ALDURAZYME 100 U/ml Concentrate for solution for infusion

What is ALDURAZYME 100 U/ml

ALDURAZYME 100 U/mL is an enzyme replacement therapy containing the recombinant human enzyme **laronidase** (α-L‑iduronidase). It is used intravenously to treat **Mucopolysaccharidosis type I (MPS I)**—a rare genetic disorder where patients lack sufficient α-L-iduronidase, leading to accumulation of glycosaminoglycans (GAGs) in tissues.

• Generic Name: Laronidase (rhIDU)
• Strength/Form: 100 U/mL concentrate for IV infusion (2.9 mg/5 mL per vial)
• Size: Supplied in a 5 mL glass vial containing 500 U total
• Indication: Treatment of non‑neurological symptoms in Hurler, Hurler‑Scheie, and Scheie syndromes
• Regulatory Status: FDA-approved 2003; EU-authorized for long-term ERT :contentReference[oaicite:1]{index=1}

By supplementing the missing enzyme, ALDURAZYME helps break down GAGs—dermatan- and heparan-sulfate—reducing organ enlargement, improving joint mobility, and enhancing overall systemic function (though central nervous system effects are limited) :contentReference[oaicite:2]{index=2}.

How to use ALDURAZYME 100 U/ml

ALDURAZYME must be administered under medical supervision, following precise preparation and infusion protocols.

• Pretreatment: Administer antihistamines ± antipyretics ~60 minutes before infusion to reduce infusion-associated reactions :contentReference[oaicite:3]{index=3}.
• Dilution: Use aseptic technique to dilute vials with 0.9% sodium chloride into infusion bags (50, 100, or 250 mL depending on weight) :contentReference[oaicite:4]{index=4}.
• Filter & Equipment: Use PVC bag, low-protein binding 0.2 µm inline filter, and infusion set :contentReference[oaicite:5]{index=5}.
• Infusion Rate: Start at 10 µg/kg/hr (≈2 U/kg/hr), increasing every 15 min to a max of 200 µg/kg/hr (≈43 U/kg/hr), over 3–4 hours :contentReference[oaicite:6]{index=6}.
• Monitoring: Watch for signs of hypersensitivity or respiratory compromise. Have resuscitation ready :contentReference[oaicite:7]{index=7}.
• Treatment Setting: Hospital or clinic equipped for managing infusion-related emergencies.

Consistent weekly administration is key to maintaining clinical benefit. Dose omissions should be followed by timely rescheduling—consult medical provider if infusions cannot be received :contentReference[oaicite:8]{index=8}.

Mode of Action ALDURAZYME 100 U/ml

ALDURAZYME provides the missing enzyme α-L‑iduronidase to patients with MPS I, enabling the breakdown of glycosaminoglycans (GAGs) accumulated in lysosomes.

• Enzyme Replacement: Laronidase hydrolyzes terminal α-L‑iduronic acid in dermatan sulfate and heparan sulfate within lysosomes :contentReference[oaicite:9]{index=9}.
• GAG Clearance: Reduces pathological GAG accumulation in tissues, mitigating organ enlargement (hepatosplenomegaly), airway obstruction, and musculoskeletal issues.
• Systemic Impact: Administered IV, with systemic distribution via mannose-6-phosphate receptor uptake in target cells; does not cross blood–brain barrier, thus no direct CNS benefit.
• Chronic Therapy: Weekly dosing maintains enzyme levels and slows disease progression.

This biochemical correction can improve physical functioning, airway dynamics, joint flexibility, and quality of life in MPS I patients :contentReference[oaicite:10]{index=10}.

ALDURAZYME 100 U/ml Interactions ALDURAZYME 100 U/ml

Drug–drug interactions with ALDURAZYME are minimal due to its enzyme nature, but certain medications or comorbidities may require caution.

• Minor Drug Interactions: Chloroquine and procaine are listed as minor interactors; clinical relevance remains limited :contentReference[oaicite:11]{index=11}.
• Comorbidity Concern: Patients with cardiac or pulmonary compromise may experience infusion-associated respiratory or cardiovascular risks and should receive slower rates or closer observation :contentReference[oaicite:12]{index=12}.
• Avoid Concomitant Infusions: Do not mix ALDURAZYME with other medications in the same infusion line or bag due to unknown compatibility.

