ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Ovitrelle
250 micrograms powder and solvent for solution for injection
2.
To ensure delivery of a 250 microgram dose, each vial contains 285 micrograms of
choriogonadotropin alfa.
Choriogonadotropin alfa is produced by recombinant DNA technology in Chinese Hamster Ovary
cells.
A dose of 250 micrograms is equivalent to approximately 6500 IU.
Excipients: 30 mg sucrose
For a full list of excipients, see section 6.1.
3.
Powder and solvent for solution for injection
Appearance of the powder: White to off-white pellet
Appearance of the solvent: Clear colourless solution
The pH of the reconstituted solution is 6.5 – 7.5
4.
Ovitrelle is indicated in the treatment of:
Women undergoing superovulation prior to assisted reproductive techniques such as in vitro
fertilisation (IVF): Ovitrelle is administered to trigger final follicular maturation and luteinisation after
stimulation of follicular growth.
Anovulatory or oligo-ovulatory women: Ovitrelle is administered to trigger ovulation and luteinisation
in anovulatory or oligo-ovulatory patients after stimulation of follicular growth
Ovitrelle is intended for subcutaneous administration. The powder should be reconstituted
immediately prior to use with the solvent provided.
Treatment with Ovitrelle should be performed under the supervision of a physician experienced in the
treatment of fertility problems.
The following dosing regimen should be used:
Women undergoing superovulation prior to assisted reproductive techniques such as in vitro
fertilisation (IVF):
One vial of Ovitrelle (250 micrograms) is administered 24 to 48 hours after the last administration of
an FSH- or hMG preparation, i.e. when optimal stimulation of follicular growth is achieved.
2
Anovulatory or oligo-ovulatory women:
One vial of Ovitrelle (250 micrograms) is administered 24 to 48 hours after optimal stimulation of
follicular growth is achieved. The patient is recommended to have coitus on the day of, and the day
after, Ovitrelle injection.
Ovitrelle is contraindicated for safety reasons in case of:
• Tumours of the hypothalamus and pituitary gland
• Hypersensitivity to the active substance or to any of the excipients
• Ovarian enlargement or cyst due to reasons other than polycystic ovarian disease
• Gynaecological haemorrhages of unknown aetiology
• Ovarian, uterine or mammary carcinoma
• Extrauterine pregnancy in the previous 3 months
• Active thrombo-embolic disorders
Ovitrelle must not be used when an effective response cannot be obtained, for example:
• Primary ovarian failure
• Malformations of sexual organs incompatible with pregnancy
• Fibroid tumours of the uterus incompatible with pregnancy
• Postmenopausal women
To date, there is no clinical experience with Ovitrelle in other indications commonly treated with urine
derived human chorionic gonadotrophin.
Before starting treatment, the couple's infertility should be assessed as appropriate and putative
contraindications for pregnancy evaluated. In particular, patients should be evaluated for
hypothyroidism, adrenocortical deficiency, hyperprolactinemia and pituitary or hypothalamic tumours,
and appropriate specific treatment given.
Special precautions should be taken before administering Ovitrelle to patients with clinically
significant systemic disease where pregnancy could lead to a worsening of the condition.
Patients undergoing ovarian stimulation are at an increased risk of developing ovarian
hyperstimulation syndrome (OHSS) due to multiple follicular development
Ovarian hyperstimulation syndrome may become a serious medical event characterised by large
ovarian cysts which are prone to rupture and the presence of ascites within a clinical picture of
circulatory dysfunction. Ovarian hyperstimulation syndrome due to excessive ovarian response can be
avoided by withholding hCG administration. Patients should be advised to refrain from coitus or use
barrier methods for at least 4 days.
Careful monitoring of estradiol levels and ovarian response, based on ultrasound is recommended
prior to and during stimulation therapy, for all patients.
The risk of multiple pregnancy following assisted reproductive technologies is related to the number
of embryos replaced. In patients undergoing induction of ovulation, the incidence of multiple
pregnancies and births (mostly twins) is increased compared with natural conception.
To minimise the risk of OHSS and of multiple pregnancy, ultrasound scans as well as estradiol
measurements are recommended. In anovulation, the risk of OHSS is increased by a serum estradiol
level > 1500 pg/ml (5400 pmol/l) and more than 3 follicles of 14 mm or more in diameter. In assisted
reproductive techniques, there is an increased risk of OHSS with a serum estradiol > 3000 pg/ml
(11000 pmol/l) and 20 or more follicles of 12 mm or more in diameter. When the estradiol level is
3
> 5500 pg/ml (20000 pmol/l) and when there are 40 or more follicles in total, it may be necessary to
withhold hCG administration.
Severe ovarian hyperstimulation syndrome could be complicated in rare cases by haemoperitoneum,
acute pulmonary distress, ovarian torsion, and thromboembolism.
Adherence to recommended Ovitrelle dosage, regimen of administration and careful monitoring of
therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy.
The rate of miscarriage, in both anovulatory patients and women undergoing assisted reproductive
techniques, is higher than that found in the normal population but comparable with the rates observed
in women with other fertility problems.
During Ovitrelle therapy, a minor thyroid stimulation is possible, of which the clinical relevance is
unknown.
Self-administration of Ovitrelle should only be performed by patients who are adequately trained and
have access to expert advice.
No specific interaction studies with Ovitrelle and other medicines have been performed however no
clinically significant drug interactions have been reported during hCG therapy.
Following administration, Ovitrelle may interfere for up to ten days with the immunological
determination of serum / urinary hCG, leading to a false positive pregnancy test .
Considering the indication, Ovitrelle should not be administered during pregnancy and lactation. No
clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin
alfa in animals were performed (see section 5.3). The potential risk for humans is unknown.
There are no data on the excretion of choriogonadotropin alfa in milk.
No studies on the effects on the ability to drive and use machines have been performed.
In comparative trials with different doses of Ovitrelle, the following undesirable effects were found to
be associated with Ovitrelle in a dose-related fashion: ovarian hyperstimulation syndrome, and
vomiting and nausea. Ovarian hyperstimulation syndrome was observed in approximately 4% of
patients treated with Ovitrelle. Severe ovarian hyperstimulation syndrome was reported in less than
0.5% patients (see section 4.4).
In rare instances, thromboembolisms have been associated with menotrophin/hCG therapy. Although
this adverse event was not observed, there is the possibility that this may also occur with Ovitrelle.
Ectopic pregnancy, ovarian torsion and other complications have been reported in patients after hCG
administration. These are considered concomitant effects related to Assisted Reproductive
Technologies (ART).
After best evidence assessment, the following undesirable effects may be observed after
administration of Ovitrelle. Within each frequency grouping, undesirable effects are presented in order
of decreasing seriousness.
4
Common (>1/100, < 1/10)
Gastrointestinal disorders
: Vomiting/nausea, abdominal pain
Reproductive system and breast disorders
: Mild or moderate ovarian hyperstimulation syndrome
General disorders and administration site conditions
: Headache, tiredness, local reaction/pain at
injection site.
Uncommon (>1/1,000, <1/100)
Psychiatric disorders
: Depression, irritability, restlessness
Gastrointestinal disorders
: Diarrhoea
Reproductive system and breast disorders
: Severe ovarian hyperstimulation syndrome, Breast pain
Very rare (<1/10,000)
Immune system disorders
: allergic reactions
Skin and subcutaneous tissue disorders
: Mild reversible skin reactions manifesting as rash,
No case of overdose has been reported.
Nevertheless, there is a possibility that ovarian hyperstimulation syndrome (OHSS) may result from an
overdosage of Ovitrelle (see section 4.4).
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: gonadotropins, ATC code: G03G A08
Ovitrelle is a medicinal product of choriogonadotropin alfa produced by recombinant DNA
techniques. It shares the amino acid sequence with urinary hCG. Chorionic gonadotropin binds on the
ovarian theca (and granulosa) cells to a transmembrane receptor shared with the luteinising hormone,
the LH/CG receptor.
