, accounting for 20% ± 15% of the total volume of resection.
After completion of SOC lumpectomy, prior to LUMISIGHT-guided tissue removal, 62 of 357 patients (17%) had at least one cancer-positive margin. After LUMISIGHT-guided surgery, 9 of these 62 (15%) patients changed to having all cancer-negative margins, and 2 of the remaining 295 (1%) patients changed from having all cancer-negative margins to having at least one cancer-positive margin.
How Supplied
LUMISIGHT (pegulicianine) for injection is supplied as a dark blue lyophilized powder for reconstitution in a clear, glass single-dose vial in cartons of 10 vials (NDC 82292-040-10). After reconstitution, each vial delivers 39 mg pegulicianine.
Storage
Store vials of LUMISIGHT frozen at -25°C to -15°C (-13°F to 5°F) in the original carton to protect from light.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Anaphylaxis and Other Serious Hypersensitivity Reactions
Inform patients of the risk of hypersensitivity reactions, including anaphylaxis, and instruct them to alert healthcare providers immediately if they experience signs and symptoms of a hypersensitivity reaction
Urine Discoloration
Inform patients that LUMISIGHT may cause blue discoloration of the urine that in most cases will resolve within 48 hours
Skin Discoloration After Extravasation
Inform patients that if extravasation occurs, it may result in blue discoloration of the skin at the injection site that will be evident for several weeks
Precautions with Alcohol
Alcohol-Pegulicianine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
LUMISIGHT
Look-Alike Drug Names
There is limited information regarding Pegulicianine Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.