Index of drugs

Long-term enzymatic substitution in patients with a confirmed diagnosis of type I mucopolysaccharidosis (MPS I, α-L-iduronidase deficiency) to treat non-neurological symptoms of the disease.

1 ml contains 100 U (approximately 0.58 mg) of laronidase. One vial (5 ml) contains 500 U of laronidase (and 1.29 mmol sodium).

Laronidase is a lysosomal hydrolase that catalyzes the hydrolysis of the terminal α-L-iduronic residues of dermatan sulfate and heparan sulfate. The deficiency of this enzyme leads to the accumulation of glycosaminoglycans in the cells of many tissues. The use of the preparation allows to reproduce the enzymatic activity, sufficient to hydrolyze the accumulated substrate and prevent its further accumulation. The controlled studies showed improvement in lung function, reduction of left ventricular hypertrophy, normalization of liver volume and reduction of glycosaminoglycans in the urine after use. After intravenous administration, laronidase is rapidly removed from the circulation and captured by lysosomal cells. T_0,5 at steady state is about 2 hours.

Severe hypersensitivity (eg anaphylactic reaction) to the active substance or any of the excipients.

In patients treated with the preparation, infusion-related reactions (IARs) may occur, by which any undesirable reactions occurring during or before the end of the infusion day are understood. Patients treated with the product should be closely monitored and reported with all cases of infusion reactions, delayed reactions and possible immunological reactions. Antibodies should be regularly monitored and reported. Patients with pre-existing severe disease including upper respiratory tract infections have experienced severe infusion-related reactions, and these patients should therefore be closely monitored and infused only under appropriate clinical conditions with immediate access to emergency resuscitation devices. The risk of IAR-related reactions during the infusion of the drug appears to be higher in patients with acute comorbidities. Before commencing administration of the preparation, the patient's condition should be carefully assessed. Almost all patients can be expected to develop IgG antibodies against laronidase, generally within 3 months of starting treatment. Caution should be exercised when administering to patients who have developed antibodies or have symptoms of IAR. In clinical trials, it was usually possible to control the symptoms of IAR by reducing the rate of infusion and by administering antihistamines and / or antipyretics (paracetamol or ibuprofen) to the patient, thus enabling further treatment. Due to limited experience in resuming treatment after a longer break, caution should be exercised on the theoretically increased risk of hypersensitivity reactions after discontinuation of treatment. To reduce the risk of IAR symptoms about 60 minutes before the first infusion or before re-use after prolonged interruption, premedication is recommended (antihistamines and / or antipyretics). If these are clinical indications, premedication should also be considered prior to subsequent infusions of the preparation. For mild or moderate IARs, treatment with antihistamines and Paracetamol or Ibuprofen should be considered and / or the infusion rate should be halved less than half that at which the reaction occurred. For single severe IARs, infusion should be discontinued until symptoms disappear and consideration should be given to antihistamines and paracetamol or ibuprofen. The infusion can be resumed at a rate of 1 / 2-1 / 4 of the rate at which the reaction occurred. For recurrent moderate IARs or re-attempted treatment after single severe IARs, premedication (antihistamines and paracetamol / ibuprofen and / or corticosteroids) and reduction of infusion rate to 1 / 2-1 / 4 should be considered, with previous reaction. In the event of serious hypersensitivity reactions, immediate discontinuation of the preparation and appropriate treatment is recommended. Observe the current standards of emergency procedures. The medicinal preparation contains sodium.The preparation is administered intravenously in a 0.9% sodium chloride solution - this should be taken into account in the case of patients using the low-sodium diet.

The preparation should not be used during pregnancy unless there is a clear need. Laronidase can be secreted with milk. It is recommended to stop breastfeeding during treatment with the preparation.

Most of the side effects are associated with infusion (IAR). Side effects in patients aged 5 years and more treated for up to 4 years. Very common: headache, hot flushes, vomiting, abdominal pain, rash, arthritis, back pain, limb pain, fever, reaction at the injection site. Common: anaphylactic reaction, anxiety paresthesia, dizziness, tachycardia, hypotension, pallor, coldness, peripheral tissues, respiratory failure, shortness of breath, cough, diarrhea, angioneurotic edema, swelling of the face, urticaria, pruritus, cold sweat, alopecia, hyperhidrosis, musculoskeletal pain, chills, feeling hot, feeling cold, tired, flu-like symptoms, increased body temperature, decreased saturation. Frequency unknown: cyanosis, hypoxia of organs and tissues, accelerated breathing, bronchospasm, erythema breath retention, facial edema, laryngeal edema, peripheral edema, extravasation. One patient with pre-existing airway obstruction experienced a severe response after 3 hours from the start of infusion (at 62 weeks of treatment) in the form of urticaria and airway obstruction, which required tracheostomy. The result of the IgE determination in this patient was positive. In addition, severe severe reactions including bronchospasm, respiratory arrest and facial swelling have occurred in several severe type I patients with a history of severe type I mucopolysaccharidosis (a history of upper respiratory tract and lungs). Side effects in patients under 5 years of age, mainly with severe phenotype, treated for up to 12 months: very common: tachycardia, fever, chills, increased blood pressure, decreased saturation. Almost all patients developed IgG antibodies against laronidase. In the majority of patients, seroconversion occurred within 3 months of starting treatment; although in patients aged less than 5 years with severe phenotype, seroconversion occurred mainly within 1 month. The presence of antibodies does not appear to be related to the occurrence of IAR reactions, however, the onset of IARs generally coincides with the initiation of antibody formation.

Treatment should be carried out under the supervision of a doctor with experience in the treatment of patients with MPS I or other congenital metabolic diseases. The drug should be administered in appropriate clinical conditions, with immediate access to the resuscitation equipment needed to treat sudden life-threatening conditions. The recommended dose is 100 U / kg. administered once a week. There is no need to adjust the dose for children and adolescents.Special groups of patients. The safety and efficacy of the medicine have not been established in patients over the age of 65; these patients can not be prescribed any dosage regimen. The safety and efficacy of the medicine have not been evaluated in patients with renal or hepatic impairment; these patients can not be prescribed any dosage regimen.Method of administration. The drug should be administered as an intravenous infusion. The initial infusion rate of 2 U / kg / h can be increased gradually, every 15 minutes in case of good toleration, up to a maximum rate of 43 U / kg / h. The total infusion volume should be administered within approximately 3-4 hours.