The principal pharmacodynamic activity in women is oocyte meiosis resumption, follicular rupture
(ovulation), corpus luteum formation and production of progesterone and estradiol by the corpus
luteum.
In women, Chorionic gonadotropin acts as a surrogate LH- surge that triggers ovulation.
Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal
products for stimulation of follicular growth.
In comparative clinical trials, administration of a dose of 250 micrograms of Ovitrelle was as effective
as 5000 IU and 10000 IU of urinary hCG in inducing final follicular maturation and early luteinisation
in assisted reproductive techniques, and as effective as 5000 IU of urinary hCG in ovulation induction.
So far, there are no signs of antibody development in humans to Ovitrelle. Repeated exposure to
Ovitrelle was investigated in male patients only. Clinical investigation in women for the indication of
ART and anovulation was limited to one treatment cycle.
5.2 Pharmacokinetic properties
Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid
space with a distribution half-life of around 4.5 hours. The steady-state volume of distribution and the
total clearance are 6 l and 0.2 l/h, respectively. There are no indications that choriogonadotropin alfa is
metabolised and excreted differently than endogenous hCG.
5
Following subcutaneous administration, choriogonadotropin alfa is eliminated from the body with a
terminal half-life of about 30 hours, and the absolute bioavailability is about 40 %.
A comparative study between the freeze-dried and the liquid formulation showed bioequivalence
between the two formulations.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity and genotoxicity. Studies on carcinogenic potential were not
performed. This is justified, given the proteinous nature of the active substance and the negative
outcome of the genotoxicity testing.
Studies on reproduction were not performed in animals.
6.
6.1 List of excipients
Powder for solution for injection:
Sucrose
Phosphoric acid, concentrated
Sodium hydroxide
Solvent:
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
2 years. For immediate and single use following first opening and reconstitution.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
The powder container is a neutral colourless (type 1, Ph. Eur.) glass vial with a bromobutyl rubber
stopper.
The solvent container is a neutral, colourless glass type 1 vial with a bromobutyl rubber stopper or a
neutral, colourless glass type 1 ampoule.
The product is supplied in packs of 1, 2, 10 vials with the corresponding number of solvent containers.
Not all pack sizes may be marketed.
6
6.6 Special precautions for disposal
Ovitrelle is for single use only. One vial of Ovitrelle can be reconstituted with 1 ml of the solvent
before use. The reconstituted solution should not be administered if it contains particles or is not clear.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Merck Serono Europe Limited
56, Marsh Wall
London E14 9TP
United Kingdom
8.
EU/1/00/165/001-006
9.
Date of first authorization: 2 February 2001
Date of last renewal: 6 February 2006
7
1.
Ovitrelle 250 micrograms/0.5 ml, solution for injection in a pre-filled syringe
2.
Choriogonadotropin alfa* 250 micrograms in 0.5 ml. (equivalent to approximately 6500 IU)
Excipients: 27.3 mg mannitol, 0.05 mg poloxamer 188, 0.1 mg L-methionine
Produced by recombinant DNA technology in CHO
For a full list of excipients, see section 6.1.
3.
Solution for injection
Clear, colourless solution.
The pH of the solution is 7.0 ± 0.3, its osmolarity 250-400 mOsm/L
4.
Ovitrelle is indicated in the treatment of
Women undergoing superovulation prior to assisted reproductive techniques such as in vitro
fertilisation (IVF): Ovitrelle is administered to trigger final follicular maturation and luteinisation after
stimulation of follicular growth,
Anovulatory or oligo-ovulatory women: Ovitrelle is administered to trigger ovulation and luteinisation
in anovulatory or oligo-ovulatory patients after stimulation of follicular growth.
Ovitrelle is intended for subcutaneous administration.
Treatment with Ovitrelle should be performed under the supervision of a physician experienced in the
treatment of fertility problems.
The following dosing regimen should be used:
Women undergoing superovulation prior to assisted reproductive techniques such as in vitro
fertilisation (IVF):
One pre-filled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after the last
administration of an FSH- or hMG preparation, i.e. when optimal stimulation of follicular growth is
achieved.
Anovulatory or oligo-ovulatory women:
One pre-filled syringe of Ovitrelle (250 micrograms) is administered 24 to 48 hours after optimal
stimulation of follicular growth is achieved. The patient is recommended to have coitus on the day of,
and the day after, Ovitrelle injection.
8
Ovitrelle is contraindicated for safety reasons in case of:
• Tumours of the hypothalamus and pituitary gland
• Hypersensitivity to the active substance or to any of the excipients
• Ovarian enlargement or cyst due to reasons other than polycystic ovarian disease
• Gynaecological haemorrhages of unknown aetiology
• Ovarian, uterine or mammary carcinoma
• Extrauterine pregnancy in the previous 3 months
• Active thrombo-embolic disorders
Ovitrelle must not be used when an effective response cannot be obtained, for example:
• Primary ovarian failure
• Malformations of sexual organs incompatible with pregnancy
• Fibroid tumours of the uterus incompatible with pregnancy
• Postmenopausal women
To date, there is no clinical experience with Ovitrelle in other indications commonly treated with urine
derived human chorionic gonadotropin.
Before starting treatment, the couple's infertility should be assessed as appropriate and putative
contraindications for pregnancy evaluated. In particular, patients should be evaluated for
hypothyroidism, adrenocortical deficiency, hyperprolactinemia and pituitary or hypothalamic tumours,
and appropriate specific treatment given.
Special precautions should be taken before administering Ovitrelle to patients with clinically
significant systemic disease where pregnancy could lead to a worsening of the condition.
Patients undergoing ovarian stimulation are at an increased risk of developing ovarian
hyperstimulation syndrome (OHSS) due to multiple follicular development.
Ovarian hyperstimulation syndrome may become a serious medical event characterised by large
ovarian cysts, which are prone to rupture and the presence of ascites within a clinical picture of
circulatory dysfunction. Ovarian hyperstimulation syndrome due to excessive ovarian response can be
avoided by withholding hCG administration. Patients should be advised to refrain from coitus or use
barrier methods for at least 4 days.
Careful monitoring of estradiol levels and ovarian response, based on ultrasound is recommended
prior to and during stimulation therapy, for all patients.
The risk of multiple pregnancy following assisted reproductive technologies is related to the number
of embryos replaced. In patients undergoing induction of ovulation, the incidence of multiple
pregnancies and births (mostly twins) is increased compared with natural conception.
To minimise the risk of OHSS and of multiple pregnancy, ultrasound scans as well as estradiol
measurements are recommended. In anovulation, the risk of OHSS is increased by a serum estradiol
level > 1500 pg/ml (5400 pmol/l) and more than 3 follicles of 14 mm or more in diameter. In assisted
reproductive techniques, there is an increased risk of OHSS with a serum estradiol > 3000 pg/ml
(11000 pmol/l) and 20 or more follicles of 12 mm or more in diameter. When the estradiol level is
> 5500 pg/ml (20000 pmol/l) and when there are 40 or more follicles in total, it may be necessary to
withhold hCG administration.
Severe ovarian hyperstimulation syndrome could be complicated in rare cases by haemoperitoneum,
acute pulmonary distress, ovarian torsion, and thromboembolism.
9
Adherence to recommended Ovitrelle dosage, regimen of administration and careful monitoring of
therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy.
The rate of miscarriage, in both anovulatory patients and women undergoing assisted reproductive
techniques, is higher than that found in the normal population but comparable with the rates observed
in women with other fertility problems.
During Ovitrelle therapy, a minor thyroid stimulation is possible, of which the clinical relevance is
unknown.
Self-administration of Ovitrelle should only be performed by patients who are adequately trained and
have access to expert advice.
No specific interaction studies with Ovitrelle and other medicines have been performed however no
clinically significant drug interactions have been reported during hCG therapy.
