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  • CLASSES

    Gauchers Disease Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Metabolic enzyme replacement.
    Used in the treatment of patients with Gaucher's disease.
    First plant-made recombinant pharmaceutical.

    COMMON BRAND NAMES

    ELELYSO

    HOW SUPPLIED

    ELELYSO Intravenous Inj Pwd F/Sol: 200IU

    DOSAGE & INDICATIONS

    For replacement therapy of glucosylceramidase in confirmed (type 1) Gaucher's disease:.
    NOTE: Taliglucerase alfa is designated as an orphan drug by the FDA for this indication.
    Intravenous dosage
    Adults, Adolescents, and Children >= 4 years

    Dosage must be individualized according to patient need and response. The recommended dose is 60 Units/kg IV infusion once every 2 weeks. Patients with Type I Gaucher disease who are changing therapy from a dose of imiglucerase to taliglucerase should begin treatment with taliglucerase at that same dose. Titrate dose to individual patient response and therapeutic goals.

    MAXIMUM DOSAGE

    Adults

    60 Units/kg/dose IV every 2 weeks.

    Geriatric

    60 Units/kg/dose IV every 2 weeks.

    Adolescents

    60 Units/kg/dose IV every 2 weeks.

    Children

    >= 4 years: 60 Units/kg/dose IV every 2 weeks.
    < 4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    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.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Administer via intravenous (IV) infusion only.
     
    Reconstitution
    Each vial provides 200 Units. Determine the number of vials that will be needed to provide the patient's dose; round up to the next whole vial.
    Remove vials from refrigerator; do not leave them longer than 24 hours at room temperature. Do not heat.
    Reconstitute each 200 unit vial with 5.1 mL Sterile Water for Injection. Mix gently; do not shake the vials. This yields a reconstituted product with a concentration of 40 units/mL and a withdrawal volume of 5 mL.
    Any vials exhibiting opaque particles or discoloration should not be used to prepare the infusion.
    Pediatric patients: Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection to a final volume of 100 to 120 mL. Mix gently and do not shake.
    Adult patients: Withdraw the calculated dose of drug from the appropriate number of vials and dilute with 0.9% Sodium Chloride Injection. A final volume of 130 to 150 mL may be used; if the volume of reconstituted drug alone is equal to or greater than 130 to 150 mL, then the maximum final volume should be 200 mL. Mix gently and do not shake.
    Being a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after preparing the infusion.
    Storage: Solution should be used promptly after dilution and not stored for later use. If immediate use is not possible, the reconstituted product is stable for 24 hours at 2 to 8 degrees C (36 to 46 degrees F) under protection from light or 4 hours at 20 to 25 degrees C (68 to 77 degrees F) without protection from light. After dilution, the infusion is stable up to 24 hours if stored at 2 to 8 degrees C (36 to 46 degrees F) under protection from light. Do not freeze.
     
    Intravenous infusion
    During administration, the diluted solution should be filtered through an in-line low protein-binding 0.2 micron filter.
    Pediatric patients: Infuse over 1 to 2 hours. Begin with an initial infusion rate of 1 mL/minute; once tolerability is established, the rate may be increased to a maximum of 2 mL/minute.
    Adult patients: Infuse over 1 to 2 hours. Begin with an initial infusion rate of 1.2 mL/minute; once tolerability is established, the rate may be increased to a maximum of 2.2 mL/minute.
    The total volume of the infusion solution should be delivered over a period of no less than 1 hour.

    STORAGE

    ELELYSO:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from light
    - Reconstituted product should be refrigerated and used within 24 hours if not used immediately
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Infusion-related reactions

    Although there are no known contraindications, taliglucerase alfa should be used with caution in patients with a known hypersensitivity to other enzyme replacement therapies. Patients receiving taliglucerase have developed IgG antibodies to the product. In clinical studies, 29% of patients experienced hypersensitivity and/or infusion-related reactions. Serious hypersensitivity reactions, including anaphylactoid reactions and anaphylaxis, are possible and have occurred during and up to 3 hours after the start of taliglucerase infusion. For this reason, appropriate medical support should be readily available during administration. Observe patients closely for an appropriate period of time after administration. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical attention if such signs and symptoms occur.  If a severe reaction occurs, immediately discontinue taliglucerase and initiate appropriate medical treatment. For mild reactions, slow or temporarily interrupt the infusion and/or administer antihistamines, antipyretics, and/or corticosteroids. Pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions. Consider the risks and benefits of re-administration of taliglucerase in patients who have experienced a severe reaction; exercise great caution upon re-challenge.

    Pregnancy

    Taliglucerase alfa is classified in FDA pregnancy risk category B. There are no adequate and well controlled studies in pregnant women. Reproduction studies have been performed in pregnant rats and rabbits at doses about 5 times the recommended human dose of 60 Units/kg based on the BSA); results did not show impaired fertility or harm to the fetus. Because animal reproduction studies are not always predictive of human response, taliglucerase alfa should be used during pregnancy only if clearly needed. However, a report from a panel of clinicians that treat Gaucher's disease indicated that treatment with enzyme replacement therapy during pregnancy led to a reduced risk of spontaneous abortion and a reduced risk of Gaucher-related complications during delivery and during the postpartum period. Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.

