Drugs List

Therapeutic Indications

Uses

Anovulation unresponsive to clomifene citrate
Controlled superovulation in medically assisted conception programmes

Administration

For subcutaneous or intramuscular injection only.
Not all brands are licensed for both routes of administration.
Self-administration (subcutaneous route only) of urofollitropin should only be performed by patients who are well-motivated, adequately trained and with access to expert advice.

Contraindications

Uterine cancer
Breast cancer
Breastfeeding
Hypothalamic neoplasm
Non-polycystic ovarian cyst
Ovarian carcinoma
Pituitary neoplasm
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Predisposition to thromboembolic disease
Polycystic ovarian syndrome

Treat other endocrine disorders and causes of infertility first
Treatment to be prescribed under the supervision of a specialist
Rotate injection sites to minimise the risk of lipoatrophy
Self-admin. - only if adequately trained and have access to expert advice
Use only if the solution is clear and colourless
Exclude other causes of infertility before commencing treatment
Monitor ovarian response using ultrasound prior to and during treatment
Close medical supervision during initial dosing
Examine patients complaining of abdominal/pelvic pain for ovarian cysts
Monitor urinary oestrogens, plasma estradiol + follicle diameter in women
Pregnancy: Increased risk of multiple pregnancies
Discontinue immediately if ovarian hyperstimulation occurs
In cases of OHSS withhold hCG & use barrier contraception for 4 days

Patients undergoing stimulation of follicular growth are at increased risk of developing ovarian hyperstimulation. Adherence to recommended dosage and regimen of administration, and careful monitoring of therapy will minimise the incidence of such events. 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 serious, but rare cases, an ovarian hyperstimulation syndrome with clearly enlarged ovaries, can go hand in hand with possible accumulation of fluid in the abdomen or thorax as well as more serious thromboembolic complications. Should the above mentioned symptoms occur a careful medical and ultrasound examination is indicated. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events. Very rarely, severe OHSS may be complicated by pulmonary embolism, myocardial infarction and ischaemic stroke.

OHSS may be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum at about 7 to 10 days following treatment. Usually OHSS resolves spontaneously with the onset of menses.

If severe OHSS occurs, gonadotrophin treatment should be stopped if still ongoing, the patient hospitalised and specific therapy for OHSS started.

In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.

The risk of multiple pregnancy following assisted reproductive technologies is related to the number of oocytes/embryos replaced, their quality and the patient age. 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.

Ectopic pregnancy may occur in women with a history of prior tubal disease.

The incidence of spontaneous miscarriage is higher in patients treated with FSH than in the general population, but it is comparable to the incidence found in women with other fertility problems.

Pregnancy and Lactation

Pregnancy

Urofollitropin contraindicated in pregnancy.

Animal experiments do not reveal teratogenicity, and at the time of writing there are no sufficient studies on pregnancy in humans. Schaefer (2007) considers that inadvertent exposure during pregnancy is not an indication for invasive diagnostic procedures or termination.

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

Urofollitropin is contraindicated in lactation.

No paediatric concerns reported via milk. FSH is very unlikely to penetrate milk, and it would not be orally bioavailable. However, observe closely for reduced milk production (Medications and Mothers' Milk, 2014).

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 pain
Acne
Arthralgia
Ascites
Bloating
Breast tenderness
Constipation
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Exacerbation of pre-existing asthma
Facial swelling
Fatigue
Fever
Gastro-intestinal symptoms
Headache
Hot flushes
Hypersensitivity reactions
Hyperthyroidism
Hypovolaemia
Increased risk of ectopic pregnancy
Increased risk of multiple pregnancy
Joint pain
Lethargy
Local reaction at injection site
Miscarriage
Mood changes
Muscle spasm
Nasopharyngitis
Nausea
Oedema
Ovarian cysts
Ovarian enlargement
Ovarian hyperstimulation syndrome (OHSS)
Ovarian torsion
Pleural effusion
Pruritus
Rash
Shock
Thromboembolic disorders
Urinary tract infections
Urticaria
Vaginal discharge
Vaginal haemorrhage
Vomiting
Weight gain

Presentation

Solution for injection containing urofollitropin (follicle stimulating hormone)

Drugs List

Therapeutic Indications

Uses

Anovulation unresponsive to clomifene citrate
Controlled superovulation in medically assisted conception programmes

Dosage

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

Adults

Administration

For subcutaneous or intramuscular injection only.
Not all brands are licensed for both routes of administration.
Self-administration (subcutaneous route only) of urofollitropin should only be performed by patients who are well-motivated, adequately trained and with access to expert advice.