Following administration, Ovitrelle may interfere for up to ten days with the immunological
determination of serum / urinary hCG, leading to a false positive pregnancy test.
Considering the indication, Ovitrelle should not be administered during pregnancy and lactation. No
clinical data on exposed pregnancies are available. No reproduction studies with choriogonadotropin
alfa in animals were performed (see section 5.3). The potential risk for humans is unknown.
There are no data on the excretion of choriogonadotropin alfa in milk.
No studies on the effects on the ability to drive and use machines have been performed.
In comparative trials with different doses of Ovitrelle, the following undesirable effects were found to
be associated with Ovitrelle in a dose-related fashion: ovarian hyperstimulation syndrome, and
vomiting and nausea. Ovarian hyperstimulation syndrome was observed in approximately 4% of
patients treated with Ovitrelle. Severe ovarian hyperstimulation syndrome was reported in less than
0.5% patients (see section 4.4).
In rare instances, thromboembolisms have been associated with menotropin/hCG therapy. Although
this adverse event was not observed, there is the possibility that this may also occur with Ovitrelle.
Ectopic pregnancy, ovarian torsion and other complications have been reported in patients after hCG
administration. These are considered concomitant effects related to Assisted Reproductive
Technologies (ART).
After best evidence assessment, the following undesirable effects may be observed after
administration of Ovitrelle. Within each frequency grouping, undesirable effects are presented in order
of decreasing seriousness.
Common (>1/100, <1/10)
Gastrointestinal disorders
: Vomiting/nausea, abdominal pain
Reproductive system and breast disorders
: Mild or moderate ovarian hyperstimulation syndrome
General disorders and administration site conditions
: Headache, tiredness, local reaction/pain at
injection site.
10
Uncommon (>1/1,000, <1/100)
Psychiatric disorders
: Depression, irritability, restlessness,
Gastrointestinal disorders
: Diarrhoea,
Reproductive system and breast disorders
: Severe ovarian hyperstimulation syndrome, breast pain.
Very rare (<1/10,000)
Immune system disorders
: allergic reactions
Skin and subcutaneous tissue disorders
: Mild reversible skin reactions manifesting as rash,
No case of overdose has been reported.
Nevertheless, there is a possibility that ovarian hyperstimulation syndrome (OHSS) may result from an
overdosage of Ovitrelle (see section 4.4 ).
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: gonadotropins, ATC code: G03G A08
Ovitrelle is a medicinal product of choriogonadotropin alfa produced by recombinant DNA
techniques. It shares the amino acid sequence with urinary hCG. Chorionic gonadotropin binds on the
ovarian theca (and granulosa) cells to a transmembrane receptor shared with the luteinising hormone,
the LH/CG receptor.
The principal pharmacodynamic activity in women is oocyte meiosis resumption, follicular rupture
(ovulation), corpus luteum formation and production of progesterone and estradiol by the corpus
luteum.
In women, chorionic gonadotropin acts as a surrogate LH- surge that triggers ovulation.
Ovitrelle is used to trigger final follicular maturation and early luteinisation after use of medicinal
products for stimulation of follicular growth.
In comparative clinical trials, administration of a dose of 250 micrograms of Ovitrelle was as effective
as 5000 IU and 10000 IU of urinary hCG in inducing final follicular maturation and early luteinisation
in assisted reproductive techniques, and as effective as 5000 IU of urinary hCG in ovulation induction.
So far, there are no signs of antibody development in humans to Ovitrelle. Repeated exposure to
Ovitrelle was investigated in male patients only. Clinical investigation in women for the indication of
ART and anovulation was limited to one treatment cycle.
5.2 Pharmacokinetic properties
Following intravenous administration, choriogonadotropin alfa is distributed to the extracellular fluid
space with a distribution half-life of around 4.5 hours. The steady-state volume of distribution and the
total clearance are 6 l and 0.2 l/h, respectively. There are no indications that choriogonadotropin alfa is
metabolised and excreted differently than endogenous hCG.
Following subcutaneous administration, choriogonadotropin alfa is eliminated from the body with a
terminal half-life of about 30 hours, and the absolute bioavailability is about 40%.
11
A comparative study between the freeze-dried and the liquid formulation showed bioequivalence
between the two formulations.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity and genotoxicity. Studies on carcinogenic potential were not
performed. This is justified, given the proteinous nature of the drug substance and the negative
outcome of the genotoxicity testing.
Studies on reproduction were not performed in animals.
6.
6.1 List of excipients
Mannitol
Methionine
Poloxamer 188
Diluted phosphoric acid
Sodium hydroxide
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
2 years.
After opening, the product should be used immediately. However, the in-use stability has been
demonstrated for 24 hours at +2° to 8° C.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C). Store in the original package. Within its shelf-life, the solution may
be stored at or below 25°C for up to 30 days without being refrigerated again during this period. It
must be discarded if not used after these 30 days.
6.5 Nature and contents of container
0.5 ml of solution in a pre-filled syringe (type I glass) with a plunger stopper (halobutyl rubber) and
plunger (plastic), and with a needle for injection (stainless) – pack of 1.
6.6 Special precautions for disposal
Only clear solution without particles should be used. Any unused product or waste material should be
disposed of in accordance with local requirements.
For single use only.
12
7.
Merck Serono Europe Limited
56, Marsh Wall
London E14 9TP
United Kingdom
8.
EU/1/00/165/007
9.
Date of first authorization: 2 February 2001
Date of last renewal: 6 February 2006
13
ANNEX II
A. MANUFACTUREROF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR
BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
14
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer of the biological active substance
Merck Serono S.A.
1170 Aubonne
Switzerland
Name and address of the manufacturer responsible for batch release
Merck Serono S.p.A.
Via delle Magnolie 15
I-70026 Modugno (Bari)
Italy
B. CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product
Characteristics, section 4.2)
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
15
ANNEX III
LABELLING AND PACKAGE LEAFLET
16
A. LABELLING
17
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OVITRELLE 250 MICROGRAMS, POWDER AND SOLVENT FOR SOLUTION FOR
INJECTION, SOLVENT IN AMPOULES
1.
Ovitrelle 250 micrograms powder and solvent for solution for injection.
Choriogonadotropin alfa.
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Composition: one vial delivers: Choriogonadotropin alfa 250 micrograms (6500 IU).
3.
LIST OF EXCIPIENTS
Other ingredients
:
Sucrose, phosphoric acid, sodium hydroxide.
One ampoule of solvent contains:1 ml water for injections.
4.
1 vial of powder for solution for injection.
EU/1/00/165/001
2 vials of powder for solution for injection
EU/1/00/165/002
10 vials of powder for solution for injection
EU/1/00/165/003
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous 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
18
1 ampoule of solvent.
2 ampoules of solvent
10 ampoules of solvent
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25
o
C. Store in the original package.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Discard any unused solution.
Merck
Serono Europe Limited
56, Marsh Wall
London E14 9TP
United Kingdom
EU/1/00/165/001 1 vial of powder/1 ampoule of solvent
EU/1/00/165/002 2 vials of powder/2 ampoules of solvent
EU/1/00/165/003 10 vials of powde/10 ampoules of solvent
13. BATCH NUMBER
Batch
Solvent Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
ovitrelle 250
19
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OVITRELLE 250 MICROGRAMS, POWDER AND SOLVENT FOR SOLUTION FOR
INJECTION, SOLVENT IN VIALS
1.
Ovitrelle 250 micrograms powder and solvent for solution for injection.
Choriogonadotropin alfa.
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Composition: one vial delivers: Choriogonadotropin alfa 250 micrograms (6500 IU).
3.
LIST OF EXCIPIENTS
Other ingredients
:
Sucrose, phosphoric acid, sodium hydroxide.
One vial of solvent contains:1 ml water for injections.
4.
1 vial of powder for solution for injection.
