ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
KIOVIG 100 mg/ml solution for infusion
2.
1 ml contains:
Human normal immunoglobulin (IVIg)……………...100 mg*
*corresponding to human protein content, of which at least 98% is IgG
One vial of 10 ml contains: 1 g of IVIg
One vial of 25 ml contains: 2.5 g of IVIg
One vial of 50 ml contains: 5 g of IVIg
One vial of 100 ml contains: 10 g of IVIg
One vial of 200 ml contains: 20 g of IVIg
One vial of 300 ml contains: 30 g of IVIg
Distribution of IgG subclasses:
IgG1
≥
56.9%
IgG2
≥
26.6%
IgG3
≥
3.4%
IgG4
≥
1.7%
Maximum immunoglobulin A (IgA) content: 140 micrograms/ml.
For a full list of excipients, see section 6.1.
3.
Solution for infusion
The solution is clear or slightly opalescent and colourless or pale yellow.
4.
IVIg can be used in all age ranges, unless otherwise specified below.
Replacement therapy in:
Primary immunodeficiency syndromes with impaired antibody production (see section 4.4).
Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic
leukaemia, in whom prophylactic antibiotics have failed.
Hypogammaglobulinaemia and recurrent bacterial infections in plateau phase multiple myeloma
patients who have failed to respond to pneumococcal immunisation.
Children and adolescents (age 0-18) with congenital AIDS and recurrent bacterial infections.
2
Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation
(HSCT).
Immunomodulation
Primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to
correct the platelet count.
Guillain Barré syndrome.
Kawasaki disease.
Posology
The dose and dose regimen is dependent on the indication.
In replacement therapy the dose may need to be individualised for each patient dependent on the
pharmacokinetic and clinical response. The following dose regimens are given as a guideline.
Replacement therapy in primary immunodeficiency syndromes
The dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least
5 to 6 g/l. Three to six months are required after the initiation of therapy for equilibration to occur. The
recommended starting dose is 0.4-0.8 g/kg given once, followed by at least 0.2 g/kg given every three
to four weeks.
The dose required to achieve a trough level of 5-6 g/l is of the order of 0.2-0.8 g/kg/month. The dose
interval when steady state has been reached varies from 3-4 weeks.
Trough levels should be measured and assessed in conjunction with the incidence of infection. To
reduce the rate of infection, it may be necessary to increase the dose and aim for higher trough levels.
Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic
leukaemia, in whom prophylactic antibiotics have failed; hypogammaglobulinaemia and recurrent
bacterial infections in plateau phase multiple myeloma patients who have failed to respond to
pneumococcal immunisation; children and adolescents with congenital AIDS and recurrent bacterial
infections
The recommended dose is 0.2-0.4 g/kg every three to four weeks.
Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation
The recommended dose is 0.2-0.4 g/kg every three to four weeks. The trough levels should be
maintained above 5g/l.
Primary immune thrombocytopenia
There are two alternative treatment schedules:
•
0.8-1g/kg given on day one; this dose may be repeated once within 3 days
0.4 g/kg given daily for two to five days.
The treatment can be repeated if relapse occurs.
Guillain Barré syndrome
0.4 g/kg/day over 5 days.
Kawasaki Disease
1.6-2.0 g/kg should be administered in divided doses over two to five days or 2.0 g/kg as a single dose.
Patients should receive concomitant treatment with acetylsalicylic acid.
3
•
The dose recommendations are summarised in the following table:
Indication
Dose
Frequency of injections
Replacement therapy in primary
immunodeficiency
- starting dose:
0.4 – 0.8 g/kg
- thereafter:
0.2 – 0.8 g/kg
0.2 – 0.4 g/kg
every 3 – 4 weeks to obtain IgG
trough level of at least 5 – 6 g/l
Replacement therapy in secondary
immunodeficiency
every 3 – 4 weeks to obtain IgG
trough level of at least 5 – 6 g/l
0.2 – 0.4 g/kg
0.2 – 0.4 g/kg
Children and adolescents with AIDS
every 3 – 4 weeks
Hypogammaglobulinaemia (< 4 g/l) in
patients after allogeneic haematopoietic
stem cell transplantation
every 3 – 4 weeks to obtain IgG
trough level above 5g/l
Immunomodulation:
0.8 – 1 g/kg
or
0.4 g/kg/d
0.4 g/kg/d
1.6 – 2 g/kg
or
2 g/kg
Primary immune thrombocytopenia
on day 1, possibly repeated once
within 3 days
for 2 – 5 days
Guillain Barré syndrome
for 5 days
Kawasaki disease
in divided doses for 2 – 5 days in
association with acetylsalicylic acid
in one dose in association with
acetylsalicylic acid
Paediatric population
The posology in children and adolescents (0-18 years) is not different to that of adults as the posology
for each indication is given by body weight and adjusted to the clinical outcome of the above
mentioned conditions.
Method of administration
Human normal immunoglobulin should be infused intravenously at an initial rate of 0.5 ml/kg BW/hr
for 30 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum
of 6 ml/kg BW/hr. Clinical data obtained from a limited number of patients also indicate that adult
PID patients may tolerate an infusion rate of up to 8 ml/kg BW/hr. For further precautions for use see
section 4.4.
KIOVIG should only be administered intravenously. Other routes of administration have not been
evaluated.
If dilution prior to infusion is required, KIOVIG may be diluted with 5% glucose solution to a final
concentration of 50 mg/ml (5% immunoglobulin). For instructions on dilution of the medicinal
product before administration, see section 6.6.
Any infusion-related adverse events should be treated by lowering infusion rates or by stopping the
infusion.
4
Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to human immunoglobulins, especially in very rare cases of IgA deficiency when the
patient has antibodies against IgA.
