Pegademase Bovine Dosage

Applies to the following strengths: 250 units/mL

Usual Pediatric Dose for:

Adenosine Deaminase Deficiency

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Pediatric Dose for Adenosine Deaminase Deficiency

First dose: 10 units/kg intramuscularly
Second dose: 15 units/kg intramuscularly
Third dose: 20 units/kg intramuscularly

Maintenance dose: 20 units/kg/week intramuscularly
Maximum dose: 30 units/kg intramuscularly

Comments:

This drug should be administered every 7 days.
Dose should be individualized based on monitoring of plasma adenosine deaminase (ADA) activity levels and red blood cell deoxyadenosine triphosphate (dATP) content.
Dose increases of 5 units/kg/week may be necessary.
Dose proportionality has not been established and patients should be closely monitored when the dosage is increased.

Use: Enzyme replacement therapy for ADA deficiency in infants from birth and children of any age with severe combined immunodeficiency disease (SCID) who are not suitable candidates for, or have failed, bone marrow transplantation.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Antibody Formation:

Dosage adjustments may be required to induce tolerance and restore ADA activity.

Thrombocytopenia: Use with Caution.
Severe Thrombocytopenia: Contraindicated.

Biochemical Goals for Maintenance Dosage:

Maintain plasma ADA activity (trough levels before maintenance injection) in the range of 15 to 35 micromoles/hr/mL (assayed at 37 degrees Celsius).
Decline in erythrocyte dATP to 0.005 to 0.015 micromoles/mL or less packed erythrocytes, or 1% or less of the total erythrocyte adenine nucleotide (ATP + dATP) content, with a normal ATP level as measured in a pre-injection sample.

Precautions

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:

Inspect for particulate matter and discoloration prior to administration.
Do not dilute or mix with any other drug prior to administration.
IV administration is not recommended.
Use only one dose per vial; do not re-enter the vial.
Discard unused portions; do not save for later administration.

Reconstitution/Preparation Techniques:

Consult the manufacturer's product information.

Storage Requirements:

Refrigerate (2 to 8 degrees Celsius/36 to 46 degrees Fahrenheit); do not store at room temperature and do not freeze.
Do not use if there are any indications that this drug may have been frozen.

General:

In contrast to the natural history of SCID due to ADA deficiency, a trend toward diminished frequency of opportunistic infections and fewer complications of infections has occurred in patients receiving this drug.
Improvement in immune function only occurs after metabolic abnormalities that are directly toxic to lymphocytes are corrected; this drug corrects those metabolic abnormalities.
The lag time between the correction of the metabolic abnormalities and improved immune function is variable, and has been reported to be from a few weeks to approximately 6 months.
Improvement in the general clinical status of the patient may be gradual, but should be apparent by the end of the first year of treatment.
There is no evidence that maintaining pre-injection plasma ADA above 35 micromoles/hr/mL produces any additional clinical benefits.
This drug is not intended as a replacement for HLA identical bone marrow transplant therapy nor is it intended to replace continued close medical supervision and the initiation of appropriate diagnostic tests and therapy as indicated for intercurrent illnesses.
This drug will not benefit patients with immunodeficiency due to causes other than ADA deficiency.

Monitoring:

Prior to and During Treatment: Immune function and clinical status.
Prior to Treatment: Plasma ADA activity levels (trough levels before maintenance injection), biochemical markers of ADA deficiency (primarily red blood cell dATP level), and parameters of immune function.
Once Treatment Initiated: Plasma ADA activity (desirable range: 15 to 35 micromoles/hr/mL trough level before maintenance injection).
First 8 to 12 Weeks of Treatment: Plasma ADA activity (pre-injection) every 1 to 2 weeks in order to establish an effective dose.
After 2 Months of Maintenance Treatment: Red blood cell dATP levels (desirable range: 0.005 to 0.015 micromoles/mL or less; dATP normal value: below 0.001 micromoles/mL).
Once dATP Level has Fallen Adequately: Red blood cell dATP levels 2 to 4 times a year during the remainder of the first year and 2 to 3 times a year thereafter, assuming no interruption in therapy.
Between 3 and 9 Months: Plasma ADA activity twice a month, then monthly until after 18 to 24 months of treatment.
Patients on Therapy for 2 Years: Plasma ADA activity every 2 to 4 months and red blood cell dATP twice yearly. More frequent monitoring if therapy interrupted or if an enhanced rate of clearance develops.