elapegademase (Rx)

Brand and Other Names:Revcovi, elapegademase-lvlr
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Dosing & Uses

AdultPediatric

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
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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

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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

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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.

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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
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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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Images

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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.