Certain adverse reactions such as headache and flushing may be related to the rate of infusion (see
section 4.8). The recommended infusion rate given under “4.2 Method of administration” must be
closely followed. Patients must be closely monitored and carefully observed for any symptoms
throughout the infusion period.
Certain adverse reactions may occur more frequently
−
in case of high rate of infusion
−
in patients with hypo- or agammaglobulinemia with or without IgA deficiency
−
in patients who receive human normal immunoglobulin for the first time or, in rare cases, when
the human normal immunoglobulin product is switched or when there has been a long interval
since the previous infusion.
True hypersensitivity reactions are rare. They can occur in the very seldom cases of IgA deficiency
with anti-IgA antibodies. KIOVIG is not indicated in patients with selective IgA deficiency where the
IgA deficiency is the only abnormality of concern.
Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic
reaction,even in patients who had tolerated previous treatment with human normal immunoglobulin.
Potential complications can often be avoided by ensuring
−
that patients are not sensitive to human normal immunoglobulin by first infusing the product
slowly (0.01 ml/kg BW/min);
−
that patients are carefully monitored for any symptoms throughout the infusion period. In
particular, patients naive to human normal immunoglobulin, patients switched from an
alternative IVIg product or when there has been a long interval since the previous infusion
should be monitored during the first infusion and for the first hour after the first infusion, in
order to detect potential adverse signs. All other patients should be observed for at least
20 minutes after administration.
There is clinical evidence of an association between IVIg administration and thromboembolic events
such as myocardial infarction, cerebral vascular accident (including
stroke), pulmonary embolism and
deep vein thrombosis which is assumed to be related to a relative increase in blood viscosity through
the high influx of immunoglobulin. Caution should be exercised in prescribing and infusion of IVIg in
obese patients and in patients with pre-existing risk factors for thrombotic events such as a history of
atherosclerosis, multiple cardiovascular risk factors,
advanced age, impaired cardiac output,
hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with
acquired or inherited thrombophilic disorders, hypercoagulable disorders, patients with prolonged
periods of immobilisation, severely hypovolemic patients, patients with diseases which increase blood
viscosity.
Severe renal adverse reactions have been reported in patients receiving IVIg therapy. These include
acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis. In
most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes
mellitus, hypovolemia, overweight, concomitant nephrotoxic medicinal products, age over 65, sepsis
or paraproteinemia.
In case of renal impairment, IVIg discontinuation should be considered.
While these reports of renal dysfunction and acute renal failure have been associated with the use of
many of the licensed IVIg products, those containing sucrose as a stabilizer accounted for a
disproportionate share of the total number. In patients at risk, the use of IVIg products that do not
contain sucrose may be considered.
5
In patients at risk for acute renal failure or thromboembolic adverse reactions, IVIg products should be
administered at the minimum rate of infusion and dose practicable.
There have been reports of noncardiogenic pulmonary edema (Transfusion Related Acute
Lung Injury, TRALI) in patients administered IVIG (including KIOVIG).
An aseptic meningitis syndrome (AMS) has been reported to occur in association with IVIG
(including Kiovig) treatment. Discontinuation of IVIG treatment has resulted in remission of AMS
within several days without sequelae. The syndrome usually begins within several hours to 2 days
following IVIG treatment.
−
Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells
per mm
3
, predominantly from the granulocytic series, and elevated protein levels up to several
hundred mg/dL.
−
AMS may occur more frequently in association with high-dose (2 g/kg) IVIG treatment.
Hemolytic anemia can develop subsequent to IVIG (including Kiovig) therapy. IVIG products can
contain blood group antibodies that may act as hemolysins and induce in vivo coating of red blood
cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.
In all patients, IVIg administration requires:
−
adequate hydration prior to the initiation of the infusion of IVIg
−
monitoring of urine output
−
monitoring of serum creatinine levels
−
avoidance of concomitant use of loop diuretics.
In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped.
The treatment required depends on the nature and severity of the adverse reaction.
In case of shock, standard medical treatment for shock should be implemented.
If dilution of KIOVIG to lower concentrations is required for patients suffering from diabetes mellitus,
the use of 5% glucose solution for dilution may have to be reconsidered.
Interference with serological testing
After infusion of immunoglobulin the transitory rise of the various passively transferred antibodies in
the patients blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D, may interfere with some
serological tests for red cell antibodies, for example the antiglobulin test (Coombs test).
KIOVIG is made from human plasma. Standard measures to prevent infections resulting from the use
of medicinal products prepared from human blood or plasma include selection of donors, screening of
individual donations and plasma pools for specific markers of infection and the inclusion of effective
manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products
prepared from human blood or plasma are administered, the possibility of transmitting infectious
agents cannot be totally excluded. This also applies to unknown or emerging viruses and other
pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV, and
for the non-enveloped viruses HAV and parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or Parvovirus B19
transmission with immunoglobulins and it is also assumed that the antibody content makes an
important contribution to the viral safety.
It is strongly recommended that every time that KIOVIG is administered to a patient, the name and
batch number of the product are recorded in order to maintain a link between the patient and the batch
of the product.
6
Live attenuated virus vaccines
Immunoglobulin administration may impair for a period of at least 6 weeks and up to 3 months the
efficacy of live attenuated virus vaccines such as measles
,
rubella, mumps and varicella. After
administration of this product, an interval of 3 months should elapse before vaccination with live
attenuated virus vaccines. In the case of measles, this impairment may persist for up to 1 year.
Therefore patients receiving measles vaccine should have their antibody status checked.
In case of dilution with a 5% glucose solution, the KIOVIG administration may interfere with
determination of blood glucose levels.
Paediatric population
There are no interaction studies with KIOVIG in paediatric population.
