Members Login
Medical NewsEPG Search
Frequent Searches:
Browse Other Languages
Spanish Drug Data (España)
German Drug Data (Deutsch)
Norwegian Drug Data (Norge)
Netherlands Drug Data (Nederlands)
Swedish Drug Data (Sverige)
German Drug Data (Deutsch)
Norwegian Drug Data (Norge)
Netherlands Drug Data (Nederlands)
Swedish Drug Data (Sverige)
YouTube - Featured Content
Want to submit or suggest content for the epgonline.org YouTube Clinical channel?
Contact us here
epgonline.org is not responsible for content on any 3rd party website
Are you a Doctor or Healthcare Professional? Authorise Viewing
Please register to access disease diagnosis, patient management, physician tools.
By viewing the content of this web page you are both confirming your status as a healthcare professional and agreeing to our terms of use.
Change language
Current language database:
United Kingdom
Medicine information : REPLAGAL 1 mg/ml concentrate for solution for infusion.
| Drug class description : | Other alimentary tract and metabolism products - Enzymes |
| Generic Name : | Agalsidase alfa |
| Drug description : | Concentrate for solution for infusion. |
| Presentation : | Agalsidase alfa is the human protein a-galactosidase A produced in a human cell line by genetic engineering technology. Each 1 ml vial contains 1 mg of agalsidase alfa. Each 3.5 ml vial contains 3.5 mg of agalsidase alfa. |
| Indications : | Replagal is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry Disease (a-galactosidase A deficiency). |
| Adult Dosage : | Replagal treatment should be supervised by a physician experienced in the management of patients with Fabry Disease or other inherited metabolic diseases. Replagal is administered at a dose of 0.2 mg/kg body weight every other week by intravenous infusion over 40 minutes. No studies have been performed in patients with hepatic impairment. No dose adjustment is necessary in patients with renal impairment. |
| Child Dosage : | Studies in children and adolescents (0-17 years) have not been performed and no dosage regimen can presently be recommended in these patients as safety and efficacy have not yet been established. |
| Elderly Dosage : | Studies patients over the age of 65 have not been performed and no dosage regimen can presently be recommended in these patients as safety and efficacy have not yet been established. |
| Contra Indications : | Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or any of the excipients. |
| Special Precautions : | 13.7% of patients treated with Replagal in clinical trials have experienced idiosyncratic infusion related reactions (See Adverse Reactions). Overall, the percentage of infusion related reactions was significantly lower in females than males. The most common symptoms have been rigors, headache, nausea, pyrexia, flushing and fatigue. Serious infusion reactions have been reported uncommonly; symptoms reported include pyrexia, rigors, tachycardia, urticaria, nausea/vomiting, angioneurotic oedema with throat tightness, stridor and swollen tongue. The onset of infusion related reactions has generally occurred within the first 2-4 months after initiation of treatment with Replagal although later onset (after 1 year) has been reported as well. If mild or moderate acute infusion reactions occur, medical attention must be sought immediately and appropriate actions instituted. The infusion can be temporarily interrupted (5 to 10 minutes) until symptoms subside and the infusion may then be restarted. Mild and transient effects may not require medical treatment or discontinuation of the infusion. In addition, oral or intravenous pre-treatment with antihistamines and/or corticosteroids, from 1 to 24 hours prior to infusion may prevent subsequent reactions in those cases where symptomatic treatment was required. As with any intravenous protein product, allergic-type hypersensitivity reactions are possible. If severe allergic or anaphylactic-type reactions occur, the administration of Replagal should be discontinued immediately and appropriate treatment initiated. The current medical standards for emergency treatment are to be observed. As with all protein pharmaceutical products, patients may develop IgG antibodies to the protein. A low titre IgG antibody response has been observed in approximately 24% of the male patients treated with Replagal. These IgG antibodies appeared to develop following approximately 3-12 months of treatment. After 12 to 54 months of therapy, 17% of Replagal treated patients were still antibody positive whereas 7% showed evidence for the development of immunologic tolerance, based on the disappearance of IgG antibodies over time. The remaining 76% remained antibody negative throughout. No IgE antibodies have been detected in any patient receiving Replagal. The presence of extensive renal damage may limit the renal response to enzyme replacement therapy, possibly due to underlying irreversible pathological changes. In such cases, the loss of renal function remains within the expected range of the natural progression of disease. |
