Pergoveris

1

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



2

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris 150 IU/75 IU powder and solvent for solution for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial contains 150 IU (equivalent to 11 micrograms) of follitropin alfa* (r-hFSH) and 75 IU 
(equivalent to 3 micrograms) of lutropin alfa* (r-hLH).

After reconstitution, each mL of the solution contains 150 IU r-hFSH and 75 IU r-hLH per milliliter.

* produced in genetically engineered Chinese hamster ovary (CHO) cells.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder and solvent for solution for injection.

Powder: white to off-white lyophilised pellet.
Solvent: clear colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pergoveris is indicated for the stimulation of follicular development in adult women with severe LH 
and FSH deficiency.
In clinical trials, these patients were defined by an endogenous serum LH level < 1.2 IU/L.

4.2 Posology and method of administration

Treatment with Pergoveris should be initiated under the supervision of a physician experienced in the 
treatment of fertility problems.

Posology

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Pergoveris 
therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after 
the administration of human chorionic gonadotrophin (hCG). Pergoveris should be given as a course 
of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen 
secretion, treatment can commence at any time.

Treatment should be tailored to the individual patient’s response as assessed by measuring follicle 
size by ultrasound and oestrogen response.

A recommended regimen commences with one vial of Pergoveris daily. If less than one vial daily is 
used, the follicular response may be unsatisfactory because the amount of lutropin alfa may be 
insufficient (see section 5.1).

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day 
intervals and preferably by 37.5-75 IU increments using a licensed follitropin alfa preparation. It may 
be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.



3

When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 IU to 
10,000 IU hCG should be administered 24-48 hours after the last Pergoveris injection. The patient is 
recommended to have coitus on the day of, and on the day following, hCG administration. 
Alternatively, intrauterine insemination (IUI) may be performed.

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) 
after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment 
should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Special populations

Elderly
There is no relevant indication for the use of Pergoveris in the elderly population. Safety and 
effectiveness of this medicinal product in elderly patients have not been established.

Renal and hepatic impairment
Safety, efficacy, and pharmacokinetics of this medicinal product in patients with renal or hepatic 
impairment have not been established. 

Paediatric population
There is no relevant use of this medicinal product in the paediatric population.

Method of administration

Pergoveris is intended for subcutaneous administration. The first injection should be performed under 
direct medical supervision. The powder should be reconstituted immediately prior to use with the 
solvent provided. Self-administration should only be performed by patients who are well motivated, 
adequately trained and with access to expert advice.

For further instructions on reconstitution of the medicinal product before administration, see 
section 6.6.

4.3 Contraindications

Pergoveris is contraindicated in patients with:
 hypersensitivity to the active substances or to any of the excipients listed in section 6.1
 tumours of the hypothalamus and pituitary gland
 ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown 

origin
 gynaecological haemorrhages of unknown origin
 ovarian, uterine or mammary carcinoma

Pergoveris must not be used when an effective response cannot be obtained, such as:
 primary ovarian failure
 malformations of sexual organs incompatible with pregnancy
 fibroid tumours of the uterus incompatible with pregnancy

4.4 Special warnings and precautions for use

Pergoveris contains potent gonadotrophic substances capable of causing mild to severe adverse 
reactions, and should only be used by physicians who are thoroughly familiar with infertility problems 
and their management.



4

Gonadotrophin therapy requires a certain time commitment by physicians and supportive health care 
professionals, as well as the availability of appropriate monitoring facilities. In women, safe and 
effective use of Pergoveris calls for monitoring of ovarian response with ultrasound, alone or 
preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may 
be a degree of interpatient variability in response to FSH/LH administration, with a poor response to 
FSH/LH in some patients. The lowest effective dose in relation to the treatment objective should be 
used in women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatment 
with Pergoveris. In these patients, Pergoveris may increase the risk of an acute attack. Deterioration or 
a first appearance of this condition may require cessation of treatment.

Treatment in women

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 appropriate specific treatment 
should be given.

Patients undergoing stimulation of follicular growth are at an increased risk of developing 
hyperstimulation in view of possible excessive oestrogen response and multiple follicular 
development.

Ovarian hyperstimulation syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, 
abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and 
gastrointestinal symptoms including nausea, vomiting and diarrhoea.

Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, 
haemoperitoneum, pleural effusions, hydrothorax, or acute pulmonary distress, and thromboembolic 
events.

Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as 
pulmonary embolism, ischaemic stroke or myocardial infarction.

Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotrophins, high absolute or rapidly rising serum oestradiol 
level (> 900 pg/mL or > 3,300 pmol/L in anovulation), previous episodes of OHSS and large number 
of developing ovarian follicles (3 follicles of ≥ 14 mm in diameter in anovulation).

Adherence to recommended Pergoveris and FSH dosage and regimen of administration can minimise 
the risk of ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as 
oestradiol measurements are recommended to early identify risk factors.



5

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of OHSS occur such as 
serum oestradiol level > 5,500 pg/mL or > 20,200 pmol/L and/or ≥ 40 follicles in total, it is 
recommended that hCG be withheld and the patient be advised to refrain from coitus or to use barrier 
contraceptive methods for at least 4 days. OHSS may progress rapidly (within 24 hours) or over 
several days to become a serious medical event. It most often occurs after hormonal treatment has 
been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, 
OHSS resolves spontaneously with the onset of menses. Therefore patients should be followed for at 
least two weeks after hCG administration.
If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing. The patient should 
be hospitalised and specific therapy for OHSS started. This syndrome occurs with higher incidence in 
patients with polycystic ovarian disease.

When a risk of OHSS is assumed, treatment discontinuation should be considered.

Ovarian torsion

Ovarian torsion has been reported after treatment with other gonadotropins. This may be associated
with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian
torsion, previous or current ovarian cyst and polycystic ovarian syndrome. Damage to the ovary due to 
reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multiple pregnancy

In patients undergoing induction of ovulation, the incidence of multiple pregnancies and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancy, especially high order, carry an increased risk of adverse maternal and perinatal outcomes.
To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

The patients should be advised of the potential risk of multiple births before starting treatment. When 
risk of multiple pregnancies is assumed, treatment discontinuation should be considered.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction than in the normal population.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is 
obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy 
after assisted reproductive technologies (ART) was reported to be higher than in the general 
population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and 
malignant, in women who have undergone multiple regimens for infertility treatment. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in 
infertile women.



6

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneous 
conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, 
sperm characteristics) and multiple pregnancies.

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk 
factors for thromboembolic events, such as personal or family history, thrombophilia or severe obesity 
(body mass index > 30 kg/m2), treatment with gonadotrophins may further increase the risk. In these 
women, the benefits of gonadotrophin administration need to be weighed against the risks. It should 
be noted however, that pregnancy itself as well as OHSS also carries an increased risk of 
thromboembolic events.

Sodium

Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Pergoveris should not be administered as a mixture with other medicinal products, in the same 
injection, except follitropin alfa for which studies have shown that co-administration does not 
significantly alter the activity, stability, pharmacokinetic nor pharmacodynamic properties of the 
active substances.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no indication for the use of Pergoveris during pregnancy. Data on a limited number of 
exposed pregnancies indicate no adverse reactions of follitropin alfa and lutropin alfa on pregnancy, 
embryonal or foetal development, parturition or postnatal development following controlled ovarian 
stimulation. No teratogenic effect of such gonadotropins has been reported in animal studies. In case 
of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of 
Pergoveris.

Breast-feeding

Pergoveris is not indicated during breast-feeding.

Fertility

Pergoveris is indicated for use in infertility (see section 4.1).

4.7 Effects on ability to drive and use machines

Pergoveris has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are headache, ovarian cysts and local injection site 
reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection). 



7

Mild or moderate OHSS has been commonly reported and should be considered as an intrinsic risk of 
the stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely, usually associated with severe OHSS (see section 4.4).

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 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 
the available data).

Immune system disorders
Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and 

shock

Nervous system disorders
Very common: Headache

Vascular disorders
Very rare: Thromboembolism, usually associated with severe OHSS

Respiratory, thoracic and mediastinal disorders
Very rare: Exacerbation or aggravation of asthma

Gastrointestinal disorders
Common: Abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, 

diarrhoea

Reproductive system and breast disorders
Very common: Ovarian cysts
Common: Breast pain, pelvic pain, mild or moderate OHSS (including associated 

symptomatology)
Uncommon: Severe OHSS (including associated symptomatology) (see section 4.4)
Rare: Complication of severe OHSS

General disorders and administration site conditions
Very common: Mild to severe injection site reactions (e.g. pain, erythema, haematoma, bruising, 

swelling and/or irritation at the site of injection)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Symptoms

The effects of an overdose of Pergoveris are unknown. Nevertheless there is a possibility that OHSS 
may occur, which is further described in section 4.4.

Management

Treatment is directed to symptoms.



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5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins. ATC 
code: G03GA30.

Pergoveris is a preparation of recombinant human follicle stimulating hormone (follitropin alfa, 
r-hFSH) and recombinant human luteinising hormone (lutropin alfa, r-hLH) produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

Mechanism of action

In clinical trials the efficacy of the combination of follitropin alfa and lutropin alfa has been 
demonstrated in women with hypogonadotropic hypogonadism.

In the stimulation of follicular development in anovulatory women deficient in LH and FSH, the 
primary effect resulting from administration of lutropin alfa is an increase in oestradiol secretion by 
the follicles, the growth of which is stimulated by FSH.

Pharmacodynamic effects

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum 
LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account that 
there are variations between LH measurements performed in different laboratories. In these trials the 
ovulation rate per cycle was 70-75%.

Clinical efficacy 

In one clinical study of women with hypogonadotrophic hypogonadism and an endogenous serum LH 
concentration below 1.2 IU/L the appropriate dose of r-hLH was investigated. A dose of 75 IU r-hLH 
daily (in combination with 150 IU r-hFSH) resulted in adequate follicular development and oestrogen 
production. A dose of 25 IU r-hLH daily (in combination with 150 IU r-hFSH) resulted in insufficient 
follicular development. 
Therefore, administration of less than one vial of Pergoveris daily may provide too little LH-activity 
to ensure adequate follicular development.

5.2 Pharmacokinetic properties

Follitropin alfa and lutropin alfa have shown the same pharmacokinetic profile as follitropin alfa and 
lutropin alfa separately.

Follitropin alfa

Distribution
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space 
with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of 
about one day. The steady state volume of distribution is 10 L.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated 
administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women 
whose endogenous gonadotrophin secretion is suppressed, follitropin alfa has nevertheless been 
shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH 
levels.



9

Elimination
Total clearance is 0.6 L/h and one-eighth of the follitropin alfa dose is excreted in the urine.

Lutropin alfa

Distribution
Following intravenous administration, lutropin alfa is rapidly distributed with an initial half-life of 
approximately one hour and eliminated from the body with a terminal half-life of about 10-12 hours. 
The steady state volume of distribution is around 10-14 L. Lutropin alfa shows linear 
pharmacokinetics, as assessed by AUC which is directly proportional to the dose administered.
Following subcutaneous administration, the absolute bioavailability is approximately 60%; the 
terminal half-life is slightly prolonged. The lutropin alfa pharmacokinetics following single and 
repeated administration of lutropin alfa are comparable and the accumulation ratio of lutropin alfa is 
minimal. The mean residence time is approximately 5 hours.

Elimination
Total clearance is around 2 L/h, and less than 5% of the dose is excreted in the urine. 

Pharmacokinetic/pharmacodynamic relationships
There is no pharmacokinetic interaction with follitropin alfa when administered simultaneously.

Clinical studies with Pergoveris were conducted with a freeze-dried formulation. A comparative 
clinical 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, genotoxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Powder

Sucrose
Polysorbate 20
Methionine
Disodium phosphate dihydrate
Sodium dihydrogen phosphate monohydrate
Phosphoric acid, concentrated (for pH adjustment)
Sodium hydroxide (for pH adjustment)

Solvent

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.



10

6.3 Shelf life

Unopened vials

3 years.

Reconstituted solution

Pergoveris is for an immediate and single use following first opening and reconstitution. Therefore 
the product may not be stored once opened and reconstituted.

6.4 Special precautions for storage

Do not store above 25°C.
Store in the original package in order to protect from light.

6.5 Nature and contents of container

Powder: 3 mL vials (Type I glass) with a stopper (bromobutyl rubber) and aluminium flip-off cap.
1 vial contains 11 micrograms r-hFSH and 3 micrograms r-hLH.

Solvent: 3 mL vials (Type I glass) with a Teflon coated rubber stopper and aluminium flip-off cap.
1 vial of solvent contains 1 mL of water for injections.

Pack sizes of 1, 3 and 10 vials with the corresponding number of solvent’s vial (1, 3 and 10 vials).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For immediate and single use following first opening and reconstitution.

Reconstitution

The pH of the reconstituted solution is 6.5-7.5.

Pergoveris must be reconstituted with the solvent before use by gentle swirling.
The reconstituted solution should not be administered if it contains particles or is not clear.

Pergoveris may be mixed with follitropin alfa and co-administered as a single injection.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands



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8. MARKETING AUTHORISATION NUMBERS

EU/1/07/396/001
EU/1/07/396/002
EU/1/07/396/003

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 June 2007
Date of latest renewal: 8 May 2017

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



12

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (300 IU + 150 IU)/0.48 mL solution for injection in pre-filled pen

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each multidose pre-filled pen contains 300 IU (equivalent to 22 micrograms) of follitropin alfa* 
(r-hFSH) and 150 IU (equivalent to 6 micrograms) of lutropin alfa* (r-hLH) in 0.48 mL solution. 

*recombinant human follitropin alfa and recombinant human lutropin alfa are produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection (injection).
Clear, colourless to slightly yellow solution.

The pH of the solution is 6.5 – 7.5, its osmolality is 250 – 400 mOsm/kg.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pergoveris is indicated for the stimulation of follicular development in adult women with severe LH 
and FSH deficiency.
In clinical trials, these patients were defined by an endogenous serum LH level < 1.2 IU/L.

4.2 Posology and method of administration

Treatment with Pergoveris should be initiated under the supervision of a physician experienced in the 
treatment of fertility problems.

Posology

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Pergoveris 
therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after 
the administration of human chorionic gonadotrophin (hCG). Pergoveris should be given as a course 
of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen 
secretion, treatment can commence at any time.

Treatment should be tailored to the individual patient’s response as assessed by measuring follicle 
size by ultrasound and oestrogen response. 

A treatment regimen commences with the recommended dose of Pergoveris containing 150 IU 
r-hFSH/75 IU r-hLH daily. If less than the recommended dose daily is used, the follicular response 
may be unsatisfactory because the amount of lutropin alfa may be insufficient (see section 5.1).

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day 
intervals and preferably by 37.5-75 IU increments using a licensed follitropin alfa preparation. It may 
be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.



13

When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 IU to 
10,000 IU hCG should be administered 24-48 hours after the last Pergoveris injection. The patient is 
recommended to have coitus on the day of, and on the day following, hCG administration. 
Alternatively, intrauterine insemination (IUI) may be performed.

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) 
after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment 
should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Special populations

Elderly
There is no relevant indication for the use of Pergoveris in the elderly population. Safety and 
effectiveness of this medicinal product in elderly patients have not been established.

Renal and hepatic impairment
Safety, efficacy, and pharmacokinetics of this medicinal product in patients with renal or hepatic 
impairment have not been established. 

Paediatric population
There is no relevant use of this medicinal product in the paediatric population.

Method of administration

Pergoveris is intended for subcutaneous administration. The first injection should be performed under 
direct medical supervision. Self-administration should only be performed by patients who are well 
motivated, adequately trained and with access to expert advice.

For instructions on the use of this medicinal product, see section 6.6.

4.3 Contraindications

Pergoveris is contraindicated in patients with:
 hypersensitivity to the active substances or to any of the excipients listed in section 6.1
 tumours of the hypothalamus and pituitary gland
 ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown 

origin
 gynaecological haemorrhages of unknown origin
 ovarian, uterine or mammary carcinoma

Pergoveris must not be used when an effective response cannot be obtained, such as:
 primary ovarian failure
 malformations of sexual organs incompatible with pregnancy
 fibroid tumours of the uterus incompatible with pregnancy

4.4 Special warnings and precautions for use

Pergoveris contains potent gonadotrophic substances capable of causing mild to severe adverse 
reactions, and should only be used by physicians who are thoroughly familiar with infertility problems 
and their management.

Gonadotrophin therapy requires a certain time commitment by physicians and supportive health care 
professionals, as well as the availability of appropriate monitoring facilities. In women, safe and 



14

effective use of Pergoveris calls for monitoring of ovarian response with ultrasound, alone or 
preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may 
be a degree of interpatient variability in response to FSH/LH administration, with a poor response to 
FSH/LH in some patients. The lowest effective dose in relation to the treatment objective should be 
used in women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatment 
with Pergoveris. In these patients, Pergoveris may increase the risk of an acute attack. Deterioration or 
a first appearance of this condition may require cessation of treatment.