EU/1/00/165/004
2 vials of powder for solution for injection
EU/1/00/165/005
10 vials of powder for solution for injection
EU/1/00/165/006
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous 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
20
1 vial of solvent.
2 vials of solvent
10 vials of solvent
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25
o
C. Store in the original package.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Discard any unused solution.
Merck
Serono Europe Limited
56, Marsh Wall
London E14 9TP
United Kingdom
EU/1/00/165/004
1 vial of powder/1 vial of solvent
EU/1/00/165/005
2 vials of powder/2 vials of solvent
EU/1/00/165/006
10 vials of powder/10 vials of solvent
13. BATCH NUMBER
Batch
Solvent Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
ovitrelle 250
21
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OVITRELLE 250 MICROGRAMS, SOLUTION FOR INJECTION
1.
Ovitrelle 250 micrograms/0.5 ml solution for injection in a pre-filled syringe.
Choriogonadotropin alfa.
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
One pre-filled syringe contains: 250 micrograms (6500 IU) of Choriogonadotropin alfa
3.
LIST OF EXCIPIENTS
Other ingredients
:
Mannitol, methionine, poloxamer 188, diluted phosphoric acid, sodium hydroxide,
water for injections.
4.
1 pre-filled syringe with 0.5 ml solution for injection
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Subcutaneous use.
For single use only.
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
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator. Store in the original package. May be stored at or below + 25° C for up to 30
days without being refrigerated again during this period and must be discarded if not used during these
30 days.
22
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Any unused solution or waste material should be disposed of in accordance with local requirements
Merck Serono Europe Limited
56, Marsh Wall
London E14 9TP
United Kingdom
EU/1/00/165/007
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
ovitrelle 250/0.5 ml
23
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OVITRELLE 250 MICROGRAMS s, POWDER
1.
Ovitrelle 250 micrograms powder for injection
Subcutaneous use.
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Batch
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
250 micrograms
6.
OTHER
24
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OVITRELLE 250 MICROGRAMS s, SOLVENT VIALS AND AMPOULES
1.
Water for Injections
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Batch
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
1 ml
6.
OTHER
25
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OVITRELLE 250 MICROGRAMS s, PRE-FILLED SYRINGE
1.
Ovitrelle 250 micrograms/0.5 ml solution for injection in a pre-filled syringe
Choriogonadotropin alfa
Subcutaneous use.
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Batch
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
250 micrograms/0.5 ml
6.
OTHER
26
B. PACKAGE LEAFLET
27
PACKAGE LEAFLET: INFORMATION FOR THE USER
(Solvent container: Ampoule)
Ovitrelle
250 micrograms powder and solvent for solution for injection.
Choriogonadotropin alfa.
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 you doctor or pharmacist.
In this leaflet
:
1.
What Ovitrelle is and what it is used for
3.
How to use Ovitrelle
4.
Possible side effects
5.
How to store Ovitrelle
6.
Further information
1.
WHAT OVITRELLE IS AND WHAT IT IS USED FOR
Ovitrelle is a medicinal product containing choriogonadotropin alfa, which is very similar to chorionic
gonadotrophin found naturally in humans, but it is made in laboratories by special recombinant DNA
techniques. It belongs to the family of hormones called gonadotrophins, which are involved in the
normal control of reproduction.
Ovitrelle is used in women undergoing assisted reproductive techniques such as in vitro fertilisation
(IVF). Other medicines are given first to bring about the growth and development of several follicles,
to produce eggs. Ovitrelle is then used to ripen (mature) these follicles.
Ovitrelle is also used in women who do not produce eggs (a condition called anovulation) or who
produce too few eggs (oligo-ovulation). It is given to bring about the release of eggs (ovulation), after
other medicines have been used to develop the follicles.
2.
BEFORE YOU USE OVITRELLE
You and your partner's fertility should be evaluated before the treatment is started.
Do not take Ovitrelle:
-
If you are pregnant or breast-feeding
-
If you have ovarian enlargement or one or more large ovarian cysts
-
if you have been diagnosed as having ovarian, uterine or breast cancer
-
if you had a tumour of the hypothalamus or pituitary gland
-
If you suffer from severe inflammation of the veins or blood clotting in the veins (active
thrombo-embolic disorders)
-
if you have any condition which would make a normal pregnancy impossible (e.g. absent uterus,
ovaries which have not developed properly, fibroids) or you have been through menopause
-
if you had an extrauterine pregnancy within the last 3 months
28
2.
Before you use Ovitrelle
-
if you have unexplained vaginal bleeding
-
if you are allergic (hypersensitive) to choriogonadotropin, or any of the ingredients of Ovitrelle
Take special care with Ovitrelle:
Treatment with Ovitrelle may increase your risk of developing a condition called ovarian
hyperstimulation syndrome (OHSS) (see also ‘Possible side effects’). This is when the ovaries over-
react to the treatment and develop too many follicles. The most common symptom is abdominal pain.
If you have significant abdominal pain or discomfort,
do not
take the injection, and speak to your
doctor or nurse as soon as possible. You should not have intercourse for at least 4 days, or otherwise
you should use a barrier method for contraception.
Compared with natural conception, the frequency of multiple pregnancies and births is increased in
patients receiving this treatment. The majority of these are twins. In assisted conception techniques,
the number of babies is related to the number of embryos replaced.
Your risk of OHSS or multiple pregnancy is reduced if the usual dose of Ovitrelle is used, and you are
monitored closely throughout your treatment cycle (e.g. blood tests for estradiol levels and
ultrasound).
Using other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Pregnancy and breast-feeding
You should not take Ovitrelle if you are pregnant or breast-feeding.
3.
HOW TO USE OVITRELLE
Always take Ovitrelle exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure.
The usual dose of Ovitrelle is 1 vial (250 micrograms) given as a single injection. Your doctor will
have explained exactly when to give the injection.
Ovitrelle is intended for subcutaneous use, that means given by injection under the skin. Each vial is
for single use only.
Sometimes the injection will be given to you by a doctor or nurse, or you or your partner may be
trained to give the injection at home.
If you administer Ovitrelle to yourself, please carefully read the following instructions:
1.
Wash your hands. It is important that your hands and the items you use be as clean as possible.
2.
Assemble everything you need. Please note that alcohol swabs, syringes and needles are not
contained in the package. Find a clean area and lay out everything:
-
-
one solvent ampoule,
-
one vial containing the medicinal product
-
one syringe,
-
one big needle for reconstitution,
-
a fine-bore needle for subcutaneous injection.
29
two alcohol swabs,
3.
Opening the ampoule of s
olvent:
On the head of the solvent ampoule, you will see a small coloured
dot. Directly below it is where the neck of the ampoule has been
treated to make it easier to break. Gently flick the top section of the
ampoule so that any fluid in the neck of the ampoule drops into the
bottom chamber. Now press the ampoule firmly over the neck, and
break the ampoule away from the coloured dot. Carefully place the
open ampoule upright on the work-surface.
4.
Drawing up the solvent:
Attach the
needle for reconstitution
to the syringe, with the syringe
in one hand, pick up the open ampoule, insert the needle and draw up
all of the solvent. Carefully set the syringe down on the work-
surface, taking care not to touch the needle.
5.
P
reparation of the inject
ion solution:
Remove the protective cap from the
Ovitrelle powder vial
, pick up
your syringe and slowly inject the solvent into the vial of Ovitrelle.
Swirl gently.
Do not shake
. The powder should dissolve into a clear
solution immediately.
Turn the vial upside down, gently draw the solution back into the
syringe.
6.
Injection:
Change the needle for the
fine-bore needle
and remove any air
bubbles: If you see air bubbles in the syringe, hold the syringe
with the needle pointing upwards and gently flick the syringe until
all the air collects at the top. Gently push the plunger until the air
bubbles are gone.
