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  • Myozyme
    / Sanofi


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 X 50 mg

    partial basket chart 30994 13696

    Related information


    Dosage

    The treatment should be supervised by a physician experienced in the management of patients with Pompe disease or other inherited metabolic or neuromuscular diseases. The recommended dosage regimen of alglucosidase alfa is 20 mg/kg of body weight administered once every 2 weeks. Patient response to treatment should be routinely evaluated based on a comprehensive evaluation of all clinical manifestations of the disease.
    Paediatric and older people: There is no evidence for special considerations when this product is administered to paediatric patients of all ages or older people.
    Patients with renal and hepatic impairment: The safety and efficacy of this product in patients with renal or hepatic impairment have not been evaluated and no specific dose regimen can be recommended for these patients.
    Method of administration: This product should be administered as an intravenous infusion. Infusions should be administered incrementally. It is recommended that the infusion begin at an initial rate of 1 mg/kg/hr and be gradually increased by 2 mg/kg/hr every 30 minutes if there are no signs of infusion associated reactions (IARs) until a maximum rate of 7 mg/kg/hr is reached.
    See prescribing information for full details.


    Indications

    Indicated for long-term enzyme replacement therapy (ERT) in patients with a confirmed diagnosis of pompe disease (acid alpha-glucosidase deficiency). The benefits of this product in patients with late-onset Pompe disease have not been established.


    Contra-Indications

    Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients, when rechallenge was unsuccessful.


    Special Precautions

    Serious and life-threatening anaphylactic reactions, including anaphylactic shock, have been reported in infantile- and late-onset patients during infusions. Because of the potential for severe infusion associated reactions, appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when this product is administered. If severe hypersensitivity or anaphylactic reactions occur, immediate discontinuation of infusion should be considered and appropriate medical treatment should be initiated. The current medical standards for emergency treatment of anaphylactic reactions are to be observed.
    Infusion Associated Reactions: Approximately half of the patients treated with this product in infantile-onset clinical studies and 28% of the patients treated with this product in a late-onset clinical study developed infusion associated reactions (IARs). IARs are defined as any related adverse event occurring during the infusion or during the hours following infusion. Some reactions were severe. A tendency was observed in infantile patients treated with a higher dose (40 mg/kg) to experience more symptoms when developing IARs. Infantile-onset patients who develop high antibody titres appear to be at higher risk for developing more frequent IARs. Patients with an acute illness (e.g. pneumonia, sepsis) at the time of infusion appear to be at greater risk for IARs. Careful consideration should be given to the patient’s clinical status prior to administration of this product. Patients who have experienced IARs (and in particular anaphylactic reactions) should be treated with caution when re-administering this product. Mild and transient effects may not require medical treatment or discontinuation of the infusion. Reduction of the infusion rate, temporary interruption of the infusion, or pre-treatment, generally with oral antihistamine and/or antipyretics and/or corticosteroids, has effectively managed most reactions. IARs may occur at any time during the infusion or generally up to 2 hours after, and are more likely with higher infusion rates.
    Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from infusion associated reactions. Therefore, these patients should be monitored more closely during administration.
    Immunogenicity: In clinical studies, the majority of patients developed IgG antibodies to alglucosidase alfa typically within 3 months of treatment. Thus seroconversion is expected to occur in most patients treated with this product. A tendency was observed for infantile-onset patients treated with a higher dose (40 mg/kg) to develop higher titers of IgG antibodies. There does not appear to be a correlation between the onset of IARs and the time of IgG antibody formation. A limited number of the IgG positive patients evaluated tested positive for inhibitory effects on in vitro testing. Due to the rarity of the condition and the limited experience to date, the effect of IgG antibody formation on safety and efficacy is currently not fully established. The probability of a poor outcome and of developing high and sustained IgG antibody titers appears higher among CRIM-negative patients (Cross Reactive Immunologic Material; patients in whom no endogenous GAA protein was detected by Western blot analysis) than among CRIM-positive patients (patients in whom endogenous GAA protein was detected by Western blot analysis). However, high and sustained IgG antibody titers also occur in some CRIM-positive patients. The cause of a poor clinical outcome and of developing high and sustained IgG antibody titers is thought to be multi-factorial. IgG antibody titers should be regularly monitored. Patients who experience hypersensitivity reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis. Patients who develop IgE antibodies to this product appear to be at a higher risk for the occurrence of IARs when this product is re-administered. Therefore, these patients should be monitored more closely during administration. Some IgE positive patients were successfully rechallenged with this product using a slower infusion rate at lower initial doses and have continued to receive this product under close clinical supervision.
    Immune-mediated reactions: Severe cutaneous reactions, possibly immune-mediated, have been reported with alglucosidase alfa, including ulcerative and necrotizing skin lesions. Nephrotic syndrome was observed in a few Pompe patients treated with alglucosidase alfa and who had high IgG antibody titres (≥ 102,400). In these patients renal biopsy showed immune complex deposition. Patients improved following treatment interruption. It is therefore recommended to perform periodic urinalysis among patients with high IgG antibody titres. Patients should be monitored for signs and symptoms of systemic immune mediated reactions involving skin and other organs while receiving alglucosidase alfa. If immune-mediated reactions occur, discontinuation of the administration of alglucosidase alfa should be considered and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune-mediated reaction should be considered. Some patients have been successfully rechallenged and continued to receive alglucosidase alfa under close clinical supervision.
    Immunomodulation: Patients with Pompe disease are at risk of respiratory infections due to the progressive effects of the disease on the respiratory muscles. Immunosuppressive agents have been administered in experimental settings in a small number of patients, in an attempt to reduce or prevent the development of antibodies to alglucosidase alfa. Fatal and life-threatening respiratory infections have been observed in some of these patients. Therefore, treating patients with Pompe disease with immunosuppressive agents may further increase the risk of developing severe respiratory infections and vigilance is recommended.
    Risk of Cardio-Respiratory failure due to volume overload: A few reports of fluid overload have been received. Infantile patients with underlying cardiac hypertrophy are at risk. Patients with an acute underlying illness at the time of infusion may be at greater risk for experiencing acute cardiorespiratory failure. Acute cardiorespiratory failure requiring intubation and inotropic support has been observed after infusion with alglucosidase alfa in a few infantile-onset patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa.
    See prescribing information for full details.