Treatment in women

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 appropriate specific treatment 
should be given.

Patients undergoing stimulation of follicular growth are at an increased risk of developing 
hyperstimulation in view of possible excessive oestrogen response and multiple follicular 
development.

Ovarian hyperstimulation syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, 
abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and 
gastrointestinal symptoms including nausea, vomiting and diarrhoea.

Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, 
haemoperitoneum, pleural effusions, hydrothorax, or acute pulmonary distress, and thromboembolic 
events.

Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as 
pulmonary embolism, ischaemic stroke or myocardial infarction.
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotrophins, high absolute or rapidly rising serum oestradiol 
level (> 900 pg/mL or > 3,300 pmol/L in anovulation), previous episodes of OHSS and large number 
of developing ovarian follicles (3 follicles of ≥ 14 mm in diameter in anovulation).

Adherence to recommended Pergoveris and FSH dosage and regimen of administration can minimise 
the risk of ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as 
oestradiol measurements are recommended to early identify risk factors.

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of OHSS occur such as 
serum oestradiol level > 5,500 pg/mL or > 20,200 pmol/L and/or ≥ 40 follicles in total, it is 



15

recommended that hCG be withheld and the patient be advised to refrain from coitus or to use barrier 
contraceptive methods for at least 4 days. OHSS may progress rapidly (within 24 hours) or over 
several days to become a serious medical event. It most often occurs after hormonal treatment has 
been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, 
OHSS resolves spontaneously with the onset of menses. Therefore patients should be followed for at 
least two weeks after hCG administration.
If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing. The patient should 
be hospitalised and specific therapy for OHSS started. This syndrome occurs with higher incidence in 
patients with polycystic ovarian disease.

When a risk of OHSS is assumed, treatment discontinuation should be considered.

Ovarian torsion

Ovarian torsion has been reported after treatment with other gonadotropins. This may be associated 
with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian 
torsion, previous or current ovarian cyst and polycystic ovarian syndrome. Damage to the ovary due to 
reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multiple pregnancy

In patients undergoing induction of ovulation, the incidence of multiple pregnancies and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancy, especially high order, carry an increased risk of adverse maternal and perinatal outcomes. 
To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

The patients should be advised of the potential risk of multiple births before starting treatment. When 
risk of multiple pregnancies is assumed, treatment discontinuation should be considered.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction than in the normal population.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is 
obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy 
after assisted reproductive technologies (ART) was reported to be higher than in the general 
population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and 
malignant, in women who have undergone multiple regimens for infertility treatment. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in 
infertile women.

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneous 
conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, 
sperm characteristics) and multiple pregnancies.



16

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk 
factors for thromboembolic events, such as personal or family history, thrombophilia or severe obesity 
(body mass index > 30 kg/m2), treatment with gonadotrophins may further increase the risk. In these 
women, the benefits of gonadotrophin administration need to be weighed against the risks. It should 
be noted however, that pregnancy itself as well as OHSS also carries an increased risk of 
thromboembolic events.

Sodium

Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Pergoveris solution for injection in pre-filled pen must not be administered as a mixture with other 
medicinal products in the same injection.

Pergoveris solution for injection in pre-filled pen may be administered concomitantly with a licensed 
follitropin alfa preparation as separate injections.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no indication for the use of Pergoveris during pregnancy. Data on a limited number of 
exposed pregnancies indicate no adverse reactions of follitropin alfa and lutropin alfa on pregnancy, 
embryonal or foetal development, parturition or postnatal development following controlled ovarian 
stimulation. No teratogenic effect of such gonadotropins has been reported in animal studies. In case 
of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of 
Pergoveris.

Breast-feeding

Pergoveris is not indicated during breast-feeding.

Fertility

Pergoveris is indicated for use in infertility (see section 4.1).

4.7 Effects on ability to drive and use machines

Pergoveris has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are headache, ovarian cysts and local injection site 
reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection). 
Mild or moderate OHSS has been commonly reported and should be considered as an intrinsic risk of 
the stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely, usually associated with severe OHSS (see section 4.4).



17

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 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 
the available data).

Immune system disorders
Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and 

shock

Nervous system disorders
Very common: Headache

Vascular disorders
Very rare: Thromboembolism, usually associated with severe OHSS

Respiratory, thoracic and mediastinal disorders
Very rare: Exacerbation or aggravation of asthma

Gastrointestinal disorders
Common: Abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, 

diarrhoea

Reproductive system and breast disorders
Very common: Ovarian cysts
Common: Breast pain, pelvic pain, mild or moderate OHSS (including associated 

symptomatology)
Uncommon: Severe OHSS (including associated symptomatology) (see section 4.4)
Rare: Complication of severe OHSS

General disorders and administration site conditions
Very common: Mild to severe injection site reactions (e.g. pain, erythema, haematoma, bruising, 

swelling and/or irritation at the site of injection)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Symptoms

The effects of an overdose of Pergoveris are unknown. Nevertheless there is a possibility that OHSS 
may occur, which is further described in section 4.4.

Management

Treatment is directed to symptoms.



18

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins. ATC 
code: G03GA30.

Pergoveris is a preparation of recombinant human follicle stimulating hormone (follitropin alfa, 
r-hFSH) and recombinant human luteinising hormone (lutropin alfa, r-hLH) produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

Mechanism of action

In clinical trials the efficacy of the combination of follitropin alfa and lutropin alfa has been 
demonstrated in women with hypogonadotropic hypogonadism.

In the stimulation of follicular development in anovulatory women deficient in LH and FSH, the 
primary effect resulting from administration of lutropin alfa is an increase in oestradiol secretion by 
the follicles, the growth of which is stimulated by FSH.

Pharmacodynamic effects

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum 
LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account that 
there are variations between LH measurements performed in different laboratories. In these trials the 
ovulation rate per cycle was 70-75%.

Clinical efficacy 

In one clinical study of women with hypogonadotrophic hypogonadism and an endogenous serum LH 
concentration below 1.2 IU/L the appropriate dose of r-hLH was investigated. A dose of 75 IU r-hLH 
daily (in combination with 150 IU r-hFSH) resulted in adequate follicular development and oestrogen 
production. A dose of 25 IU r-hLH daily (in combination with 150 IU r-hFSH) resulted in insufficient 
follicular development. 
Therefore, administration of Pergoveris containing less than 75 IU r-hLH daily may provide too little 
LH-activity to ensure adequate follicular development.

5.2 Pharmacokinetic properties

Follitropin alfa and lutropin alfa have shown the same pharmacokinetic profile as follitropin alfa and 
lutropin alfa separately.

Follitropin alfa

Distribution
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space 
with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of 
about one day. The steady state volume of distribution is 10 L.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated 
administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women 
whose endogenous gonadotrophin secretion is suppressed, follitropin alfa has nevertheless been 
shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH 
levels.

Elimination
Total clearance is 0.6 L/h and one-eighth of the follitropin alfa dose is excreted in the urine.



19

Lutropin alfa

Distribution
Following intravenous administration, lutropin alfa is rapidly distributed with an initial half-life of 
approximately one hour and eliminated from the body with a terminal half-life of about 10-12 hours. 
The steady state volume of distribution is around 10-14 L. Lutropin alfa shows linear 
pharmacokinetics, as assessed by AUC which is directly proportional to the dose administered.
Following subcutaneous administration, the absolute bioavailability is approximately 60%; the 
terminal half-life is slightly prolonged. The lutropin alfa pharmacokinetics following single and 
repeated administration of lutropin alfa are comparable and the accumulation ratio of lutropin alfa is 
minimal. The mean residence time is approximately 5 hours.

Elimination
Total clearance is around 2 L/h, and less than 5% of the dose is excreted in the urine. 

Pharmacokinetic/pharmacodynamic relationships
There is no pharmacokinetic interaction with follitropin alfa when administered simultaneously.

Clinical studies with Pergoveris were conducted with a freeze-dried formulation. A comparative 
clinical 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, genotoxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose
Arginine monohydrochloride
Poloxamer 188 
Methionine
Phenol
Disodium phosphate dihydrate
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Phosphoric acid, concentrated (for pH adjustment)
Water for injections

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.
Once opened, the product may be stored for a maximum of 28 days at 25°C. Other in-use storage 
times and conditions are the responsibility of the user.



20

6.4 Special precautions for storage

Store in refrigerator (2°C- 8°C). Do not freeze.
Store in the original package in order to protect from light.

For in-use storage conditions, see section 6.3.

6.5 Nature and contents of container

Colourless 3 mL glass cartridge (type I borosilicate glass, with a grey bromobutyl rubber plunger 
stopper and a crimp cap made with grey rubber stopper septum and aluminium) pre-assembled in a 
pre-filled pen.

Each Pergoveris (300 IU + 150 IU)/0.48 mL pre-filled pen contains 0.48 mL of solution for injection 
and can deliver two doses of Pergoveris 150 IU/75 IU. 

Pack of 1 Pergoveris (300 IU + 150 IU)/0.48 mL pre-filled pen and 5 injection needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Only clear solution without particles should be used. 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

For instructions on the use of this medicinal product, see the package leaflet, section ’Instructions for 
use’.

7. MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

8. MARKETING AUTHORISATION NUMBERS

EU/1/07/396/004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 June 2007
Date of latest renewal: 8 May 2017

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}



21

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



22

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (450 IU + 225 IU)/0.72 mL solution for injection in pre-filled pen

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each multidose pre-filled pen contains 450 IU (equivalent to 33 micrograms) of follitropin alfa* 
(r-hFSH) and 225 IU (equivalent to 9 micrograms) of lutropin alfa* (r-hLH) in 0.72 mL solution.

*recombinant human follitropin alfa and recombinant human lutropin alfa are produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection (injection).
Clear, colourless to slightly yellow solution.

The pH of the solution is 6.5 – 7.5, its osmolality is 250 – 400 mOsm/kg.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pergoveris is indicated for the stimulation of follicular development in adult women with severe LH 
and FSH deficiency.
In clinical trials, these patients were defined by an endogenous serum LH level < 1.2 IU/L.

4.2 Posology and method of administration

Treatment with Pergoveris should be initiated under the supervision of a physician experienced in the 
treatment of fertility problems.

Posology

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Pergoveris 
therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after 
the administration of human chorionic gonadotrophin (hCG). Pergoveris should be given as a course 
of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen 
secretion, treatment can commence at any time.

Treatment should be tailored to the individual patient’s response as assessed by measuring follicle 
size by ultrasound and oestrogen response. 

A treatment regimen commences with the recommended dose of Pergoveris containing 150 IU 
r-hFSH/75 IU r-hLH daily. If less than the recommended dose daily is used, the follicular response 
may be unsatisfactory because the amount of lutropin alfa may be insufficient (see section 5.1).

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day 
intervals and preferably by 37.5-75 IU increments using a licensed follitropin alfa preparation. It may 
be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.



23

When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 IU to 
10,000 IU hCG should be administered 24-48 hours after the last Pergoveris injection. The patient is 
recommended to have coitus on the day of, and on the day following, hCG administration. 
Alternatively, intrauterine insemination (IUI) may be performed.

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) 
after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment 
should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Special populations

Elderly
There is no relevant indication for the use of Pergoveris in the elderly population. Safety and 
effectiveness of this medicinal product in elderly patients have not been established.

Renal and hepatic impairment
Safety, efficacy, and pharmacokinetics of this medicinal product in patients with renal or hepatic 
impairment have not been established. 

Paediatric population
There is no relevant use of this medicinal product in the paediatric population.

Method of administration

Pergoveris is intended for subcutaneous administration. The first injection should be performed under 
direct medical supervision. Self-administration should only be performed by patients who are well 
motivated, adequately trained and with access to expert advice.

For instructions on the use of this medicinal product, see section 6.6.

4.3 Contraindications

Pergoveris is contraindicated in patients with:
 hypersensitivity to the active substances or to any of the excipients listed in section 6.1
 tumours of the hypothalamus and pituitary gland
 ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown 

origin
 gynaecological haemorrhages of unknown origin
 ovarian, uterine or mammary carcinoma

Pergoveris must not be used when an effective response cannot be obtained, such as:
 primary ovarian failure
 malformations of sexual organs incompatible with pregnancy
 fibroid tumours of the uterus incompatible with pregnancy

4.4 Special warnings and precautions for use

Pergoveris contains potent gonadotrophic substances capable of causing mild to severe adverse 
reactions, and should only be used by physicians who are thoroughly familiar with infertility problems 
and their management.

Gonadotrophin therapy requires a certain time commitment by physicians and supportive health care 
professionals, as well as the availability of appropriate monitoring facilities. In women, safe and 



24

effective use of Pergoveris calls for monitoring of ovarian response with ultrasound, alone or 
preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may 
be a degree of interpatient variability in response to FSH/LH administration, with a poor response to 
FSH/LH in some patients. The lowest effective dose in relation to the treatment objective should be 
used in women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatment 
with Pergoveris. In these patients, Pergoveris may increase the risk of an acute attack. Deterioration or 
a first appearance of this condition may require cessation of treatment.

Treatment in women

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 appropriate specific treatment 
should be given.

Patients undergoing stimulation of follicular growth are at an increased risk of developing 
hyperstimulation in view of possible excessive oestrogen response and multiple follicular 
development.

Ovarian hyperstimulation syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, 
abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and 
gastrointestinal symptoms including nausea, vomiting and diarrhoea.

Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, 
haemoperitoneum, pleural effusions, hydrothorax, or acute pulmonary distress, and thromboembolic 
events.

Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as 
pulmonary embolism, ischaemic stroke or myocardial infarction.
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotrophins, high absolute or rapidly rising serum oestradiol 
level (> 900 pg/mL or > 3,300 pmol/L in anovulation), previous episodes of OHSS and large number 
of developing ovarian follicles (3 follicles of ≥ 14 mm in diameter in anovulation).

Adherence to recommended Pergoveris and FSH dosage and regimen of administration can minimise 
the risk of ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as 
oestradiol measurements are recommended to early identify risk factors.

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of OHSS occur such as 
serum oestradiol level > 5,500 pg/mL or > 20,200 pmol/L and/or ≥ 40 follicles in total, it is 



25

recommended that hCG be withheld and the patient be advised to refrain from coitus or to use barrier 
contraceptive methods for at least 4 days. OHSS may progress rapidly (within 24 hours) or over 
several days to become a serious medical event. It most often occurs after hormonal treatment has 
been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, 
OHSS resolves spontaneously with the onset of menses. Therefore patients should be followed for at 
least two weeks after hCG administration.
If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing. The patient should 
be hospitalised and specific therapy for OHSS started. This syndrome occurs with higher incidence in 
patients with polycystic ovarian disease.

When a risk of OHSS is assumed, treatment discontinuation should be considered.

Ovarian torsion

Ovarian torsion has been reported after treatment with other gonadotropins. This may be associated 
with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian 
torsion, previous or current ovarian cyst and polycystic ovarian syndrome. Damage to the ovary due to 
reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multiple pregnancy

In patients undergoing induction of ovulation, the incidence of multiple pregnancies and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancy, especially high order, carry an increased risk of adverse maternal and perinatal outcomes. 
To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

The patients should be advised of the potential risk of multiple births before starting treatment. When 
risk of multiple pregnancies is assumed, treatment discontinuation should be considered.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction than in the normal population.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is 
obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy 
after assisted reproductive technologies (ART) was reported to be higher than in the general 
population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and 
malignant, in women who have undergone multiple regimens for infertility treatment. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in 
infertile women.

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneous 
conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, 
sperm characteristics) and multiple pregnancies.



26

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk 
factors for thromboembolic events, such as personal or family history, thrombophilia or severe obesity 
(body mass index > 30 kg/m2), treatment with gonadotrophins may further increase the risk. In these 
women, the benefits of gonadotrophin administration need to be weighed against the risks. It should 
be noted however, that pregnancy itself as well as OHSS also carries an increased risk of 
thromboembolic events.

Sodium

Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Pergoveris solution for injection in pre-filled pen must not be administered as a mixture with other 
medicinal products in the same injection.

Pergoveris solution for injection in pre-filled pen may be administered concomitantly with a licensed 
follitropin alfa preparation as separate injections.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no indication for the use of Pergoveris during pregnancy. Data on a limited number of 
exposed pregnancies indicate no adverse reactions of follitropin alfa and lutropin alfa on pregnancy, 
embryonal or foetal development, parturition or postnatal development following controlled ovarian 
stimulation. No teratogenic effect of such gonadotropins has been reported in animal studies. In case 
of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of 
Pergoveris.

Breast-feeding

Pergoveris is not indicated during breast-feeding.

Fertility

Pergoveris is indicated for use in infertility (see section 4.1).

4.7 Effects on ability to drive and use machines

Pergoveris has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are headache, ovarian cysts and local injection site 
reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection). 
Mild or moderate OHSS has been commonly reported and should be considered as an intrinsic risk of 
the stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely, usually associated with severe OHSS (see section 4.4).



27

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 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 
the available data).

