Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Denileukin diftitox-cxdl is a fusion protein designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors. 12.2 Pharmacodynamics Higher denileukin diftitox-cxdl exposures were associated with higher incidence of capillary leak syndrome, hepatotoxicity, treatment discontinuations due to adverse reactions, and adverse reactions Grade ≥3 following administration of LYMPHIR.
Indications
- 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 )
Common Doses
- 3 g
- 9 mcg
- 650 mg
- 25 mg
Dosage
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.
Black Box Warning
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.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 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...
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.