Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intramuscular [preservative free]:
Revcovi: elapegademase-lvlr 2.4 mg/1.5 mL (1.5 mL)
Pharmacology
Mechanism of Action
Adenosine deaminase is an enzyme that catalyzes the deamination of both adenosine and deoxyadenosine. Hereditary lack of adenosine deaminase activity results in severe immunodeficiency disease, an often fatal disorder. Elapegademase is an exogenous source of adenosine deaminase enzyme that reduces levels of toxic adenosine and deoxyadenosine and increases lymphocytes.
Pharmacokinetics/Pharmacodynamics
Time to Peak
27.2 to 72 hours
Use: Labeled Indications
Adenosine deaminase severe combined immune deficiency: Treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.
Contraindications
There are no contraindications listed in the manufacturer's labelling.
Dosage and Administration
Dosing: Adult
Adenosine deaminase severe combined immune deficiency: IM: Note: Optimal long-term dose and administration schedule should be individualized based on laboratory values (eg, adenosine deaminase [ADA] activity, trough deoxyadenosine nucleotides [dAXP] concentration) and clinical response.
Pegademase bovine naive patients:Initial: 0.2 mg/kg (based on ideal body weight) twice weekly for a minimum of 12 to 24 weeks. After immune reconstitution is achieved, adjust dose to maintain trough ADA activity >30 mmol/hour/L, trough dAXP <0.02 mmol/L, and/or to maintain immune reconstitution based on clinical response.
Patients transitioning from pegademase bovine:
Pegademase bovine weekly dose unknown or dose ≤30 units/kg: Initial: Minimum of 0.2 mg/kg once weekly
Pegademase bovine weekly dose >30 units/kg: Initial: Calculate dose based on following formula:
Elapegademase dose (mg/kg) = (pegademase bovine dose [units/kg])/150
Increase dose by increments of 0.033 mg/kg once weekly if ADA trough activity <30 mmol/hour/L, trough dAXP >0.02 mmol/L, and/or immune reconstitution is inadequate based on clinical response; may divide total weekly dose into multiple administrations during a week
Dosing: Pediatric
Adenosine deaminase severe combined immune deficiency (ADA-SCID): Note: Treatment should be individualized and based on laboratory values (eg, adenosine deaminase [ADA] activity, deoxyadenosine nucleotides [dAXP] concentrations) and clinical response; the youngest patient treated in a study was 3 months of age.
Pegademase bovine (Adagen)-naive patients: Note: Dose should be based on IBW: Infants, Children, and Adolescents: IM: 0.4 mg/kg/week divided into 2 weekly doses (0.2 mg/kg/dose twice weekly); continue for a minimum of 12 to 24 weeks until immune reconstitution is achieved. Following achievement of immune reconstitution, adjust dose down to maintain trough ADA activity >30 mmol/hour/L, trough dAXP concentration <0.02 mmol/L, and/or to maintain immune reconstitution based on clinical assessment.
Conversion from pegademase bovine (Adagen) to elapegademase (Revcovi): Infants, Children, and Adolescents:
Initial dose:
Previous pegademase bovine (Adagen) dose unknown or ≤30 units/kg: IM: 0.2 mg/kg/week of elapegademase administered once weekly
Previous pegademase bovine (Adagen) dose >30 units/kg: Calculate weekly elapegademase dose based on the following equation; may administer calculated dose once weekly or may divide into multiple doses in a week: IM:
Elapegademase dose (mg/kg/week) = Pegademase bovine (Adagen) dose (units/kg/week)/150
Subsequent elapegademase doses: IM: Increase dose by increments of 0.033 mg/kg/week if trough ADA activity <30 mmol/hour/L, trough dAXP level >0.02 mmol/L, and/or if immune reconstitution is inadequate based on clinical assessment
Reconstitution
Prior to administration, remove from refrigerator and allow to warm to room temperature for 30 minutes. Solution is clear and colorless; do not use if cloudy, discolored or contains particulate matter. Solution should not be diluted or mixed with any other drugs. Draw solution from vial with ≥25 gauge needle; change the needle to patient appropriate size and gauge prior to administration. Discard unused medication.
Administration
IM: Administer intramuscularly; do not administer IV or SubQ. Do not dilute or mix with other medications prior to administration. Administer immediately after syringe preparation with an appropriate needle (size and gauge) for IM administration for the patient. Avoid administration near an artery or nerve. Periodically alternate injection site.
Storage
Refrigerate at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light; do not freeze or shake. Do not use if previously frozen.
Drug Interactions
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Monitor therapy
Adverse Reactions
Frequency not defined:
Central nervous system: Abnormal gait, fatigue, migraine, seizures
Dermatologic: Facial swelling, fungal skin infection, skin rash
Gastrointestinal: Dental caries, diarrhea, gastrointestinal infection, hematochezia, nausea, oral candidiasis, tooth loss (extraction), upper abdominal pain, vomiting
Hematologic & oncologic: Lymphadenopathy, neutropenia, pulmonary hemorrhage
Infection: Abscess (groin), infection (stoma), influenza, tooth abscess
Local: Discomfort at injection site
Neuromuscular & skeletal: Arthralgia, asthenia
Ophthalmic: Conjunctivitis
Otic: Ear residue, debris, or precipitate; ear sign or symptom (canal irritation); otitis externa
Renal: Nephrolithiasis
Respiratory: Cough, ENT infection (ear lobe), epistaxis, hemoptysis, nasal mucosa swelling, oropharyngeal pain, pneumonitis, productive cough, pulmonary infection, respiratory failure, upper respiratory tract infection (CMV)
Miscellaneous: Laceration
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: Development of antibodies may occur. In patients who experience a persistent decrease in preinjection levels of plasma adenosine deaminase (ADA) to <15 mmol/hour/L and have had other causes ruled out (eg, noncompliance), antibody formation should be considered and a specific assay for antibody ADA should be performed. Dosage adjustments may be required in patients developing antibodies.
Disease-related concerns:
- Immune deficiency: Immune deficient patients are at increased risk of infection; maintain adequate precautions until improvement in immune function.
- Thrombocytopenia: Use with caution in patients with thrombocytopenia due to risk of injection site bleeding; avoid use in patients with severe thrombocytopenia.
Monitoring Parameters
Trough plasma adenosine deaminase (ADA) activity; trough plasma deoxyadenosine nucleotides (dAXP) levels; total lymphocyte counts. More frequent monitoring may be necessary if therapy interrupted or clearance increases. Blood samples for analysis should be collected prior to the first administration for the week.
Plasma ADA activity (trough preinjection): Every 2 weeks (pegademase bovine naive patients) and every 4 weeks (patients transitioning from pegademase bovine) for the first 8 to 12 weeks of therapy, then every 3 to 6 months. Perform testing for antibodies to elapegademase if persistent decrease in levels below 15 mmol/hour/L occurs. Monitor immune function and clinical response closely and take precautions to minimize infection if a persistent decrease in ADA activity occurs.
Erythrocyte dAXP levels (trough preinjection): After 2 months, then a minimum of twice yearly
Lymphocyte counts (total and subset): Every 4 to 8 weeks for up to 1 year, then every 3 to 6 months (pegademase bovine naive patients) or every 3 to 6 months (all other patients)
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted.
If treatment with elapegademase is needed during pregnancy, close monitoring is recommended.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience cough or vomiting (HCAHPS). Have patient report immediately to prescriber signs of infection.
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