Immune system disorders
Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and 

shock

Nervous system disorders
Very common: Headache

Vascular disorders
Very rare: Thromboembolism, usually associated with severe OHSS

Respiratory, thoracic and mediastinal disorders
Very rare: Exacerbation or aggravation of asthma

Gastrointestinal disorders
Common: Abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, 

diarrhoea

Reproductive system and breast disorders
Very common: Ovarian cysts
Common: Breast pain, pelvic pain, mild or moderate OHSS (including associated 

symptomatology)
Uncommon: Severe OHSS (including associated symptomatology) (see section 4.4)
Rare: Complication of severe OHSS

General disorders and administration site conditions
Very common: Mild to severe injection site reactions (e.g. pain, erythema, haematoma, bruising, 

swelling and/or irritation at the site of injection)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Symptoms

The effects of an overdose of Pergoveris are unknown. Nevertheless there is a possibility that OHSS 
may occur, which is further described in section 4.4.

Management

Treatment is directed to symptoms.



28

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins. ATC 
code: G03GA30.

Pergoveris is a preparation of recombinant human follicle stimulating hormone (follitropin alfa, 
r-hFSH) and recombinant human luteinising hormone (lutropin alfa, r-hLH) produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

Mechanism of action

In clinical trials the efficacy of the combination of follitropin alfa and lutropin alfa has been 
demonstrated in women with hypogonadotropic hypogonadism.

In the stimulation of follicular development in anovulatory women deficient in LH and FSH, the 
primary effect resulting from administration of lutropin alfa is an increase in oestradiol secretion by 
the follicles, the growth of which is stimulated by FSH.

Pharmacodynamic effects

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum 
LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account that 
there are variations between LH measurements performed in different laboratories. In these trials the 
ovulation rate per cycle was 70-75%.

Clinical efficacy 

In one clinical study of women with hypogonadotrophic hypogonadism and an endogenous serum LH 
concentration below 1.2 IU/L the appropriate dose of r-hLH was investigated. A dose of 75 IU r-hLH 
daily (in combination with 150 IU r-hFSH) resulted in adequate follicular development and oestrogen 
production. A dose of 25 IU r-hLH daily (in combination with 150 IU r-hFSH) resulted in insufficient 
follicular development. 
Therefore, administration of Pergoveris containing less than 75 IU r-hLH daily may provide too little 
LH-activity to ensure adequate follicular development.

5.2 Pharmacokinetic properties

Follitropin alfa and lutropin alfa have shown the same pharmacokinetic profile as follitropin alfa and 
lutropin alfa separately.

Follitropin alfa

Distribution
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space 
with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of 
about one day. The steady state volume of distribution is 10 L.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated 
administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women 
whose endogenous gonadotrophin secretion is suppressed, follitropin alfa has nevertheless been 
shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH 
levels.

Elimination
Total clearance is 0.6 L/h and one-eighth of the follitropin alfa dose is excreted in the urine.



29

Lutropin alfa

Distribution
Following intravenous administration, lutropin alfa is rapidly distributed with an initial half-life of 
approximately one hour and eliminated from the body with a terminal half-life of about 10-12 hours. 
The steady state volume of distribution is around 10-14 L. Lutropin alfa shows linear 
pharmacokinetics, as assessed by AUC which is directly proportional to the dose administered.
Following subcutaneous administration, the absolute bioavailability is approximately 60%; the 
terminal half-life is slightly prolonged. The lutropin alfa pharmacokinetics following single and 
repeated administration of lutropin alfa are comparable and the accumulation ratio of lutropin alfa is 
minimal. The mean residence time is approximately 5 hours.

Elimination
Total clearance is around 2 L/h, and less than 5% of the dose is excreted in the urine. 

Pharmacokinetic/pharmacodynamic relationships
There is no pharmacokinetic interaction with follitropin alfa when administered simultaneously.

Clinical studies with Pergoveris were conducted with a freeze-dried formulation. A comparative 
clinical 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, genotoxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose
Arginine monohydrochloride
Poloxamer 188 
Methionine
Phenol
Disodium phosphate dihydrate
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Phosphoric acid, concentrated (for pH adjustment)
Water for injections

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.
Once opened, the product may be stored for a maximum of 28 days at 25°C. Other in-use storage 
times and conditions are the responsibility of the user.



30

6.4 Special precautions for storage

Store in refrigerator (2°C- 8°C). Do not freeze.
Store in the original package in order to protect from light.

For in-use storage conditions, see section 6.3.

6.5 Nature and contents of container

Colourless 3 mL glass cartridge (type I borosilicate glass, with a grey bromobutyl rubber plunger 
stopper and a crimp cap made with grey rubber stopper septum and aluminium) pre-assembled in a 
pre-filled pen.

Each Pergoveris (450 IU + 225 IU)/0.72 mL pre-filled pen contains 0.72 mL of solution for injection 
and can deliver three doses of Pergoveris 150 IU/75 IU.

Pack of 1 Pergoveris (450 IU + 225 IU)/0.72 mL pre-filled pen and 7 injection needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Only clear solution without particles should be used. 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

For instructions on the use of this medicinal product, see the package leaflet, section ’Instructions for 
use’.

7. MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

8. MARKETING AUTHORISATION NUMBERS

EU/1/07/396/005

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 June 2007
Date of latest renewal: 8 May 2017

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}



31

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



32

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (900 IU + 450 IU)/1.44 mL solution for injection in pre-filled pen

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each multidose pre-filled pen contains 900 IU (equivalent to 66 micrograms) of follitropin alfa* 
(r-hFSH) and 450 IU (equivalent to 18 micrograms) of lutropin alfa* (r-hLH) in 1.44 mL solution.

*recombinant human follitropin alfa and recombinant human lutropin alfa are produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection (injection).
Clear, colourless to slightly yellow solution.

The pH of the solution is 6.5 – 7.5, its osmolality is 250 – 400 mOsm/kg.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pergoveris is indicated for the stimulation of follicular development in adult women with severe LH 
and FSH deficiency.
In clinical trials, these patients were defined by an endogenous serum LH level < 1.2 IU/L.

4.2 Posology and method of administration

Treatment with Pergoveris should be initiated under the supervision of a physician experienced in the 
treatment of fertility problems.

Posology

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of Pergoveris 
therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after 
the administration of human chorionic gonadotrophin (hCG). Pergoveris should be given as a course 
of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen 
secretion, treatment can commence at any time.

Treatment should be tailored to the individual patient’s response as assessed by measuring follicle 
size by ultrasound and oestrogen response. 

A treatment regimen commences with the recommended dose of Pergoveris containing 150 IU 
r-hFSH/75 IU r-hLH daily. If less than the recommended dose daily is used, the follicular response 
may be unsatisfactory because the amount of lutropin alfa may be insufficient (see section 5.1).

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day 
intervals and preferably by 37.5-75 IU increments using a licensed follitropin alfa preparation. It may 
be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.



33

When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 IU to 
10,000 IU hCG should be administered 24-48 hours after the last Pergoveris injection. The patient is 
recommended to have coitus on the day of, and on the day following, hCG administration. 
Alternatively, intrauterine insemination (IUI) may be performed.

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) 
after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment 
should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Special populations

Elderly
There is no relevant indication for the use of Pergoveris in the elderly population. Safety and 
effectiveness of this medicinal product in elderly patients have not been established.

Renal and hepatic impairment
Safety, efficacy, and pharmacokinetics of this medicinal product in patients with renal or hepatic 
impairment have not been established. 

Paediatric population
There is no relevant use of this medicinal product in the paediatric population.

Method of administration

Pergoveris is intended for subcutaneous administration. The first injection should be performed under 
direct medical supervision. Self-administration should only be performed by patients who are well 
motivated, adequately trained and with access to expert advice.

For instructions on the use of this medicinal product, see section 6.6.

4.3 Contraindications

Pergoveris is contraindicated in patients with:
 hypersensitivity to the active substances or to any of the excipients listed in section 6.1
 tumours of the hypothalamus and pituitary gland
 ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown 

origin
 gynaecological haemorrhages of unknown origin
 ovarian, uterine or mammary carcinoma

Pergoveris must not be used when an effective response cannot be obtained, such as:
 primary ovarian failure
 malformations of sexual organs incompatible with pregnancy
 fibroid tumours of the uterus incompatible with pregnancy

4.4 Special warnings and precautions for use

Pergoveris contains potent gonadotrophic substances capable of causing mild to severe adverse 
reactions, and should only be used by physicians who are thoroughly familiar with infertility problems 
and their management.

Gonadotrophin therapy requires a certain time commitment by physicians and supportive health care 
professionals, as well as the availability of appropriate monitoring facilities. In women, safe and 



34

effective use of Pergoveris calls for monitoring of ovarian response with ultrasound, alone or 
preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may 
be a degree of interpatient variability in response to FSH/LH administration, with a poor response to 
FSH/LH in some patients. The lowest effective dose in relation to the treatment objective should be
used in women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatment 
with Pergoveris. In these patients, Pergoveris may increase the risk of an acute attack. Deterioration or 
a first appearance of this condition may require cessation of treatment.

Treatment in women

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 appropriate specific treatment 
should be given.

Patients undergoing stimulation of follicular growth are at an increased risk of developing 
hyperstimulation in view of possible excessive oestrogen response and multiple follicular 
development.

Ovarian hyperstimulation syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is 
more commonly seen in women with polycystic ovarian syndrome and usually regresses without 
treatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with 
increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and 
an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, 
pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, 
abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and 
gastrointestinal symptoms including nausea, vomiting and diarrhoea.

Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, 
haemoperitoneum, pleural effusions, hydrothorax, or acute pulmonary distress, and thromboembolic 
events.

Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as 
pulmonary embolism, ischaemic stroke or myocardial infarction.
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian 
syndrome, higher doses of exogenous gonadotrophins, high absolute or rapidly rising serum oestradiol 
level (> 900 pg/mL or > 3,300 pmol/L in anovulation), previous episodes of OHSS and large number 
of developing ovarian follicles (3 follicles of ≥ 14 mm in diameter in anovulation).

Adherence to recommended Pergoveris and FSH dosage and regimen of administration can minimise 
the risk of ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as 
oestradiol measurements are recommended to early identify risk factors.

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may 
be more severe and more protracted if pregnancy occurs. Therefore, if signs of OHSS occur such as 
serum oestradiol level > 5,500 pg/mL or > 20,200 pmol/L and/or ≥ 40 follicles in total, it is 



35

recommended that hCG be withheld and the patient be advised to refrain from coitus or to use barrier 
contraceptive methods for at least 4 days. OHSS may progress rapidly (within 24 hours) or over 
several days to become a serious medical event. It most often occurs after hormonal treatment has 
been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, 
OHSS resolves spontaneously with the onset of menses. Therefore patients should be followed for at 
least two weeks after hCG administration.
If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing. The patient should 
be hospitalised and specific therapy for OHSS started. This syndrome occurs with higher incidence in 
patients with polycystic ovarian disease.

When a risk of OHSS is assumed, treatment discontinuation should be considered.

Ovarian torsion

Ovarian torsion has been reported after treatment with other gonadotropins. This may be associated 
with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian 
torsion, previous or current ovarian cyst and polycystic ovarian syndrome. Damage to the ovary due to 
reduced blood supply can be limited by early diagnosis and immediate detorsion.

Multiple pregnancy

In patients undergoing induction of ovulation, the incidence of multiple pregnancies and births is 
increased compared with natural conception. The majority of multiple conceptions are twins. Multiple 
pregnancy, especially high order, carry an increased risk of adverse maternal and perinatal outcomes. 
To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

The patients should be advised of the potential risk of multiple births before starting treatment. When 
risk of multiple pregnancies is assumed, treatment discontinuation should be considered.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing 
stimulation of follicular growth for ovulation induction than in the normal population.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is 
obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy 
after assisted reproductive technologies (ART) was reported to be higher than in the general 
population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and 
malignant, in women who have undergone multiple regimens for infertility treatment. It is not yet 
established whether or not treatment with gonadotropins increases the risk of these tumours in 
infertile women.

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneous 
conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, 
sperm characteristics) and multiple pregnancies.



36

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk 
factors for thromboembolic events, such as personal or family history, thrombophilia or severe obesity 
(body mass index > 30 kg/m2), treatment with gonadotrophins may further increase the risk. In these 
women, the benefits of gonadotrophin administration need to be weighed against the risks. It should 
be noted however, that pregnancy itself as well as OHSS also carries an increased risk of 
thromboembolic events.

Sodium

Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Pergoveris solution for injection in pre-filled pen must not be administered as a mixture with other 
medicinal products in the same injection.

Pergoveris solution for injection in pre-filled pen may be administered concomitantly with a licensed 
follitropin alfa preparation as separate injections.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no indication for the use of Pergoveris during pregnancy. Data on a limited number of 
exposed pregnancies indicate no adverse reactions of follitropin alfa and lutropin alfa on pregnancy, 
embryonal or foetal development, parturition or postnatal development following controlled ovarian 
stimulation. No teratogenic effect of such gonadotropins has been reported in animal studies. In case 
of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of 
Pergoveris.

Breast-feeding

Pergoveris is not indicated during breast-feeding.

Fertility

Pergoveris is indicated for use in infertility (see section 4.1).

4.7 Effects on ability to drive and use machines

Pergoveris has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are headache, ovarian cysts and local injection site 
reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection). 
Mild or moderate OHSS has been commonly reported and should be considered as an intrinsic risk of 
the stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely, usually associated with severe OHSS (see section 4.4).



37

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA system organ class and by frequency. The frequency 
categories used are: 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 
the available data).

Immune system disorders
Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and 

shock

Nervous system disorders
Very common: Headache

Vascular disorders
Very rare: Thromboembolism, usually associated with severe OHSS

Respiratory, thoracic and mediastinal disorders
Very rare: Exacerbation or aggravation of asthma

Gastrointestinal disorders
Common: Abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, 

diarrhoea

Reproductive system and breast disorders
Very common: Ovarian cysts
Common: Breast pain, pelvic pain, mild or moderate OHSS (including associated 

symptomatology)
Uncommon: Severe OHSS (including associated symptomatology) (see section 4.4)
Rare: Complication of severe OHSS

General disorders and administration site conditions
Very common: Mild to severe injection site reactions (e.g. pain, erythema, haematoma, bruising, 

swelling and/or irritation at the site of injection)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Symptoms

The effects of an overdose of Pergoveris are unknown. Nevertheless there is a possibility that OHSS 
may occur, which is further described in section 4.4.

Management

Treatment is directed to symptoms.



38

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, gonadotropins. ATC 
code: G03GA30.

Pergoveris is a preparation of recombinant human follicle stimulating hormone (follitropin alfa, 
r-hFSH) and recombinant human luteinising hormone (lutropin alfa, r-hLH) produced in Chinese 
hamster ovary (CHO) cells by recombinant DNA technology.

Mechanism of action

In clinical trials the efficacy of the combination of follitropin alfa and lutropin alfa has been 
demonstrated in women with hypogonadotropic hypogonadism.

In the stimulation of follicular development in anovulatory women deficient in LH and FSH, the 
primary effect resulting from administration of lutropin alfa is an increase in oestradiol secretion by 
the follicles, the growth of which is stimulated by FSH.

Pharmacodynamic effects

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum 
LH level < 1.2 IU/L as measured in a central laboratory. However, it should be taken into account that 
there are variations between LH measurements performed in different laboratories. In these trials the 
ovulation rate per cycle was 70-75%.

Clinical efficacy 

In one clinical study of women with hypogonadotrophic hypogonadism and an endogenous serum LH 
concentration below 1.2 IU/L the appropriate dose of r-hLH was investigated. A dose of 75 IU r-hLH 
daily (in combination with 150 IU r-hFSH) resulted in adequate follicular development and oestrogen 
production. A dose of 25 IU r-hLH daily (in combination with 150 IU r-hFSH) resulted in insufficient 
follicular development. 
Therefore, administration of Pergoveris containing less than 75 IU r-hLH daily may provide too little 
LH-activity to ensure adequate follicular development.

5.2 Pharmacokinetic properties

Follitropin alfa and lutropin alfa have shown the same pharmacokinetic profile as follitropin alfa and 
lutropin alfa separately.

Follitropin alfa

Distribution
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space 
with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of 
about one day. The steady state volume of distribution is 10 L.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated 
administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women 
whose endogenous gonadotrophin secretion is suppressed, follitropin alfa has nevertheless been 
shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH 
levels.

Elimination
Total clearance is 0.6 L/h and one-eighth of the follitropin alfa dose is excreted in the urine.



39

Lutropin alfa

Distribution
Following intravenous administration, lutropin alfa is rapidly distributed with an initial half-life of 
approximately one hour and eliminated from the body with a terminal half-life of about 10-12 hours. 
The steady state volume of distribution is around 10-14 L. Lutropin alfa shows linear 
pharmacokinetics, as assessed by AUC which is directly proportional to the dose administered.
Following subcutaneous administration, the absolute bioavailability is approximately 60%; the 
terminal half-life is slightly prolonged. The lutropin alfa pharmacokinetics following single and 
repeated administration of lutropin alfa are comparable and the accumulation ratio of lutropin alfa is 
minimal. The mean residence time is approximately 5 hours.

