Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 1.6mg/mL (1.5mL single-dose vial)
Adenosine Deaminase Severe Combined Immunodeficiency
Indicated for treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID)
Initial dose dependent on current treatment (ie, if transitioning from pegademase [Adagen]) or not on treatment
Pegademase naïve
- Dose based on ideal body weight or actual weight whichever is greater
- 0.2 mg/kg IM 2 times per week (0.4 mg/kg/week) for at least 12-24 weeks until immune reconstitution achieved
- Establish optimal long-term dose and schedule for each patient individually
- Adjust dose gradually down to maintain trough ADA activity >30 mmol/hr/L, trough dAXP level <0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment
Transition from pegademase to elapegademase
- Unknown pegademase dose OR weekly pegademase dose ≤30 U/kg: 0.2 mg/kg IM qWeek
-
Weekly pegademase dose >30 U/kg
- Calculate an equivalent weekly elapegademase dose (mg/kg) using the following conversion formula
- Elapegademase weekly dose (mg/kg) = pegademase dose (U/kg)/150
- May increase subsequent doses by 0.033-mg/kg/week increments if trough ADA activity <30 mmol/hr/L, trough dAXP >0.02 mmol/L, and/or immune reconstitution is inadequate based on clinical assessment
- May divide total weekly dose into multiple IM administrations during a week
Dosing Considerations
Monitoring parameters
- Monitor frequently if therapy interrupted OR an enhanced clearance rate of plasma ADA activity develops; collect blood samples to analyze trough plasma ADA activity and trough dAXP level before first administration for the week
-
ADA activity (during treatment)
- Target trough plasma ADA activity: ≥30 mmol/hr/L
- Monitor trough plasma ADA (trough preinjection) q2Weeks (pegademase-naïve) and q4Weeks (transitioning from pegademase) during first 8-12 weeks of treatment, and q3-6 months thereafter
- Decreased ADA activity (<30 mmol/hr/L) suggests noncompliance to treatment or antibody development (antidrug, anti-polyethylene glycol, and neutralizing antibodies)
- Perform test to detect antibodies to elapegademase if persistent fall in trough plasma ADA activity <15 mmol/hr/L occurs
- If persistent decline in trough plasma ADA activity occurs, closely monitor immune function and clinical status and take precautions to minimize infection risk
- If antibodies cause persistent fall in trough plasma ADA activity, adjust dose and consider other measures to induce tolerance and restore adequate ADA activity
-
Erythrocyte dAXP
- Tough erythrocyte dAXP levels: Maintain <0.02 mmol/L
- Monitor 2 months after starting treatment and at least 2x/year thereafter
-
Immune function
- Degree of immune function varies among each patient
- Consistently monitor based immunologic status
- Monitor total and subset lymphocytes in pegademase-naïve q4-8Weeks for up to 1 year, and every 3-6 months thereafter; in other patients assess q3-6 months
- Immune function generally improves after 2-6 months of therapy; improvement in general clinical status should be apparent by the end of the first year of therapy
Dosage Forms & Strengths
injectable solution
- 1.6mg/mL (1.5mL single-dose vial)
Adenosine Deaminase Severe Combined Immunodeficiency
Indicated for treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID)
Initial dose dependent on current treatment (ie, if transitioning from pegademase [Adagen]) or not on treatment
Pegademase naïve
- Dose based on ideal body weight or actual weight whichever is greater
- 0.2 mg/kg IM 2 times per week (0.4 mg/kg/week) for at least 12-24 weeks until immune reconstitution achieved
- Establish optimal long-term dose and schedule for each patient individually
- Adjust dose gradually down to maintain trough ADA activity >30 mmol/hr/L, trough dAXP level <0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment
Transition from pegademase to elapegademase
- Unknown pegademase dose OR weekly pegademase dose ≤30 U/kg: 0.2 mg/kg IM qWeek
-
Weekly pegademase dose >30 U/kg
- Calculate an equivalent weekly elapegademase dose (mg/kg) using the following conversion formula
- Elapegademase weekly dose (mg/kg) = pegademase dose (U/kg)/150
- May increase subsequent doses by 0.033-mg/kg/week increments if trough ADA activity <30 mmol/hr/L, trough dAXP >0.02 mmol/L, and/or immune reconstitution is inadequate based on clinical assessment
- May divide total weekly dose into multiple IM administrations during a week
Dosing Considerations
Monitoring parameters
- Monitor frequently if therapy interrupted OR an enhanced clearance rate of plasma ADA activity develops; collect blood samples to analyze trough plasma ADA activity and trough dAXP level before first administration for the week
-
ADA activity (during treatment)
- Target trough plasma ADA activity: ≥30 mmol/hr/L
- Monitor trough plasma ADA (trough preinjection) q2Weeks (pegademase-naïve) and q4Weeks (transitioning from pegademase) during first 8-12 weeks of treatment, and q3-6 months thereafter
- Decreased ADA activity (<30 mmol/hr/L) suggests noncompliance to treatment or antibody development (antidrug, anti-polyethylene glycol, and neutralizing antibodies)
- Perform test to detect antibodies to elapegademase if persistent fall in trough plasma ADA activity <15 mmol/hr/L occurs
