REVCOVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVCOVI (REVCOVI).
Recombinant adenosine deaminase (ADA) enzyme replacement therapy; degrades adenosine and deoxyadenosine, reducing toxic metabolites and restoring immune function.
| Metabolism | Degraded by proteolysis into small peptides and amino acids; not metabolized by CYP450 enzymes. |
| Excretion | Renal excretion of unchanged drug and metabolites: approximately 100% eliminated renally; no significant biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 3-6 months (mean ~100 days) in patients with PEG-ADA deficiency; clinical context: sustained enzyme replacement allows weekly or biweekly dosing. |
| Protein binding | Approximately 0% bound to plasma proteins (the drug is a pegylated enzyme, minimal protein binding). |
| Volume of Distribution | Volume of distribution is approximately 0.1-0.2 L/kg; primarily confined to the vascular space and extracellular fluid, reflecting limited tissue distribution. |
| Bioavailability | Subcutaneous injection: approximately 100% bioavailability (intended route; no oral formulation). |
| Onset of Action | Subcutaneous injection: clinical improvement in immune function observed within 2-4 weeks; full metabolic correction (normalization of deoxyadenosine nucleotides) may take 3-6 months. |
| Duration of Action | Duration of action: 1-2 weeks after subcutaneous injection; sustained adenosine deaminase activity maintains immune function; dosing every 7 days (or 14 days) based on trough ADA activity monitoring. |
25 mg/kg body weight administered intramuscularly once weekly.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; monitor renal function during therapy. |
| Liver impairment | No dose adjustment required for hepatic impairment; monitor liver function during therapy. |
| Pediatric use | Pediatric patients: 25 mg/kg body weight intramuscularly once weekly. |
| Geriatric use | No specific dose adjustment recommended; monitor renal and hepatic function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVCOVI (REVCOVI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Caution recommended due to potential for adverse reactions in the infant. M/P ratio not determined. |
| Teratogenic Risk | Revcovi (elapegademase-lvlr) is a recombinant adenosine deaminase (ADA) enzyme replacement therapy for ADA-SCID. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, no teratogenic effects were observed at doses up to 25 times the human dose. However, immunodeficiency in offspring may occur if maternal ADA deficiency is untreated. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Severe hypersensitivity to bovine-derived products or any component of the formulation"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Neutralizing antibody development with potential loss of efficacy","Coagulation disorders and thrombocytopenia","Hematologic abnormalities (e.g., hemolytic anemia, thrombotic microangiopathy)"] |
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| Fetal Monitoring | Monitor maternal immune function (e.g., ADA activity, lymphocyte counts) and signs of infection. Fetal monitoring via ultrasonography for growth and development. Assess for potential teratogenicity given underlying maternal disease. |
| Fertility Effects | Effects on fertility not studied in humans. In animal studies, no adverse effects on male or female fertility at doses up to 25 times the human dose. |