taliglucerase alfa (Rx)

>10%

Treatment-naïve adults

• Headache (19%)
• Arthralgia (13%)

Treatment naïve children and adolescents

• Vomiting (≥10%)

Switch from imiglucerase adults and children

• Arthralgia (13%)
• Headache (13%)

1-10%

Treatment-naïve adults

• Fatigue (9%)
• Nausea (9%)
• Dizziness (9%)
• Abdominal pain (6%)
• Pruritus (6%)
• Flushing (6%)
• Vomiting (6%)
• Urticaria (6%)

Switch from imiglucerase adults and children

• Pain in extremity (10%)

Postmarketing Reports

Gastrointestinal disorders: Vomiting, diarrhea

General disorders and administration site conditions: Fatigue

Immune system disorders: Anaphylaxis, Type III immune-mediated fixed drug eruption

Musculoskeletal and connective tissue disorders: Back pain

Contraindications

None

Cautions

Anaphylaxis reported; if anaphylaxis occurs, discontinue infusion immediately and initiate appropriate treatment

Allergic and infusion reactions are common and include headache, chest pain or discomfort, asthenia, fatigue, urticaria, erythema, increased blood pressure, back pain, arthralgia, and flushing; if allergic or infusion reactions occur, decrease the infusion rate or temporarily stop the infusion; antihistamines and/or antipyretics may be administered; medical support should be readily available when taliglucerase alfa administered; observe patients closely for an appropriate period of time after administration; reactions have occurred up to 3 hr after the start of infusion

Consider risks and benefits of re-administering taliglucerase alfa in patients who have experienced severe reaction associated with taliglucerase alfa; use caution upon rechallenge; appropriate medical support should be readily available

As with all therapeutic proteins, development of IgG anti-drug antibodies (ADA) has been reported (53%); unknown if presence of ADA is associated with higher risk of infusion reactions or immunogenicity

Monitor patients that have had an immune response to other enzyme replacement therapies or who are switching to taliglucerase alfa; unknown if these patients are at higher risk of infusion reactions

Dizziness and fatigue reported; caution patients against performing dangerous tasks that require mental alertness, including driving heavy machinery

Hypersensitivity reactions

• Reactions, including serious hypersensitivity reactions such as anaphylaxis, reported; due to potential for anaphylaxis, appropriate medical support should be readily available during infusion
• Observe patients closely for 3 hr after start of infusion; inform patients of signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur
• Base management of hypersensitivity reactions on severity of reaction and should include slowing or temporary interruption of infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions
• To reduce risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids; if severe hypersensitivity reactions including anaphylaxis occur, immediately stop infusion and initiate appropriate treatment
• Consider risks and benefits of re-administering therapy in patients who have experienced severe hypersensitivity reaction associated with this medication; exercise caution upon rechallenge

Pregnancy

Insufficient data available on use in pregnant females to inform a drug-associated risk

Animal data

• When pregnant rats and rabbits were administered IV taliglucerase alfa at doses up to 5 times the recommended human dose, there was no evidence of embryofetal toxicity

Clinical considerations

• Women with Type 1 Gaucher disease have an increased risk of spontaneous abortion if disease symptoms are not treated and controlled preconception and during pregnancy
• Pregnancy may exacerbate existing Type 1 Gaucher disease symptoms or result in new disease manifestations
• Type 1 Gaucher disease manifestations may lead to adverse pregnancy outcomes, including hepatosplenomegaly which can interfere with the normal growth of a fetus and thrombocytopenia which can lead to increased bleeding and possible postpartum hemorrhage requiring transfusion

Lactation

There are no data on taliglucerase alfa in human milk, effects on breast fed infants, or effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Gaucher disease is caused by a deficiency of the enzyme to catalyze glucocerebrosidase resulting in lipid accumulation in the spleen, liver, kidneys, and other organs; major signs include liver or spleen damage, anemia, and thrombocytopenia

Taliglucerase alfa catalyzes the hydrolysis of glucocerebroside to glucose and ceramide which results in reduced spleen and liver enlargement, and increased RBCs and platelets

Absorption

AUC

• Children and adolescents (30 units/kg): 1416 ng⋅hr/mL
• Children and adolescents (60 units/kg): 2984 ng⋅hr/mL
• Adults (30 units/kg): 2007 ng⋅hr/mL
• Adults (60 units/kg): 6459 ng⋅hr/mL

Distribution

Vd (steady-state)

• Children and adolescents (30 units/kg): 14.9 L
• Children and adolescents (60 units/kg): 8.8 L
• Adults (30 units/kg): 11.7 L
• Adults (60 units/kg): 10.7 L

Elimination

Clearance

• Children and adolescents (30 units/kg): 30.5 L/hr
• Children and adolescents (60 units/kg): 15.8 L/hr
• Adults (30 units/kg): 30.5 L/hr
• Adults (60 units/kg): 18.5 L/hr

Half-life

• Children and adolescents (30 units/kg): 37.1 min
• Children and adolescents (60 units/kg): 32.5 min
• Adults (30 units/kg): 18.9 min
• Adults (60 units/kg): 28.7 min

IV Preparation

Remove required number of vials from refrigerator; do not leave vials at room temperature >24 hr before reconstitution; do not heat or microwave vials

Reconstitute each vial with 5.1 mL of Sterile Water for Injection to yield concentration of 40 units/mL

Upon reconstitution, mix vials gently; DO NOT SHAKE

Before further dilution, visually inspect vials; solution should be clear and colorless; discard if solution is discolored or if foreign particulate matter is present

Withdraw calculated dose from reconstituted vials and dilute with 0.9% NaCl, to a final volume of 100-120 mL (in children and adolescents) and 130-150 mL (in adults) should be used

For adults, if volume of reconstituted product alone ≥130 to 150 mL, then final volume should not exceed 200 mL

Mix gently; DO NOT SHAKE

Since this is a protein solution, slight flocculation (described as translucent fibers) occurs occasionally after dilution

IV Administration

Infuse diluted solution IV and filtered through in-line, low protein-binding 0.2 micron filter

Pediatric patients weighing <30 kg (actual body weight): 1 mL/min

Pediatric patients weighing ≥30 kg (actual body weight): 1 mL/min initially; may increase up to 2 mL/min after tolerability established

Adults: 1.2 mL/min initially; may increase up to 2.2 mL/min after tolerability established

Storage

Unused vials

• Refrigerate at 2-8ºC (36-46ºF); protect from light

Reconstituted vials

• Contains no preservative
• Use immediately once reconstituted
• If immediate use not possible, refrigerate at 2-8ºC (36-46ºF) for up to 24 hr; protect from light OR
• Store at room temperature (20-25ºC [68-77ºF]) for up to 4 hr without protection from light

Diluted solution

• Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr; protect from light
• Do not freeze; discard any unused product