Denileukin Diftitox-Cxdl
FDA Drug Information • Also known as: Lymphir
- Brand Names
- Lymphir
- Drug Class
- CD25-directed Cytotoxin [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: CAPILLARY LEAK SYNDROME Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity [see Dosage and Administration ( 2.1 , 2.4 ) and Warnings and Precautions ( 5.1 )] . WARNING: CAPILLARY LEAK SYNDROME See full prescribing information for complete boxed warning. Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves or permanently discontinue based on severity. ( 2.1 , 2.4 , 5.1 )
Description
11 DESCRIPTION Denileukin diftitox-cxdl, an IL2-receptor-directed cytotoxin, is a recombinant DNA-derived fusion protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met 1 -Thr 387 )-His and the sequence for human interleukin-2 (IL-2; Ala 1 -Thr 133 ). It is produced in an E. coli expression system and has a molecular weight of 58 kD. Neomycin is used in the fermentation process but is undetectable in the final product. LYMPHIR (denileukin diftitox-cxdl) for injection is supplied as a sterile, white, lyophilized cake in a single-dose vial for intravenous use after reconstitution and dilution. Each vial of LYMPHIR contains 300 mcg of denileukin diftitox-cxdl, citric acid monohydrate (4.2 mg), edetate disodium (0.04 mg), methionine (3 mg), polysorbate 20 (1.2 mg), and trehalose (100.4 mg). Sodium hydroxide is used to adjust the pH of the formulation buffer. Following reconstitution with 2.1 mL of Sterile Water for Injection, USP, the resulting concentration of denileukin diftitox-cxdl is 150 mcg/mL at pH approximately 7.
What Is Denileukin Diftitox-Cxdl Used For?
1 INDICATIONS AND USAGE LYMPHIR is indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Delay start of treatment cycle if serum albumin level is below 3 g/dL. ( 2.1 ) The recommended dosage of LYMPHIR is 9 mcg/kg/day actual body weight administered as an intravenous infusion on Days 1 through 5 of a 21-day cycle. ( 2.2 ) Administer premedication as recommended. ( 2.3 ) See full prescribing information for preparation and administration instructions. ( 2.5 ) 2.1 Important Dosing Instructions Prior to starting each treatment cycle, assess hepatic and renal function. If serum albumin is less than 3 g/dL, delay administration of LYMPHIR until serum albumin is greater than or equal to 3 g/dL [see Warnings and Precautions ( 5.1 )] . 2.2 Recommended Dosage The recommended dosage of LYMPHIR is 9 mcg/kg/day actual body weight administered as an intravenous infusion over 60 minutes on Days 1 through 5 of a 21-day treatment cycle. Administer LYMPHIR until disease progression or unacceptable toxicity. 2.3 Recommended Premedications Administer premedications prior to starting a LYMPHIR infusion in Cycles 1 through 3, as outlined in Table 1, to reduce the risk of infusion-related reactions [see Warnings and Precautions ( 5.3 )] . Table 1. Premedication to be Administered to Patients Prior to LYMPHIR Infusion Treatment Cycle Premedication Dosage Administration Cycles 1-3 (optional thereafter) Antipyretic Oral acetaminophen 650 mg or per local institutional guidelines At least 30 minutes prior to infusion Antihistamine Diphenhydramine 25 mg intravenously or other antihistamine per local institutional guidelines At least 30 minutes prior to infusion Antiemetic Per institutional guidelines At least 30 minutes prior to infusion Hydration 250 to 500 mL 0.9% Sodium Chloride Injection intravenously (or other amount of fluid considered to be most appropriate for the subject’s condition) At least 30 minutes prior to infusion If patients experience a Grade 2 or higher infusion reaction, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid such as dexamethasone 4 mg (or equivalent) via slow intravenous push, for at least 3 cycles. 2.4 Dosage Modifications for Adverse Reactions Dosage modifications for adverse reactions with LYMPHIR are shown in Table 2 below. Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity* Dosage Modification Capillary leak syndrome (CLS) [see Warnings and Precautions ( 5.1 )] Grade 2 Withhold LYMPHIR until CLS resolves to Grade 1. Grade 3 Withhold LYMPHIR and provide supportive care until CLS resolves to Grade 1. Resume LYMPHIR at 50% dose. Consider steroid premedication for subsequent infusions. Permanently discontinue upon recurrence. Grade 4 Permanently discontinue LYMPHIR. Visual impairment [see Warnings and Precautions ( 5.2 )] Grade 1 or 2 Consider withholding or discontinuing LYMPHIR as appropriate. Refer for ophthalmic evaluation. Grade 3 or 4 Withhold LYMPHIR until resolved to Grade 1 or baseline. Refer for ophthalmic...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Capillary Leak Syndrome [see Warnings and Precautions ( 5.1 )] Visual Impairment [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Citius Oncology, Inc. at 1-844-459-6744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LYMPHIR as a single agent in 119 patients with CTCL across 3 clinical trials. Patients received treatment with LYMPHIR as an intravenous infusion at 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle until disease progression or unacceptable toxicity. Among 119 patients who received LYMPHIR the median number of cycles received was 5 (range: 1 to 42), with 13% exposed for 6 months or longer. In this pooled safety population, the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were increased transaminases (70%), albumin decreased (53%), nausea (40%), edema (35%), hemoglobin decreased (34%), fatigue (30%), musculoskeletal pain (26%), rash (23%), chills (22%), constipation (22%), pyrexia (21%), and capillary leak syndrome (20%). Relapsed or Refractory Stage I-III CTCL Study 302 The safety of LYMPHIR was evaluated in Study 302, an open-label, single-arm, multicenter trial that included 69 patients with relapsed or refractory Stage I-III CTCL [see Clinical Studies ( 14 )] . Patients received treatment with LYMPHIR 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle. Treatment was administered until disease progression or unacceptable toxicity. The median number of LYMPHIR cycles was 6 (range: 1 to 42). The median age of patients was 64 years (range: 28 to 87 years), 49% were 65 years of age or older, 65% were men, 72% were White, 19% were Black or African American, 1.4% were Asian, and 14% were Hispanic or Latino. Serious adverse reactions occurred in 38% of patients who received LYMPHIR. Serious adverse reactions in > 2% of patients included capillary leak syndrome (10%), infusion-related reaction (9%), sepsis (7%), skin infection (2.9%), pyrexia (2.9%), and rash (2.9%). Permanent discontinuation of LYMPHIR due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of LYMPHIR included capillary leak syndrome, infusion-related reaction, renal insufficiency, respiratory failure, and sepsis. Dosage interruptions of LYMPHIR due to an adverse reaction occurred in 38% of patients. Adverse reactions requiring dosage interruption of LYMPHIR included capillary leak syndrome, infusion-related reaction, weight increase, nausea, and tachycardia. Table 3 summarizes the adverse reactions in Study 302. Table 3: Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory Stage I-III CTCL Who Received LYMPHIR in Study 302 Adverse Reaction LYMPHIR N=69 All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Nausea 43 1.4 # Diarrhea 19 0 Vomiting 13 0 Constipation 12 0 General disorders and administration site conditions Fatigue a 38 0 Edema b 33 1.4 Chills 27 1.4 Pyrexia 16 1.4 Musculoskeletal and connective tissue disorders Musculoskeletal pain c 27 2.9 Arthralgia 12 0 Nervous system disorders Headache d 25 0...
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox. Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied LYMPHIR (denileukin diftitox-cxdl) for injection is supplied as a sterile, white, lyophilized cake for reconstitution in a single-dose vial containing 300 mcg denileukin diftitox-cxdl. Each carton contains one vial: NDC 52658-7777-1 Storage and Handling Store LYMPHIR in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.