Elimination
Total clearance is around 2 L/h, and less than 5% of the dose is excreted in the urine. 

Pharmacokinetic/pharmacodynamic relationships
There is no pharmacokinetic interaction with follitropin alfa when administered simultaneously.

Clinical studies with Pergoveris were conducted with a freeze-dried formulation. A comparative 
clinical 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, genotoxicity.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose
Arginine monohydrochloride
Poloxamer 188 
Methionine
Phenol
Disodium phosphate dihydrate
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Phosphoric acid, concentrated (for pH adjustment)
Water for injections

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C.
Once opened, the product may be stored for a maximum of 28 days at 25°C. Other in-use storage 
times and conditions are the responsibility of the user.



40

6.4 Special precautions for storage

Store in refrigerator (2°C- 8°C). Do not freeze.
Store in the original package in order to protect from light.

For in-use storage conditions, see section 6.3.

6.5 Nature and contents of container

Colourless 3 mL glass cartridge (type I borosilicate glass, with a grey bromobutyl rubber plunger 
stopper and a crimp cap made with grey rubber stopper septum and aluminium) pre-assembled in a 
pre-filled pen.

Each Pergoveris (900 IU + 450 IU)/1.44 mL pre-filled pen contains 1.44 mL of solution for injection 
and can deliver six doses of Pergoveris 150 IU/75 IU.

Pack of 1 Pergoveris (900 IU + 450 IU)/1.44 mL pre-filled pen and 14 injection needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Only clear solution without particles should be used. 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

For instructions on the use of this medicinal product, see the package leaflet, section ’Instructions for 
use’.

7. MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

8. MARKETING AUTHORISATION NUMBERS

EU/1/07/396/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 25 June 2007
Date of latest renewal: 8 May 2017

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}



41

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



42

ANNEX II

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



43

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substances

Merck Serono S.A.
Zone Industrielle de l’Ouriettaz
CH-1170 Aubonne
Switzerland

Merck S.L.
C/ Batanes 1
Tres Cantos
E-28760 Madrid
Spain

Name and address of the manufacturer responsible for batch release

Merck Serono S.p.A.
Via delle Magnolie 15 (Zona Industriale)
I-70026 Modugno (Bari)
Italy

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



44

ANNEX III

LABELLING AND PACKAGE LEAFLET



45

A. LABELLING



46

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris 150 IU/75 IU powder and solvent for solution for injection
Follitropin alfa/Lutropin alfa

2. STATEMENT OF THE ACTIVE SUBSTANCE(S)

One vial contains 150 IU (equivalent to 11 micrograms) of follitropin alfa (r-hFSH) and 75 IU 
(equivalent to 3 micrograms) of lutropin alfa (r-hLH).

3. LIST OF EXCIPIENTS

Other ingredients:
Powder: disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, methionine, 
polysorbate 20, sucrose, sodium hydroxide (for pH adjustment) and concentrated phosphoric acid (for 
pH adjustment).
Solvent: water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Powder and solvent for solution for injection.

1 vial of powder.
1 vial of solvent.
3 vials of powder.
3 vials of solvent.
10 vials of powder.
10 vials of solvent.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN 

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



47

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25°C. Store in the original package in order to protect from light.
Read the leaflet for the shelf life of the reconstituted medicine.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/07/396/001 1 vial of powder for solution for injection.
1 vial of solvent.

EU/1/07/396/002 3 vials of powder for solution for injection.
3 vials of solvent.

EU/1/07/396/003 10 vials of powder for solution for injection.
10 vials of solvent.

13. BATCH NUMBER

Batch
Solvent Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

pergoveris 150 iu/75 iu



48

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



49

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PERGOVERIS 150 IU/75 IU
VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Pergoveris 150 IU/75 IU powder for solution for injection
Follitropin alfa/Lutropin alfa
SC

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

150 IU r-hFSH/75 IU r-hLH

6. OTHER



50

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SOLVENT VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

Solvent for Pergoveris
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



51

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

PERGOVERIS (300 IU + 150 IU)/0.48 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (300 IU + 150 IU)/0.48 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

2. STATEMENT OF THE ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 300 IU (equivalent to 22 micrograms) of follitropin alfa (r-hFSH) and 
150 IU (equivalent to 6 micrograms) of lutropin alfa (r-hLH) in 0.48 mL.

3. LIST OF EXCIPIENTS

Excipients: sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium 
phosphate dihydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide and concentrated 
phosphoric acid (for pH adjustment), and water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 multidose pre-filled pen of 0.48 mL solution
5 injection needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN 

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP
Once opened, the medicinal product may be stored for a maximum of 28 days at 25°C.



52

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/07/396/004

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

pergoveris (300 iu + 150 iu)/0.48 ml pen

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 
SN: 
NN: 



53

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PERGOVERIS (300 IU + 150 IU)/0.48 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN, PEN LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

Pergoveris (300 IU + 150 IU)/0.48 mL injection
Follitropin alfa/Lutropin alfa
Subcutaneous use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP
Shelf life after first use: 28 days

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

300 IU r-hFSH-150 IU r-hLH/0.48 mL

6. OTHER



54

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

PERGOVERIS (450 IU + 225 IU)/0.72 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (450 IU + 225 IU)/0.72 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 450 IU (equivalent to 33 micrograms) of follitropin alfa (r-hFSH) and 
225 IU (equivalent to 9 micrograms) of lutropin alfa (r-hLH) in 0.72 mL.

3. LIST OF EXCIPIENTS

Excipients: sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium 
phosphate dihydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide and concentrated 
phosphoric acid (for pH adjustment), and water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 multidose pre-filled pen of 0.72 mL solution
7 injection needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous 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
Once opened, the medicinal product may be stored for a maximum of 28 days at 25°C.



55

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/396/005

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

pergoveris (450 iu + 225 iu)/0.72 ml pen

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 
SN: 
NN: 



56

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PERGOVERIS (450 IU + 225 IU)/0.72 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN, PEN LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Pergoveris (450 IU + 225 IU)/0.72 mL injection 
Follitropin alfa/Lutropin alfa
Subcutaneous use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP
Shelf life after first use: 28 days 

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

450 IU r-hFSH-225 IU r-hLH/0.72 mL

6. OTHER



57

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

PERGOVERIS (900 IU + 450 IU)/1.44 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN

1. NAME OF THE MEDICINAL PRODUCT

Pergoveris (900 IU + 450 IU)/1.44 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 900 IU (equivalent to 66 micrograms) of follitropin alfa (r-hFSH) and 
450 IU (equivalent to 18 micrograms) of lutropin alfa (r-hLH) in 1.44 mL.

3. LIST OF EXCIPIENTS

Excipients: sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium 
phosphate dihydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide and concentrated 
phosphoric acid (for pH adjustment), and water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 multidose pre-filled pen of 1.44 mL solution 
14 injection needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous 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
Once opened, the medicinal product may be stored for a maximum of 28 days at 25°C.



58

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/396/006

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

pergoveris (900 iu + 450 iu)/1.44 ml pen

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 
SN: 
NN:



59

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PERGOVERIS (900 IU + 450 IU)/1.44 ML SOLUTION FOR INJECTION IN PRE-FILLED 
PEN, PEN LABEL 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Pergoveris (900 IU + 450 IU)/1.44 mL injection 
Follitropin alfa/Lutropin alfa
Subcutaneous use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP
Shelf life after first use: 28 days 

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

900 IU r-hFSH- 450 IU r-hLH/1.44 mL

6. OTHER



60

B. PACKAGE LEAFLET



61

Package leaflet: Information for the user

Pergoveris 150 IU/75 IU powder and solvent for solution for injection
Follitropin alfa/Lutropin alfa

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Pergoveris is and what it is used for
2. What you need to know before you use Pergoveris
3. How to use Pergoveris
4. Possible side effects
5. How to store Pergoveris
6. Contents of the pack and other information

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called “follitropin alfa” and “lutropin alfa”. Both 
belong to the family of hormones called “gonadotropins”, which are involved in reproduction and 
fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in your 
ovaries. This is to help you get pregnant. It is for use in adult women (18 years old or above) who 
have low levels (severe deficiency) of “follicle stimulating hormone” (FSH) and “luteinising 
hormone” (LH). These women are usually infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In your body:
 FSH stimulates the production of eggs
 LH stimulates the release of the eggs.

By replacing the missing hormones, Pergoveris allows women with low levels of FSH and LH to 
develop a follicle. This will then release an egg, after an injection of the hormone “human chorionic 
gonadotropin (hCG)”. This helps the women to become pregnant.

2. What you need to know before you use Pergoveris

You and your partner's fertility should be evaluated before the treatment is started by a doctor 
experienced in treating fertility problems.

Do not use Pergoveris
 if you are allergic to follicle stimulating hormone (FSH), luteinising hormone (LH) or any of 

the other ingredients of this medicine (listed in section 6)



62

 if you have a brain tumour (in your hypothalamus or pituitary gland)
 if you have large ovaries or sacs of fluid within your ovaries (ovarian cysts) of unknown origin
 if you have unexplained vaginal bleeding
 if you have cancer in your ovaries, womb or breasts
 if you have a condition that would make a normal pregnancy impossible, such as an early 

menopause, malformed sex organs or benign tumours of the womb.

Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, 
pharmacist or nurse before using this medicine.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Pergoveris.

Porphyria
Talk to your doctor before you start your treatment.If you or any member of your family have 
porphyria (an inability to breakdown porphyrins that may be passed on from parents to children).
Tell your doctor straight away if:
 your skin becomes fragile and easily blistered, especially skin that has been frequently exposed 

to sunlight
 you have stomach, arm or leg pain.

In case of above events your doctor may recommend that you stop treatment.

Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates your ovaries. This increases your risk of developing ovarian 
hyperstimulation syndrome (OHSS). This is when your follicles develop too much and become large 
cysts. If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting or if you 
have difficulty in breathing, talk to your doctor straight away. They might ask you to stop using this 
medicine (see in section 4. under “Most serious side effects”).

In case you are not ovulating and if the recommended dose and schedule of administration are adhered 
to, the occurrence of severe OHSS is less likely. Pergoveris treatment seldom causes severe OHSS. 
This becomes more likely if the medicine that is used for final follicular maturation (containing 
human chorionic gonadotrophin, hCG) is administered (see in section 3. under “How much to use” for 
details). If you are developing OHSS your doctor may not give you any hCG in this treatment cycle 
and you may be told not to have sex or that you should use a barrier contraceptive method for at least 
four days.
Your doctor will ensure, careful monitoring of the ovarian response, based on ultrasound and blood 
tests (oestradiol measurements) before and during the course of treatment.

Multiple pregnancy
When using Pergoveris, you have a higher risk of being pregnant with more than one child at the same 
time (“multiple pregnancy”, mostly twins), than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy 
by using the right dose of Pergoveris at the right times.

To minimise the risk of multiple pregnancy, ultrasound scans as well as blood tests are recommended.

Miscarriage
When undergoing stimulation of your ovaries to produce eggs, you are more likely to have a 
miscarriage than the average woman.



63

Ectopic pregnancy
Women who have ever had blocked or damaged fallopian tubes (tubal disease) are at risk of 
pregnancy where the embryo is implanted outside the womb (ectopic pregnancy). This is whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments.

Blood clotting problems (thromboembolic events)
Talk to your doctor before using Pergoveris if you or a member of your family have ever had blood 
clots in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood 
clots or existing clots might become worse with Pergoveris treatment.

Tumours of sex organs
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment.

Allergic reactions
There have been isolated reports of non-serious allergic reactions to Pergoveris. If you have ever had 
this type of reaction to a similar medicine, talk to your doctor before using Pergoveris.

Children and adolescents
Pergoveris is not for use in children and adolescents below 18 years old.

Other medicines and Pergoveris
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Do not use Pergoveris with other medicines in the same injection, except for follitropin alfa, if 
prescribed by your doctor.

Pregnancy and breast-feeding
Do not use Pergoveris if you are pregnant or breast-feeding.

Driving and using machines
It is not expected that this medicine will affect your ability to drive or use machines.

Pergoveris contains sodium
Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

3. How to use Pergoveris

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Using this medicine
 Pergoveris is intended to be given by injection just under the skin (subcutaneously). To 

minimise skin irritation, select a different injection site each day. 
 It comes as a powder and liquid, which you need to mix together and then use straight away.
 Your doctor or nurse will show you how to prepare and inject this medicine. They will 

supervise your first injection.
 If they are satisfied that you can administer Pergoveris safely, you can then prepare and inject 

the medicine yourself at home. When you do this, please carefully read and follow the 
instructions hereafter called “How to prepare and use the Pergoveris powder and solvent”.



64

How much to use
The usual starting dose is one vial of Pergoveris every day.
 According to your response, your doctor may decide to add every day a dose of a licensed 

follitropin alfa preparation to your Pergoveris injection. In this case, the follitropin alfa dose is 
usually increased every 7 or every 14 days by 37.5 to 75 IU.

 Treatment is continued until you get the desired response. This is when you have developed a 
suitable follicle, as assessed using ultrasound scans and blood tests. 

 This may take up to 5 weeks. 

When you get the desired response, you will be given a single injection of human chorionic 
gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time to have sex is 
on the day of the hCG injection and the day after. Alternatively, intrauterine insemination (IUI) may 
be performed.

If your body responds too strongly, your treatment will be stopped and you will not be given any hCG 
(see in section 2. under ”Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will 
give you a lower follitropin alfa dose in the following cycle.

How to prepare and use the Pergoveris powder and solvent
Before starting the preparation, please read these instructions the whole way through first:
Give yourself the injection at the same time each day.

1. Wash your hands and find a clean area

 It is important that your hands and the items you use be as clean as possible
 A good place is a clean table or kitchen surface

2. Get together everything you need and lay them out

 1 vial containing Pergoveris powder
 1 vial containing water for injections (solvent)

Not provided in the pack:
 2 alcohol swabs
 1 empty syringe for injection
 1 needle for preparation
 1 fine bore needle for injection under the skin
 one sharps container for safe disposal of glass and needles

3. Preparing the solution

 Remove the protective cap from the vial filled with water (solvent vial).
 Attach the needle for preparation to the empty syringe for injection.
 Draw up some air into the syringe by pulling the plunger to 

approximately the 1 mL mark.
 Insert the needle into the vial, push the plunger to expel the air.
 Turn the vial upside down and gently draw up all the water (solvent).
 Remove the syringe from the vial and set it down carefully. Do not 

touch the needle and do not allow the needle to touch any surface.



65

 Remove the protective cap from the vial filled with Pergoveris powder.
 Pick up your syringe and slowly inject the contents of the syringe into 

the vial of powder. 
 Swirl gently without removing the syringe. Do not shake.
 After the powder has dissolved (which usually occurs immediately), 

check that the resulting solution is clear and does not contain any 
particles.

 Turn the vial upside down, gently draw the solution back into the 
syringe. Check for particles as before, and do not use if the solution is 
not clear.

4. Getting the syringe ready for injection

 Change the needle for the fine bore needle.
 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. Push the plunger until the air bubbles 
are gone.

5. Injecting the dose

 Immediately inject the solution. Your doctor or nurse will have already 
advised you where to inject (e.g. tummy, front of thigh). To minimise 
skin irritation, select a different injection site each day.

 Clean the chosen skin area with an alcohol swab using a circular 
motion.

 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. 

 Then withdraw the needle and clean the skin with a new alcohol swab 
using a circular motion.

6. After the injection

Dispose of all used items. Once you have finished your injection, immediately discard all needles and 
empty vials in your sharps container. Any unused solution must be discarded.

If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown, nevertheless one could expect OHSS to occur. 
However this will only occur if hCG is administered (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”).

If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Please contact your doctor.

If you have any further question on the use of this medicine, ask your doctor, pharmacist or nurse.



66

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects
Contact your doctor straight away if you notice any of the below listed side effects. The doctor 
might ask you to stop using Pergoveris.

Allergic reactions
Allergic reactions such as rash, red skin, hives, swelling of your face with difficulty breathing can 
sometimes be serious. This side effect is very rare.

Ovarian hyperstimulation syndrome (OHSS)
 Lower abdominal pain together with nausea or vomiting. These may be the symptoms of 

ovarian hyperstimulation syndrome (OHSS). Your ovaries may have over-reacted to the 
treatment and formed large sacs of fluid or cysts (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”). This side effect is common. If this happens, your doctor 
will need to examine you as soon as possible.

 The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and/or possible fluid accumulation in your stomach or chest. 
This side effect is uncommon (may affect up to 1 in 100 people).

 Complications of OHSS such as twisting of ovaries or blood clotting occur rarely (may affect 
up to 1 in 1,000 people).

 Serious blood clotting problems (thromboembolic events) usually with severe OHSS are found 
very rarely. This could cause chest pain, breathlessness, stroke or heart attack. In rare cases this 
can also happen independently of OHSS (see in section 2. under “Blood clotting problems
(thromboembolic events)”).