30
Immediately inject the solution: Your doctor or nurse will have
already advised you where to inject (e.g. tummy, front of thigh).
Wipe the chosen area with an alcohol swab. Firmly pinch the skin
together and insert the needle at a 45° to 90° angle using a dart-like
motion. Inject under the skin, as you were taught. Do not inject
directly into a vein. Inject the solution by pushing gently on the
plunger. Take as much time as you need to inject all the solution.
Immediately withdraw the needle and clean the skin with an
alcohol swab using a circular motion.
7.
Dispose of all used items:
Once you have finished your injection, immediately discard all needles and empty glass
containers in a sharps container. Any unused solution must be discarded.
If you take more Ovitrelle than you should:
If too much Ovitrelle is used, there is a possibility that ovarian hyperstimulation syndrome may occur,
which is further described under ‘Take special care with Ovitrelle’ and ‘Possible side effects'. You
should consult your doctor if symptoms of this syndrome occur.
If you forget to take Ovitrelle:
You should contact your doctor.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Ovitrelle can cause side effects, although not everybody gets them.. The majority
of side effects seen to date have been mild or moderate. The most frequent side effects reported have
been tiredness, pain and local reactions at the site of injection.
Ovarian hyperstimulation syndrome has been observed in approximately 4% of the patients in clinical
studies; most of these cases were mild or moderate in nature. Blood in the peritoneal cavity, respiratory
difficulties are possible complications of ovarian hyperstimulation syndrome.
This syndrome is characterized by large ovarian cysts. First symptoms of ovarian hyperstimulation are
pain in the lower abdominal region, possibly in combination with nausea, vomiting and weight gain.
Should the above mentioned symptoms occur, a careful medical examination is indicated as soon as
possible.
Common side effects reported include abdominal pain, nausea and vomiting, headache, injection site
inflammation and reaction, dizziness. Diarrhoea, depression, irritability, restlessness and breast pain
have also been reported in some cases and are considered uncommon.
Extrauterine pregnancy, ovarian torsion (a condition affecting the ovaries) and other complications
may arise from the assisted conception techniques your doctor may use.
Isolated cases of mild allergic reactions to Ovitrelle (rash) have been reported.
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 OVITRELLE
Keep out of the reach and sight of children.
31
Do not use after the expiry date which is stated on the label after EXP. The expiry date refers to the
last day of that month.
Do not store above 25°C. Store in the original package.
Once the medicine is reconstituted (made up with the solvent), it should be used immediately.
Do not use Ovitrelle if you notice any visible signs of deterioration.
The reconstituted solution should not be administered if it contains particles or is not clear.
Ovitrelle is for single use only. Any unused solution should be discarded.
6.
FURTHER INFORMATION
What Ovitrelle contains
The active substance is choriogonadotropin alfa, each vial contains 285 micrograms.
After reconstitution 250 micrograms, which is the equivalent of 6500 IU, is delivered because some
choriogonadotropin alfa will be left in the vial, in the syringe and in the needle.
The other ingredients are sucrose, phosphoric acid, and sodium hydroxide.
The solvent is water for injections.
What Ovitrelle looks like and contents of the pack
Ovitrelle is provided as a powder and solvent for solution for injection. It is available in packs
containing 1, 2, or 10 vials of powder containing the active substance which are accompanied by the
corresponding number of solvent containers. Not all pack sizes may be marketed.
Each vial of powder contains 285 micrograms of choriogonadotropin alfa and each container of
solvent contains 1 ml of water for injections. When one vial is reconstituted with 1 ml of solvent you
will receive a dose of 250 micrograms.
Marketing Authorisation Holder
Merck Serono Europe Limited, 56 Marsh Wall, London E14 9TP,
United Kingdom
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, I-70026 Modugno (Bari), Italy
For any information about this medicine e, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse
Tél/Tel: +32-2-686 07 11
Luxembourg/Luxemburg
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse, Belgique/Belgien
Tél/Tel: +32-2-686 07 11
32
България
MERCK d.o.o.
Dunajska cesta 119
SI 1000 Любляна, Словения
Teл: +386 1 560 3 800
Magyarország
Merck Kft.
Bocskai út 134-146.
H-1113 Budapest
Tel: +36-1-463-8100
Česká republika
Merck spol.s.r.o
Na Hrebenech II. 1718/10
CZ-140 00 Praha 4
Tel. +420 272084211
Malta
Cherubino Ltd
Delf Building
Sliema Road
MT-GZR 06 Gzira Malta
Tel: +356-21-343270/1/2/3/4
Danmark
E. Merck AB
Strandvejen 102 B, 4th
DK-2900 Hellerup
Tlf: +45 35253550
Nederland
Merck BV
Tupolevlaan 41-61
NL-1119 NW Schiphol-Rijk
Tel: +31-20-6582800
Deutschland
Serono GmbH
Alsfelder Straße 17
D-64289 Darmstadt
Tel: +49-6151-6285-0
Norge
Merck Serono Norge
Luhrtoppen 2
1470 Lørenskog
Tlf: +47 67 90 35 90
Eesti
Merck Serono
Esindaja
C/o Ares Trading SA Baltic States
Zamenhofo 11-3, LT-44287
Kaunas, Leedu
Tel: +370 37320603
Österreich
Merck GesmbH.
Zimbagasse 5
A-1147 Wien
Tel: +43 1 57600-0
Ελλάδα
Merck A.E.
Κηφισίας 41-45, Κτίριο Β
GR-151 23 Μαρούσι
Αθήνα
Tηλ: +30-210-61 65 100
Polska
Merck Sp. z o.o.
Al. Jerozolimskie 178
02-486 Warszawa
Polska
Tel.: +48 22 53 59 700
España
Merck S.L.
María de Molina, 40
E-28006 Madrid
Línea de Información: 900 200 400
Tel: +34-91-745 44 00
Portugal
Merck, s.a.
Rua Alfredo da Silva, 3-C
P-1300-040 Lisboa
Tel: +351-21-361 35 00
France
Merck Serono s.a.s.
37, rue Saint-Romain
F-69379 Lyon cedex 08
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024
România
MERCK d.o.o.,
Dunajska cesta 119
SI-1000 Lubliana, Slovenia
Tel: +386 1 560 3 800
33
Ireland
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
United Kingdom
Tel: +44-20 8818 7200
Slovenija
MERCK d.o.o.
Dunajska cesta 119
SI-1000 Ljubljana
Tel: +386 1 560 3 800
Ísland
Icepharma hf
Lynghálsi 13
110 Reykjavík
Íceland
Tel: + 354 540 8000
Slovenská
republika
Merck spol. s r.o.
Tuhovská 3
SK-831 06 Bratislava
Tel: + 421 2 49 267 111
Italia
Merck Serono S.p.A.
Via Casilina 125
I-00176 Roma
Tel: +39-06-70 38 41
Suomi
/
Finland
Merck Oy
Pihatörmä 1 C
FI-02240 Espoo
Puh/Tel: +358-9-8678 700
Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Λεωφόρος Κιλκίς 35,
2234 Λατσιά, Λευκωσία
Τηλ.: +357 22490305
Sverige
E. Merck AB
S-195 87 Stockholm
Tel: +46-8-562 445 00
Latvija
Merck Serono
Pārstāvniecība
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kauņa, Lietuva
Tel: +370 37320603
United Kingdom
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
Tel: +44-20 8818 7200
Lietuva
Merck Serono
Atstovybė
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kaunas
Tel: +370 37320603
This leaflet was last approved on
34
PACKAGE LEAFLET: INFORMATION FOR THE USER
(Solvent container: Vial)
Ovitrelle
250 micrograms powder and solvent for solution for injection.
Choriogonadotropin alfa.
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 you doctor or pharmacist.
In this leaflet
:
1.
What Ovitrelle is and what it is used for
3.
How to use Ovitrelle
4.
Possible side effects
5.
How to store Ovitrelle
6.
Further information
1.
