Download Replagal (agalsidase alfa) Prescribing Information: Please consult

Replagal (agalsidase alfa) Prescribing
Information: Please consult the Summary
of Product Characteristics (SmPC) before
prescribing.
Presentation: Concentrate solution for IV
infusion. 1ml of concentrate for solution for
infusion contains 1mg of agalsidase alfa.
Indication:
Long-term
enzyme
replacement therapy in patients with a
confirmed diagnosis of Fabry disease (agalactosidase A deficiency)
Dosage and administration: Replagal
0.2mg/kg body weight by IV infusion over
40 min every other week. No dosage
regimen in children (0-6 years) can
presently be recommended as safety and
efficacy have not yet been sufficiently
established. Because no unexpected
safety issues were encountered in the 6
month study with Replagal administered at
0.2mg/kg, this dose regimen is suggested
for children between 7–18 years of age.
Contraindications: Hypersensitivity to the
active substance or any of the excipients.
Warnings and precautions: 13.7% of
adult patients receiving Replagal in clinical
trials had idiosyncratic infusion-related
reactions (generally within 2–4 months of
starting treatment although later onset
[after 1 year] has been reported as well).
Four of 17 paediatric patients >7 years of
age and 3 of 8 paediatric patients <7 years
experienced at least one infusion reaction
over a period of approx. 4 years of
treatment. These effects have decreased
with time. If mild or moderate acute
infusion reactions occur, seek medical
attention immediately. The infusion can be
temporarily interrupted (for 5–10 minutes)
until symptoms subside. If severe allergic
or anaphylactic-type reactions occur,
discontinue Replagal immediately and
initiate appropriate treatment. A review of
cardiac events showed that infusion
reactions may be associated with
hemodynamic stress triggering cardiac
events in patients with pre-existing cardiac
manifestations of Fabry disease. Patients
may develop IgG antibodies to the protein.
A low titre antibody response was seen in
approximately 24% of male patients; the
remaining
76%
remained
antibody
negative throughout. In paediatric patients
>7 yrs of age, 1/16 male patients tested
positive for IgG anti-agalsidase alfa
antibodies. No increase in the incidence of
adverse events was apparent for this
patient. In paediatric patients <7 yrs of
age, 0/7 male patients tested positive for
IgG anti-agalsidase alfa antibodies. No IgE
antibodies have been detected in any
patient receiving Replagal. Extensive renal
damage may limit the renal response to
enzyme replacement therapy. Do not give
Replagal together with chloroquine,
amiodarone, benoquin or gentamicin
because these substances can inhibit
intracellular
a-galactosidase
activity.
Caution should be exercised in pregnant
or breast-feeding women.
Side effects: Most reported adverse
effects have been mild to moderate. Very
common (>1/10 patients): headache,
flushes,
nausea,
rigors,
pyrexia,
pain/discomfort, fatigue; common (>1/100,
<1/10 patients): peripheral oedema,
dizziness, dysgeusia, neuropathic pain,
tremor,
hypersomnia,
hypoesthesia,
paraesthesia,
increased
lacrimation,
tinnitus, tinnitus aggravated, tachycardia,
palpitations,
hypertension,
cough,
hoarseness, throat tightness, dyspnoea,
nasopharyngitis, pharyngitis, increased
throat secretion, rhinorrhoea, diarrhoea,
vomiting, abdominal pain/discomfort, acne,
erythema, pruritus, rash, livedo reticularis,
musculoskeletal discomfort, myalgia, back
pain, limb pain, peripheral swelling,
arthralgia, joint swelling, aggravated
fatigue, feeling hot, feeling cold, asthenia,
chest pain, chest tightness, influenza-like
illness, injection-site rash, malaise,
decreased corneal reflex; uncommon
(>1/1000, <1/100 patients): parosmia,
angioneurotic oedema, urticaria, sensation
of
heaviness,
decreased
oxygen
saturation. Not known (since derived from
post-marketing spontaneous reports):
cardiac arrhythmias (atrial fibrillation,
ventricular
extrasystoles,
tachyarrhythmia), myocardial ischaemia,
heart failure, hypotension, hyperhidrosis.
Infusion related reactions reported in the
post marketing setting may also include
cardiac
events
such
as
cardiac
arrhythmias (atrial fibrillation, ventricular
extrasystoles,
tachyarrhythmia),
myocardial ischemia, and heart failure in
patients with Fabry disease involving the
heart
structures.
Infusion-related
symptoms
may
include
dizziness,
hyperhidrosis, and hypotension. The most
frequent were mild infusion-related
reactions that mainly included rigors,
pyrexia, flushing, headache, nausea, and
dyspnoea.
Package quantity and price: Vials of 5ml
(containing 3.5ml concentrate) in a pack
size of 1 vial. Price: £1049.94 for one 5ml
vial.
Pharmaceutical precautions: Store in a
refrigerator (2°C–8°C).
Marketing authorisation number and
holder:
EU/1/01/189/001-006.
Shire
Human
Genetic
Therapies
AB,
Svärdvägen 11D, 182 33 Danderyd,
Sweden.
Legal category: POM. Further information
is available in the Summary of Product
Characteristics (SmPC), or on request
from the marketing authorisation holder.
Date of preparation: 30th March 2012
Item code: UK/HG/REP/12/0015
Adverse events should be reported. Reporting forms and information can be
found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported
to Shire Human Genetic Therapies on +44 (0)1256 894000 or faxed on +44
(0)1256 894715 or emailed to [email protected]