Other side effects

Very common (may affect more than 1 in 10 people):
 sacs of fluid within the ovaries (ovarian cysts)
 headache
 local reactions at the injection site such as pain, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people):
 diarrhoea
 breast pain
 feeling sick or vomiting
 abdominal or pelvic pain
 abdominal cramp or bloating.

Very rare (may affect up to 1 in 10,000 people):
 Your asthma may get worse.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.



67

Do not use this medicine after the expiry date which is stated on the vials and the carton after EXP. 
The expiry date refers to the last day of that month.

Do not store above 25 C. Store in the original package in order to protect from light.

The medicine must be administered immediately after reconstitution.

Do not use Pergoveris if you notice any visible signs of deterioration.

The reconstituted solution should not be administered if it contains particles or is not clear.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information 

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa. 
 One vial contains 150 IU (equivalent to 11 micrograms) of follitropin alfa and 75 IU 

(equivalent to 3 micrograms) of lutropin alfa.
After reconstitution, each mL of the solution contains 150 IU follitropin alfa and 75 IU lutropin 
alfa per milliliter.

The other ingredients are
 Sucrose, disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, 

methionine, polysorbate 20, as well as concentrated phosphoric acid and sodium hydroxide for 
pH-adjustment.

What Pergoveris looks like and contents of the pack
 Pergoveris is presented as a powder and solvent for solution for injection.
 The powder is a white to off-white lyophilised pellet in a glass vial with a bromobutyl rubber 

stopper containing 150 IU (equivalent to 11 micrograms) of follitropin alfa and 75 IU 
(equivalent to 3 micrograms) of lutropin alfa.

 The solvent is a clear colourless liquid in a glass vial containing1 mL of water for injections.
 Pergoveris is supplied in packs of 1, 3 and 10 vials of powder with the corresponding number 

of solvent’s vials (1, 3 and 10 vials). Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands

Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 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
Tél/Tel: +32-2-686 07 11

Lietuva
Merck Serono UAB 
Tel: +370 37320603



68

България
„Мерк България“ ЕАД
Teл.: +359 24461 111

Luxembourg/Luxemburg
MERCK NV/SA, Belgique/Belgien
Tél/Tel: +32-2-686 07 11

Česká republika
Merck spol.s.r.o
Tel. +420 272084211

Magyarország
Merck Kft. 
Tel: +36-1-463-8100

Danmark
Merck A/S
Tlf: +45 35253550

Malta
Vivian Corporation Ltd
Tel: +356-22-588600

Deutschland
Merck Serono GmbH
Tel: +49-6151-6285-0

Nederland
Merck BV
Tel: +31-20-6582800

Eesti
Merck Serono OÜ
Tel: +372 682 5882

Norge
Merck Serono Norge 
Tlf: +47 67 90 35 90

Ελλάδα
Merck A.E.
T: +30-210-61 65 100

Österreich
Merck GesmbH.
Tel: +43 1 57600-0

España
Merck S.L.
Línea de Información: 900 102 964
Tel: +34-91-745 44 00

Polska
Merck Sp. z o.o.
Tel.: +48 22 53 59 700

France
Merck Serono s.a.s.
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024

Portugal
Merck, s.a.
Tel: +351-21-361 35 00

Hrvatska
Merck d.o.o,
Tel: +385 1 4864 111

România
MERCK d.o.o., Slovenia
Tel: +386 1 560 3 800

Íreland
Merck Serono Ltd, United Kingdom
Tel: +44-20 8818 7200

Slovenija
MERCK d.o.o.
Tel: +386 1 560 3 800

Ísland
Icepharma hf
Tel: + 354 540 8000

Slovenská republika
Merck spol. s r.o.
Tel: + 421 2 49 267 111

Italia
Merck Serono S.p.A.
Tel: +39-06-70 38 41

Suomi/Finland
Merck Oy
Puh/Tel: +358-9-8678 700

Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Τηλ.: +357 22490305

Sverige
Merck AB
Tel: +46-8-562 445 00



69

Latvija
Merck Serono SIA
Tel: +371 67152500

United Kingdom
Merck Serono Ltd
Tel: +44-20 8818 7200

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicine Agency web site:
http://www.ema.europa.eu.



70

Package leaflet: Information for the user

Pergoveris (300 IU + 150 IU)/0.48 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Pergoveris is and what it is used for
2. What you need to know before you use Pergoveris
3. How to use Pergoveris
4. Possible side effects
5. How to store Pergoveris
6. Contents of the pack and other information

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called “follitropin alfa” and “lutropin alfa”. Both 
belong to the family of hormones called “gonadotropins”, which are involved in reproduction and 
fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in your 
ovaries. This is to help you get pregnant. It is for use in adult women (18 years old or above) who 
have low levels (severe deficiency) of “follicle stimulating hormone” (FSH) and “luteinising 
hormone” (LH). These women are usually infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In your body:
 FSH stimulates the production of eggs
 LH stimulates the release of the eggs.

By replacing the missing hormones, Pergoveris allows women with low levels of FSH and LH to 
develop a follicle. This will then release an egg, after an injection of the hormone “human chorionic 
gonadotropin (hCG)”. This helps the women to become pregnant.

2. What you need to know before you use Pergoveris

You and your partner's fertility should be evaluated before the treatment is started by a doctor 
experienced in treating fertility problems.

Do not use Pergoveris
 if you are allergic to follicle stimulating hormone (FSH), luteinising hormone (LH) or any of 

the other ingredients of this medicine (listed in section 6)



71

 if you have a brain tumour (in your hypothalamus or pituitary gland)
 if you have large ovaries or sacs of fluid within your ovaries (ovarian cysts) of unknown origin
 if you have unexplained vaginal bleeding
 if you have cancer in your ovaries, womb or breasts
 if you have a condition that would make a normal pregnancy impossible, such as an early 

menopause, malformed sex organs or benign tumours of the womb.

Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, 
pharmacist or nurse before using this medicine.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Pergoveris.

Porphyria
Talk to your doctor before you start your treatment.If you or any member of your family have 
porphyria (an inability to breakdown porphyrins that may be passed on from parents to children).
Tell your doctor straight away if:
 your skin becomes fragile and easily blistered, especially skin that has been frequently exposed 

to sunlight
 you have stomach, arm or leg pain.

In case of above events your doctor may recommend that you stop treatment.

Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates your ovaries. This increases your risk of developing ovarian 
hyperstimulation syndrome (OHSS). This is when your follicles develop too much and become large 
cysts. If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting or if you 
have difficulty in breathing, talk to your doctor straight away. They might ask you to stop using this 
medicine (see in section 4. under “Most serious side effects”).

In case you are not ovulating and if the recommended dose and schedule of administration are adhered 
to, the occurrence of severe OHSS is less likely. Pergoveris treatment seldom causes severe OHSS. 
This becomes more likely if the medicine that is used for final follicular maturation (containing 
human chorionic gonadotrophin, hCG) is administered (see in section 3. under “How much to use” for 
details). If you are developing OHSS your doctor may not give you any hCG in this treatment cycle 
and you may be told not to have sex or that you should use a barrier contraceptive method for at least 
four days.
Your doctor will ensure, careful monitoring of the ovarian response, based on ultrasound and blood 
tests (oestradiol measurements) before and during the course of treatment.

Multiple pregnancy
When using Pergoveris, you have a higher risk of being pregnant with more than one child at the same 
time (“multiple pregnancy”, mostly twins), than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy 
by using the right dose of Pergoveris at the right times.

To minimise the risk of multiple pregnancy, ultrasound scans as well as blood tests are recommended.

Miscarriage
When undergoing stimulation of your ovaries to produce eggs, you are more likely to have a 
miscarriage than the average woman.



72

Ectopic pregnancy
Women who have ever had blocked or damaged fallopian tubes (tubal disease) are at risk of 
pregnancy where the embryo is implanted outside the womb (ectopic pregnancy). This is whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments.

Blood clotting problems (thromboembolic events)
Talk to your doctor before using Pergoveris if you or a member of your family have ever had blood 
clots in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood 
clots or existing clots might become worse with Pergoveris treatment.

Tumours of sex organs
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment.

Allergic reactions
There have been isolated reports of non-serious allergic reactions to Pergoveris. If you have ever had 
this type of reaction to a similar medicine, talk to your doctor before using Pergoveris.

Children and adolescents
Pergoveris is not for use in children and adolescents below 18 years old.

Other medicines and Pergoveris
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Do not use Pergoveris with other medicines in the same injection. You can use Pergoveris with a 
licensed follitropin alfa preparation as separate injections, if prescribed by your doctor.

Pregnancy and breast-feeding
Do not use Pergoveris if you are pregnant or breast-feeding.

Driving and using machines
It is not expected that this medicine will affect your ability to drive or use machines.

Pergoveris contains sodium
Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

3. How to use Pergoveris

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Using this medicine
 Pergoveris is intended to be given by injection just under the skin (subcutaneously). To 

minimise skin irritation, select a different injection site each day. 

 Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the 
medicine.

 If they are satisfied that you can administer Pergoveris safely, you can then prepare and inject 
the medicine yourself at home.

 If you administer Pergoveris to yourself, please carefully read and follow section “Instructions 
for Use”.

How much to use
A treatment regimen commences with the recommended dose of Pergoveris containing 
150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa every day.



73

 According to your response, your doctor may decide to add every day a dose of a licensed 
follitropin alfa preparation to your Pergoveris injection. In this case, the follitropin alfa dose is 
usually increased every 7 or every 14 days by 37.5 to 75 IU.

 Treatment is continued until you get the desired response. This is when you have developed a 
suitable follicle, as assessed using ultrasound scans and blood tests. 

 This may take up to 5 weeks. 

When you get the desired response, you will be given a single injection of human chorionic 
gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time to have sex is 
on the day of the hCG injection and the day after. Alternatively, intrauterine insemination (IUI) may 
be performed.

If your body responds too strongly, your treatment will be stopped and you will not be given any hCG 
(see in section 2. under ”Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will 
give you a lower follitropin alfa dose in the following cycle.

If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown, nevertheless one could expect OHSS to occur. 
However this will only occur if hCG is administered (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”).

If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Please contact your doctor.

If you have any further question on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects
Contact your doctor straight away if you notice any of the below listed side effects. The doctor 
might ask you to stop using Pergoveris.

Allergic reactions
Allergic reactions such as rash, red skin, hives, swelling of your face with difficulty breathing can 
sometimes be serious. This side effect is very rare.

Ovarian hyperstimulation syndrome (OHSS)
 Lower abdominal pain together with nausea or vomiting. These may be the symptoms of 

ovarian hyperstimulation syndrome (OHSS). Your ovaries may have over-reacted to the 
treatment and formed large sacs of fluid or cysts (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”). This side effect is common. If this happens, your doctor 
will need to examine you as soon as possible.

 The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and/or possible fluid accumulation in your stomach or chest. 
This side effect is uncommon (may affect up to 1 in 100 people).

 Complications of OHSS such as twisting of ovaries or blood clotting occur rarely (may affect 
up to 1 in 1,000 people).

 Serious blood clotting problems (thromboembolic events) usually with severe OHSS are found 
very rarely. This could cause chest pain, breathlessness, stroke or heart attack. In rare cases this 
can also happen independently of OHSS (see in section 2. under “Blood clotting problems 
(thromboembolic events)”).



74

Other side effects

Very common (may affect more than 1 in 10 people):
 sacs of fluid within the ovaries (ovarian cysts)
 headache
 local reactions at the injection site such as pain, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people):
 diarrhoea
 breast pain
 feeling sick or vomiting
 abdominal or pelvic pain
 abdominal cramp or bloating.

Very rare (may affect up to 1 in 10,000 people):
 Your asthma may get worse.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and the carton after EXP. 
The expiry date refers to the last day of that month.

Store in a refrigerator (2°C-8°C). Do not freeze. 
Store in the original package in order to protect from light.

Once opened, the pre-filled pen may be stored for a maximum of 28 days outside of the refrigerator 
(at 25°C).

Do not use Pergoveris if you notice any visible signs of deterioration, if the liquid contains particles 
or is not clear.

After the injection, dispose of the used needle safely.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information 

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa. 

 Each pre-filled pen of Pergoveris (300 IU + 150 IU)/0.48 mL contains 300 IU (International 
Units) of follitropin alfa and 150 IU of lutropin alfa in 0.48 mL and can deliver two doses of 
Pergoveris 150 IU/75 IU.



75

The other ingredients are
 Sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium phosphate 

dihydrate, sodium dihydrogen phosphate monohydrate and water for injections. Tiny amounts 
of concentrated phosphoric acid and sodium hydroxide are added to keep acidity levels (pH 
levels) normal.

What Pergoveris looks like and contents of the pack
Pergoveris is presented as a clear, colourless to slightly yellow solution for injection in a mulitidose 
pre-filled pen: 

 Pergoveris (300 IU +150 IU)/0.48 mL is supplied in packs of 1 multidose pre-filled pen and 
5 disposable injection needles. 

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands

Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 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
Tél/Tel: +32-2-686 07 11

Lietuva
Merck Serono UAB 
Tel: +370 37320603

България
„Мерк България“ ЕАД
Teл.: +359 24461 111

Luxembourg/Luxemburg
MERCK NV/SA, Belgique/Belgien
Tél/Tel: +32-2-686 07 11

Česká republika
Merck spol.s.r.o
Tel. +420 272084211

Magyarország
Merck Kft. 
Tel: +36-1-463-8100

Danmark
Merck A/S
Tlf: +45 35253550

Malta
Vivian Corporation Ltd
Tel: +356-22-588600

Deutschland
Merck Serono GmbH
Tel: +49-6151-6285-0

Nederland
Merck BV
Tel: +31-20-6582800

Eesti
Merck Serono OÜ
Tel: +372 682 5882

Norge
Merck Serono Norge 
Tlf: +47 67 90 35 90

Ελλάδα
Merck A.E.
T: +30-210-61 65 100

Österreich
Merck GesmbH.
Tel: +43 1 57600-0

España
Merck S.L.
Línea de Información: 900 102 964
Tel: +34-91-745 44 00

Polska
Merck Sp. z o.o.
Tel.: +48 22 53 59 700



76

France
Merck Serono s.a.s.
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024

Portugal
Merck, s.a.
Tel: +351-21-361 35 00

Hrvatska
Merck d.o.o,
Tel: +385 1 4864 111

România
MERCK d.o.o., Slovenia
Tel: +386 1 560 3 800

Íreland
Merck Serono Ltd, United Kingdom
Tel: +44-20 8818 7200

Slovenija
MERCK d.o.o.
Tel: +386 1 560 3 800

Ísland
Icepharma hf
Tel: + 354 540 8000

Slovenská republika
Merck spol. s r.o.
Tel: + 421 2 49 267 111

Italia
Merck Serono S.p.A.
Tel: +39-06-70 38 41

Suomi/Finland
Merck Oy
Puh/Tel: +358-9-8678 700

Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Τηλ.: +357 22490305

Sverige
Merck AB
Tel: +46-8-562 445 00

Latvija
Merck Serono SIA
Tel: +371 67152500

United Kingdom
Merck Serono Ltd
Tel: +44-20 8818 7200

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicine Agency web site:
http://www.ema.europa.eu.



77

Pergoveris pre-filled pen 

Instructions for Use
Contents
1. Important information about the Pergoveris pre-filled pen
2. How to use your Pergoveris pre-filled pen treatment diary
3. Gathering your supplies
4. Getting familiar with the parts of your Pergoveris pre-filled pen
5. Getting your Pergoveris pre-filled pen ready for injection
6. Setting the dose prescribed by your doctor
7. Injecting the dose
8. After the injection
9. Pergoveris pre-filled pen treatment diary (See table at the end)

Warning: Please read these instructions for use before using your Pergoveris pre-filled pen.
Follow the instructions exactly, as it may differ from your past experience.

1. Important information about the Pergoveris pre-filled pen 

 The Pergoveris pre-filled pen is for subcutaneous injection only.
 Only use the Pergoveris pre-filled pen if your healthcare provider trains you on how to 

use it correctly.

Warning: Do not reuse needles. Remove the needle immediately after each injection.
Do not share the pen and/or needles with another person, because doing so can cause an 
infection.

 The pen comes in 3 different multi-dose presentations:

 Contains 0.48 mL of Pergoveris solution
 Contains 300 IU follitropin alfa and 150 IU lutropin alfa.

 Contains 0.72 mL of Pergoveris solution
 Contains 450 IU follitropin alfa and 225 IU lutropin alfa.

 Contains 1.44 mL of Pergoveris solution
 Contains 900 IU follitropin alfa and 450 IU lutropin alfa.

Warning: Refer to the Package leaflet for more information on the recommended dose regimen and 
always follow the dose recommended by your doctor.

 The numbers in the Dose Feedback Window present the number of International Units, or IUs, 
and show the dose of follitropin alfa. Your doctor will tell you how many IUs of follitropin alfa 
to inject each day.

 The numbers displayed in the Dose Feedback Window help you to:

a. Dial your prescribed dose.