WHAT OVITRELLE IS AND WHAT IT IS USED FOR
Ovitrelle is a medicinal product containing choriogonadotropin alfa, which is very similar to chorionic
gonadotrophin found naturally in humans, but it is made in laboratories by special recombinant DNA
techniques. It belongs to the family of hormones called gonadotrophins, which are involved in the
normal control of reproduction.
Ovitrelle is used in women undergoing assisted reproductive techniques such as in vitro fertilisation
(IVF). Other medicines are given first to bring about the growth and development of several follicles,
to produce eggs. Ovitrelle is then used to ripen (mature) these follicles.
Ovitrelle is also used in women who do not produce eggs (a condition called anovulation) or who
produce too few eggs (oligo-ovulation). It is given to bring about the release of eggs (ovulation), after
other medicines have been used to develop the follicles.
2.
BEFORE YOU USE OVITRELLE
You and your partner's fertility should be evaluated before the treatment is started.
Do not take Ovitrelle:
-
If you are pregnant or breast-feeding
-
If you have ovarian enlargement or one or more large ovarian cysts
-
if you have been diagnosed as having ovarian, uterine or breast cancer
-
if you had a tumour of the hypothalamus or pituitary gland
-
If you suffer from severe inflammation of the veins or blood clotting in the veins (active
thrombo-embolic disorders)
-
if you have any condition which would make a normal pregnancy impossible (e.g. absent uterus,
ovaries which have not developed properly, fibroids) or you have been through menopause
-
if you had an extrauterine pregnancy within the last 3 months
35
2.
Before you use Ovitrelle
-
if you have unexplained vaginal bleeding
-
if you are allergic (hypersensitive) to choriogonadotropin, or any of the ingredients of Ovitrelle.
Take special care with Ovitrelle:
Treatment with Ovitrelle may increase your risk of developing a condition called ovarian
hyperstimulation syndrome (OHSS) (see also ‘Possible side effects’). This is when the ovaries over-
react to the treatment and develop too many follicles. The most common symptom is abdominal pain.
If you have significant abdominal pain or discomfort,
do not
take the injection, and speak to your
doctor or nurse as soon as possible. You should not have intercourse for at least 4 days, or otherwise
you should use a barrier method for contraception.
Compared with natural conception, the frequency of multiple pregnancies and births is increased in
patients receiving this treatment. The majority of these are twins. In assisted conception techniques,
the number of babies is related to the number of embryos replaced.
Your risk of OHSS or multiple pregnancy is reduced if the usual dose of Ovitrelle is used, and you are
monitored closely throughout your treatment cycle (e.g. blood tests for estradiol levels and
ultrasound).
Using other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Pregnancy and breast-feeding
You should not take Ovitrelle if you are pregnant or breast-feeding.
3.
HOW TO USE OVITRELLE
Always take Ovitrelle exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure.
The usual dose of Ovitrelle is 1 vial (250 micrograms) given as a single injection. Your doctor will
have explained exactly when to give the injection.
Ovitrelle is intended for subcutaneous use, that means given by injection under the skin. Each vial is
for single use only.
Sometimes the injection will be given to you by a doctor or nurse, or you or your partner may be
trained to give the injection at home.
If you administer Ovitrelle to yourself, please carefully read the following instructions:
1.
Wash your hands. It is important that your hands and the items you use be as clean as possible.
2.
Assemble everything you need. Please note that alcohol, swabs, syringes and needles are not
contained in the package. Find a clean area and lay out everything:
-
two alcohol swabs,
-
one solvent vial,
-
one vial containing the medicinal product
-
one big needle for reconstitution,
-
a fine-bore needle for subcutaneous injection.
36
-
one syringe,
3.
Drawing up the solven
t:
Remove the protective cap from the
solvent vial
. Attach the
needle for reconstitution
(the bigger needle) to the syringe
and draw up some air into the syringe by pulling the plunger
to approximately the 1 ml mark. Then, insert the needle into
the vial, push the plunger to expel the air, turn the vial
upside down and gently draw up all the solvent.
Set the syringe down carefully on the work-surface taking
care not to touch the needle.
4.
P
reparing the injection s
olution
:
Remove the protective cap from the
Ovitrelle powder vial
, pick up
your syringe and slowly inject the solvent into the vial of Ovitrelle.
Swirl gently.
Do not shake
. The powder should dissolve into a clear
solution immediately.
Turn the vial upside down, gently draw the solution back into the
syringe.
5.
Injection:
Change the needle for the fine-bore needle and remove any air
bubbles: If you see air bubbles in the syringe, hold the syringe with
the needle pointing upwards and gently flick the syringe until all the
air collects at the top. Gently push the plunger until the air bubbles
are gone.
Immediately inject the solution: Your doctor or nurse will have
already advised you where to inject (e.g. tummy, front of thigh).
Wipe the chosen area with an alcohol swab. Firmly pinch the skin
together and insert the needle at a 45° to 90° angle using a dart-like
motion. Inject under the skin, as you were taught. Do not inject
directly into a vein. Inject the solution by pushing gently on the
plunger. Take as much time as you need to inject all the solution.
Immediately withdraw the needle and clean the skin with an alcohol
swab using a circular motion.
6.
Dispose of all used items:
Once you have finished your injection, immediately discard all needles and empty glass
containers in a sharps container. Any unused solution must be discarded.
37
If you take more Ovitrelle than you should:
If too much Ovitrelle is used, there is a possibility that ovarian hyperstimulation syndrome may occur,
which is further described under ‘Take special care with Ovitrelle’ and ‘Possible side effects'. You
should consult your doctor if symptoms of this syndrome occur.
If you forget to take Ovitrelle:
You should contact your doctor.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Ovitrelle can cause side effects, although not everybody gets them. The majority of
side effects seen to date have been mild or moderate. The most frequent side effects reported have
been tiredness, pain and local reactions at the site of injection.
Ovarian hyperstimulation syndrome has been observed in approximately 4% of the patients in clinical
studies; most of these cases were mild or moderate in nature. Blood in the peritoneal cavity, respiratory
difficulties are possible complications of ovarian hyperstimulation syndrome.
This syndrome is characterized by large ovarian cysts. First symptoms of ovarian hyperstimulation are
pain in the lower abdominal region, possibly in combination with nausea, vomiting and weight gain.
Should the above mentioned symptoms occur, a careful medical examination is indicated as soon as
possible.
Common side effects reported include abdominal pain, nausea and vomiting, headache, injection site
inflammation and reaction, dizziness. Diarrhoea, depression, irritability, restlessness and breast pain
have also been reported in some cases and are considered uncommon.
Extrauterine pregnancy, ovarian torsion (a condition affecting the ovaries) and other complications
may arise from the assisted conception techniques your doctor may use.
Isolated cases of mild allergic reactions to Ovitrelle (rash) have been reported.
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 OVITRELLE
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label after EXP. The expiry date refers to the
last day of that month.
Do not store above 25°C. Store in the original package.
Once the medicine is reconstituted (made up with the solvent), it should be used immediately.
Do not use Ovitrelle if you notice any visible signs of deterioration.
The reconstituted solution should not be administered if it contains particles or is not clear.
Ovitrelle is for single use only. Any unused solution should be discarded.
38
6.
FURTHER INFORMATION
What Ovitrelle contains
The active substance is choriogonadotropin alfa, each vial contains 285 micrograms.
After reconstitution 250 micrograms, which is the equivalent of 6500 IU, is delivered because some
choriogonadotropin alfa will be left in the vial, in the syringe and in the needle.
The other ingredients are sucrose, phosphoric acid, and sodium hydroxide.
The solvent is water for injections.
What Ovitrelle looks like and contents of the pack
Ovitrelle is provided as a powder and solvent for solution for injection. It is available in packs
containing 1, 2, or 10 vials of powder containing the active substance which are accompanied by the
corresponding number of solvent containers. Not all pack sizes may be marketed.