    Breast-feeding

    It is not known if taliglucerase alfa is distributed into breast milk. According to the manufacturer, it should be used with caution in breast-feeding women. Enzymes such as taliglucerase alfa are likely to be degraded by the infant's digestive sytem and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with enzyme replacement therapy postpartum. Consider reducing the overall duration of breast-feeding to avoid excessive bone loss in the mother. Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data. 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.

    Children, infants, neonates

    The safety and efficacy of taliglucerase alfa in children < 4 years, infants, or neonates have not been established.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / 3.0-3.0
    angioedema / Rapid / Incidence not known

    Moderate

    antibody formation / Delayed / 16.0-53.0
    hypotension / Rapid / Incidence not known
    erythema / Early / Incidence not known
    infusion-related reactions / Rapid / Incidence not known
    wheezing / Rapid / Incidence not known

    Mild

    headache / Early / 13.0-19.0
    arthralgia / Delayed / 13.0-13.0
    fatigue / Early / 9.0-9.0
    dizziness / Early / 9.0-9.0
    nausea / Early / 9.0-9.0
    abdominal pain / Early / 6.0-6.0
    pruritus / Rapid / 6.0-6.0
    urticaria / Rapid / 6.0-6.0
    flushing / Rapid / 6.0-6.0
    vomiting / Early / 6.0
    back pain / Delayed / Incidence not known
    throat irritation / Early / Incidence not known
    cough / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known
    diarrhea / Early / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Taliglucerase Alfa products.

    PREGNANCY AND LACTATION

    Pregnancy

    Taliglucerase alfa is classified in FDA pregnancy risk category B. There are no adequate and well controlled studies in pregnant women. Reproduction studies have been performed in pregnant rats and rabbits at doses about 5 times the recommended human dose of 60 Units/kg based on the BSA); results did not show impaired fertility or harm to the fetus. Because animal reproduction studies are not always predictive of human response, taliglucerase alfa should be used during pregnancy only if clearly needed. However, a report from a panel of clinicians that treat Gaucher's disease indicated that treatment with enzyme replacement therapy during pregnancy led to a reduced risk of spontaneous abortion and a reduced risk of Gaucher-related complications during delivery and during the postpartum period. Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.

    It is not known if taliglucerase alfa is distributed into breast milk. According to the manufacturer, it should be used with caution in breast-feeding women. Enzymes such as taliglucerase alfa are likely to be degraded by the infant's digestive sytem and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with enzyme replacement therapy postpartum. Consider reducing the overall duration of breast-feeding to avoid excessive bone loss in the mother. Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data. 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.

    MECHANISM OF ACTION

    Taliglucerase alfa substitutes for the deficient enzyme glucosylceramidase in patients with Gaucher's disease. Gaucher's disease is a congenital disorder of lipid metabolism. It results from a deficiency of glucosylceramidase, a necessary catalyst for the hydrolysis of glucosylceramide, an endogenous, very insoluble glycolipid. Patients with this condition have a build-up of this glycolipid in lysosomes of phagocytic cells, which are found in storage cells of the liver, spleen, and bone marrow as well as in the lung, kidney, and intestine. Clinically, this build-up is associated with splenomegaly, hepatomegaly, increased skin pigmentation, and lesions of bone.
     
    Taliglucerase alfa is designed to be preferentially taken up by macrophages, the drug's site of action. Treatment with taliglucerase alfa results in hydrolysis of the accumulated glycolipid within macrophages and improvement in hemoglobin, hematocrit, and platelet counts, and a decrease in hepatomegaly and splenomegaly. Reductions in size of an enlarged liver and spleen correspond to hematological improvement and patients' subjective improvement. Treatment with taliglucerase alfa does not cure the underlying condition, but it does provide improvement. Continued use is required to maintain suppression of symptoms.

    PHARMACOKINETICS

    Taliglucerase alfa is administered by intravenous (IV) infusion because glycoproteins are destroyed in the gastrointestinal tract and cannot be administered orally. In adult clinical trials (n = 29), the median systemic clearance values were 30.5 L/hour and 18.5 L/hour for the 30 and 60 units/kg dose groups, respectively. The median volume of distribution at steady state (Vss) ranged from 10.7—11.7 L for both adult dose groups. At the end of the infusion, taliglucerase alfa serum concentrations decreased rapidly with a median terminal half-life of 18.9—28.7 minutes for both adult dose groups.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    Taliglucerase alfa exhibits nonlinear pharmacokinetics with a greater than dose-proportional increase in exposure at the intravenous infusion doses studied. Median AUC values were 2007 and 6459 ng x hr/ml after 30 and 60 units/kg doses, respectively, in adult patients.