| Interactions : | Replagal should not be co-administered with chloroquine, amiodarone, benoquin or gentamicin since these substances have the potential to inhibit intra-cellular a-galactosidase activity. As a-galactosidase A is itself an enzyme, it would be an unlikely candidate for cytochrome P450 mediated drug-drug interactions. In clinical studies, neuropathic pain medicinal products (such as carbamazepine, phenytoin and gabapentin) were administered concurrently to most patients without any evidence of interaction. Pregnancy and lactation For Replagal, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/foetal development when exposed during organogenesis (see Section 5.3). It is not known whether Replagal is excreted in human milk. Caution should be exercised when prescribing to pregnant or nursing women. |
| Adverse Reactions : | The most commonly reported undesirable effects were infusion associated reactions, which occurred in 13.7% of patients treated with Replagal in clinical trials. Most undesirable effects were mild to moderate in severity. Table 1 lists adverse drug reactions (ADRs) reported for the 153 patients treated with Replagal in clinical trials, including 21 patients with history of endstage renal disease and 17 female patients. Information is presented by system organ class and frequency (very common >1/10; common >1/100, <1/10; uncommon >1/1000,<1/100). The occurrence of an event in a single patient is defined as uncommon in view of the number of patients treated. A single patient could be affected by several ADRs. Table 1 Metabolism and nutrition disorders Common: peripheral oedema Nervous system disorders Very common: headache Common: dizziness, dysgeusia, neuropathic pain, tremor, hypersomnia, hypoesthesia, paraesthesia Uncommon: parosmia Eye disorders Common: lacrimation increased Ear and labyrinth disorders Common: tinnitus, tinnitus aggravated Cardiac disorders Common: tachycardia, palpitations Vascular disorders Very Common: flushing Common: hypertension Respiratory, thoracic and mediastinal disorders Common: cough, hoarseness, throat tightness, dyspnoea, nasopharyngitis, pharyngitis, throat secretion increased, rhinorrhoea Gastrointestinal disorders Very common: nausea Common: diarrhoea , vomiting, abdominal pain/discomfort Skin and subcutaneous tissue disorders Common: acne, erythema, pruritus, rash, livedo reticularis Uncommon: angioneurotic oedema, urticaria Musculoskeletal, connective tissue and bone disorders Common: musculoskeletal discomfort, myalgia, back pain, limb pain, peripheral swelling, arthralgia, joint swelling Uncommon: sensation of heaviness General disorders and administration site conditions Very common: rigors pyrexia, pain and discomfort, fatigue Common: fatigue aggravated, feeling hot, feeling cold, asthenia, chest pain, chest tightness, influenza like illness, injection site rash, malaise Investigations Common: corneal reflex decreased Uncommon: oxygen saturation decreased In clinical trials 13.7% of Replagal treated patients have experienced idiosyncratic infusion related reactions (See Special Precautions. The percentage of patients affected was significantly lower in females than males. These effects have decreased with time, the majority of them being reported within the first 6 months of treatment. Symptoms have included predominantly rigors, headache, nausea, pyrexia, flushing and fatigue with patients commonly experiencing pain/discomfort including exacerbated neuropathic pain, vomiting, chest or throat tightness and dizziness. All symptoms resolved with appropriate intervention, such as, stopping the infusion prior to restarting or medical therapy with antihistamines and/or corticosteroids. Serious infusion reactions have been reported uncommonly; symptoms reported include pyrexia, rigors, tachycardia, urticaria, nausea/vomiting, angioneurotic oedema with throat tightness, stridor and swollen tongue. Adverse drug reactions reported in patients with history of end stage renal disease were similar to those reported in the general patient population. |
| Manufacturer : | TKT Europe AB |
| Drug Availability : | (POM) |
Free registration to access disease diagnosis, patient management, physician tools.
Only registered users have access to the full EPG Online Knowledge Base including drug search tools, interactive disease Knowledge Centres via the EPG Knowledge Library - with clinical and evidence based physician and research tools, MiMedia (build your own clinical media collection with everything from key opinion leader essays to mode of action videos and other multi-media content), the EPG Survey panel, health news updates and much much more.
Already Registered?
Please log-in now using our member login box.
Not a member?
Don't worry, registration is quick and FREE! We welcome all Healthcare professionals, doctors, nurses and medical students.
Register today to have full access to a wealth of drug data, educational and evidence based interactive guides across all major therapeutic areas, disease management, and clinical tools.
As a practicing Healthcare professional, you can also opt-in to join our market research panel – www.epgsurvey.com – and get paid for sharing your expert clinical opinions!
REGISTER today it only takes a minute! and it's FREE
Having problems?
Use our forgotten password facility or email us at: contact@epgonline.org