Each vial of powder contains 285 micrograms of choriogonadotropin alfa and each container of
solvent contains 1 ml of water for injections. When one vial is reconstituted with 1 ml of solvent you
will receive a dose of 250 micrograms.
Marketing Authorisation Holder
Merck Serono Europe Limited, 56 Marsh Wall, London E14 9TP,
United Kingdom
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, I-70026 Modugno (Bari), Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse
Tél/Tel: +32-2-686 07 11
Luxembourg/Luxemburg
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse, Belgique/Belgien
Tél/Tel: +32-2-686 07 11
България
MERCK d.o.o.
Dunajska cesta 119
SI 1000 Любляна, Словения
Teл: +386 1 560 3 800
Magyarország
Merck Kft.
Bocskai út 134-146.
H-1113 Budapest
Tel: +36-1-463-8100
Česká republika
Merck spol.s.r.o
Na Hrebenech II. 1718/10
CZ-140 00 Praha 4
Tel. +420 272084211
Malta
Cherubino Ltd
Delf Building
Sliema Road
MT-GZR 06 Gzira Malta
Tel: +356-21-343270/1/2/3/4
39
Danmark
E. Merck AB
Strandvejen 102 B, 4th
DK-2900 Hellerup
Tlf: +45 35253550
Nederland
Merck BV
Tupolevlaan 41-61
NL-1119 NW Schiphol-Rijk
Tel: +31-20-6582800
Deutschland
Serono GmbH
Alsfelder Straße 17
D-64289 Darmstadt
Tel: +49-6151-6285-0
Norge
Merck Serono Norge
Luhrtoppen 2
1470 Lørenskog
Tlf: +47 67 90 35 90
Eesti
Merck Serono
Esindaja
C/o Ares Trading SA Baltic States
Zamenhofo 11-3, LT-44287
Kaunas, Leedu
Tel: +370 37320603
Österreich
Merck GesmbH.
Zimbagasse 5
A-1147 Wien
Tel: +43 1 57600-0
Ελλάδα
Merck A.E.
Κηφισίας 41-45, Κτίριο Β
GR-151 23 Μαρούσι
Αθήνα
Tηλ: +30-210-61 65 100
Polska
Merck Sp. z o.o.
Al. Jerozolimskie 178
02-486 Warszawa
Polska
Tel.: +48 22 53 59 700
España
Merck S.L.
María de Molina, 40
E-28006 Madrid
Línea de Información: 900 200 400
Tel: +34-91-745 44 00
Portugal
Merck, s.a.
Rua Alfredo da Silva, 3-C
P-1300-040 Lisboa
Tel: +351-21-361 35 00
France
Merck Serono s.a.s.
37, rue Saint-Romain
F-69379 Lyon cedex 08
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024
România
MERCK d.o.o.,
Dunajska cesta 119
SI-1000 Lubliana, Slovenia
Tel: +386 1 560 3 800
Ireland
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
United Kingdom
Tel: +44-20 8818 7200
Slovenija
MERCK d.o.o.
Dunajska cesta 119
SI-1000 Ljubljana
Tel: +386 1 560 3 800
Ísland
Icepharma hf
Lynghálsi 13
110 Reykjavík
Íceland
Tel: + 354 540 8000
Slovenská
republika
Merck spol. s r.o.
Tuhovská 3
SK-831 06 Bratislava
Tel: + 421 2 49 267 111
40
Italia
Merck Serono S.p.A.
Via Casilina 125
I-00176 Roma
Tel: +39-06-70 38 41
Suomi
/
Finland
Merck Oy
Pihatörmä 1 C
FI-02240 Espoo
Puh/Tel: +358-9-8678 700
Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Λεωφόρος Κιλκίς 35,
2234 Λατσιά, Λευκωσία
Τηλ.: +357 22490305
Sverige
E. Merck AB
S-195 87 Stockholm
Tel: +46-8-562 445 00
Latvija
Merck Serono
Pārstāvniecība
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kauņa, Lietuva
Tel: +370 37320603
United Kingdom
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
Tel: +44-20 8818 7200
Lietuva
Merck Serono
Atstovybė
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kaunas
Tel: +370 37320603
This leaflet was last approved on
41
PACKAGE LEAFLET: INFORMATION FOR THE USER
Ovitrelle
250 micrograms/0.5 ml solution for injection in a pre-filled syringe.
Choriogonadotropin alfa
Read all of this leaflet carefully before you start using this medicine.
-
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 you doctor or pharmacist.
In this leaflet
:
1.
What Ovitrelle is and what it is used for
2.
Before you use Ovitrelle
4.
Possible side effects
5.
How to store Ovitrelle
6.
Further information
1.
WHAT OVITRELLE IS AND WHAT IT IS USED FOR
Ovitrelle is a medicinal product containing choriogonadotropin alfa, which is very similar to chorionic
gonadotrophin found naturally in humans, but it is made in laboratories by special recombinant DNA
techniques. It belongs to the family of hormones called gonadotrophins, which are involved in the
normal control of reproduction.
Ovitrelle is used in women undergoing assisted reproductive techniques such as in vitro fertilisation
(IVF). Other medicines are given first to bring about the growth and development of several follicles,
to produce eggs. Ovitrelle is then used to ripen (mature) these follicles.
Ovitrelle is also used in women who do not produce eggs (a condition called anovulation), or who
produce too few eggs (oligo-ovulation). It is given to bring about the release of eggs (ovulation), after
other medicines have been used to develop the follicles.
2.
BEFORE YOU USE OVITRELLE
You and your partner's fertility should be evaluated before the treatment is started.
Do not take Ovitrelle:
-
If you are pregnant or breast-feeding
-
If you have ovarian enlargement or one or more large ovarian cysts
-
If you have been diagnosed as having ovarian, uterine or breast cancer
-
If you have had a tumour of the hypothalamus or pituitary gland
-
If you suffer from severe inflammation of the veins or blood clotting in the veins (active
thrombo-embolic disorders)
-
If you are allergic (hypersensitive) to choriogonadotropin or any of the ingredients of Ovitrelle
-
If you have any condition which would make a normal pregnancy impossible (e.g. absent
uterus, ovaries which have not developed properly, fibroids) or you have been through the
menopause
-
If you have had an extrauterine pregnancy within the last 3 months
42
-
Keep this leaflet. You may need to read it again.
3.
How to use Ovitrelle
-
If you have unexplained vaginal bleeding
Take special care with Ovitrelle:
Treatment with Ovitrelle may increase your risk of developing a condition called ovarian
hyperstimulation syndrome (OHSS) (see also ‘Possible side effects’). This is when the ovaries over-
react to the treatment and develop too many follicles. The most common symptom is abdominal pain.
If you have significant abdominal pain or discomfort,
do not
give yourself the injection, and speak to
your doctor or nurse as soon as possible. You should not have intercourse for at least 4 days, or
otherwise you should use a barrier method for contraception.
Compared with natural conception, the frequency of multiple pregnancies and births is increased in
patients receiving this treatment. The majority of these are twins. In assisted conception techniques,
the number of babies is related to the number of embryos replaced.
Your risk of OHSS or multiple pregnancy is reduced if the usual dose of Ovitrelle is used, and you are
monitored closely throughout your treatment cycle (e.g. blood tests for estradiol levels and
ultrasound).
Using other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Pregnancy and breast-feeding
You should not take Ovitrelle if you are pregnant or breast-feeding.
3.
HOW TO USE OVITRELLE
Always take Ovitrelle exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure
The usual dose of Ovitrelle is 1 pre-filled syringe (250 micrograms/0.5 ml) given as a single injection.
Your doctor will have explained exactly when to give the injection.
Ovitrelle is intended for subcutaneous use, that means given by injection under the skin. Each pre-
filled syringe is for single use only, only clear solution without particles should be used.
