alglucosidase alfa (Rx)

>10%

Pyrexia (92%)

Diarrhea (62%)

Rash (54%)

Infusion reactions (51%)

Vomiting (49%)

Cough (46%)

Diaper dermatitis (46%)

Pneumonia (46%)

Otitis media (44%)

URI (44%)

O2 saturation decreased (41%)

Gastroenteritis (41%)

Pharyngitis (36%)

Respiratory distress (33%)

Respiratory failure (31%)

Anemia (31%)

Oral candidiasis (31%)

Rhinorrhea (28%)

Catheter-related infection (28%)

GERD (26%)

Post-procedural pain (26%)

Bronchiolitis (23%)

Constipation (23%)

Nasopharyngitis (23%)

Tachycardia (23%)

Tachypnea (23%)

Bradycardia (21%)

Flushing (21%)

Urticaria (21%)

Frequency Not Defined

Bronchospasm

Blurred vision

Abdominal pain

Agitation

Cyanosis

Dyspnea

Facial Erythema

Insomnia

Irritability

Pallor

Restlessness

Tremor

Vertigo

Coronary artery disease

Hypokalemia

Conjunctivitis

Postmarketing Reports

Anaphylactic shock, respiratory failure, respiratory arrest, cardiac arrest, hypoxia, dyspnea, wheezing, convulsions, peripheral coldness, restlessness, nervousness, back pain, stridor, pharyngeal edema, abdominal pain, apnea, muscle spasm, conjunctivitis, hyperparathyroidism

Proteinuria and nephrotic syndrome secondary to membranous glomerulonephritis, and necrotizing skin lesions reported

Contraindications

None

Cautions

Anaphylaxis and hypersensitivity reactions have been observed in patients during and up to 3 hr after infusion; some of the reactions were life-threatening and included anaphylactic shock, cardiac arrest, respiratory arrest, respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria Immune-mediated cutaneous reactions have been reported including necrotizing skin lesions; these reactions occurred several weeks to 3 yr after initiation

Severe reactions are managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated; epinephrine may be administered; appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when alglucosidase alfa is administered

Consider risks and benefits of re-administering alglucosidase alfa following anaphylactic or hypersensitivity reaction; monitor closely with appropriate resuscitation measures available, if decision is made to re-administer product

Nephrotic syndrome secondary to membranous glomerulonephritis was observed in some Pompe disease patients treated with alglucosidase alfa who had persistently positive anti-rhGAA IgG antibody titers; patients receiving alglucosidase alfa should undergo periodic urinalysis

Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions

General anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness; extreme caution should be used when administering general anesthesia; ventricular arrhythmias and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in patients with infantile-onset Pompe disease with cardiac hypertrophy during general anesthesia for central venous catheter placement

As with all therapeutic proteins, there is potential for immunogenicity; monitor patients for IgG antibody formation every 3 months for 2 years and annually thereafter; consider testing for IgG titers if patients develop hypersensitivity reactions, other immune-mediated reactions, or lose clinical response; may also test patients who experience reduced clinical response for inhibitory antibody activity; patients who experience anaphylactic or hypersensitivity reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis

Immune Mediated Reactions

• Immune tolerance induction administered in conjunction with may also aid tolerability of alglucosidase alfa under management of a clinical specialist knowledgeable in immune tolerance induction in pediatric Pompe disease to optimize treatment
• Immune tolerance induction administered prior to and in conjunction with initiation of alglucosidase alfa reported to aid tolerability of alglucosidase alfa in CRIM-negative patients; CRIM status has been shown to be associated with immunogenicity and patients’ responses to enzyme replacement therapies
• CRIM-negative infants with infantile-onset Pompe disease treated with alglucosidase alfa have shown poorer clinical response in the presence of high sustained IgG antibody titers and positive inhibitory antibodies compared to CRIM-positive infants

Pregnancy

Data from postmarketing reports and published case reports with alglucosidase alfa use in pregnant women have not identified an associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; the continuation of treatment during pregnancy should be individualized to pregnant woman; untreated disease may result in worsening disease symptoms in pregnant women

Pregnant women and women of reproductive potential should be encouraged to enroll in the Pompe patient registry; the registry will monitor effect of therapy on pregnant women and their offspring; for more information, visit www.registrynxt.com or call 1-800-745-4447, extension 15500

Disease-associated maternal and/or embryo-fetal risk; untreated Pompe disease has been associated with worsening respiratory and musculoskeletal symptoms in some pregnant women

Animal data

• Reproduction studies performed in mice and rabbits at doses resulting in exposures up to 0.4 or 0.5 times the human steady-state AUC (area under the plasma concentration-time curve), respectively, during the period of organogenesis revealed no evidence of effects on embryo-fetal development; in mice there was an increase in pup mortality during lactation at maternal exposures 0.4 times the human steady-state AUC

Lactation

Available published literature suggests presence of alglucosidase alfa in human milk; there are no reports of adverse effects on the breastfed infant; there is no information on effects of alglucosidase alfa on milk production; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Lactating women with Pompe disease receiving treatment should be encouraged to enroll in Pompe disease registry

A lactating woman may consider interrupting breastfeeding, pumping and discarding breast milk during treatment and for 24 hours after therapy administration in order to minimize drug exposure to a breastfed infant

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

Recombinant acid alpha-glucosidase (GAA)

Carbohydrate groups on GAA molecule bind to mannose-6-phosphate receptors, then GAA is transported into cell where it undergoes proteolytic cleavage resulting in increased enzymatic glycogen cleavage

Pharmacokinetics

Half-Life: 2-3 hr

Peak Plasma Concentration: 162±31 mcg/m

AUC: 811±141 mcg-hr/mL

Vd: 80-110 mL/kg

Clearance: 20-30 mL/hr/kg

IV Incompatibilities

Do not mix with other drugs in same infusion line

IV Preparation

Do not use filter needles during preparation

Determine number of vials required for dose (20 mg/kg)

Remove the required number of vials from the refrigerator and allow them to reach room temperature prior to reconstitution (approximately 30 minutes)

Reconstitute each vial by slowly injecting 10.3 mL sterile water for injection

Avoid foaming & forceful addition of fluid

Protect reconstituted solution from light

Discard if discoloration or particulate matter present

Dilute (slowly) reconstituted solution in 0.9% NaCl to final concentration of 0.5-4 mg/mL

Filter diluted solution through 0.2 micron low protein-binding, in-line filter during administration

IV Administration

Administer by IV infusion over ~4 hr

Infuse with an inline protein binding 0.2-micron filter

1 mg/kg/hr IV infusion initially, may increase by 2 mg/kg/hr q30 min; not to exceed 7 mg/kg/hr

Do not infuse in same IV line with other products

Recommended infusion volume:

• 1.25-2.5 kg: 25 mL
• 2.6-10 kg: 50 mL
• 10.1-20 kg: 100 mL
• 20.1-30 kg: 150 mL
• 30.1-35 kg: 200 mL
• 35.1-50 kg: 250 mL
• 50.1-60 kg: 300 mL
• 60.1-100 kg: 500 mL
• 100.1-120 kg: 600 mL
• 120.1-140 kg: 700 mL
• 140.1-160 kg: 800 mL
• 160.1-180 kg: 900 mL
• 180.1-200 kg: 1000 mL

Storage

Unreconstituted vials: Store at 2-8°C (36-46°F)

Protect from freezing

Do not shake

Reconstituted/diluted solution stable up to 24 hr at 2-8°C (36-46°F)

Protect from light