Drug Class Description
Alimentary tract and metabolism products – enzymes
Generic Name
Alglucosidase Alfa
Drug Description
One vial contains 50 mg of alglucosidase alfa.After reconstitution, the solution contains 5 mg of alglucosidase alfa/ml and after dilution, the concentration varies from 0.5 mg to 4 mg/ml.
Presentation
Powder for concentrate for solution for infusion.White to off-white powder.
Indications
Myozyme is indicated for long-term enzyme replacement therapy (ERT) in patients with a confirmed diagnosis of Pompe disease (acid α-glucosidase deficiency).The benefits of Myozyme in patients with late-onset Pompe disease have not been established.
Adult Dosage
Myozyme 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 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.Posology for children, adolescents, adults and elderly:The safety and efficacy of Myozyme have been primarily eva luated in children with ages ranging from infancy to adolescence.There is no evidence for special considerations when Myozyme is administered to children, adolescents, adults or elderly patients.The safety and efficacy of Myozyme in patients with renal or hepatic insufficiency have not been eva luated and no specific dosage regimen can be recommended for these patients.Patient response to treatment should be routinely eva luated based on a comprehensive eva luation of all clinical manifestations of the disease.
Child Dosage
Posology for children and adolescents:The safety and efficacy of Myozyme have been primarily eva luated in children with ages ranging from infancy to adolescence. There is no evidence for special considerations when Myozyme is administered to children.
Elderly Dosage
Posology for the elderly:There is no evidence for special considerations when Myozyme is administered to elderly patients.
Contra Indications
Hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients.
Special Precautions
Life-threatening anaphylactic reactions, including anaphylactic shock, have been observed in infantile and late onset patients during Myozyme infusions. Because of the potential for severe infusion associated reactions, appropriate medical support measures should be readily available when Myozyme is administered. If severe or anaphylactic reactions occur, immediate discontinuation of Myozyme 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.Approximately half of the patients treated with Myozyme in infantile onset clinical studies developed infusion associated reactions (IARs), 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 Myozyme infusion appear to be at greater risk for IARs. Careful consideration should be given to the patient's clinical status prior to administration of Myozyme. Patients should be closely monitored and all cases of IARs, delayed reactions and possible immunological reactions should be reported.Patients who have experienced IARs should be treated with caution when re-administering Myozyme. 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 of Myozyme 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 of Myozyme.In clinical studies, the majority of patients developed IgG antibodies to rhGAA typically within 3 months of treatment. Thus seroconversion is expected to occur in most patients treated with Myozyme. A tendency was observed for patients treated with a higher dose (40 mg/kg) to develop higher titers of antibodies. There does not appear to be a correlation between the onset of IARs and the time of antibody formation. A small number of the IgG positive patients eva luated 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 antibody formation on safety and efficacy is currently not fully established.. The probability of a poor outcome and of developing high and sustained 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 antibody titers also occur in some CRIM-positive patients. The cause of a poor clinical outcome and of developing high and sustained antibody titers is thought to be multi-factorial. Antibody titers should be regularly monitored.Transient nephrotic syndrome which resolved following temporary interruption of ERT was observed in one patient with infantile-onset Pompe disease who received very frequent dosing of rhGAA (10 mg/kg 5 times weekly) over an extended period.
Interactions
No formal drug-drug interactions studies have been carried out with alglucosidase alfa. Because it is a recombinant human protein, alglucosidase alfa is an unlikely candidate for cytochrome P450 mediated drug-drug interactions..
Adverse Reactions
In clinical trials, 39 infantile-onset patients were treated with Myozyme for more than three years (168 weeks with a median of 121 weeks;. Most adverse events reported in these 39 patients were due to manifestations of Pompe disease and not related to the administration of Myozyme. Adverse Drug Reactions (ADRs) are listed in Table 1 by System Organ Class. The ADRs listed are reported in more than 1 patient and shown as percentage of patients experiencing the ADR with the absolute number of patients in brackets. ADRs 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.Table 1. Adverse Drug Reactions by System Organ Class in more than one patient. System Organ ClassPreferred termFrequency (no. of patients) N = 39Psychiatric disordersAgitation5% (2 pts)Nervous system disordersTremor5% (2 pts)Cardiac disordersTachycardia10% (4 pts)Cyanosis5% (2 pts)Vascular disordersFlushing13% (5 pts)Hypertension8% (3 pts)Pallor5% (2 pts)Respiratory, thoracic and mediastinal disordersCoughTachypnoea13% (5 pts)Gastrointestinal disordersVomiting10% (4 pts)Retching5% (2 pts)Nausea5% (2 pts) /td>Skin and subcutaneous tissue disordersUrticaria18% (7 pts)Rash15% (6 pts)Rash macular5% (2 pts)Erythema8% (3 pts)Rash maculo-papular8% (3 pts)Rash papular5% (2 pts)Pruritis5% (2 pts)General disorders and administration site conditionsPyrexia28% (11 pts)Irritability5% (2 pts)Chills5% (2 pts)InvestigationsOxygen saturation decreased18% (7 pts)Blood pressure increased5% (2 pts)Body temperature increased5% (2 pts)Heart rate increased5% (2 pts)A limited number of patients with late-onset Pompe disease have been treated with Myozyme. ADRs reported in 2 of 9 late-onset patients treated with Myozyme for up to 1 year in 3 different studies included increased heart rate, hypertension, headache, peripheral coldness, paresthesia, flushing, infusion site pain, infusion site reaction, increased blood pressure and dizziness. The 2 late onset patients did not experience the same ADRs. The ADRs were mild in intensity and assessed as an IAR.IARs in patients treated with Myozyme in clinical studies and expanded access programs and reported in more than 1 patient included rash, flushing, urticaria, pyrexia, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure, cyanosis, hypertension, irritability, pallor, pruritus, retching, chills, tremor, hypotension, heart rate increased, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, lacrimation increased, livedo reticularis, nausea, periorbital edema, restlessness and wheezing. Those IARs reported as severe in more than 1 patient included pyrexia, decreased oxygen saturation, tachycardia, cyanosis and hypotension. A single event of angioneurotic edema of severe intensity has been reported. A small number of patients (< 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/or cardiac arrest during Myozyme 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. Patients with moderate to severe or recurrent IARs have been eva luated for Myozyme specific IgE antibodies; some patients tested positive including one patient who experienced an anaphylactic reaction.Post marketing data: unknown frequency (cannot be estimated from the available data)Additional IARs included: bradycardia, chest discomfort, chest pain, dyspnoea, respiratory distress, pharyngeal oedema and throat tightness.
Manufacturer
Genzyme Therapeutics
Drug Availability
(POM)
Updated
17 August 2009