- If persistent decline in trough plasma ADA activity occurs, closely monitor immune function and clinical status and take precautions to minimize infection risk
- If antibodies cause persistent fall in trough plasma ADA activity, adjust dose and consider other measures to induce tolerance and restore adequate ADA activity
-
Erythrocyte dAXP
- Tough erythrocyte dAXP levels: Maintain <0.02 mmol/L
- Monitor 2 months after starting treatment and at least 2x/year thereafter
-
Immune function
- Degree of immune function varies among each patient
- Consistently monitor based immunologic status
- Monitor total and subset lymphocytes in pegademase-naïve q4-8Weeks for up to 1 year, and every 3-6 months thereafter; in other patients assess q3-6 months
- Immune function generally improves after 2-6 months of therapy; improvement in general clinical status should be apparent by the end of the first year of therapy
Adverse Effects
>10%
Cough (50% [3 of 6 patients])
Vomiting (33% [2 of 6 patients])
Frequency Not Defined
Upper abdominal pain
Arthralgia
Asthenia
Cerumen impaction
Conjunctivitis
Convulsion
Dental caries
Diarrhea
Ear canal irritation
Ear lobe infection
Epistaxis
Fatigue
Fungal skin infection
Gait disturbance
Gastrointestinal infection
Groin abscess
Hematochezia
Haemophilus infection (pulmonary)
Hemoptysis
Influenza
Injection site discomfort
Laceration
Lymphadenopathy
Migraine
Nasal edema
Nausea
Nephrolithiasis
Oral candidiasis
Oropharyngeal pain
Otitis externa
Productive cough
Rash
Stoma site infection
Swelling face
Tooth abscess
Tooth extraction
Upper respiratory tract infection
Postmarketing Reports
Hemolytic anemia, autoimmune hemolytic anemia, thrombocythemia, thrombocytopenia, autoimmune thrombocytopenia
Injection site erythema, urticaria
Lymphomas
Warnings
Contraindications
None
Cautions
Caution with thrombocytopenia; avoid use if thrombocytopenia is severe
Maintain precautions to protect immune-deficient patients from infections until improvement in immune function achieved; timing and degree of improvement in immune function may vary from patient to patient
Pregnancy & Lactation
Pregnancy
Adequate and well-controlled studies have not been conducted in pregnant women to inform a drug-associated risk
Unknown whether fetal harm may occur when administered to a pregnant woman or can affect reproduction capacity
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
ADA enzyme is involved in purine metabolism, catalyzing the irreversible hydrolytic deamination of adenosine or deoxyadenosine to inosine or deoxyinosine, respectively, as well as several naturally occurring methylated adenosine compounds
Maintaining a low level of 2'-deoxyadenosine and adenosine is crucial for proper number and function of immune cells, as well as decreasing the frequency of opportunistic infections
Elevated adenosine levels, as occurring in ADA deficiency, contribute to apoptosis and a block in the differentiation of thymocytes, causing severe T-lymphopenia
Elapegademase-lvlr provides an exogenous source of ADA enzyme that is associated with a decrease in toxic adenosine and dAXP levels, as well as an increase in lymphocyte number
Absorption
Dose-normalized AUC
- Male, Hispanic/Latino (10-10.2 mg/kg): 31,343-32,718 (hr·mmol/hr/L)/(mg/kg)
- Male, Black/African American (19.6 mg/kg): 42,400 (hr·mmol/hr/L)/(mg/kg)
- Male, Asian (48 mg/kg): 37,605 (hr·mmol/hr/L)/(mg/kg)
- Female, White: 24,564 (hr·mmol/hr/L)/(mg/kg)
- Female, Asian (4.99 mg/kg): 19,013 (hr·mmol/hr/L)/(mg/kg)
Dose-normalized peak plasma concentration
- Male, Hispanic/Latino (10-10.2 mg/kg): 219-237 (mmol/hr/L)/(mg/kg)
- Male, Black/African American (19.6 mg/kg): 292 (mmol/hr/L)/(mg/kg)
- Male, Asian (48 mg/kg): 251 (mmol/hr/L)/(mg/kg)
- Female, White: 166 (mmol/hr/L)/(mg/kg)
- Female, Asian (4.99 mg/kg): 150 (mmol/hr/L)/(mg/kg)
Peak plasma time
- Male, Hispanic/Latino (10-10.2 mg/kg): 47.7-71.9 hr
- Male, Black/African American (19.6 mg/kg): 48.2 hr
- Male, Asian (48 mg/kg): 48 hr
- Female, White: 72 hr Female, Asian (4.99 mg/kg): 27.2 hr
Administration
IM Preparation
Do not dilute or mix with any other drug
Visually inspect for particulate matter and discoloration prior to administration; drug is a clear, colorless solution; discard if solution is discolored, cloudy, or contains particulate matter
Do not freeze or shake
Do not use if there are any indications that the drug may have been frozen
Once removed from refrigeration, allow to equilibrate to room temperature for 30 min
IM Administration
IM use only
Administer using polypropylene syringes
Draw solution from vial with ≥25-gauge needle; change needle to a size and gauge appropriate for the patient’s IM injection
Follow sterile IM administration technique guidelines appropriate to the patient’s age and anatomy (ie, choice of needle gauge and length, site of administration)
Take precautions not to inject into or near an artery or nerve
Alternate injection site periodically
Administer immediately after syringe preparation; discard any remaining medication in vial immediately
Storage
Refrigerate between 2-8°C (36-46°F) in original carton to protect from light
Do not freeze or shake
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Formulary
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