Pregnancy
The safety of this medicinal product for use in human pregnancy has not been established in controlled
clinical trials and therefore it should only be given with caution to pregnant women and breast-feeding
mothers. Maternally administered IVIG products have been shown to cross the placenta, increasingly
during the third trimester. Clinical experience with immunoglobulins suggests that no harmful effects
on the course of pregnancy, or on the foetus and the neonate are to be expected.
Breast-feeding
Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies
to the neonate.
Fertility
Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be
expected.
The ability to drive and operate machines may be impaired by some adverse reactions associated with
KIOVIG. Patients who experience adverse reactions during treatment should wait for these to resolve
before driving or operating machines.
Summary of the safety profile
Adverse reactions such as chills, headache, fever, vomiting, allergic reactions, nausea, arthralgia, low
blood pressure and moderate low back pain may occur occasionally.
Rarely human normal immunoglobulins may cause a sudden fall in blood pressure and, in isolated
cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous
administration.
Cases of reversible aseptic meningitis, isolated cases of reversible haemolytic anaemia/haemolysis,
and rare cases of transient cutaneous reactions, have been observed with human normal
immunoglobulin.
Increase in serum creatinine level and/or acute renal failure have been observed.
Very rarely: Thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism,
and deep vein thromboses.
7
Two clinical trials with KIOVIG were performed in primary immunodeficiency (PID) patients in
Europe and the US. In the European study, 22 subjects with hypo- and agammaglobulinemia received
KIOVIG for about 6 months. The US clinical trial was performed with 61 subjects with PID, who
received KIOVIG for about 12 months. In Europe, an additional clinical study in 23 patients with
idiopathic thrombocytopenic purpura (ITP) was performed. No serious adverse reaction (AR) was
observed during the studies, with the exception of two episodes of aseptic meningitis in one patient of
the US PID study, which were deemed possibly related to the medicinal product. Most ARs observed
were mild to moderate in nature.
In the European and US PID studies the overall rate of ARs per infusion was 0.27. As expected due to
the much higher dosage, the AR rate per infusion was higher (0.49) in the ITP trial; 87.5% of these
ARs were assessed as mild. The ARs reported in the three studies and post-marketing are summarized
and categorized according to the MedDRA System organ class and frequency in the table below.
Tabulated summary of adverse reactions
The summary table presented below is according to the MedDRA system organ classification (SOC
and Preferred Term Level).
Frequencies have been evaluated according to the following convention: very common (≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare
(<1/10,000); not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Frequency of Adverse Reactions (ARs)
MedDRA
System Organ Class
(SOC)
MedDRA preferred term
AR frequency
category
Infections and infestations
Bronchitis, nasopharyngitis
Common
Chronic sinusitis, fungal infection, infection, kidney
infection, sinusitis, upper respiratory tract infection,
urinary tract infection, bacterial urinary tract infection
Uncommon
Meningitis aseptic
Rare
Blood and lymphatic
system disorders
Anaemia, lymphadenopathy
Uncommon
Hemolysis
Not known
Immune system disorders
Anaphylactic shock, anaphylactic reaction,
hypersensitivity
Not known
Endocrine disorders
Thyroid disorder
Uncommon
Psychiatric disorders
Anxiety
Uncommon
Nervous system disorders
Headache
Very common
Dizziness, migraine
Common
Amnesia, burning sensation, dysarthria, dysgeusia,
insomnia
Uncommon
Transient ischemic attack, tremor
Not known
Eye disorders
Conjunctivitis, eye pain, eye swelling
Uncommon
Ear and labyrinth disorders
Vertigo
Common
Fluid in middle ear
Uncommon
Cardiac disorders
Tachycardia
Common
Vascular disorders
Flushing, hypertension
Common
Peripheral coldness, phlebitis
Uncommon
Deep vein thrombosis, hypotension
Not known
Respiratory, thoracic and
mediastinal disorders
Cough, rhinorrhoea
Common
Asthma, nasal congestion, oropharyngeal swelling,
pharyngolaryngeal pain
Uncommon
Pulmonary embolism, pulmonary edema, dyspnea
Not known
Gastrointestinal disorders
Diarrhoea, nausea, vomiting
Common
8
Frequency of Adverse Reactions (ARs)
MedDRA
System Organ Class
(SOC)
MedDRA preferred term
AR frequency
category
Abdominal pain
Not known
Skin and subcutaneous
tissue disorders
Pruritus, rash, urticaria
Common
Angioneurotic oedema, acute urticaria, cold sweat,
contusion, dermatitis, erythematous rash, pruritic rash
Uncommon
Hyperhidrosis
Not known
Musculoskeletal and
connective tissue disorders
Muscle spasms
Back pain, myalgia, pain in extremity
Common
Uncommon
General disorders and
administration site
conditions
Pyrexia
Very common
Fatigue, influenza-like illness, infusion site pain,
infusion site swelling, rigors,
Common
Application site pruritus, chest tightness, feeling hot,
infusion site phlebitis, infusion site reaction, infusion
site tenderness, malaise, peripheral oedema, swelling
Uncommon
Chest pain, chills
Not known
Investigations
Body temperature increased
Common
Blood cholesterol increased, blood creatinine
increased, blood urea increased, haematocrit decreased,
red blood cell count decreased, respiratory rate
increased, white blood cell count decreased
Uncommon
Coombs direct test positive, oxygen saturation
decreased
Not known
Injury, poisoning and
procedural complications
Transfusion-related acute lung injury
Not known
For safety with respect to transmissible agents, see section 4.4.
elderly patients or patients with cardiac or renal impairment.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human,
for intravascular administration, ATC code: J06BA02
Human normal immunoglobulin contains mainly functionally intact immunoglobulin G (IgG) with a
broad spectrum of antibodies against infectious agents.