78

b. Verify a complete injection.

c. Read the dose remaining to be 
injected with a second pen.

 Give yourself the injection at the same time each day.    

 Your doctor/pharmacist will tell you how many pens of Pergoveris you need to complete your 
treatment.

2. How to use your Pergoveris pre-filled pen treatment diary

A treatment diary is included on the last page. Use the treatment diary to record the amount injected.

 Record the treatment day number (column 1), date (column 2), time of your injection (column 
3), and volume of your pen (column 4).

 Record your prescribed dose (column 5).
 Verify you dialed the right dose before injecting (column 6).
 After injection, read the number shown in the Dose Feedback Window.
 Confirm you receive a complete injection (column 7) OR record the number shown in the Dose 

Feedback Window if other than ‘’0’’ (column 8).

 When needed, inject youself using a second pen, dialing your remaining dose written in the 
“Amount to Be Set for a Second Injection” section (column 8).

 Record this remaining dose in the “Amount Set to Inject” section in the next row (column 6).

NOTE: Using your treatment diary to record your daily injection(s) allows you to verify that you 
received the full prescribed dose every day.

An example of a treatment diary using a pen:

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

#1 10/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150

if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#2 11/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150
if "0",

injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#3 12/06 19:00 450 IU + 225 IU 225IU/ 112.5IU 225

�if "0",
injection complete

if not "0", need second injection
Inject this amount .75..using new pen

#3 12/06 19:00 450 IU + 225 IU N/A

75 if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen



79

3. Gathering your supplies

3.1. Wash your hands with soap and water (Fig. 1).
3.2. Pepare a clean area and a flat surface, such as a table 

or countertop, in a well-lit area.
3.3. Select your Pergoveris pre-filled pen.

Fig. 1
3.4. Verify you select the prescribed pen.

3.5. Verify the expiration date on the pen label (Fig. 2).

Fig.2 
3.6. You will also need:

 Needles (included in the pack)
 Alcohol swabs (not included in the pack)
 A sharps disposal bin (not included in the pack)

4. Getting familiar with the parts of your Pergoveris pre-filled pen

* The numbers on the Dose Feedback Window and reservoir holder represent the number of 
International Units (IU) of medication.



80

5. Getting your Pergoveris pre-filled pen ready for injection

5.1. Take off the pen cap.
5.2. Verify that the Dose Feedback Window is set to "0".

5.3. Prepare your needle. 

 Get a new needle - only use the "single-use" needles 
supplied.

 Hold the outer needle cap firmly.
 Check that the peel-off seal on the outer needle cap is not 

damaged or loose (Fig.3).

Fig. 3

 Remove the peel-off seal (Fig. 4).

Fig. 4

Caution: If the peel-off seal is damaged or loose, do not use the needle. Throw it away in a 
sharps disposal container. Get a new needle.

5.4. Attach the needle.

 Screw the threaded tip of the Pergoveris pre-filled pen into the 
outer needle cap until you feel a light resistance.

Caution: Do not attach the needle too tightly; the needle could be 
difficult to remove after the injection.

 Remove the outer needle cap by pulling it gently.

 Put it aside for later use. DO NOT discard it.

 Hold the Pergoveris pre-filled pen with the needle pointing 
upward.

 Carefully remove and discard the green inner shield.

Warning: Do not recap the needle with the green inner shield, as it 
can lead to needle stick.



81

5.5. Check for a droplet of liquid at the tip of the needle.

 Look closely at the tip of the needle for tiny drop(s) of fluid.

IF THEN

Using a new pen Check for a droplet of liquid at the tip of 
the needle.

 If you see a droplet, proceed to 
Section 6: Setting the dose 
prescribed by your doctor.

 If no droplet is seen, follow the 
instructions on the following page.

Reusing a pen It is NOT required to check for a droplet of 
liquid.
Proceed directly to Section 6: Setting the 
dose prescribed by your doctor.

If you do not see a tiny drop(s) of fluid at or near the tip the first time you use a new pen:

Fig. 5

1. Gently turn the dose setting knob clockwise until it reads 25 in the Dose Feedback Window. 
You can turn the dose knob backwards if you turn it past 25 (Fig. 5).

Fig. 6 Fig.7 Fig.8

2 Hold the pen with the needle pointing upward.
3 Tap the reservoir holder gently (Fig. 6).
4 Press the dose setting knob as far as it will go. A tiny drop of liquid will appear at the tip of the 

needle (Fig. 7).
5. Verify that the Dose Feedback Window reads "0" (Fig. 8).
6. Proceed to Section 6: Setting the dose prescribed by your doctor.



82

6. Setting the dose prescribed by your doctor

6.1. Turn the dose setting knob until your intended dose shows in the Dose Feedback Window.

 Turn the dose setting knob forward to dial up 
according to the dose that was prescribed by your 
doctor.

 If needed, turn the dose setting knob backward 
to correct the dose.

Warning: Check that the Dose Feedback Window displays your complete prescribed dose before 
you move on to the next step.

7. Injecting the dose

7.1. Choose an injection site in the area your doctor or nurse has told you to use for the injection. To 
minimize skin irritation, select a different injection site each day.

7.2. Wipe the skin with an alcohol swab.
7.3. Verify once more that the Dose Feedback Window

displays the correct dose.

7.4. Inject the dose as you were trained to do by your 
doctor or nurse.

 Slowly push the needle into the skin entirely 
(Fig.9).

 Slowly press the dose knob down as far as it will 
go and hold it to complete the full injection.

Fig. 9

 Hold the dose knob down for a minimum of 5 
seconds to ensure you inject the full dose (Fig. 10). 

 The dose number shown in the Dose Feedback 
Window will turn back to 0.

Fig. 10

 After a minimum of 5 seconds, pull the needle out 
of the skin while keeping the dose setting knob 
pressed down (Fig. 11).

 When the needle is out of the skin, release the dose 
setting knob.

Fig. 11
Caution: Do not release the dose knob until you remove 

the needle from the skin.



83

Warning: Always make sure to use a new needle for each injection.

8. After the injection

8.1. Verify you have given a complete injection.

 Check that the Dose Feedback Window shows 
“0”.

Warning: If the Dose Feedback Window shows a number higher than 0, the Pergoveris pre-filled 
pen is empty and you have not received your full prescribed dose.

8.2. Complete a partial injection (only when needed).

 The Dose Feedback Window will indicate the 
missing amount you need to inject using a new 
pen.

 Repeat Section 4 (Getting familiar with your Pergoveris pre-filled pen) through Section 5 
(Getting your Pergoveris pre-filled pen ready for injection) with a second pen.

 Set the dose to the missing amount you recorded in the treatment diary OR the number still 
displayed in the Dose Feedback Window on your previous pen, and inject.

8.3. Removing the needle after each injection.

 Place the outer needle cap on a flat surface.
 Hold the Pergoveris pre-filled pen firmly with one hand, and 

slip the needle into the outer needle cap.

 Continue by pushing the capped needle against a firm surface 
until you hear a “click”.

 Grip the outer needle cap and 
unscrew the needle by turning anti-
clockwise.
Dispose of the used needle safely.

 Recap the pen.

Warning: Never reuse any used needle. Never share needles.

8.4. Storing the Pergoveris pre-filled pen.

Caution: Never store the pen with the needle still attached. 
Always remove the needle from the Pergoveris pre-
filled pen before replacing the pen cap.

 Store the pen in its original packaging in a safe place and as indicated in the package leaflet.
 When the pen is empty, ask your pharmacist how to dispose of it.



84

Warning: Medicine should not be disposed of via wastewater or household waste.

9. Pergoveris pre-filled pen treatment diary

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen -

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

This instructions for use was last revised in:



85

Package leaflet: Information for the user

Pergoveris (450 IU + 225 IU)/0.72 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Pergoveris is and what it is used for
2. What you need to know before you use Pergoveris
3. How to use Pergoveris
4. Possible side effects
5. How to store Pergoveris
6. Contents of the pack and other information

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called “follitropin alfa” and “lutropin alfa”. Both 
belong to the family of hormones called “gonadotropins”, which are involved in reproduction and 
fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in your 
ovaries. This is to help you get pregnant. It is for use in adult women (18 years old or above) who
have low levels (severe deficiency) of “follicle stimulating hormone” (FSH) and “luteinising 
hormone” (LH). These women are usually infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In your body:
 FSH stimulates the production of eggs
 LH stimulates the release of the eggs.

By replacing the missing hormones, Pergoveris allows women with low levels of FSH and LH to 
develop a follicle. This will then release an egg, after an injection of the hormone “human chorionic 
gonadotropin (hCG)”. This helps the women to become pregnant.

2. What you need to know before you use Pergoveris

You and your partner's fertility should be evaluated before the treatment is started by a doctor 
experienced in treating fertility problems.

Do not use Pergoveris
 if you are allergic to follicle stimulating hormone (FSH), luteinising hormone (LH) or any of 

the other ingredients of this medicine (listed in section 6)



86

 if you have a brain tumour (in your hypothalamus or pituitary gland)
 if you have large ovaries or sacs of fluid within your ovaries (ovarian cysts) of unknown origin
 if you have unexplained vaginal bleeding
 if you have cancer in your ovaries, womb or breasts
 if you have a condition that would make a normal pregnancy impossible, such as an early 

menopause, malformed sex organs or benign tumours of the womb.

Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, 
pharmacist or nurse before using this medicine.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Pergoveris.

Porphyria
Talk to your doctor before you start your treatment.If you or any member of your family have 
porphyria (an inability to breakdown porphyrins that may be passed on from parents to children).
Tell your doctor straight away if:
 your skin becomes fragile and easily blistered, especially skin that has been frequently exposed 

to sunlight
 you have stomach, arm or leg pain.

In case of above events your doctor may recommend that you stop treatment.

Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates your ovaries. This increases your risk of developing ovarian 
hyperstimulation syndrome (OHSS). This is when your follicles develop too much and become large 
cysts. If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting or if you 
have difficulty in breathing, talk to your doctor straight away. They might ask you to stop using this 
medicine (see in section 4. under “Most serious side effects”).

In case you are not ovulating and if the recommended dose and schedule of administration are adhered 
to, the occurrence of severe OHSS is less likely. Pergoveris treatment seldom causes severe OHSS. 
This becomes more likely if the medicine that is used for final follicular maturation (containing 
human chorionic gonadotrophin, hCG) is administered (see in section 3. under “How much to use” for 
details). If you are developing OHSS your doctor may not give you any hCG in this treatment cycle 
and you may be told not to have sex or that you should use a barrier contraceptive method for at least 
four days.
Your doctor will ensure, careful monitoring of the ovarian response, based on ultrasound and blood 
tests (oestradiol measurements) before and during the course of treatment.

Multiple pregnancy
When using Pergoveris, you have a higher risk of being pregnant with more than one child at the same 
time (“multiple pregnancy”, mostly twins), than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy 
by using the right dose of Pergoveris at the right times.

To minimise the risk of multiple pregnancy, ultrasound scans as well as blood tests are recommended.

Miscarriage
When undergoing stimulation of your ovaries to produce eggs, you are more likely to have a 
miscarriage than the average woman.



87

Ectopic pregnancy
Women who have ever had blocked or damaged fallopian tubes (tubal disease) are at risk of 
pregnancy where the embryo is implanted outside the womb (ectopic pregnancy). This is whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments.

Blood clotting problems (thromboembolic events)
Talk to your doctor before using Pergoveris if you or a member of your family have ever had blood 
clots in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood 
clots or existing clots might become worse with Pergoveris treatment.

Tumours of sex organs
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment.

Allergic reactions
There have been isolated reports of non-serious allergic reactions to Pergoveris. If you have ever had 
this type of reaction to a similar medicine, talk to your doctor before using Pergoveris.

Children and adolescents
Pergoveris is not for use in children and adolescents below 18 years old.

Other medicines and Pergoveris
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Do not use Pergoveris with other medicines in the same injection. You can use Pergoveris with a 
licensed follitropin alfa preparation as separate injections, if prescribed by your doctor.

Pregnancy and breast-feeding
Do not use Pergoveris if you are pregnant or breast-feeding.

Driving and using machines
It is not expected that this medicine will affect your ability to drive or use machines.

Pergoveris contains sodium
Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

3. How to use Pergoveris

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Using this medicine
 Pergoveris is intended to be given by injection just under the skin (subcutaneously). To 

minimise skin irritation, select a different injection site each day. 

 Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the 
medicine.

 If they are satisfied that you can administer Pergoveris safely, you can then prepare and inject 
the medicine yourself at home.

 If you administer Pergoveris to yourself, please carefully read and follow section “Instructions 
for Use”.

How much to use
A treatment regimen commences with the recommended dose of Pergoveris containing 
150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa every day.



88

 According to your response, your doctor may decide to add every day a dose of a licensed 
follitropin alfa preparation to your Pergoveris injection. In this case, the follitropin alfa dose is 
usually increased every 7 or every 14 days by 37.5 to 75 IU.

 Treatment is continued until you get the desired response. This is when you have developed a 
suitable follicle, as assessed using ultrasound scans and blood tests. 

 This may take up to 5 weeks. 

When you get the desired response, you will be given a single injection of human chorionic 
gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time to have sex is 
on the day of the hCG injection and the day after. Alternatively, intrauterine insemination (IUI) may 
be performed.

If your body responds too strongly, your treatment will be stopped and you will not be given any hCG 
(see in section 2. under ”Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will 
give you a lower follitropin alfa dose in the following cycle.

If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown, nevertheless one could expect OHSS to occur. 
However this will only occur if hCG is administered (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”).

If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Please contact your doctor.

If you have any further question on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects
Contact your doctor straight away if you notice any of the below listed side effects. The doctor 
might ask you to stop using Pergoveris.

Allergic reactions
Allergic reactions such as rash, red skin, hives, swelling of your face with difficulty breathing can 
sometimes be serious. This side effect is very rare.

Ovarian hyperstimulation syndrome (OHSS)
 Lower abdominal pain together with nausea or vomiting. These may be the symptoms of 

ovarian hyperstimulation syndrome (OHSS). Your ovaries may have over-reacted to the 
treatment and formed large sacs of fluid or cysts (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”). This side effect is common. If this happens, your doctor
will need to examine you as soon as possible.

 The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and/or possible fluid accumulation in your stomach or chest. 
This side effect is uncommon (may affect up to 1 in 100 people).

 Complications of OHSS such as twisting of ovaries or blood clotting occur rarely (may affect 
up to 1 in 1,000 people).

 Serious blood clotting problems (thromboembolic events) usually with severe OHSS are found 
very rarely. This could cause chest pain, breathlessness, stroke or heart attack. In rare cases this 
can also happen independently of OHSS (see in section 2. under “Blood clotting problems 
(thromboembolic events)”).



89

Other side effects

Very common (may affect more than 1 in 10 people):
 sacs of fluid within the ovaries (ovarian cysts)
 headache
 local reactions at the injection site such as pain, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people):
 diarrhoea
 breast pain
 feeling sick or vomiting
 abdominal or pelvic pain
 abdominal cramp or bloating.

Very rare (may affect up to 1 in 10,000 people):
 Your asthma may get worse.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and the carton after EXP. 
The expiry date refers to the last day of that month.

Store in a refrigerator (2°C-8°C). Do not freeze. 
Store in the original package in order to protect from light.

Once opened, the pre-filled pen may be stored for a maximum of 28 days outside of the refrigerator 
(at 25°C).

Do not use Pergoveris if you notice any visible signs of deterioration, if the liquid contains particles 
or is not clear.

After the injection, dispose of the used needle safely.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information 

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa. 

 Each pre-filled pen of Pergoveris (450 IU + 225 IU)/0.72 mL contains 450 IU (International 
Units) of follitropin alfa and 225 IU of lutropin alfa in 0.72 mL and can deliver three doses of 
Pergoveris 150 IU/75 IU.



90

The other ingredients are
 Sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium phosphate 

dihydrate, sodium dihydrogen phosphate monohydrate and water for injections. Tiny amounts 
of concentrated phosphoric acid and sodium hydroxide are added to keep acidity levels (pH 
levels) normal.

What Pergoveris looks like and contents of the pack
Pergoveris is presented as a clear, colourless to slightly yellow solution for injection in a mulitidose 
pre-filled pen: 

 Pergoveris (450 IU + 225 IU)/0.72 mL is supplied in packs of 1 multidose pre-filled pen and 
7 disposable injection needles. 

