Revcovi (Elapegademase) is a PEGylated recombinant adenosine deaminase (rADA) enzyme that is used to treat severe combined immunodeficiency (due to the deficiency of adenosine deaminase enzyme) in children and adults.

Revcovi (Elapegademase) Uses:

• Adenosine deaminase severe combined immune deficiency:

  • It is indicated in the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.

Adult dose:

Revcovi (Elapegademase) Dose in the treatment of Adenosine deaminase severe combined immune deficiency: IM:

Note: Its dose, long-term use, and administration should be individualized on the basis of laboratory values and clinical response e.g. adenosine deaminase (ADA) activity, trough deoxyadenosine nucleotides (dAXP) concentration).

• Pegademase bovine naive patients:

  • Initial: 0.2 mg/kg (based on ideal body weight) twice a week for a minimum of 12 to 24 weeks.
  • When immune reconstitution is achieved, adjust the dose to maintain trough ADA activity >30 mmol/hour/L, trough dAXP <0.02 mmol/L, and/or to maintain immune reconstitution built 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 a week
  • Pegademase bovine weekly dose >30 units/kg:
    • Initial: calculate the dose on the basis of the following formula:

Elapegademase dose (mg/kg) = (pegademase bovine dose [units/kg])/150

• • • Increase dose by increments of 0.033 mg/kg once a week if ADA trough activity <30 mmol/hour/L, trough dAXP >0.02 mmol/L, and/or immune reconstitution is inadequate based on clinical response;
    • Its weekly dose can be divided into multiple administrations in a week.

Dose in children:

Dose in the treatment of Adenosine deaminase severe combined immune deficiency (ADA-SCID):

Note: Treatment should be based on laboratory values and clinical response e.g. adenosine deaminase (ADA) activity, deoxyadenosine nucleotides (dAXP) concentrations.

• Pegademase bovine (Adagen)-naive patients:

Note: Dose should be based on IBW:

• • Infants, Children, and Adolescents:
    • intramuscular (IM): 0.4 mg/kg/week in 2 divided doses in a week (0.2 mg/kg/dose twice a week) for a minimum period of 12 - 24 weeks until immune reconstitution is achieved.
    • The dose should be adjusted 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 once a week
    • Prior pegademase bovine (Adagen) dose >30 units/kg:
      • IM: Calculate the weekly dose based on the following equation (can be administered once a week or divide into doses in a week)

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 the trough ADA activity <30 mmol/hour/L, trough dAXP level >0.02 mmol/L, and/or if immune reconstitution is inadequate on basis of clinical assessment.

Revcovi (Elapegademase) Pregnancy Category: N

• Studies on animal reproduction have not been done.
• It is recommended to monitor your baby closely if elapegademase treatment is required during pregnancy.

Use of Elapegademase during lactation

• It is unknown if Elapegademase is present in breast milk.
• According to the manufacturer of the product, the decision to use it while breastfeeding should be based on the risks to infants and the benefits to the mother.

Dose in Kidney disease:

No dose adjustments listed in the manufacturer’s labeling.

Dose in Liver disease:

No dose adjustments listed in the manufacturer’s labeling. 

Side effects of Revcovi (Elapegademase):

• 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

Contraindications to Revcovi (Elapegademase):

There are no contraindications in the labeling.

Warnings and precautions

• • Formation of antibodies:

    • It may also cause antibodies.
    • If the plasma ADA levels are persistently decreasing, it should be 15 mmol/hour/L. Other causes must be ruled out, e.g. Noncompliance should be considered, and a specific test for antibody ADA should also be done.
    • These patients may require dose adjustments.

  • Immune deficiency:

    • Patients with immuno-deficient conditions are more at risk for infection. However, it is important to take precautions to avoid infection.

  • Thrombocytopenia:

    • It is administered intramuscularly. If the patient has severe thrombocytopenia, avoid its use. Avoid using it if the patient has severe thrombocytopenia.

Elapegademase: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

  Risk Factor C (Monitor therapy).
  Pegloticase	This may reduce the therapeutic effects of PEGylated Drug Products.
  Pegvaliase	Pegvaliase may be more toxic than usual if it is combined with PEGylated Drug Products. In particular, there may be an increase in the risk of hypersensitivity reactions or anaphylaxis.

Monitoring parameters:

• Trough plasma adenosine deaminase (ADA) activity:
  • Every 2 weeks (pegademase bovine naive patients) and every 4 weeks (patients transitioning from pegademase bovine) for the first 8 - 12 weeks of therapy, then every 3 to 6 months
• Trough plasma deoxyadenosine nucleotides (dAXP) levels:
  • After 2 months, then at least  twice yearly
• Lymphocyte counts (total and subset):
  • Every 4 - 8 weeks for up to 1 year, then every 3 - 6 months (pegademase bovine naive patients) or
  • Every 3 - 6 months (all other patients). Blood samples should be collected before the first dose to be given for the week.

Check antibodies to elapegademase if there are persistent ADA levels < 15 mmol/hour/L. In case of a persistent decrease in ADA activity occurs, monitor immune function and clinical status closely and precaution should be taken to reduce the chances of infection

How to administer Revcovi (Elapegademase)?

• Intramuscular (IM) administration is recommended,  Intravenous or subcutaneous should not be given
• Do not dilute or mix with other medications.
• Administer immediately after syringe preparation.
• Avoid administration near an artery or nerve.
• Periodically alternate the injection site

Mechanism of action of Revcovi (Elapegademase):

The ADA enzyme is responsible for the deamination and elimination of both adenosine as well as deoxyadenosine. SID, a severe immunodeficiency disorder (SID) can result from a lack of ADA enzyme activity. This can lead to death. Elapegademase, an exogenous source for adenosine-deaminase enzyme (ADA), reduces toxic adenosine levels and deoxyadenosine, and increases lymphocytes. Time to peak:

• 27.2 - 72 hours

International Brands of Elapegademase:

• Revcovi

Elapegademase Brand Names in Pakistan:

No Brands Available in Pakistan.