Follitropin alfa parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Solution for injection containing follitropin alfa
These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.
Drugs List
Therapeutic Indications
Uses
Anovulation unresponsive to clomifene citrate
Controlled superovulation in medically assisted conception programmes
Stimulation of follicular development (+LH) in severe LH & FSH deficiency
Stimulation of spermatogenesis with concomitant hCG therapy in hypogonadism
Dosage
Adults
Women with anovulation (including polycystic ovarian syndrome)
In menstruating patients, treatment should start within first 7 days of the menstrual cycle.
Treatment should be determined by individual response as assessed by measuring follicle size by ultrasound and/or oestrogen secretion. A commonly used regimen commences at 75 to 150 units daily increasing by 37.5 units or 75 units at 7 or preferably 14 day intervals if necessary to obtain an adequate, but not excessive response. The maximum daily dose is not usually higher than 225 units of FSH. If no response after 4 weeks of treatment, that cycle should be abandoned and the patient should recommence treatment after evaluation at a higher starting dose than in the abandoned cycle.
When an optimal response is obtained, a single injection of 250 micrograms of recombinant hCG (r-hCG) or 5,000 units up to 10,000 units of hCG should be administered 24 to 48 hours after the last follitropin alfa injection. The patient is recommended to have coitus on the day of, and the day following, hCG administration. Alternatively, intrauterine insemination (IUI) may be performed.
If an excessive response is obtained, discontinue treatment, withhold hCG, and recommence in the next cycle at a lower dose.
Women undergoing ovarian stimulation for multiple follicular development prior to in vitro fertilisation or other assisted reproductive technologies
A commonly used regimen for superovulation involves the administration of 150 to 225 units of follitropin alfa daily, commencing on day 2 or 3 of the cycle. Treatment is continued until adequate follicular development has been achieved (as assessed by monitoring of serum oestrogen concentrations and/or ultrasound examination), with the dose adjusted according to the patient's response, to usually not higher than 450 units daily. In general, adequate follicular development is usually achieved on average by the tenth day of treatment (range of 5 to 20 days).
A single injection of 250 micrograms of recombinant hCG (r-hCG) or 5,000 units up to 10,000 units of hCG is administered 24 to 48 hours after the last injection to induce final follicular maturation.
Down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist is now commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. In a commonly used protocol, follitropin alfa is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved. For example, following 2 weeks of treatment with an agonist, 150 to 225 units follitropin alfa are administered for the first 7 days. The dose is then adjusted according to the ovarian response.
Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.
Women with anovulation resulting from severe LH and FSH deficiency
In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of follitropin alfa therapy in association with lutropin alfa is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotrophin (hCG). Follitropin alfa should be given as a course of daily injections simultaneously with lutropin alfa. 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 at 75 units of lutropin alfa daily with 75 to 150 units FSH.
If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7 to 14 day intervals and preferably by 37.5 to 75 unit increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.
When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 units up to 10,000 units of hCG should be administered 24 to 48 hours after the last follitropin alfa and lutropin alfa injections. 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.
Men with hypogonadotrophic hypogonadism
The recommended dose is 150 units three times a week in combination with hCG for at least 4 months. If no response is seen after this time treatment may be continued. Current clinical experience indicates that treatment may need to be continued for at least 18 months to achieve spermatogenesis.
Administration
For subcutaneous injection.
Contraindications
Uterine cancer
Breast cancer
Breastfeeding
Hypothalamic neoplasm
Non-polycystic ovarian cyst
Non-polycystic ovarian enlargement
Ovarian carcinoma
Pituitary neoplasm
Pregnancy
Primary ovarian failure
Primary testicular failure
Undiagnosed gynaecological haemorrhage
Uterine fibroids
Precautions and Warnings
Family history of porphyria
Predisposition to thromboembolic disease
Adrenal insufficiency
Hyperprolactinaemia
Hypothyroidism
Polycystic ovarian syndrome
Porphyria
Thromboembolic disorder
Treat other endocrine disorders and causes of infertility first
Treatment to be initiated and supervised by a specialist
May contain polysorbate
Some formulations contain metacresol
Some presentations may contain benzyl alcohol
Self-admin. - only if adequately trained and have access to expert advice
Exclude other causes of infertility before commencing treatment
Monitor ovarian response using ultrasound prior to and during treatment
If pregnancy occurs possibility of ectopic pregnancy should be considered
Monitor closely patient with porphyria during therapy
Monitor estradiol levels during treatment
Semen analysis recommended after 4 to 6 months of treatment
Consider discontinuation if first occurrence/worsening of porphyria occurs
Ovarian hyperstimulation syndrome can occur
Pregnancy: Increased risk of multiple pregnancies
Discontinue immediately if ovarian hyperstimulation occurs
In cases of OHSS withhold hCG & use barrier contraception for 4 days
Maintain treatment at the lowest effective dose
Females
Ovarian hyperstimulation syndrome (OHSS) may be caused by administration of human chorionic gonadotropin (hCG) and by pregnancy (endogenous hCG).
