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|Alglucerase

Alglucerase

Trade Names:
Ceredase
- Solution for injection 80 units/mL

Mechanism of Action

Pharmacology

Catalyzes the hydrolysis of glucocerebroside to glucose and ceramide as part of the normal degradation pathway for membrane lipids.

Pharmacokinetics

Absorption

Steady-state enzymatic activity and AUC of the activity increased linearly with the infused dose.

Distribution

Vd ranged from 49.4 to 282.1 mL/kg.

Elimination

Plasma Cl, based on plasma enzymatic activity, ranged from 6.34 to 25.39 mL/min/kg.

Onset

Following IV infusion over a 4-h period, steady-state enzymatic activity is achieved by 60 min.

Duration

Following infusion termination, plasma enzymatic activity declined rapidly with an elimination t _½ ranging from 3.6 to 10.4 min.

Indications and Usage

Long-term replacement therapy for patients with confirmed diagnosis of type 1 Gaucher disease who exhibit signs and symptoms severe enough to result in moderate to severe anemia, thrombocytopenia with bleeding tendency, bone disease, and/or hepatomegaly or splenomegaly.

Unlabeled Uses

Orphan drug status for replacement therapy in types 2 and 3 Gaucher disease.

Contraindications

Standard considerations.

Dosage and Administration

IV Infuse dose over 1 to 2 h. Individualize dosage. Initial dosage may be as little as 2.5 units/kg 3 times a week up to 60 units/kg as frequently as once a week or as infrequently as every 4 wk. After response is well established, a reduction in dosage may be attempted for maintenance therapy. Progressive reductions can be made at intervals of 3 to 6 mo while carefully monitoring response parameters.

General Advice

• Do not shake.
• Inspect for particulate matter and discoloration before use.

Storage/Stability

Store at 36° to 46°F. When diluted to 100 to 200 mL, product is stable for up to 18 h when stored at 36° to 46°F.

Drug Interactions

None well documented.

Laboratory Test Interactions

False-positive pregnancy test.

Adverse Reactions

Cardiovascular

Hypotension, vasomotor irritability or hot flash.

CNS

Fatigue, headache, weakness.

EENT

Impaired sense of smell.

GI

Diarrhea, nausea, oral ulcers, vomiting.

Genitourinary

Menstrual abnormalities.

Local

Burning and swelling or sterile abscess at venipuncture site, discomfort, pruritus.

Musculoskeletal

Backache.

Miscellaneous

Abdominal discomfort, chills, hypersensitivity (abdominal cramping, chest discomfort, flushing, nausea, pruritus, respiratory symptoms, urticaria/angioedema with occasional upper airway involvement), slight fever, transient peripheral edema.

Precautions

Pregnancy

Category C .

Lactation

May be excreted in breast milk.

Children

Safety and efficacy not established in children younger than 2 yr of age.

Hypersensitivity

Use with caution in patients exhibiting symptoms of hypersensitivity; pretreatment with antihistamines has allowed continued use in some patients.

Special Risk Patients

Use with caution in patients with androgen-sensitive malignancies.

Antibodies

Approximately 13% of patients may develop immunoglobulin G antibody during first yr of therapy, of which 25% may experience symptoms of hypersensitivity.

Infections

Because alglucerase is prepared from pooled human placental tissue, there is a risk of transmission of infectious agents (eg, viruses), including Creutzfeldt-Jakob disease.

Overdosage

Symptoms

No obvious toxicity detected after doses up to 234 units/kg.

Patient Information

• Advise patient that this medicine is usually administered at health care provider"s office, hospital, or clinic.
• Advise patient who is using the medicine at home to follow the injection procedures taught by health care provider.