Laronidase

(USAN, rINN)
Synonyms: AlphaL-iduronidase; Alronidase; Laronidasa; Laronidasum; Laronidaz. 8
Cyrillic synonym: Ларонидаз.

💊 Chemical information

CAS — 210589-09-6.
ATC — A16AB05.
ATC Vet — QA16AB05.

💊 Adverse Effects, Treatment, and Precautions

Anaphylactic and other infusion reactions, sometimes delayed in onset, have been reported in patients given laronidase and facilities for resuscitation should be available whenever laronidase is used. Common symptoms include flushing, fever, headache, and rash; bronchospasm has also been reported. Other adverse effects commonly reported include abdominal pain, arthralgia, back pain, nausea, vomiting, diarrhoea, cough, dyspnoea, urticaria, angioedema, pruritus, chills, paraesthesia, dizziness, tachycardia, increased blood pressure, and decreased oxygen saturation. Patients with existing respiratory disease may be at risk of more severe reactions. Antihistamines and/or antipyretics (e.g. paracetamol or ibuprofen) may relieve symptoms. A reduction in the rate of infusion to half the rate at which the reaction occurred should also be considered for mild or moderate reactions; for severe reactions, the infusion should be stopped until symptoms have subsided, and then restarted at one-half to one-quarter the rate at which the reaction occurred. Adrenaline should be used with caution because there is a greater incidence of coronary artery disease in patients with mucopolysaccharidosis I. Pre-treatment with antihistamines and/or antipyretics about 60 minutes before infusion is recommended to prevent reactions. IgG antibodies to laronidase are expected to develop within 3 months of starting treatment in the majority of patients, although the effect of this on safety and efficacy is not clear. However, such patients may be at increased risk of hypersensitivity reactions and should be treated with caution. Injection site reactions have also been reported.

💊 Interactions

Licensed product information for laronidase recommends that it should not be given with chloroquine or procaine because of the potential risk of interference with the intracellular uptake of the enzyme.

💊 Uses and Administration

Laronidase is recombinant human α-L-iduronidase and is used as enzyme replacement therapy for the treatment of the non-neurological manifestations of mucopolysaccharidosis I (see below). It is given by intravenous infusion in a dose of 100 units/kg each week. The initial infusion rate should be 2 units/kg per hour, increased every 15 minutes during the first hour, as tolerated, to a maximum of 43 units/kg per hour such that the infusion is completed in about 3 to 4 hours (but see also under Adverse Effects, Treatment, and Precautions, above). In some countries, the dose is expressed as mg/kg: 100 units is equivalent to about 580 micrograms of laronidase.

Mucopolysaccharidosis I.

Mucopolysaccharidosis I is a progressive disorder characterised by deficiency of the enzyme α-Liduronidase, which is necessary to catalyse the hydrolysis of terminal α-L-iduronic residues of the glycosaminoglycans, dermatan sulfate and heparan sulfate. This results in their accumulation in tissues, with many clinical manifestations including hepatomegaly, skeletal abnormalities, pulmonary disease, eye disease, and progressive deterioration of the CNS. Mucopolysaccharidosis I has traditionally been classified into three main forms based on clinical symptoms and severity: Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome. Hurler syndrome is the most severe form with a life expectancy of less than 10 years. However, there is a degree of overlap between the syndromes and they are indistinguishable by routine enzyme or urine tests. Treatment was previously limited to symptomatic management but other options to halt disease progression are now available. Haematopoietic stem-cell transplantation using bone marrow or umbilical cord blood is of benefit in systemic disease and can prevent (but not usually reverse) CNS deterioration. However, substantial adverse effects limit its use to patients with severe disease. Enzyme replacement therapy with laronidase has been reported to confer benefit on the systemic manifestations of the disease, but since it does not cross the blood-brain barrier in appreciable amounts, beneficial effect on CNS symptoms is again predicted to be unlikely. However, the improvements conferred by enzyme replacement therapy might make haematopoietic stem-cell transplantation easier to tolerate.
1. Kakkis ED, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001; 344: 182–8
2. Wraith JE. Enzyme replacement therapy in mucopolysaccharidosis type I: progress and emerging difficulties. J Inherit Metab Dis 2001; 24: 245–50
3. Kakkis ED. Enzyme replacement therapy for the mucopolysaccharide storage disorders. Expert Opin Invest Drugs 2002; 11: 675–85
4. Kakavanos R, et al. Immune tolerance after long-term enzymereplacement therapy among patients who have mucopolysaccharidosis I. Lancet 2003; 361: 1608–13
5. Muenzer J, Fisher A. Advances in the treatment of mucopolysaccharidosis type I. N Engl J Med 2004; 350: 1932–4
6. Staba SL, et al. Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med 2004; 350: 1960–9
7. Wraith JE, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human α-L-iduronidase (laronidase). J Pediatr 2004; 144: 581–8
8. Grewal SS, et al. Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome. Genet Med 2005: 7: 143–6
9. Miebach E. Enzyme replacement therapy in mucopolysaccharidosis type I. Acta Paediatr Suppl 2005; 94 (suppl 447): 58–60
10. Wraith JE, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human α-iduronidase (laronidase). Abstract: Pediatrics 2007; 120: 158. Full version: http://pediatrics.aappublications.org/cgi/reprint/120/1/e37 (accessed 07/02/08)

💊 Preparations

Proprietary Preparations

Belg.: Aldurazyme; Canad.: Aldurazyme; Cz.: Aldurazyme; Denm.: Aldurazyme; Fin.: Aldurazyme; Fr.: Aldurazyme; Ger.: Aldurazyme; Israel: Aldurazyme; Ital.: Aldurazyme; Neth.: Aldurazyme; Norw.: Aldurazyme; NZ: Aldurazyme; Pol.: Aldurazyme; Spain: Aldurazyme; Swed.: Aldurazyme; UK: Aldurazyme; USA: Aldurazyme.
Published May 08, 2019.