Human normal immunoglobulin contains the IgG antibodies present in the normal population. It is
usually prepared from pooled plasma from not fewer than 1000 donations. It has a distribution of
immunoglobulin G subclasses closely proportional to that in native human plasma. Adequate doses of
human normal immunoglobulin may restore abnormally low immunoglobulin G levels to the normal
range.
The mechanism of action in indications other than replacement therapy is not fully elucidated, but
includes immunomodulatory effects.
9
5.2 Pharmacokinetic properties
Human normal immunoglobulin is immediately and completely bioavailable in the recipient’s
circulation after intravenous administration. It is distributed relatively rapidly between plasma and
extravascular fluid; after approximately 3 to 5 days equilibrium is reached between the intra- and
extravascular compartments.
Pharmacokinetic parameters for KIOVIG were determined in the two clinical studies in PID patients
performed in Europe and the US. In these studies, a total of 83 subjects at least 2 years of age were
treated with doses of 300 to 600 mg/kg body weight every 21 to 28 days for 6 to 12 months. The
median IgG half-life after administration of KIOVIG was 32.5 days. This half-life may vary from
patient to patient, in particular in primary immunodeficiency. Pharmacokinetic parameters for the
product are summarized in the table below. All parameters were analysed separately for three age
groups, children (below 12 years, n=5), adolescents (13 to 17 years, n=10), and adults (above 18 years
of age, n=64). The values obtained in the studies are comparable to parameters reported for other
human immunoglobulins.
Parameter
Summary of KIOVIG pharmacokinetic parameters
Children
(12 years or below)
Adolescents
(13 to 17 years)
Adults
(18 years or above)
Median
95% CI*
Median
95% CI
Median
95% CI
Terminal half-life (days)
41.3
20.2 to 86.8
45.1 27.3 to 89.3
31.9 29.6 to 36.1
C
min
(mg/dl)/(mg/kg)
(trough level)
2.28
1.72 to 2.74
2.25 1.98 to 2.64
2.24 1.92 to 2.43
C
max
(mg/dl)/(mg/kg)
(peak level)
4.44
3.30 to 4.90
4.43 3.78 to 5.16
4.50 3.99 to 4.78
In-vivo
recovery (%)
121
87 to 137
99
75 to 121
104
96 to 114
Incremental recovery
(mg/dl)/(mg/kg)
2.26
1.70 to 2.60
2.09 1.78 to 2.65
2.17 1.99 to 2.44
AUC
0-21d
(g·h/dl) (area
under the curve)
1.49
1.34 to 1.81
1.67 1.45 to 2.19
1.62 1.50 to 1.78
*CI – Confidence Interval
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
5.3
Preclinical safety data
Immunoglobulins are normal constituents of the human body.
The safety of KIOVIG has been demonstrated in several non-clinical studies. Non-clinical data reveal
no special risk for humans based on conventional studies of safety pharmacology and toxicity.
Studies of repeated dose toxicity, genotoxicity, and toxicity to reproduction in animals are
impracticable due to induction of and interference by developing antibodies to heterologous proteins.
Since clinical experience provides no evidence for carcinogenic potential of immunoglobulins, no
experimental studies in heterogeneous species were performed.
6.
6.1
List of excipients
Glycine
Water for injections
10
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.
6.3 Shelf life
2 years.
If dilution to lower concentrations is required, immediate use after dilution is recommended. The in-
use stability of KIOVIG after dilution with a 5% glucose solution to a final concentration of 50 mg/ml
(5%) immunoglobulin has been demonstrated for 21 days at 2°C to 8°C as well as 28°C to 30°C;
however, these studies did not include the microbial contamination and safety aspect.
6.4 Special precautions for storage
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage condition of the diluted medicinal product, see section 6.3.
During the shelf life, the product may be stored at room temperature (not more than 25°C) for up to 1
year. The date of transfer to room temperature and the end of the 1 year period should be recorded on
the outer carton. Once the product is stored at room temperature it must not be returned to the
refrigerator and must be discarded, if not used by the end of the 1 year period.
6.5
Nature and contents of container
10, 25, 50, 100, 200 or 300 ml of solution in a vial (Type I glass) with a stopper (bromobutyl).
Pack size: 1 vial
Not all presentations may be marketed.
6.6 Special precautions for disposal and other handling
The product should be brought to room or body temperature before use.
If dilution is required, 5% glucose solution is recommended. For obtaining an immunoglobulin solution
of 50 mg/ml (5%), KIOVIG 100 mg/ml (10%) should be diluted with an equal volume of the glucose
solution. It is recommended that during dilution the risk of microbial contamination is minimised.
The product should be inspected visually for particulate matter and discolouration prior to
administration. Do not use if particulate matter or discolouration is observed. Only clear to slightly
opalescent and colourless to pale yellow solutions are to be administered.
KIOVIG should only be administered intravenously. Other routes of administration have not been
evaluated.
Any unused product or waste material should be disposed of in accordance with local requirements
Baxter AG
Industriestrasse 67
A-1221 Vienna, Austria
11
EU/1/05/329/001
EU/1/05/329/002
EU/1/05/329/003
EU/1/05/329/004
EU/1/05/329/005
EU/1/05/329/006
19/01/2006
12
ANNEX II
A.
MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCE AND MANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
13
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substance
Baxter AG
Industriestrasse 131
1221 Vienna
Austria
Baxter Manufacturing S.p.A.
Via della Chimica 5l
0210 – S.Rufina/Cittaducale, Rieti
Italy
Baxter Healthcare Corporation
4501 Colorado Boulevard
Los Angeles, CA
USA
Baxter S.A.