    Side Effects

    Infantile-onset Pompe disease: In clinical trials, 39 infantile-onset patients were treated with this product for more than three years (168 weeks with a median of 121 weeks). Adverse reactions reported in at least 2 patients. Adverse reactions were mostly mild to moderate in intensity and almost all occurred during the infusion or during the 2 hours following the infusion (infusion associated reactions, IARs). Serious infusion reactions including urticaria, rales, tachycardia, decreased oxygen saturation, bronchospasm, tachypnea, periorbital edema and hypertension have been reported.
    Late-onset Pompe disease: In a placebo-controlled study lasting 78 weeks, 90 patients with late-onset Pompe disease, aged 10 to 70 years, were treated with this product or placebo randomized in a 2:1 ratio. Overall, the numbers of patients experiencing adverse reactions and serious adverse reactions were comparable between the two groups. The most common adverse reactions observed were IARs. Slightly more patients in the treated group than in the placebo group experienced IARs (28% versus 23%). The majority of these reactions were non-serious, mild to moderate in intensity and resolved spontaneously. Adverse reactions reported in at least 2 patients. Serious adverse reactions reported in 4 patients treated with this product were: angioedema, chest discomfort, throat tightness, non-cardiac chest pain and supraventricular tachycardia. Reactions in 2 of these patients were IgE-mediated hypersensitivity reactions. A small number of patients (< 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/or cardiac arrest during infusion that required life-support measures. Reactions generally occurred shortly after initiation of the infusion. Patients presented with a constellation of signs and symptoms, primarily respiratory, cardiovascular, edematous and/or cutaneous in nature.
    Recurrent reactions consisting of flu-like illness or a combination of events such as fever, chills, myalgia, arthralgia, pain, or fatigue occurring post-infusion and lasting usually for a few days, have been observed in some patients treated with alglucosidase alfa. The majority of patients were successfully re-challenged with alglucosidase alfa using lower doses and/or pretreatment with anti-inflammatory drugs and/or corticosteroids and have continued to receive treatment under close clinical supervision.
    Patients with moderate to severe or recurrent IARs have been evaluated for alglucosidase alfa specific IgE antibodies; some patients tested positive including some who experienced an anaphylactic reaction. Nephrotic syndrome as well as severe cutaneous reactions, possibly immune-mediated, have been reported with alglucosidase alfa including ulcerative and necrotizing skin lesions.
    See prescribing information for full details.


    Drug interactions

    No interactions studies have been performed. Because it is a recombinant human protein, alglucosidase alfa is an unlikely candidate for cytochrome P450 mediated drug-drug interactions.


    Pregnancy and Lactation

    Pregnancy: There are no data from the use of alglucosidase alfa in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. This product should not be used during pregnancy unless clearly necessary.
    Lactation: Alglucosidase alfa may be excreted in breast milk. Because there are no data available on effects in neonates exposed to alglucosidase alfa via breast milk, it is recommended to stop breastfeeding when this product is used.
    See prescribing information for full details.


    Overdose

    There is no experience with overdose of alglucosidase alfa. In clinical studies doses up to 40 mg/kg body weight were used.


    Important notes

    In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
    After dilution, an immediate use is recommended. However, chemical and physical in-use stability has been demonstrated for 24 hours at 2 to 8°C when stored under protection from light.
    See prescribing information for full details.


    Manufacturer
    Genzyme Europe
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