Drug Guide
Asfotase Alfa
Classification
Therapeutic: Enzyme Replacement Therapy for Hereditary Skeletal Disorders
Pharmacological: Recombinant Human Tetranectinase
FDA Approved Indications
- Hypochondroplasia associated with deficiency of tissue-nonspecific isoenzyme of alkaline phosphatase (TNAP)
Mechanism of Action
Asfotase Alfa is a recombinant, human enzyme that replaces deficient tissue-nonspecific alkaline phosphatase (TNAP) in patients with hypophosphatasia, thereby increasing enzyme activity and improving mineralization of bone tissue.
Dosage and Administration
Adult: Initial dose varies; typically 1 mg/kg/day administered subcutaneously in divided doses. Dose adjustments are based on response and tolerability.
Pediatric: Dosing is weight-based; usual starting dose is 6 mg/kg/week divided into daily or every-other-day injections. Dose adjustments follow response and tolerability.
Geriatric: Pediatric dosing applies; adult dosing is not established beyond the age of 18 for this indication.
Renal Impairment: Adjust based on clinical response; specific guidelines are not established.
Hepatic Impairment: No specific adjustments outlined.
Pharmacokinetics
Absorption: Subcutaneous absorption is variable with peak levels typically reached within a few hours.
Distribution: Distributed extracellularly, with a volume of distribution approximately equal to plasma volume.
Metabolism: Metabolized by proteolytic enzymes, typical for recombinant proteins.
Excretion: Cleared via reticuloendothelial system; renal excretion not significant.
Half Life: Approximately 6-12 hours.
Contraindications
- Known hypersensitivity to asfotase alfa or its components.
Precautions
- Monitor for hypersensitivity reactions, including anaphylaxis. Use with caution in patients with pre-existing hypersensitivity to recombinant enzymes. Monitor serum alkaline phosphatase levels and mineral status regularly.
Adverse Reactions - Common
- Injection site reactions (pain, swelling, erythema) (Common)
- Hypersensitivity reactions, including anaphylaxis (Less common)
Adverse Reactions - Serious
- Anaphylaxis (Rare)
- Serious hypersensitivity reactions (Rare)
Drug-Drug Interactions
- None specifically identified.
Drug-Food Interactions
- None known.
Drug-Herb Interactions
- None established.
Nursing Implications
Assessment: Prior to administration, assess for signs of hypersensitivity. Monitor serum alkaline phosphatase, calcium, phosphate, and other minerals during therapy.
Diagnoses:
- Risk for hypersensitivity reactions
- Imbalanced nutrition: less than body requirements (due to metabolic changes)
Implementation: Administer subcutaneously as prescribed, monitoring for adverse reactions. Educate patient/caregiver on injection technique, storage, and side effects.
Evaluation: Assess for clinical improvement in bone mineralization and symptom relief. Monitor for adverse reactions.
Patient/Family Teaching
- Notify healthcare provider of any signs of allergic reactions.
- Follow storage instructions for medication.
- Report any unusual symptoms immediately.
Special Considerations
Black Box Warnings:
- Potential hypersensitivity reactions, including anaphylaxis.
Genetic Factors: Not specifically indicated.
Lab Test Interference: May alter serum alkaline phosphatase levels, complicating diagnostic interpretation.
Overdose Management
Signs/Symptoms: Allergic reactions, including anaphylaxis; other adverse effects may include injection site reactions.
Treatment: Discontinue drug immediately. Provide symptomatic treatment, including emergency management for hypersensitivity reactions.
Storage and Handling
Storage: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
Stability: Stable for up to 24 hours at room temperature after reconstitution; refer to package insert for specific details.