Boulevard René Branquart 80
B-7860 Lessines
Belgium
Name and address of the manufacturer responsible for batch release
Baxter S.A.
Boulevard René Branquart 80
B-7860 Lessines
Belgium
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official
batch release will be undertaken by a state laboratory or a laboratory designated for that purpose.
14
ANNEX III
LABELLING AND PACKAGE LEAFLET
15
A. LABELLING
16
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON (1G, 2.5G, 5G, 10G, 20G AND 30G)
1.
KIOVIG 100 mg/ml solution for infusion
Human normal immunoglobulin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Human protein, 100 mg/ml, at least 98% is IgG.
Maximum immunoglobulin A (IgA) content: 140 micrograms/ml.
1 g / 10 ml
2.5 g / 25 ml
5 g / 50 ml
10 g / 100 ml
20 g / 200 ml
30 g / 300 ml
3.
LIST OF EXCIPIENTS
Glycine
Water for injections
4.
Solution for infusion (10%)
1 vial
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intravenous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP:
Date removed from refrigerator: __/__/_____
End of 12-month period at room temperature: __/__/_____
17
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator.
Do not freeze.
Keep the container in the outer carton in order to protect from light.
KIOVIG may be stored at room temperature (not more than 25°C) for up to 1 year. Record date of
transfer to room temperature and end of 1 year period on the carton. After a maximum storage period
of 1 year at room temperature, the product must be used or discarded.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
EU/1/05/329/001 1 g / 10 ml
EU/1/05/329/002 2.5 g / 25 ml
EU/1/05/329/003 5 g / 50 ml
EU/1/05/329/004 10 g / 100 ml
EU/1/05/329/005 20 g / 200 ml
EU/1/05/329/006 30 g / 300 ml
13. BATCH NUMBER
Lot:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
KIOVIG
18
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
VIAL LABEL (5G, 10G, 20G AND 30G)
1.
KIOVIG 100 mg/ml solution for infusion
Human normal immunoglobulin
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Human protein, 100 mg/ml, at least 98% is IgG.
Maximum immunoglobulin A (IgA) content: 140 micrograms/ml.
5 g / 50 ml
10 g / 100 ml
20 g / 200 ml
30 g / 300 ml
3.
LIST OF EXCIPIENTS
Glycine
Water for injections
4.
Solution for infusion (10%)
1 vial
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intravenous use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP:
19
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator.
Do not freeze.
Keep the container in the outer carton in order to protect from light.
KIOVIG may be stored at room temperature (not more than 25°C) for up to 1 year. Record date of
transfer to room temperature and end of 1 year period on the carton. After a maximum storage period
of 1 year at room temperature, the product must be used or discarded.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
EU/1/05/329/003 5 g / 50 ml
EU/1/05/329/004 10 g / 100 ml
EU/1/05/329/005 20 g / 200 ml
EU/1/05/329/006 30 g / 300 ml
13. BATCH NUMBER
Lot:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
20
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL (1G)
1.
KIOVIG 100 mg/ml solution for infusion
Human Normal Immunoglobulin
Intravenous use.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 g / 10 ml
6.
OTHER
21
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL LABEL (2.5G)
1.
KIOVIG 100 mg/ml solution for infusion
Human Normal Immunoglobulin
Intravenous use.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
2.5 g / 25 ml
6.
OTHER
Store in a refrigerator.
Do not freeze.
Keep the container in the outer carton in order to protect from light.
KIOVIG may be stored at room temperature (not more than 25°C) for up to 1 year. Record date of
transfer to room temperature and end of 1 year period on the carton. After a maximum storage period
of 1 year at room temperature, the product must be used or discarded.
22
B. PACKAGE LEAFLET
23
PACKAGE LEAFLET: INFORMATION FOR THE USER
KIOVIG 100 mg/ml solution for infusion
Human normal immunoglobulin
Read all of this leaflet carefully before you start using this medicine
•
Keep this leaflet. You may need to read it again.
•
If you have any further questions, ask your doctor or pharmacist.
•
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
•
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What KIOVIG is and what it is used for
2.
Before you use KIOVIG
3.
How to use KIOVIG
4.
Possible side effects
5.
How to store KIOVIG
6.
Further information
1. WHAT KIOVIG IS AND WHAT IT IS USED FOR
KIOVIG belongs to a class of medications called immunoglobulins. These medicines contain human
antibodies, which are also present in your blood. Antibodies help your body to fight infections.
Medicines like KIOVIG are used in patients who do not have enough antibodies in their blood and
tend to get frequent infections. They can also be used in patients who need additional antibodies for
the cure of certain inflammatory disorders (autoimmune diseases).
KIOVIG is used for
Treatment of patients who do not have sufficient antibodies (replacement therapy). There are
five groups:
1.
Patients with inborn lack of antibody production (primary immunodeficiency syndromes).
2.
Patients with a cancer of the blood (chronic lymphocytic leukaemia) that leads to a lack of
antibody production and recurrent infections when preventative antibiotics have failed.
3.
Patients with cancer of the bone marrow (multiple myeloma) and lack of antibody production
with recurrent infections who have failed to respond to a vaccine against certain bacteria
(pneumococci).
4.
Children and adolescents (age 0 to 18) with AIDS from birth and recurrent bacterial infections.
5.
Patients with low antibody production following transplantation of bone marrow cells from
another person.
Treatment of patients with certain inflammatory disorders (immunomodulation). There are
three groups:
1.
Patients who do not have enough blood platelets (primary immune thrombocytopenia, ITP), and
who are at high risk of bleeding or will have surgery in the near future.
2.
Patients with a disease that is associated with multiple inflammations of the nerves in the whole
body (Guillain Barré syndrome).
3.