Ovarian hyperstimulation syndrome (OHSS) can rapidly progress (24 hours to several days) to become a serious medical event, therefore patients should be followed for at least 2 weeks after human chorionic gonadotropin (hCG) administration. The possibility of ovarian hyperstimulation must be taken into consideration in women presenting with pain in the lower abdominal region, possibly in combination with dyspnoea, oliguria, nausea, vomiting, diarrhoea, weight gain and mild to moderate enlargement of ovaries and ovarian cysts.
In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.
Ectopic pregnancy may occur in women with a history of prior tubal disease.
Males
Elevated endogenous FSH levels in men are indicative of primary testicular failure. These patients are unresponsive to follitropin/hCG therapy.
Pregnancy and Lactation
Pregnancy
Follitropin alfa is not indicated in pregnancy.
If inadvertent exposure of follitropin alfa occurs during pregnancy, clinical data are insufficient to rule out an adverse outcome occurring. No specific malformative effects have been observed during pregnancy. No teratogenic effect has been observed in animal studies.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Follitropin alfa is not indicated in breastfeeding.
The high molecular weight of follitropin means that it is unlikely to be secreted into breast milk. If secreted into breast milk, its low oral bioavailability suggests that there would be no adverse effect on the infant. However, follitropin may affect milk production.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal cramps
Abdominal discomfort
Abdominal distension
Abdominal pain
Acne
Anaphylactic reaction
Bloating
Breathing difficulties
Bruising at injection site
Diarrhoea
Erythema
Exacerbation of pre-existing asthma
Facial swelling
Fever
Gastro-intestinal symptoms
Gynaecomastia
Headache
Hypersensitivity reactions
Increased risk of ectopic pregnancy
Increased risk of miscarriage
Increased risk of multiple pregnancy
Irritation (injection site)
Joint pain
Local pain (injection site)
Local reaction at injection site
Nausea
Oedema
Ovarian cysts
Ovarian hyperstimulation
Ovarian torsion
Rash
Shock
Swelling (injection site)
Thromboembolic disorders
Urticaria
Varicocele
Vomiting
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Bemfola 75 IU/0.125 ml injection solution in pre-filled pen. FINOX Biotech AG. Revised March 2014.
Summary of Product Characteristics: Bemfola 150 IU/0.25 ml injection solution in pre-filled pen. FINOX Biotech AG. Revised March 2014.
Summary of Product Characteristics: Bemfola 225 IU/0.375 ml injection solution in pre-filled pen. FINOX Biotech AG. Revised March 2014.
Summary of Product Characteristics: Bemfola 300 IU/0.5 ml injection solution in pre-filled pen. FINOX Biotech AG. Revised March 2014.
Summary of Product Characteristics: Bemfola 450 IU/0.75 ml injection solution in pre-filled pen. FINOX Biotech AG. Revised March 2014.
Summary of Product Characteristics: Gonal-f 75 IU (5.5 micrograms). Merck Serono. Revised April 2014.
Summary of Product Characteristics: Gonal-f 450 IU/0.75 ml (33 mcg / 0.75 ml). Merck Serono. Revised April 2014.
Summary of Product Characteristics: Gonal-f 1050 IU/1.75 ml (77 mcg / 1.75ml). Merck Serono. Revised April 2014.
Summary of Product Characteristics: Gonal-f 300 IU (22 mcg) pen. Merck Serono. Revised April 2014.
Summary of Product Characteristics: Gonal-f 450 IU (33 mcg) pen. Merck Serono. Revised April 2014.
Summary of Product Characteristics: Gonal-f 900 IU (66 mcg) pen. Merck Serono. Revised April 2014.
Summary of Product Characteristics: Ovaleap 300 IU/0.5 mL solution for injection. Teva. Revised September 2014.
Summary of Product Characteristics: Ovaleap 450 IU/0.75 mL solution for injection. Teva. Revised September 2014.
Summary of Product Characteristics: Ovaleap 900 IU/1.5 mL solution for injection. Teva. Revised September 2014.
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