Contraindications

Uterine cancer
Breast cancer
Breastfeeding
Hypothalamic neoplasm
Non-polycystic ovarian cyst
Ovarian carcinoma
Pituitary neoplasm
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Predisposition to thromboembolic disease
Polycystic ovarian syndrome

Treat other endocrine disorders and causes of infertility first
Treatment to be prescribed under the supervision of a specialist
Rotate injection sites to minimise the risk of lipoatrophy
Self-admin. - only if adequately trained and have access to expert advice
Use only if the solution is clear and colourless
Exclude other causes of infertility before commencing treatment
Monitor ovarian response using ultrasound prior to and during treatment
Close medical supervision during initial dosing
Examine patients complaining of abdominal/pelvic pain for ovarian cysts
Monitor urinary oestrogens, plasma estradiol + follicle diameter in women
Pregnancy: Increased risk of multiple pregnancies
Discontinue immediately if ovarian hyperstimulation occurs
In cases of OHSS withhold hCG & use barrier contraception for 4 days

Patients undergoing stimulation of follicular growth are at increased risk of developing ovarian hyperstimulation. Adherence to recommended dosage and regimen of administration, and careful monitoring of therapy will minimise the incidence of such events. 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 serious, but rare cases, an ovarian hyperstimulation syndrome with clearly enlarged ovaries, can go hand in hand with possible accumulation of fluid in the abdomen or thorax as well as more serious thromboembolic complications. Should the above mentioned symptoms occur a careful medical and ultrasound examination is indicated. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events. Very rarely, severe OHSS may be complicated by pulmonary embolism, myocardial infarction and ischaemic stroke.

OHSS may be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum at about 7 to 10 days following treatment. Usually OHSS resolves spontaneously with the onset of menses.

If severe OHSS occurs, gonadotrophin treatment should be stopped if still ongoing, the patient hospitalised and specific therapy for OHSS started.

In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.

The risk of multiple pregnancy following assisted reproductive technologies is related to the number of oocytes/embryos replaced, their quality and the patient age. 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.

Ectopic pregnancy may occur in women with a history of prior tubal disease.

The incidence of spontaneous miscarriage is higher in patients treated with FSH than in the general population, but it is comparable to the incidence found in women with other fertility problems.

Pregnancy and Lactation

Pregnancy

Urofollitropin contraindicated in pregnancy.

Animal experiments do not reveal teratogenicity, and at the time of writing there are no sufficient studies on pregnancy in humans. Schaefer (2007) considers that inadvertent exposure during pregnancy is not an indication for invasive diagnostic procedures or termination.

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

Urofollitropin is contraindicated in lactation.

No paediatric concerns reported via milk. FSH is very unlikely to penetrate milk, and it would not be orally bioavailable. However, observe closely for reduced milk production (Medications and Mothers' Milk, 2014).

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 pain
Acne
Arthralgia
Ascites
Bloating
Breast tenderness
Constipation
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Epistaxis
Erythema
Exacerbation of pre-existing asthma
Facial swelling
Fatigue
Fever
Gastro-intestinal symptoms
Headache
Hot flushes
Hypersensitivity reactions
Hyperthyroidism
Hypovolaemia
Increased risk of ectopic pregnancy
Increased risk of multiple pregnancy
Joint pain
Lethargy
Local reaction at injection site
Miscarriage
Mood changes
Muscle spasm
Nasopharyngitis
Nausea
Oedema
Ovarian cysts
Ovarian enlargement
Ovarian hyperstimulation syndrome (OHSS)
Ovarian torsion
Pleural effusion
Pruritus
Rash
Shock
Thromboembolic disorders
Urinary tract infections
Urticaria
Vaginal discharge
Vaginal haemorrhage
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: February 2015

Reference Sources

Summary of Product Characteristics: Fostimon 75 IU and 150 IU powder and solvent for solution for injection. IBSA Farmaceutici Italia S.r.l. Revised June 2012.

Summary of Product Characteristics: Bravelle 75 IU powder and solvent for solution for injection. Ferring Pharmaceuticals Ltd. Revised November 2011.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed 07 February 2015.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed 07 February 2015.

Medications and Mother's Milk, 12th edition (2014) Hale, T.W. Hale Publishing, Amarillo, Texas.