Patients with a disease which results in multiple inflammations of several organs of the body
(Kawasaki disease).
24
2.
BEFORE YOU USE KIOVIG
KIOVIG must not be used
If you are allergic (hypersensitive) to immunoglobulins or to any other ingredient of KIOVIG.
For example, if you have an immunoglobulin A deficiency, you may have antibodies against
immunoglobulin A in your blood. Since KIOVIG contains trace amounts of immunoglobulin A (less
than 0.14 mg/ml), you might get an allergic reaction.
Take special care with KIOVIG
How long monitoring is required during the infusion
•
You will be carefully observed during the infusion period with KIOVIG to make sure that you
do not suffer a reaction. Your doctor will make sure that the rate at which KIOVIG is infused is
suitable for you.
•
If KIOVIG is administered at a high rate, if you suffer from a condition with low antibody
levels in your blood (hypo- or agammaglobulinemia), if you have not received this medicine
before or if there has been a long interval (e.g. several weeks) since you last received it, there
may be a higher risk of side effects. In such cases, you will be closely monitored during your
infusion and for an hour after your infusion has stopped.
•
If you have already received KIOVIG previously and received the last treatment recently, then
you will only be observed during the infusion and for at least 20 minutes after your infusion.
When slowing or stopping the infusion may be required
In rare cases your body may have previously reacted to specific antibodies and therefore will be
sensitive to medicines containing antibodies. This may happen particularly if you suffer from
immunoglobulin A deficiency. In these rare cases, you may get allergic reactions such as a sudden fall
in blood pressure or shock even if you have already received treatment with medicines containing
antibodies in the past.
If you experience a reaction during the infusion of KIOVIG, tell your doctor immediately. Depending
on your doctor’s decision the rate of infusion can be slowed or the infusion can be stopped altogether.
Special patient groups
•
Your doctor will take special care if you are overweight, elderly, diabetic, or if you suffer from
high blood pressure, low blood volume (hypovolaemia), or problems with your blood vessels
(vascular diseases). In these conditions, immunoglobulins may increase the risk of cardiac
infarction, stroke, lung embolism, or deep vein thrombosis, although only in very rare cases.
Tell your doctor if you are diabetic. Although KIOVIG does not contain sugar, it may be diluted
with a special sugar solution (5% glucose), which could affect your blood sugar level.
•
Your doctor will also take special care if you have or had previously problems with your
kidneys, or if you receive medicinal products that may harm your kidney (nephrotoxic
medicinal products), as there is a very rare chance of acute kidney failure.
Please tell your doctor if you have a kidney disorder. Your doctor will choose the appropriate
intravenous immunoglobulin for you.
Information on the source material of KIOVIG
KIOVIG is made from human plasma (the liquid part of blood). When medicines are made from
human blood or plasma, a number of measures are put in place to prevent infections being passed on
to patients. These include careful selection of blood and plasma donors to make sure those at risk of
carrying infections are excluded, and the testing of each donation and pools of plasma for signs of
virus/infections. Manufacturers of these products also include steps in the processing of the blood or
plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from
human blood or plasma are administered, the possibility of passing on infection cannot be totally
excluded. This also applies to any unknown or emerging viruses or other types of infections.
25
The measures taken for the manufacture of KIOVIG are considered effective for enveloped viruses
such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-
enveloped hepatitis A virus and parvovirus B19. KIOVIG also contains certain antibodies that can
prevent an infection with hepatitis A virus and parvovirus B19.
Taking other medicines
•
Please inform your doctor if you are taking, or have recently taken any other medicines,
including medicines obtained without a prescription.
•
If you have received a vaccination during the last six weeks and up to three months, the infusion
of immunoglobulins like KIOVIG may impair the effect of some live virus vaccines such as
measles, rubella, mumps and chicken pox. Therefore, after receiving immunoglobulins you may
have to wait up to 3 months before receiving your live-attenuated vaccine. You may have to
wait for up to 1 year after receiving immunoglobulins before you receive your measles vaccine.
Effects on blood tests
KIOVIG contains a wide variety of different antibodies, some of which can affect blood tests. If you
have a blood test after receiving KIOVIG, please inform the person taking your blood or your doctor
that you have received the medication.
Pregnancy and breast-feeding
•
Please inform your doctor if you are pregnant or breast-feeding. Your doctor will decide if
KIOVIG may be used during pregnancy and breast-feeding.
•
No clinical trials have been made with KIOVIG in pregnant or breast-feeding women. However,
medicines that contain antibodies have been used in pregnant or breast-feeding women, and it
has been shown that there are no harmful effects on the course of pregnancy or the baby to be
expected.
•
If you are breast-feeding and receive KIOVIG, the antibodies of the medicine can also be found
in the breast milk. Therefore, your baby may be protected from certain infections.
Driving and using machines
Patients may experience reactions (for example dizziness or nausea) during the treatment with
KIOVIG, which might affect the ability to drive and use machines. If this happens, you should wait
until the reactions have disappeared.
3.
HOW TO USE KIOVIG
KIOVIG is intended for intravenous administration (infusion into a vein). It is given to you by your
doctor or nurse. Dose and frequency of the infusion will vary depending on your condition and your
body weight.
At the beginning of your infusion you will receive KIOVIG at a slow rate. Dependent on how
comfortable you are, your doctor may then gradually increase the infusion rate.
Use in children
The same indications, dose and frequency of infusion as for adults apply for children (age 0 to 18).
If you use more KIOVIG than you should
If you get more KIOVIG than you should, your blood may become too thick (hyperviscous). This
could particularly happen when you are a patient at risk, e.g. an elderly patient or a patient having
problems with your kidneys. Be sure that you take adequate fluids so you are not dehydrated and
notify your physician if you are known to have medical problems.