Inform your care team of all concomitant medications and preexisting conditions, especially respiratory or cardiac disease, before initiating infusions.

Dosage of ALDURAZYME 100 U/ml

The standard dosage is based on actual body weight and administered weekly via IV infusion.

• Recommended Dose: 100 U/kg (≈0.58 mg/kg) once weekly :contentReference[oaicite:13]{index=13}.
• Volume Based on Weight:
  • ≤4 kg → dilute into 50 mL
  • 4–20 kg → 100 mL
  • >20 kg → 250 mL (may consider 100 mL for ≤30 kg with cardiac/pulmonary issues) :contentReference[oaicite:14]{index=14}.
• Infusion Rate Adjustment: Increase every 15 min as per tolerance up to 43 U/kg/hr (200 µg/kg/hr) over 3–4 hours :contentReference[oaicite:15]{index=15}.
• Pediatric/Elderly/Renal/Hepatic: No dose adjustment needed in pediatrics; insufficient data for elderly (>65) or renal/hepatic impairment :contentReference[oaicite:16]{index=16}.

Delivery must occur weekly to sustain enzyme activity and therapeutic outcomes. Missed doses should be managed by contacting healthcare provider promptly :contentReference[oaicite:17]{index=17}.

Possible side effects of ALDURAZYME 100 U/ml

ALDURAZYME may cause infusion-associated and hypersensitivity reactions ranging from mild to life-threatening.

• Infusion Reactions (≤49%): Fever, chills, flushing, headache, rash, injection site reactions, tachycardia, abdominal pain, nausea, diarrhea, pruritus, back pain :contentReference[oaicite:18]{index=18}.
• Hypersensitivity/Anaphylaxis (1% severe): Urticaria, angioedema, bronchospasm, hypotension, respiratory distress—may occur during or up to 3 hours post-infusion :contentReference[oaicite:19]{index=19}.
• Serious Cardio‑Respiratory Events: Acute respiratory compromise, failure, cardiorespiratory arrest or pneumonia observed in postmarketing :contentReference[oaicite:20]{index=20}.
• Other Adverse Effects: Thrombocytopenia, corneal opacity, hyperbilirubinemia, paresthesia, hypotension, chest pain, injection-site complications :contentReference[oaicite:21]{index=21}.

Monitoring & Management: Premedicate, infuse slowly, reduce rate or stop if reactions occur. Ensure emergency equipment and medications are ready. Most reactions diminish with repeated exposure :contentReference[oaicite:22]{index=22}.

ALDURAZYME 100 U/ml Contraindications ALDURAZYME 100 U/ml

Absolute contraindication:

• **Severe hypersensitivity or anaphylaxis** to laronidase or any excipients—do not administer if history of severe reaction is documented :contentReference[oaicite:23]{index=23}.

Other considerations:

• Infusions should be administered with great caution or adjusted if patient has acute respiratory disease or cardiopulmonary compromise :contentReference[oaicite:24]{index=24}.
• In case of serious infusion-associated reaction, discontinue permanently or restart only after careful risk–benefit analysis :contentReference[oaicite:25]{index=25}.

Storage of ALDURAZYME 100 U/ml

Proper storage maintains efficacy and prevents spoilage or contamination.

• Temperature: 2 °C–8 °C (refrigerator); do not freeze :contentReference[oaicite:26]{index=26}.
• Protection: Avoid light exposure; keep vial in original packaging.
• Handling: Do not shake vials; inspect for particulates (solution should be clear to slightly opalescent, colorless to pale yellow) :contentReference[oaicite:27]{index=27}.
• After Dilution: Use infusion bags promptly or store at 2 °C–8 °C for up to 36 hrs before use :contentReference[oaicite:28]{index=28}.
• Vial Usage: Single use only; discard unused residue per biohazard guidelines.
• Expiry: Do not use past the labeled expiration date; follow local disposal protocols.