Sometimes the injection will be given to you by a doctor or nurse, or you or your partner may be
trained to give the injection at home.
If you administer Ovitrelle to yourself, please carefully read the following instructions:
1.
Wash your hands. It is important that your hands and the items you use are as clean as possible.
2.
Assemble everything you need. Please note that alcohol swabs are not contained in the package.
Find a clean area and lay out everything:
-
two alcohol swabs,
-
one pre-filled syringe containing the medicinal product
43
3.
Injection:
Immediately inject the solution: Your doctor or nurse will have
already advised you where to inject (e.g. tummy, front of thigh).
Wipe the chosen area with an alcohol swab. Firmly pinch the skin
together and insert the needle for injection at a 45° to 90° angle using
a dart-like motion. Inject under the skin, as you were taught. Do not
inject directly into a vein. Inject the solution by pushing gently on
the plunger. Take as much time as you need to inject all the solution.
Immediately withdraw the needle and clean the skin with an alcohol
swab using a circular motion.
4.
Dispose of all used items:
Once you have finished your injection, immediately discard the empty syringe in a sharps
container. Any unused solution must be discarded.
If you use more Ovitrelle than you should
If too much Ovitrelle is used, there is a possibility that ovarian hyperstimulation syndrome may occur,
which is further described under ‘Take special care with Ovitrelle’ and ‘Possible side effects'. You
should consult your doctor if symptoms of this syndrome occur.
If you forget to take Ovitrelle
You should contact your doctor.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Ovitrelle can cause side effects, although not everybody gets them. The majority of
side effects seen to date have been mild or moderate. The most frequent side effects reported have
been tiredness, pain and local reactions at the site of injection.
Ovarian hyperstimulation syndrome has been observed in approximately 4% of the patients in clinical
trials; most of these cases were mild or moderate in nature. Blood in the peritoneal cavity, respiratory
difficulties are possible complications of ovarian hyperstimulation syndrome.
This syndrome is characterized by large ovarian cysts. First symptoms of ovarian hyperstimulation are
pain in the lower abdominal region, possibly in combination with nausea, vomiting and weight gain.
Should the above mentioned symptoms occur, a careful medical examination is indicated as soon as
possible.
Common side effects reported include abdominal pain, nausea and vomiting, headache, injection site
inflammation and reaction, dizziness. Diarrhoea, depression, irritability, restlessness and breast pain
have also been reported in some cases and are considered uncommon.
Extrauterine pregnancy, ovarian torsion (a condition affecting the ovaries) and other complications
may arise from the assisted conception techniques your doctor may use.
Isolated cases of mild allergic reactions to Ovitrelle (rash) have been reported.
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 OVITRELLE
Keep out of the reach and sight of children.
44
Do not use after the expiry date which is stated on the label after EXP. The expiry date refers to the
last day of that month.
Store in a refrigerator (2°C-8°C). Store in the original package. Ovitrelle 250 micrograms solution for
injection may be stored at room temperature (at or below +25° C) for up to 30 days without being
refrigerated again during this period, and must be discarded if not used during these 30 days.
Ovitrelle is for single use only. Any unused solution should be discarded.
6.
FURTHER INFORMATION
What Ovitrelle contains
The active substance is choriogonadotropin alfa. Each pre-filled syringe contains 250 micrograms / 0.5
ml (equivalent to 6500 IU).
The other ingredients are mannitol, methionine, poloxamer 188, diluted phosphoric acid, sodium
hydroxide, water for injections.
What Ovitrelle looks like and contents of the pack
Ovitrelle is provided as solution for injection. It is available as a single pre-filled syringe (pack of 1).
Marketing Authorisation Holder
Merck Serono Europe Limited, 56 Marsh Wall, London E14 9TP,
United Kingdom
Manufacturer
Merck Serono S.p.A., Via delle Magnolie 15, I-70026 Modugno (Bari), Italy
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse
Tél/Tel: +32-2-686 07 11
Luxembourg/Luxemburg
MERCK NV/SA
Brusselsesteenweg 288
B-3090 Overijse, Belgique/Belgien
Tél/Tel: +32-2-686 07 11
България
MERCK d.o.o.
Dunajska cesta 119
SI 1000 Любляна, Словения
Teл: +386 1 560 3 800
Magyarország
Merck Kft.
Bocskai út 134-146.
H-1113 Budapest
Tel: +36-1-463-8100
Česká republika
Merck spol.s.r.o
Na Hrebenech II. 1718/10
CZ-140 00 Praha 4
Tel. +420 272084211
Malta
Cherubino Ltd
Delf Building
Sliema Road
MT-GZR 06 Gzira Malta
Tel: +356-21-343270/1/2/3/4
45
Danmark
E. Merck AB
Strandvejen 102 B, 4th
DK-2900 Hellerup
Tlf: +45 35253550
Nederland
Merck BV
Tupolevlaan 41-61
NL-1119 NW Schiphol-Rijk
Tel: +31-20-6582800
Deutschland
Serono GmbH
Alsfelder Straße 17
D-64289 Darmstadt
Tel: +49-6151-6285-0
Norge
Merck Serono Norge
Luhrtoppen 2
1470 Lørenskog
Tlf: +47 67 90 35 90
Eesti
Merck Serono
Esindaja
C/o Ares Trading SA Baltic States
Zamenhofo 11-3, LT-44287
Kaunas, Leedu
Tel: +370 37320603
Österreich
Merck GesmbH.
Zimbagasse 5
A-1147 Wien
Tel: +43 1 57600-0
Ελλάδα
Merck A.E.
Κηφισίας 41-45, Κτίριο Β
GR-151 23 Μαρούσι
Αθήνα
Tηλ: +30-210-61 65 100
Polska
Merck Sp. z o.o.
Al. Jerozolimskie 178
02-486 Warszawa
Polska
Tel.: +48 22 53 59 700
España
Merck S.L.
María de Molina, 40
E-28006 Madrid
Línea de Información: 900 200 400
Tel: +34-91-745 44 00
Portugal
Merck, s.a.
Rua Alfredo da Silva, 3-C
P-1300-040 Lisboa
Tel: +351-21-361 35 00
France
Merck Serono s.a.s.
37, rue Saint-Romain
F-69379 Lyon cedex 08
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024
România
MERCK d.o.o.,
Dunajska cesta 119
SI-1000 Lubliana, Slovenia
Tel: +386 1 560 3 800
Ireland
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
United Kingdom
Tel: +44-20 8818 7200
Slovenija
MERCK d.o.o.
Dunajska cesta 119
SI-1000 Ljubljana
Tel: +386 1 560 3 800
46
Ísland
Icepharma hf
Lynghálsi 13
110 Reykjavík
Íceland
Tel: + 354 540 8000
Slovenská
republika
Merck spol. s r.o.
Tuhovská 3
SK-831 06 Bratislava
Tel: + 421 2 49 267 111
Italia
Merck Serono S.p.A.
Via Casilina 125
I-00176 Roma
Tel: +39-06-70 38 41
Suomi
/
Finland
Merck Oy
Pihatörmä 1 C
FI-02240 Espoo
Puh/Tel: +358-9-8678 700
Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Λεωφόρος Κιλκίς 35,
2234 Λατσιά, Λευκωσία
Τηλ.: +357 22490305
Sverige
E. Merck AB
S-195 87 Stockholm
Tel: +46-8-562 445 00
Latvija
Merck Serono
Pārstāvniecība
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kauņa, Lietuva
Tel: +370 37320603
United Kingdom
Merck Serono Ltd
Bedfont Cross, Stanwell Road
Feltham, Middlesex TW14 8NX
Tel: +44-20 8818 7200
Lietuva
Merck Serono
Atstovybė
C/o Ares Trading SA Baltic States
Zamenhofo 11-3,
LT-44287 Kaunas
Tel: +370 37320603
This leaflet was last approved on
47
Source: European Medicines Agency
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