26
4.
POSSIBLE SIDE EFFECTS
Like all medicines, KIOVIG can cause side effects, although not everybody gets them. Certain side
effects, e.g. headache or flushing, may be reduced by slowing the infusion rate.
Below is a list of side effects reported with KIOVIG:
•
Very common side effects
(affects more than 1 user in 10):
•
Common side effects
(affects 1 to 10 users in 100):
Bronchitis, common cold, dizziness, migraine, vertigo, rapid heartbeat, flushing, high blood
pressure, cough, runny nose, diarrhoea, nausea, vomiting, itching, rash and hives, pain in your
back, muscles, arms or legs, tiredness, influenza-like illness, pain and swelling at the infusion
site, stiffness.
•
Uncommon side effects
(affects 1 to 10 users in 1,000):
Chronic infection of the nose, fungal infections, various infections (of the nose and throat,
kidney or bladder), low red blood cell count, swollen lymph glands, disorder of the thyroid,
anxiety, memory impairment, burning sensation, difficulty in speaking, unusual taste in the
mouth, difficulty in sleeping, eye inflammation, eye pain or swelling, fluid in middle ear,
peripheral coldness, vein inflammation, chronic cough or wheezing (asthma), ear and throat
swelling, sore throat, rapid swelling of the skin, acute inflammation of the skin, cold sweat,
contusion, muscle cramps, chest tightness, feeling hot, indisposition, changes to blood test
results.
•
Rare side effects
(affects 1 to 10 users in 10,000):
•
Frequency not known (cannot be estimated from available data)
:
Destruction of red blood cells, serious allergic reaction including life-threatening allergic shock,
transient stroke, involuntary trembling, blood clot in a major vein, low blood pressure,
accumulation of fluid in the lung, shortness of breath, abdominal pain, excessive sweating, chest
pain, positive result of Coombs test, decreased oxygen saturation in blood, transfusion-related
acute lung injury.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE KIOVIG
•
Keep out of the reach and sight of children.
•
Do not use KIOVIG after the expiry date which is printed on the label and carton after EXP.
The expiry date refers to the last day of that month.
•
Do not use if particulate matter or discolouration is observed.
•
Store in a refrigerator (2°C – 8°C).
•
Do not freeze.
•
Keep the container in the outer carton in order to protect from light.
•
KIOVIG may be stored at room temperature (not more than 25°C) for up to 1 year. Record date
of transfer to room temperature and the end of the 1 year period on the outer carton. Once stored
at room temperature KIOVIG must not be returned to the refrigerator and must be discarded, if
not used by the end of the 1 year period.
27
headache and fever.
Sterile inflammation of the layers lining the brain.
6.
FURTHER INFORMATION
What KIOVIG contains
The active substance of KIOVIG is human normal immunoglobulin.
1 ml of KIOVIG contains 100 mg of human protein of which at least 98% is immunoglobulin G (IgG).
The other ingredients are glycine and water for injections.
What KIOVIG looks like and contents of the pack
KIOVIG is a solution for infusion in vials of 10, 25, 50, 100, 200 or 300 ml. The solution is clear or
slightly opalescent and colourless or pale-yellow.
Not all presentations may be marketed.
Marketing Authorisation Holder
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
Manufacturer
Baxter S.A.
Boulevard René Branquart, 80
B-7860 Lessines
Belgium
28
For any further information about this medicine, please contact the local representative of the
Marketing Authorisation Holder:
Belgique/België/Belgien
Baxter Belgium SPRL
Bd. de la Plaine/Pleinlaan 5
B-1050 Bruxelles/Brussel/Brüssel
Tél/Tel: + 32 2 650 1711
Luxembourg
Baxter Belgium SPRL
Bd. de la Plaine 5
B-1050 Bruxelles, Belgique
Tél/Tel: + 32 2 650 1711
България
ТП БАКСТЕР АД
бул. "България" 45
Бизнес Център "България Тауър"
Офис 2, ет. 2
1404 София,
България
Teл.: + 359 2 9808482
Magyarország
Baxter Hungary Kft
Népfürdő u. 22
H-1138 Budapest
Tel.: + 361 202 19 80
Česká republika
BAXTER CZECH spol.s.r.o.
Karla Engliše 3201/6CZ-150 00 Praha 5
Tel.: + 420 225 774 111
Malta
Baxter Healthcare Ltd
Wallingford Road
Compton Berkshire RG20 7QW, United
Kingdom
Tel.: + 44 1635 206345
Kύπρoς
Baxter (Hellas) Ε.Π.Ε.Εθνάρχου
Μακαρίου 34 & Αθηνοδώρου
Ηλιούπολη
GR-163 41 Αθήνα
Τηλ: + 30-210-99 87 000
Nederland
Baxter B.V.
Kobaltweg 49
NL-3542 CE Utrecht
Tel: + 31 30 2488911
Danmark
Baxter A/S
Gydevang 43
DK-3450 Allerød
Tlf: + 45 48 16 64 00
Norge
Baxter AS
Gjerdrumsvei 11
N-0484 Oslo
Tlf: + 47 22 58 4800
Deutschland
Baxter Deutschland Gm
bH
Edisonstraße 4
D-85716 Unterschleißheim
Tel: + 49 89 31701 0
Österreich
Baxter Healthcare GmbH
Stella-Klein-Löw-Weg 15
A-1020 Wien
Tel.: + 43 1 71120 0
Eesti
AS Oriola
Kungla 2
EE-76505 Saue
Harjumaa
Tel.: + 372 6 515 100
Polska
Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
PL-00-380 Warszawa
Tel.: + 48 22 4883 777
29
Ελλάδα
Baxter (Hellas) Ε.Π.Ε.
