The effects of an overdose of follitropin alfa are unknown, nevertheless, there is a possibility that OHSS may occur.
3 years
Not applicable.
Poloxamer 188
Sucrose
Methionine
Disodium hydrogen phosphate dihydrate
Sodium dihydrogen phosphate dihydrate
Phosphoric acid
Water for injections
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 ovarian hyperstimulation syndrome (OHSS) has been commonly reported and should be considered as an intrinsic risk of the stimulation procedure. Severe OHSS is uncommon.
Thromboembolism may occur very rarely.
List of adverse reactions
The following definitions apply to the frequency terminology used hereafter:
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).
Treatment in women
| 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 (both in association with and separate from 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: | Mild or moderate OHSS (including associated symptomatology) |
| Uncommon: | Severe OHSS (including associated symptomatology) |
| Rare: | Complication of severe OHSS |
| General disorders and administration site conditions | |
| Very common: | Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection) |
| Treatment in men Immune system disorders | |
| Very rare: | Mild to severe hypersensitivity reactions including anaphylactic reactions and shock |
| Respiratory, thoracic and mediastinal disorders | |
| Very rare: | Exacerbation or aggravation of asthma |
| Skin and subcutaneous tissue disorders | |
| Common: | Acne |
| Reproductive system and breast disorders | |
| Common: | Gynaecomastia, Varicocele |
| General disorders and administration site conditions | |
| Very common: | Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection) |
| Investigations | |
| Common: | Weight gain |
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 MHRA Yellow Card Scheme (www.mhra.gov.uk/yellowcard).
Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity and genotoxicity in addition to those already stated in the other sections of this SmPC.
Impaired fertility has been reported in rats exposed to pharmacological doses of follitropin alfa (> 40 IU/kg/day) for extended periods, through reduced fecundity.
Given in high doses (> 5 IU/kg/day) follitropin alfa caused a decrease in the number of viable foetuses without being teratogenic, and dystocia similar to that observed with urinary menopausal gonadotropin (hMG). However, since Bemfola is not indicated in pregnancy, these data are of limited clinical relevance.
Pharmacotherapeutic group: Sex hormones and modulators of the genital systems, gonadotropins, ATC code: G03GA05.
Bemfola is a biosimilar medicinal product, that has been demonstrated to be similar in quality, safety and efficacy to the reference medicinal product GONAL-f. Detailed information is available on the website of the European Medicines Agency http://www.ema.europa.eu.
Pharmacodynamic effects
In women, the most important effect resulting from parenteral administration of FSH is the development of mature Graafian follicles. In women with anovulation, the objective of therapy with follitropin alfa is to develop a single mature Graafian follicle from which the ovum will be liberated after the administration of hCG.
Clinical efficacy and safety in women
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 clinical studies comparing r-hFSH (follitropin alfa) and urinary FSH in ART (see table 1 below) and in ovulation induction, follitropin alfa was more potent than urinary FSH in terms of a lower total dose and a shorter treatment period needed to trigger follicular maturation.
In ART, follitropin alfa at a lower total dose and shorter treatment period than urinary FSH, resulted in a higher number of oocytes retrieved when compared to urinary FSH.
Table 1: Results of study GF 8407 (randomised parallel group study comparing efficacy and safety of follitropin alfa with urinary FSH in assisted reproduction technologies)
|
follitropin alfa (n = 130) |
urinary FSH (n = 116) | |
|
Number of oocytes retrieved |
11.0 ± 5.9 |
8.8 ± 4.8 |
|
Days of FSH stimulation required |
11.7 ± 1.9 |
14.5 ± 3.3 |
|
Total dose of FSH required (number of FSH 75 IU ampoules) |
27.6 ± 10.2 |
40.7 ± 13.6 |
|
Need to increase the dose (%) |
56.2 |
85.3 |
Differences between the 2 groups were statistically significant (p< 0.05) for all criteria listed.
Clinical efficacy and safety in men
In men deficient in FSH, follitropin alfa administered concomitantly with hCG for at least 4 months induces spermatogenesis.
Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space with an initial half-life of around 2 hours and is eliminated from the body with a terminal half-life of about one day. The steady state volume of distribution and total clearance are 10 L and 0.6 L/h, respectively. One-eighth of the follitropin alfa dose is excreted in the urine.
Following subcutaneous administration, the absolute bioavailability is about 70%. Following repeated administration, follitropin alfa accumulates 3-fold achieving a steadystate within 3-4 days. In women whose endogenous gonadotropin secretion is suppressed, follitropin alfa has nevertheless been shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH levels.
09/08/2017
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary
Store in a refrigerator (2°C - 8°C). Do not freeze.
Before opening and within its shelf life, the medicinal product may be removed from the refrigerator, and without being refrigerated again, may be stored for up to 3 months at or below 25°C. The product must be discarded if it has not been used after 3 months.
Store in the original package in order to protect from light.
0.25 mL of solution for injection in 1.5 mL cartridge (type I glass), with a plunger stopper (halobutyl rubber) and an aluminium crimp cap with a rubber inlay.
Pack sizes of 1, 5 and 10 pre-filled pens. Not all pack sizes may be marketed. One needle and one alcohol swab to be used with the pen for administration.
EU/1/13/909/002
EU/1/13/909/008
EU/1/13/909/009
Pregnancy
There is no indication for use of Bemfola during pregnancy. Data on a limited number of exposed pregnant women (less than 300 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity of follitropin alfa.
No teratogenic effect has been observed in animal studies. In case of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of follitropin alfa.
Breast-feeding
Bemfola is not indicated during breastfeeding.
Fertility
Bemfola is indicated for use in infertility.
Bemfola is expected to have no or negligible influence on the ability to drive and use machines.
See the package leaflet.
The solution should not be administered if it contains particles or is not clear.
Bemfola 150 IU/0.25 mL (11 micrograms/0.25 mL) is not designed to allow the cartridge to be removed.
Discard used pen and needle immediately after injection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Date of first authorisation: 27/03/2014