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands

Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 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
Tél/Tel: +32-2-686 07 11

Lietuva
Merck Serono UAB 
Tel: +370 37320603

България
„Мерк България“ ЕАД
Teл.: +359 24461 111

Luxembourg/Luxemburg
MERCK NV/SA, Belgique/Belgien
Tél/Tel: +32-2-686 07 11

Česká republika
Merck spol.s.r.o
Tel. +420 272084211

Magyarország
Merck Kft. 
Tel: +36-1-463-8100

Danmark
Merck A/S
Tlf: +45 35253550

Malta
Vivian Corporation Ltd
Tel: +356-22-588600

Deutschland
Merck Serono GmbH
Tel: +49-6151-6285-0

Nederland
Merck BV
Tel: +31-20-6582800

Eesti
Merck Serono OÜ
Tel: +372 682 5882

Norge
Merck Serono Norge 
Tlf: +47 67 90 35 90

Ελλάδα
Merck A.E.
T: +30-210-61 65 100

Österreich
Merck GesmbH.
Tel: +43 1 57600-0

España
Merck S.L.
Línea de Información: 900 102 964
Tel: +34-91-745 44 00

Polska
Merck Sp. z o.o.
Tel.: +48 22 53 59 700



91

France
Merck Serono s.a.s.
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024

Portugal
Merck, s.a.
Tel: +351-21-361 35 00

Hrvatska
Merck d.o.o,
Tel: +385 1 4864 111

România
MERCK d.o.o., Slovenia
Tel: +386 1 560 3 800

Íreland
Merck Serono Ltd, United Kingdom
Tel: +44-20 8818 7200

Slovenija
MERCK d.o.o.
Tel: +386 1 560 3 800

Ísland
Icepharma hf
Tel: + 354 540 8000

Slovenská republika
Merck spol. s r.o.
Tel: + 421 2 49 267 111

Italia
Merck Serono S.p.A.
Tel: +39-06-70 38 41

Suomi/Finland
Merck Oy
Puh/Tel: +358-9-8678 700

Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Τηλ.: +357 22490305

Sverige
Merck AB
Tel: +46-8-562 445 00

Latvija
Merck Serono SIA
Tel: +371 67152500

United Kingdom
Merck Serono Ltd
Tel: +44-20 8818 7200

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicine Agency web site:
http://www.ema.europa.eu.



92

Pergoveris pre-filled pen 

Instructions for Use
Contents
1. Important information about the Pergoveris pre-filled pen
2. How to use your Pergoveris pre-filled pen treatment diary
3. Gathering your supplies
4. Getting familiar with the parts of your Pergoveris pre-filled pen
5. Getting your Pergoveris pre-filled pen ready for injection
6. Setting the dose prescribed by your doctor
7. Injecting the dose
8. After the injection
9. Pergoveris pre-filled pen treatment diary (See table at the end)

Warning: Please read these instructions for use before using your Pergoveris pre-filled pen.
Follow the instructions exactly, as it may differ from your past experience.

1. Important information about the Pergoveris pre-filled pen 

 The Pergoveris pre-filled pen is for subcutaneous injection only.
 Only use the Pergoveris pre-filled pen if your healthcare provider trains you on how to 

use it correctly.

Warning: Do not reuse needles. Remove the needle immediately after each injection.
Do not share the pen and/or needles with another person, because doing so can cause an 
infection.

 The pen comes in 3 different multi-dose presentations:

 Contains 0.48 mL of Pergoveris solution
 Contains 300 IU follitropin alfa and 150 IU lutropin alfa.

 Contains 0.72 mL of Pergoveris solution
 Contains 450 IU follitropin alfa and 225 IU lutropin alfa.

 Contains 1.44 mL of Pergoveris solution
 Contains 900 IU follitropin alfa and 450 IU lutropin alfa.

Warning: Refer to the Package leaflet for more information on the recommended dose regimen and 
always follow the dose recommended by your doctor.

 The numbers in the Dose Feedback Window present the number of International Units, or IUs, 
and show the dose of follitropin alfa. Your doctor will tell you how many IUs of follitropin alfa 
to inject each day.

 The numbers displayed in the Dose Feedback Window help you to:

a. Dial your prescribed dose.



93

b. Verify a complete injection.

c. Read the dose remaining to be 
injected with a second pen.

 Give yourself the injection at the same time each day.    

 Your doctor/pharmacist will tell you how many pens of Pergoveris you need to complete your 
treatment.

2. How to use your Pergoveris pre-filled pen treatment diary

A treatment diary is included on the last page. Use the treatment diary to record the amount injected.

 Record the treatment day number (column 1), date (column 2), time of your injection (column 
3), and volume of your pen (column 4).

 Record your prescribed dose (column 5).
 Verify you dialed the right dose before injecting (column 6).
 After injection, read the number shown in the Dose Feedback Window.
 Confirm you receive a complete injection (column 7) OR record the number shown in the Dose 

Feedback Window if other than ‘’0’’ (column 8).

 When needed, inject youself using a second pen, dialing your remaining dose written in the 
“Amount to Be Set for a Second Injection” section (column 8).

 Record this remaining dose in the “Amount Set to Inject” section in the next row (column 6).

NOTE: Using your treatment diary to record your daily injection(s) allows you to verify that you 
received the full prescribed dose every day.

An example of a treatment diary using a pen:

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

#1 10/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150

if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#2 11/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150
if "0",

injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#3 12/06 19:00 450 IU + 225 IU 225IU/ 112.5IU 225

�if "0",
injection complete

if not "0", need second injection
Inject this amount .75..using new pen

#3 12/06 19:00 450 IU + 225 IU N/A

75 if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen



94

3. Gathering your supplies

3.1. Wash your hands with soap and water (Fig. 1).
3.2. Pepare a clean area and a flat surface, such as a table 

or countertop, in a well-lit area.
3.3. Select your Pergoveris pre-filled pen.

Fig. 1
3.4. Verify you select the prescribed pen.

3.5. Verify the expiration date on the pen label (Fig. 2).

Fig.2 
3.6. You will also need:

 Needles (included in the pack)
 Alcohol swabs (not included in the pack)
 A sharps disposal bin (not included in the pack)

4. Getting familiar with the parts of your Pergoveris pre-filled pen

* The numbers on the Dose Feedback Window and reservoir holder represent the number of 
International Units (IU) of medication.



95

5. Getting your Pergoveris pre-filled pen ready for injection

5.1. Take off the pen cap.
5.2. Verify that the Dose Feedback Window is set to "0".

5.3. Prepare your needle. 

 Get a new needle - only use the "single-use" needles 
supplied.

 Hold the outer needle cap firmly.
 Check that the peel-off seal on the outer needle cap is not 

damaged or loose (Fig.3).

Fig. 3

 Remove the peel-off seal (Fig. 4).

Fig. 4

Caution: If the peel-off seal is damaged or loose, do not use the needle. Throw it away in a 
sharps disposal container. Get a new needle.

5.4. Attach the needle.

 Screw the threaded tip of the Pergoveris pre-filled pen into the 
outer needle cap until you feel a light resistance.

Caution: Do not attach the needle too tightly; the needle could be 
difficult to remove after the injection.

 Remove the outer needle cap by pulling it gently.

 Put it aside for later use. DO NOT discard it.

 Hold the Pergoveris pre-filled pen with the needle pointing 
upward.

 Carefully remove and discard the green inner shield.

Warning: Do not recap the needle with the green inner shield, as it 
can lead to needle stick.



96

5.5. Check for a droplet of liquid at the tip of the needle.

 Look closely at the tip of the needle for tiny drop(s) of fluid.

IF THEN

Using a new pen Check for a droplet of liquid at the tip of 
the needle.

 If you see a droplet, proceed to 
Section 6: Setting the dose 
prescribed by your doctor.

 If no droplet is seen, follow the 
instructions on the following page.

Reusing a pen It is NOT required to check for a droplet of 
liquid.
Proceed directly to Section 6: Setting the 
dose prescribed by your doctor.

If you do not see a tiny drop(s) of fluid at or near the tip the first time you use a new pen:

Fig. 5

2. Gently turn the dose setting knob clockwise until it reads 25 in the Dose Feedback Window. 
You can turn the dose knob backwards if you turn it past 25 (Fig. 5).

Fig. 6 Fig.7 Fig.8

2 Hold the pen with the needle pointing upward.
3 Tap the reservoir holder gently (Fig. 6).
4 Press the dose setting knob as far as it will go. A tiny drop of liquid will appear at the tip of the 

needle (Fig. 7).
5. Verify that the Dose Feedback Window reads "0" (Fig. 8).
6. Proceed to Section 6: Setting the dose prescribed by your doctor.



97

6. Setting the dose prescribed by your doctor

6.1. Turn the dose setting knob until your intended dose shows in the Dose Feedback Window.

 Turn the dose setting knob forward to dial up 
according to the dose that was prescribed by your 
doctor.

 If needed, turn the dose setting knob backward 
to correct the dose.

Warning: Check that the Dose Feedback Window displays your complete prescribed dose before 
you move on to the next step.

7. Injecting the dose

7.1. Choose an injection site in the area your doctor or nurse has told you to use for the injection. To 
minimize skin irritation, select a different injection site each day.

7.2. Wipe the skin with an alcohol swab.
7.3. Verify once more that the Dose Feedback Window

displays the correct dose.

7.4. Inject the dose as you were trained to do by your 
doctor or nurse.

 Slowly push the needle into the skin entirely 
(Fig.9).

 Slowly press the dose knob down as far as it will 
go and hold it to complete the full injection.

Fig. 9

 Hold the dose knob down for a minimum of 5 
seconds to ensure you inject the full dose (Fig. 10). 

 The dose number shown in the Dose Feedback 
Window will turn back to 0.

Fig. 10

 After a minimum of 5 seconds, pull the needle out 
of the skin while keeping the dose setting knob 
pressed down (Fig. 11).

 When the needle is out of the skin, release the dose 
setting knob.

Fig. 11
Caution: Do not release the dose knob until you remove 

the needle from the skin.



98

Warning: Always make sure to use a new needle for each injection.

8. After the injection

8.1. Verify you have given a complete injection.

 Check that the Dose Feedback Window shows 
“0”.

Warning: If the Dose Feedback Window shows a number higher than 0, the Pergoveris pre-filled 
pen is empty and you have not received your full prescribed dose.

8.2. Complete a partial injection (only when needed).

 The Dose Feedback Window will indicate the 
missing amount you need to inject using a new 
pen.

 Repeat Section 4 (Getting familiar with your Pergoveris pre-filled pen) through Section 5 
(Getting your Pergoveris pre-filled pen ready for injection) with a second pen.

 Set the dose to the missing amount you recorded in the treatment diary OR the number still 
displayed in the Dose Feedback Window on your previous pen, and inject.

8.3. Removing the needle after each injection.

 Place the outer needle cap on a flat surface.
 Hold the Pergoveris pre-filled pen firmly with one hand, and 

slip the needle into the outer needle cap.

 Continue by pushing the capped needle against a firm surface 
until you hear a “click”.

 Grip the outer needle cap and 
unscrew the needle by turning anti-
clockwise.
Dispose of the used needle safely.

 Recap the pen.

Warning: Never reuse any used needle. Never share needles.

8.4. Storing the Pergoveris pre-filled pen.

Caution: Never store the pen with the needle still attached. 
Always remove the needle from the Pergoveris pre-
filled pen before replacing the pen cap.

 Store the pen in its original packaging in a safe place and as indicated in the package leaflet.
 When the pen is empty, ask your pharmacist how to dispose of it.



99

Warning: Medicine should not be disposed of via wastewater or household waste.

9. Pergoveris pre-filled pen treatment diary

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen -

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

This instructions for use was last revised in:



100

Package leaflet: Information for the user

Pergoveris (900 IU + 450 IU)/1.44 mL solution for injection in pre-filled pen
Follitropin alfa/Lutropin alfa

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Pergoveris is and what it is used for
2. What you need to know before you use Pergoveris
3. How to use Pergoveris
4. Possible side effects
5. How to store Pergoveris
6. Contents of the pack and other information

1. What Pergoveris is and what it is used for

What Pergoveris is
Pergoveris contains two different active substances called “follitropin alfa” and “lutropin alfa”. Both 
belong to the family of hormones called “gonadotropins”, which are involved in reproduction and 
fertility.

What Pergoveris is used for
This medicine is used to stimulate the development of follicles (each containing an egg) in your 
ovaries. This is to help you get pregnant. It is for use in adult women (18 years old or above) who 
have low levels (severe deficiency) of “follicle stimulating hormone” (FSH) and “luteinising 
hormone” (LH). These women are usually infertile.

How Pergoveris works
The active substances in Pergoveris are copies of the natural hormones FSH and LH. In your body:
 FSH stimulates the production of eggs
 LH stimulates the release of the eggs.

By replacing the missing hormones, Pergoveris allows women with low levels of FSH and LH to 
develop a follicle. This will then release an egg, after an injection of the hormone “human chorionic 
gonadotropin (hCG)”. This helps the women to become pregnant.

2. What you need to know before you use Pergoveris

You and your partner's fertility should be evaluated before the treatment is started by a doctor 
experienced in treating fertility problems.

Do not use Pergoveris
 if you are allergic to follicle stimulating hormone (FSH), luteinising hormone (LH) or any of 

the other ingredients of this medicine (listed in section 6)



101

 if you have a brain tumour (in your hypothalamus or pituitary gland)
 if you have large ovaries or sacs of fluid within your ovaries (ovarian cysts) of unknown origin
 if you have unexplained vaginal bleeding
 if you have cancer in your ovaries, womb or breasts
 if you have a condition that would make a normal pregnancy impossible, such as an early 

menopause, malformed sex organs or benign tumours of the womb.

Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, 
pharmacist or nurse before using this medicine.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Pergoveris.

Porphyria
Talk to your doctor before you start your treatment.If you or any member of your family have 
porphyria (an inability to breakdown porphyrins that may be passed on from parents to children).
Tell your doctor straight away if:
 your skin becomes fragile and easily blistered, especially skin that has been frequently exposed 

to sunlight
 you have stomach, arm or leg pain.

In case of above events your doctor may recommend that you stop treatment.

Ovarian hyperstimulation syndrome (OHSS)
This medicine stimulates your ovaries. This increases your risk of developing ovarian 
hyperstimulation syndrome (OHSS). This is when your follicles develop too much and become large 
cysts. If you get lower abdominal pain, gain any weight rapidly, feel sick or are vomiting or if you 
have difficulty in breathing, talk to your doctor straight away. They might ask you to stop using this 
medicine (see in section 4. under “Most serious side effects”).

In case you are not ovulating and if the recommended dose and schedule of administration are adhered 
to, the occurrence of severe OHSS is less likely. Pergoveris treatment seldom causes severe OHSS. 
This becomes more likely if the medicine that is used for final follicular maturation (containing 
human chorionic gonadotrophin, hCG) is administered (see in section 3. under “How much to use” for 
details). If you are developing OHSS your doctor may not give you any hCG in this treatment cycle 
and you may be told not to have sex or that you should use a barrier contraceptive method for at least 
four days.
Your doctor will ensure, careful monitoring of the ovarian response, based on ultrasound and blood 
tests (oestradiol measurements) before and during the course of treatment.

Multiple pregnancy
When using Pergoveris, you have a higher risk of being pregnant with more than one child at the same 
time (“multiple pregnancy”, mostly twins), than if you conceived naturally. Multiple pregnancy may 
lead to medical complications for you and your babies. You can reduce the risk of multiple pregnancy 
by using the right dose of Pergoveris at the right times.

To minimise the risk of multiple pregnancy, ultrasound scans as well as blood tests are recommended.

Miscarriage
When undergoing stimulation of your ovaries to produce eggs, you are more likely to have a 
miscarriage than the average woman.



102

Ectopic pregnancy
Women who have ever had blocked or damaged fallopian tubes (tubal disease) are at risk of 
pregnancy where the embryo is implanted outside the womb (ectopic pregnancy). This is whether the 
pregnancy is obtained by spontaneous conception or with fertility treatments.

Blood clotting problems (thromboembolic events)
Talk to your doctor before using Pergoveris if you or a member of your family have ever had blood 
clots in the leg or in the lung, or a heart attack or stroke. You may be at a higher risk of serious blood 
clots or existing clots might become worse with Pergoveris treatment.

Tumours of sex organs
There have been reports of tumours in the ovaries and other sex organs, both benign and malignant, in 
women who have undergone multiple regimens for infertility treatment.

Allergic reactions
There have been isolated reports of non-serious allergic reactions to Pergoveris. If you have ever had 
this type of reaction to a similar medicine, talk to your doctor before using Pergoveris.

Children and adolescents
Pergoveris is not for use in children and adolescents below 18 years old.

Other medicines and Pergoveris
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Do not use Pergoveris with other medicines in the same injection. You can use Pergoveris with a 
licensed follitropin alfa preparation as separate injections, if prescribed by your doctor.

Pregnancy and breast-feeding
Do not use Pergoveris if you are pregnant or breast-feeding.

Driving and using machines
It is not expected that this medicine will affect your ability to drive or use machines.

Pergoveris contains sodium
Pergoveris contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

3. How to use Pergoveris

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Using this medicine
 Pergoveris is intended to be given by injection just under the skin (subcutaneously). To 

minimise skin irritation, select a different injection site each day. 

 Your doctor or nurse will show you how to use the Pergoveris pre-filled pen to inject the 
medicine.

 If they are satisfied that you can administer Pergoveris safely, you can then prepare and inject 
the medicine yourself at home.

 If you administer Pergoveris to yourself, please carefully read and follow section “Instructions 
for Use”.