Εθνάρχου Μακαρίου 34 & Αθηνοδώρου
Ηλιούπολη
GR-163 41 Αθήνα
Τηλ: + 30 210 99 87 000
Portugal
Baxter Médico Farmacêutica Lda
Sintra Business Park
Zona Industrial da Abrunheira, Edifício 10
P-2710-089 Sintra
Tel: + 351 21 9252500
España
Baxter S.L.
Pouet de Camilo, 2E-46394 Ribarroja del
Turia (Valencia)
Tel: + 34 96 2722800
România
FARMACEUTICA REMEDIA S.A.
B-dul Metalurgiei, nr. 78, sector 4,
041836, Bucuresti, România
Tel-Fax: +40 21 321 16
40
France
Baxter S.A.S
6 Avenue Louis Pasteur
F-78310 Maurepas
Tél: + 33 1 3461 5050
Slovenija
Baxter d.o.o.
Železna cesta 18
SI-1000 Ljubljana
Tel.: + 386 1 420 16 80
Ireland
Baxter Healthcare Ltd
Unit 7 Deansgrange Industrial Estate
IRL – Blackrock, Dublin
Tel: + 353 1 2065500
Slovenská republika
Baxter AG, o. z.
Dúbravská cesta 2
SK-841 04 Bratislava
Tel: + 421 2 59418455
Ísland
Icepharma hf
Lynghalsi 13
IS-110 Reykjavík
Sími: + 354 540 8000
Suomi/Finland
Baxter Oy
PL 270
Valimotie 15 A
FIN-00381 Helsinki
Puh/Tel: + 358 9 8621111
Italia
Baxter S.p.A.
Piazzale dell’Industria 20
I-00144 Roma
Tel: + 39 06 324911
Sverige
Baxter Medical AB
Torshamnsgatan 35
S-164 40 Kista
Tel: + 46 8 6326400
Latvija
Baxter AG Latvijas filiāle
Dzelzavas iela 117
RĪGA LV-1021
Tel.: + 371 6 7784784
United Kingdom
Baxter Healthcare Ltd
Wallingford Road
Compton Berkshire RG20 7QW
Tel: + 44 1635 206345
Lietuva
UAB TAMRO atstovybė
S. Žukausko g. 29-1
LT-09129 Vilnius
Tel.: + 370 5 269 16 91
30
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.
The following information is intended for medical or healthcare professionals only:
Method of administration
•
KIOVIG must only be administered intravenously. Other routes of administration have not been
evaluated.
•
KIOVIG should be infused intravenously at an initial rate of 0.5 ml/kg bodyweight/hour for 30
minutes. If well tolerated, the rate of administration may gradually be increased to a maximum
of 6 ml/kg bodyweight/hour. Clinical data obtained from a limited number of patients also
indicate that adult PID patients may tolerate an infusion rate of up to 8 ml/kg BW/hr.
•
If dilution to lower concentrations is required prior to infusion, KIOVIG may be diluted with
5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin).
•
Any infusion-related adverse events should be treated by lowering infusion rates or by stopping
the infusion.
Special precautions
•
Any infusion-related adverse events should be treated by lowering the infusion rate or by
stopping the infusion.
•
It is recommended that every time KIOVIG is administered, the name and batch number of the
product is recorded.
Incompatibilities
This medicinal product must not be mixed with other medicinal products.
Special precautions for storage
•
After dilution to lower concentrations, immediate use is recommended. The in-use stability of
KIOVIG after dilution with a 5% glucose solution to a final concentration of 50 mg/ml (5%
immunoglobulin) has been demonstrated for 21 days at 2°C to 8°C as well as at 28°C to 30°C;
however, these studies did not include the microbial contamination and safety aspects.
Instructions for handling and disposal
•
The product must be brought to room or body temperature before use.
•
KIOVIG should be inspected visually for particulate matter and discoloration prior to
administration. Only clear to slightly opalescent and colourless to pale yellow solutions are to
be administered. Do not use if particulate matter or discolouration is observed.
•
If dilution is required, 5% glucose solution is recommended. For obtaining an immunoglobulin
solution of 50 mg/ml (5%), KIOVIG 100 mg/ml (10%) should be diluted with an equal volume
of the glucose solution. It is recommended that during dilution the risk of microbial
contamination is minimised.
•
Any unused product or waste material should be disposed of in accordance with local
requirements.
31
Dose recommendations
Indication
Dose
Frequency of injections
Replacement therapy in primary
immunodeficiency
- starting dose:
0.4 – 0.8 g/kg
- thereafter:
0.2 – 0.8 g/kg
0.2 – 0.4 g/kg
every 3 – 4 weeks to obtain IgG
trough level of at least 5 – 6 g/l
Replacement therapy in secondary
immunodeficiency
every 3 – 4 weeks to obtain IgG
trough level of at least 5 – 6 g/l
0.2 – 0.4 g/kg
0.2 – 0.4 g/kg
Children and adolescents with AIDS
every 3 – 4 weeks
Hypogammaglobulinaemia (< 4 g/l) in
patients after allogeneic haematopoietic
stem cell transplantation
every 3 – 4 weeks to obtain IgG
trough level above 5g/l
Immunomodulation:
0.8 – 1 g/kg
or
0.4 g/kg/d
0.4 g/kg/d
1.6 – 2 g/kg
or
2 g/kg
Primary immune thrombocytopenia
on day 1, possibly repeated once
within 3 days
for 2 – 5 days
Guillain Barré syndrome
for 5 days
Kawasaki disease
in divided doses for 2 – 5 days in
association with acetylsalicylic acid
in one dose in association with
acetylsalicylic acid
d = day
32
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/kiovig.html
Copyright © 1995-2021 ITA all rights reserved.