Adagen

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Adagen

Classes

Metabolic Enzyme Therapy, Other

Administration
Injectable Administration Intramuscular Administration

Administer via intramuscular injection only.
Pegademase bovine should not be diluted or mixed with any other medication prior to administration.
Use only one dose per vial. Discard unused portion.

Adverse Reactions
Severe

hemolytic anemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known

Moderate

thrombocytosis / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
erythema / Early / Incidence not known
antibody formation / Delayed / Incidence not known

Mild

injection site reaction / Rapid / Incidence not known
headache / Early / Incidence not known
urticaria / Rapid / Incidence not known

Common Brand Names

Adagen

Dea Class

Rx

Description

Enzyme replacement therapy for severe combined immunodeficiency disease due to ADA deficiency; adherence to a strict treatment schedule eliminates toxic metabolites from ADA deficiency; immune function improves after 2—6 months.

Dosage And Indications
For the treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase (ADA) deficiency. Intramuscular dosage Neonates, Infants, and Children

Dosage must be individualized based on laboratory monitoring. Pegademase bovine should be administered every 7 days by IM injection. The manufacturer recommends initiating therapy as follows: first dose, 10 units/kg IM; second dose, 15 units/kg IM; third dose, 20 units/kg IM. The usual maintenance dose is 20 units/kg/week IM. The weekly dose may be increased by increments of 5 units/week based on laboratory monitoring to a maximum of 30 units/kg/week IM.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

There are no drug interactions associated with Pegademase Bovine products.

How Supplied

Adagen Intramuscular Sol: 1mL, 250U

Maximum Dosage
Adults

Safety and efficacy have not been established.

Adolescents

Safety and efficacy have not been established.

Children

30 units/kg/week IM.

Infants

30 units/kg/week IM.

Mechanism Of Action

Mechanism of action: Pegademase bovine injection provides exogenous replacement therapy for patients with severe combined immunodeficiency disease (SCID) associated with adenosine deaminase (ADA) deficiency. In the absence of ADA, there is an accumulation of adenosine and 2'-deoxyadenosine. The accumulation of these purine substrates causes metabolic abnormalities that are directly toxic to lymphocytes. Pegademase bovine is specific ADA enzyme replacement that corrects the metabolic abnormalities. There is a delay between the correction of the metabolic abnormalities and improved immune function. The length of this delay is patient-specific and has been reported to range from a few weeks to 6 months.In patients with ADA deficiency, the accumulation of 2'-deoxyadenosine results in an elevation in red blood cell deoxyadenosine nucleotide (dATP) and a decrease in red blood cell S-adenosylhomocysteine hydrolase (SAHase). In a pediatric pharmacokinetic study, red blood cell dATP levels were 0.056—0.899 micromol/ml of erythrocytes prior to pegademase bovine therapy. After 2 months of maintenance treatment, the levels decreased to 0.007—0.015 micromol/ml. The normal dATP level is less than 0.001 micromol/ml. Over the same time period, SAHase levels increased from 0.09—0.22 nmol/hour/mg protein to 2.37—5.16 nmol/hour/mg protein. The normal SAHase value is 4.18 +/- 1.9 nmol/hour/mg protein.

Pharmacokinetics

Pegademase bovine is administered via intramuscular injection. 
 
There is limited pharmacokinetic data available. Dose proportionality has not been established. The pharmacokinetics of pegademase bovine have been studied in six pediatric patients ranging in age from 6 weeks to 12 years. The plasma elimination half-life of ADA was variable, even for the same child, ranging from 3 to more than 6 days.

Intramuscular Route

The pharmacokinetics of pegademase bovine have been studied in six pediatric patients ranging in age from 6 weeks to 12 years. Peak plasma levels of adenosine deaminase (ADA) were reached 2 to 3 days after intramuscular injection. After weekly intramuscular injections of 15 units/kg, the average trough level of plasma ADA activity was 20—25 micromol/hour/ml (goal trough plasma ADA activity level is 15—35 micromol/hour/ml per the manufacturer).

Pregnancy And Lactation
Pregnancy

Pegademase bovine is categorized as FDA pregnancy risk category C. Animal reproduction studies have not been conducted. The effects of pegademase bovine on a developing fetus or on female reproductive abilities are not known.

According to the manufacturer, caution should be used when administering pegademase bovine to breast-feeding women. It is not know whether pegademase bovine is excreted into human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.