How much to use
A treatment regimen commences with the recommended dose of Pergoveris containing 
150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa every day.



103

 According to your response, your doctor may decide to add every day a dose of a licensed 
follitropin alfa preparation to your Pergoveris injection. In this case, the follitropin alfa dose is 
usually increased every 7 or every 14 days by 37.5 to 75 IU.

 Treatment is continued until you get the desired response. This is when you have developed a 
suitable follicle, as assessed using ultrasound scans and blood tests. 

 This may take up to 5 weeks. 

When you get the desired response, you will be given a single injection of human chorionic 
gonadotropin (hCG) 24 to 48 hours after your last Pergoveris injection. The best time to have sex is 
on the day of the hCG injection and the day after. Alternatively, intrauterine insemination (IUI) may 
be performed.

If your body responds too strongly, your treatment will be stopped and you will not be given any hCG 
(see in section 2. under ”Ovarian hyperstimulation syndrome (OHSS)”). In this case, your doctor will 
give you a lower follitropin alfa dose in the following cycle.

If you use more Pergoveris than you should
The effects of an overdose of Pergoveris are unknown, nevertheless one could expect OHSS to occur. 
However this will only occur if hCG is administered (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”).

If you forget to use Pergoveris
Do not use a double dose to make up for a forgotten dose. Please contact your doctor.

If you have any further question on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects
Contact your doctor straight away if you notice any of the below listed side effects. The doctor 
might ask you to stop using Pergoveris.

Allergic reactions
Allergic reactions such as rash, red skin, hives, swelling of your face with difficulty breathing can 
sometimes be serious. This side effect is very rare.

Ovarian hyperstimulation syndrome (OHSS)
 Lower abdominal pain together with nausea or vomiting. These may be the symptoms of 

ovarian hyperstimulation syndrome (OHSS). Your ovaries may have over-reacted to the 
treatment and formed large sacs of fluid or cysts (see in section 2. under “Ovarian 
hyperstimulation syndrome (OHSS)”). This side effect is common. If this happens, your doctor 
will need to examine you as soon as possible.

 The OHSS may become severe with clearly enlarged ovaries, decreased urine production, 
weight gain, difficulty in breathing and/or possible fluid accumulation in your stomach or chest. 
This side effect is uncommon (may affect up to 1 in 100 people).

 Complications of OHSS such as twisting of ovaries or blood clotting occur rarely (may affect 
up to 1 in 1,000 people).

 Serious blood clotting problems (thromboembolic events) usually with severe OHSS are found 
very rarely. This could cause chest pain, breathlessness, stroke or heart attack. In rare cases this 
can also happen independently of OHSS (see in section 2. under “Blood clotting problems 
(thromboembolic events)”).



104

Other side effects

Very common (may affect more than 1 in 10 people):
 sacs of fluid within the ovaries (ovarian cysts)
 headache
 local reactions at the injection site such as pain, itching, bruising, swelling or irritation.

Common (may affect up to 1 in 10 people):
 diarrhoea
 breast pain
 feeling sick or vomiting
 abdominal or pelvic pain
 abdominal cramp or bloating.

Very rare (may affect up to 1 in 10,000 people):
 Your asthma may get worse.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Pergoveris

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and the carton after EXP. 
The expiry date refers to the last day of that month.

Store in a refrigerator (2°C-8°C). Do not freeze. 
Store in the original package in order to protect from light.

Once opened, the pre-filled pen may be stored for a maximum of 28 days outside of the refrigerator 
(at 25°C).

Do not use Pergoveris if you notice any visible signs of deterioration, if the liquid contains particles 
or is not clear.

After the injection, dispose of the used needle safely.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information 

What Pergoveris contains
The active substances are follitropin alfa and lutropin alfa. 

 Each pre-filled pen of Pergoveris (900 IU + 450 IU)/1.44 mL contains 900 IU (International 
Units) of follitropin alfa and 450 IU of lutropin alfa in 1.44 mL and can deliver six doses of 
Pergoveris 150 IU/75 IU.



105

The other ingredients are
 Sucrose, arginine monohydrochloride, poloxamer 188, methionine, phenol, disodium phosphate 

dihydrate, sodium dihydrogen phosphate monohydrate and water for injections. Tiny amounts 
of concentrated phosphoric acid and sodium hydroxide are added to keep acidity levels (pH 
levels) normal.

What Pergoveris looks like and contents of the pack
Pergoveris is presented as a clear, colourless to slightly yellow solution for injection in a mulitidose 
pre-filled pen: 

 Pergoveris (900 IU + 450 IU)/1.44 mL is supplied in packs of 1 multidose pre-filled pen and 
14 disposable injection needles. 

Marketing Authorisation Holder
Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands

Manufacturer
Merck Serono S.p.A, Via delle Magnolie 15 (Zona industriale), 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
Tél/Tel: +32-2-686 07 11

Lietuva
Merck Serono UAB 
Tel: +370 37320603

България
„Мерк България“ ЕАД
Teл.: +359 24461 111

Luxembourg/Luxemburg
MERCK NV/SA, Belgique/Belgien
Tél/Tel: +32-2-686 07 11

Česká republika
Merck spol.s.r.o
Tel. +420 272084211

Magyarország
Merck Kft. 
Tel: +36-1-463-8100

Danmark
Merck A/S
Tlf: +45 35253550

Malta
Vivian Corporation Ltd
Tel: +356-22-588600

Deutschland
Merck Serono GmbH
Tel: +49-6151-6285-0

Nederland
Merck BV
Tel: +31-20-6582800

Eesti
Merck Serono OÜ
Tel: +372 682 5882

Norge
Merck Serono Norge 
Tlf: +47 67 90 35 90

Ελλάδα
Merck A.E.
T: +30-210-61 65 100

Österreich
Merck GesmbH.
Tel: +43 1 57600-0

España
Merck S.L.
Línea de Información: 900 102 964
Tel: +34-91-745 44 00

Polska
Merck Sp. z o.o.
Tel.: +48 22 53 59 700



106

France
Merck Serono s.a.s.
Tél.: +33-4-72 78 25 25
Numéro vert : 0 800 888 024

Portugal
Merck, s.a.
Tel: +351-21-361 35 00

Hrvatska
Merck d.o.o,
Tel: +385 1 4864 111

România
MERCK d.o.o., Slovenia
Tel: +386 1 560 3 800

Íreland
Merck Serono Ltd, United Kingdom
Tel: +44-20 8818 7200

Slovenija
MERCK d.o.o.
Tel: +386 1 560 3 800

Ísland
Icepharma hf
Tel: + 354 540 8000

Slovenská republika
Merck spol. s r.o.
Tel: + 421 2 49 267 111

Italia
Merck Serono S.p.A.
Tel: +39-06-70 38 41

Suomi/Finland
Merck Oy
Puh/Tel: +358-9-8678 700

Κύπρος
Χρ. Γ. Παπαλοϊζου Λτδ
Τηλ.: +357 22490305

Sverige
Merck AB
Tel: +46-8-562 445 00

Latvija
Merck Serono SIA
Tel: +371 67152500

United Kingdom
Merck Serono Ltd
Tel: +44-20 8818 7200

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicine Agency web site:
http://www.ema.europa.eu.



107

Pergoveris pre-filled pen 

Instructions for Use
Contents
1. Important information about the Pergoveris pre-filled pen
2. How to use your Pergoveris pre-filled pen treatment diary
3. Gathering your supplies
4. Getting familiar with the parts of your Pergoveris pre-filled pen
5. Getting your Pergoveris pre-filled pen ready for injection
6. Setting the dose prescribed by your doctor
7. Injecting the dose
8. After the injection
9. Pergoveris pre-filled pen treatment diary (See table at the end)

Warning: Please read these instructions for use before using your Pergoveris pre-filled pen.
Follow the instructions exactly, as it may differ from your past experience.

1. Important information about the Pergoveris pre-filled pen 

 The Pergoveris pre-filled pen is for subcutaneous injection only.
 Only use the Pergoveris pre-filled pen if your healthcare provider trains you on how to 

use it correctly.

Warning: Do not reuse needles. Remove the needle immediately after each injection.
Do not share the pen and/or needles with another person, because doing so can cause an 
infection.

 The pen comes in 3 different multi-dose presentations:

 Contains 0.48 mL of Pergoveris solution
 Contains 300 IU follitropin alfa and 150 IU lutropin alfa.

 Contains 0.72 mL of Pergoveris solution
 Contains 450 IU follitropin alfa and 225 IU lutropin alfa.

 Contains 1.44 mL of Pergoveris solution
 Contains 900 IU follitropin alfa and 450 IU lutropin alfa.

Warning: Refer to the Package leaflet for more information on the recommended dose regimen and 
always follow the dose recommended by your doctor.

 The numbers in the Dose Feedback Window present the number of International Units, or IUs, 
and show the dose of follitropin alfa. Your doctor will tell you how many IUs of follitropin alfa 
to inject each day.

 The numbers displayed in the Dose Feedback Window help you to:

a. Dial your prescribed dose.



108

b. Verify a complete injection.

c. Read the dose remaining to be 
injected with a second pen.

 Give yourself the injection at the same time each day.    

 Your doctor/pharmacist will tell you how many pens of Pergoveris you need to complete your 
treatment.

2. How to use your Pergoveris pre-filled pen treatment diary

A treatment diary is included on the last page. Use the treatment diary to record the amount injected.

 Record the treatment day number (column 1), date (column 2), time of your injection (column 
3), and volume of your pen (column 4).

 Record your prescribed dose (column 5).
 Verify you dialed the right dose before injecting (column 6).
 After injection, read the number shown in the Dose Feedback Window.
 Confirm you receive a complete injection (column 7) OR record the number shown in the Dose 

Feedback Window if other than ‘’0’’ (column 8).

 When needed, inject youself using a second pen, dialing your remaining dose written in the 
“Amount to Be Set for a Second Injection” section (column 8).

 Record this remaining dose in the “Amount Set to Inject” section in the next row (column 6).

NOTE: Using your treatment diary to record your daily injection(s) allows you to verify that you 
received the full prescribed dose every day.

An example of a treatment diary using a pen:

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

#1 10/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150

if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#2 11/06 19:00 450 IU + 225 IU 150 IU/ 75IU 150
if "0",

injection complete

�if not "0", need second injection
Inject this amount ..........using new pen

#3 12/06 19:00 450 IU + 225 IU 225IU/ 112.5IU 225

�if "0",
injection complete

if not "0", need second injection
Inject this amount .75..using new pen

#3 12/06 19:00 450 IU + 225 IU N/A

75 if "0",
injection complete

�if not "0", need second injection
Inject this amount ..........using new pen



109

3. Gathering your supplies

3.1. Wash your hands with soap and water (Fig. 1).
3.2. Pepare a clean area and a flat surface, such as a table 

or countertop, in a well-lit area.
3.3. Select your Pergoveris pre-filled pen.

Fig. 1
3.4. Verify you select the prescribed pen.

3.5. Verify the expiration date on the pen label (Fig. 2).

Fig.2 
3.6. You will also need:

 Needles (included in the pack)
 Alcohol swabs (not included in the pack)
 A sharps disposal bin (not included in the pack)

4. Getting familiar with the parts of your Pergoveris pre-filled pen

* The numbers on the Dose Feedback Window and reservoir holder represent the number of 
International Units (IU) of medication.



110

5. Getting your Pergoveris pre-filled pen ready for injection

5.1. Take off the pen cap.
5.2. Verify that the Dose Feedback Window is set to "0".

5.3. Prepare your needle. 

 Get a new needle - only use the "single-use" needles 
supplied.

 Hold the outer needle cap firmly.
 Check that the peel-off seal on the outer needle cap is not 

damaged or loose (Fig.3).

Fig. 3

 Remove the peel-off seal (Fig. 4).

Fig. 4

Caution: If the peel-off seal is damaged or loose, do not use the needle. Throw it away in a 
sharps disposal container. Get a new needle.

5.4. Attach the needle.

 Screw the threaded tip of the Pergoveris pre-filled pen into the 
outer needle cap until you feel a light resistance.

Caution: Do not attach the needle too tightly; the needle could be 
difficult to remove after the injection.

 Remove the outer needle cap by pulling it gently.

 Put it aside for later use. DO NOT discard it.

 Hold the Pergoveris pre-filled pen with the needle pointing 
upward.

 Carefully remove and discard the green inner shield.

Warning: Do not recap the needle with the green inner shield, as it 
can lead to needle stick.



111

5.5. Check for a droplet of liquid at the tip of the needle.

 Look closely at the tip of the needle for tiny drop(s) of fluid.

IF THEN

Using a new pen Check for a droplet of liquid at the tip of 
the needle.

 If you see a droplet, proceed to 
Section 6: Setting the dose 
prescribed by your doctor.

 If no droplet is seen, follow the 
instructions on the following page.

Reusing a pen It is NOT required to check for a droplet of 
liquid.
Proceed directly to Section 6: Setting the 
dose prescribed by your doctor.

If you do not see a tiny drop(s) of fluid at or near the tip the first time you use a new pen:

Fig. 5

3. Gently turn the dose setting knob clockwise until it reads 25 in the Dose Feedback Window. 
You can turn the dose knob backwards if you turn it past 25 (Fig. 5).

Fig. 6 Fig.7 Fig.8

2 Hold the pen with the needle pointing upward.
3 Tap the reservoir holder gently (Fig. 6).
4 Press the dose setting knob as far as it will go. A tiny drop of liquid will appear at the tip of the 

needle (Fig. 7).
5. Verify that the Dose Feedback Window reads "0" (Fig. 8).
6. Proceed to Section 6: Setting the dose prescribed by your doctor.



112

6. Setting the dose prescribed by your doctor

6.1. Turn the dose setting knob until your intended dose shows in the Dose Feedback Window.

 Turn the dose setting knob forward to dial up 
according to the dose that was prescribed by your 
doctor.

 If needed, turn the dose setting knob backward 
to correct the dose.

Warning: Check that the Dose Feedback Window displays your complete prescribed dose before 
you move on to the next step.

7. Injecting the dose

7.1. Choose an injection site in the area your doctor or nurse has told you to use for the injection. To 
minimize skin irritation, select a different injection site each day.

7.2. Wipe the skin with an alcohol swab.
7.3. Verify once more that the Dose Feedback Window

displays the correct dose.

7.4. Inject the dose as you were trained to do by your 
doctor or nurse.

 Slowly push the needle into the skin entirely 
(Fig.9).

 Slowly press the dose knob down as far as it will 
go and hold it to complete the full injection.

Fig. 9

 Hold the dose knob down for a minimum of 5 
seconds to ensure you inject the full dose (Fig. 10). 

 The dose number shown in the Dose Feedback 
Window will turn back to 0.

Fig. 10

 After a minimum of 5 seconds, pull the needle out 
of the skin while keeping the dose setting knob 
pressed down (Fig. 11).

 When the needle is out of the skin, release the dose 
setting knob.

Fig. 11
Caution: Do not release the dose knob until you remove 

the needle from the skin.



113

Warning: Always make sure to use a new needle for each injection.

8. After the injection

8.1. Verify you have given a complete injection.

 Check that the Dose Feedback Window shows 
“0”.

Warning: If the Dose Feedback Window shows a number higher than 0, the Pergoveris pre-filled 
pen is empty and you have not received your full prescribed dose.

8.2. Complete a partial injection (only when needed).

 The Dose Feedback Window will indicate the 
missing amount you need to inject using a new 
pen.

 Repeat Section 4 (Getting familiar with your Pergoveris pre-filled pen) through Section 5 
(Getting your Pergoveris pre-filled pen ready for injection) with a second pen.

 Set the dose to the missing amount you recorded in the treatment diary OR the number still 
displayed in the Dose Feedback Window on your previous pen, and inject.

8.3. Removing the needle after each injection.

 Place the outer needle cap on a flat surface.
 Hold the Pergoveris pre-filled pen firmly with one hand, and 

slip the needle into the outer needle cap.

 Continue by pushing the capped needle against a firm surface 
until you hear a “click”.

 Grip the outer needle cap and 
unscrew the needle by turning anti-
clockwise.
Dispose of the used needle safely.

 Recap the pen.

Warning: Never reuse any used needle. Never share needles.

8.4. Storing the Pergoveris pre-filled pen.

Caution: Never store the pen with the needle still attached. 
Always remove the needle from the Pergoveris pre-
filled pen before replacing the pen cap.

 Store the pen in its original packaging in a safe place and as indicated in the package leaflet.
 When the pen is empty, ask your pharmacist how to dispose of it.



114

Warning: Medicine should not be disposed of via wastewater or household waste.

9. Pergoveris pre-filled pen treatment diary

1
Treatment

Day
Number

2
Date

3
Time

4
Pen Volume

5
Prescribed

Dose

6 7 8

Dose Feedback Window

Amount Set 
to Inject

Amount to Be Set for a Second Injection

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen -

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

/ :
�if "0",

injection complete
�if not "0", need second injection

Inject this amount ..........using new pen

This instructions for use was last revised in:


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET