Drugs List

Contraindications

Children under 18 years
Undiagnosed gynaecological bleeding
Breastfeeding
Pregnancy - exclude pregnancy before use - see Pregnancy section

Precautions and Warnings

Metabolic bone disease.

A small loss of trabecula bone mineral content occurs during 6 months of treatment. Although this is mainly reversible within 6 months of stopping treatment, there are no data on the effect of repeat courses on bone loss. Retreatment or use for longer than 6 months is therefore contraindicated.

Bone mineral density should be assessed before retreatment after a course of therapy if further treatment of endometriosis and fibroids is contemplated.

Exclude pregnancy prior to commencing treatment and advise patients to use non-hormonal barrier methods of contraception.

Nafarelin inhibits ovulation, however breakthrough ovulation and a potential for conception may occur if doses are missed. Discontinue if pregnancy occurs and inform patient of potential risk to foetal development.

Nafarelin treatment must be stopped at least 3 days before fertilised embryos are placed in the uterine cavity.

There is an increased risk of incident depression, which may be severe. Patients should be informed accordingly and treated as appropriate if required.

Ovarian cysts have been reported to occur in the first two months of therapy with nafarelin; many of these events have occurred in patients with polycystic ovarian disease. These cyst enlargements may resolve spontaneously, generally by about four to six weeks of therapy, but occasionally require discontinuation of the drug and/or surgical intervention.

In controlled ovarian stimulation prior to in vitro fertilisation, transient ovarian cyst formation is a recognised complication of GnRH agonist use. These cysts tend to progress spontaneously over a number of weeks and are more common when GnRH agonists are commenced in the follicular phase of the cycle.

Use with caution in patients with polycystic ovarian syndrome as they are greater risk of excessive follicular recruitment when undergoing ovulation induction regimes.

Suppression of the pituitary-gonadal system occurs with administration of nafarelin. Normal function is usually restored within 8 weeks after discontinuation. Diagnostic tests of pituitary gonadal function conducted during treatment and up to 8 weeks after discontinuation of therapy may be misleading.

Sneezing during or immediately after dosing may impair absorption of nafarelin. If sneezing occurs upon administration, repeating the dose, may be advisable.

If the use of a nasal decongestant is required at the time of nafarelin administration, administer 30 minutes after nafarelin dose.

Contains benzalkonium chloride which may cause contractions of the respiratory passage. It may cause oedema in the nasal mucosa, especially on long term use.

Pregnancy and Lactation

Pregnancy

Contraindicated as the safety in human pregnancy has not been established. Exclude pregnancy before commencing treatment.
Should pregnancy occur, therapy should be discontinued and the woman informed of the potential risk to foetal development.
Non hormonal barrier methods of contraception should be employed during therapy.

Animal studies in rats have shown dose related foetal mortality and a decrease in foetal weight when administered intramuscularly. These effects on rat foetal mortality are logical consequences of the alterations in hormonal levels brought about by nafarelin in this species.
Use of nafarelin in human pregnancy has not been studied.

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 14-17 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

Contraindicated as it is not known whether or to what extent nafarelin is secreted in the breast milk.

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

Hypersensitivity reactions
Dyspnoea
Chest pain
Urticaria
Rash
Pruritus
Hot flushes
Changes in libido
Vaginal dryness
Headache
Migraine
Emotional lability
Acne
Myalgia
Changes in breast size
Irritation of nasal mucosa
Palpitations
Depression
Ovarian cysts
Decrease in trabecular bone density
Increases in serum transaminases (reversible)
Increase in serum alkaline phosphatase (reversible)
Paraesthesia
Blurred vision
Alopecia
Weight gain
Weight loss
Insomnia
Hypertension
Hypotension
Rhinitis
Seborrhoea
Hirsutism
Arthralgia
Menopausal-like symptoms
Uterine haemorrhage
Oedema
Oestrogen deficiency

Drugs List

Dosage

Adults

Elderly

Children

Additional Dosage Information

Contraindications

Children under 18 years
Undiagnosed gynaecological bleeding
Breastfeeding
Pregnancy - exclude pregnancy before use - see Pregnancy section

Precautions and Warnings

Metabolic bone disease.

A small loss of trabecula bone mineral content occurs during 6 months of treatment. Although this is mainly reversible within 6 months of stopping treatment, there are no data on the effect of repeat courses on bone loss. Retreatment or use for longer than 6 months is therefore contraindicated.

Bone mineral density should be assessed before retreatment after a course of therapy if further treatment of endometriosis and fibroids is contemplated.

Exclude pregnancy prior to commencing treatment and advise patients to use non-hormonal barrier methods of contraception.

Nafarelin inhibits ovulation, however breakthrough ovulation and a potential for conception may occur if doses are missed. Discontinue if pregnancy occurs and inform patient of potential risk to foetal development.

Nafarelin treatment must be stopped at least 3 days before fertilised embryos are placed in the uterine cavity.

There is an increased risk of incident depression, which may be severe. Patients should be informed accordingly and treated as appropriate if required.

Ovarian cysts have been reported to occur in the first two months of therapy with nafarelin; many of these events have occurred in patients with polycystic ovarian disease. These cyst enlargements may resolve spontaneously, generally by about four to six weeks of therapy, but occasionally require discontinuation of the drug and/or surgical intervention.

In controlled ovarian stimulation prior to in vitro fertilisation, transient ovarian cyst formation is a recognised complication of GnRH agonist use. These cysts tend to progress spontaneously over a number of weeks and are more common when GnRH agonists are commenced in the follicular phase of the cycle.

Use with caution in patients with polycystic ovarian syndrome as they are greater risk of excessive follicular recruitment when undergoing ovulation induction regimes.

Suppression of the pituitary-gonadal system occurs with administration of nafarelin. Normal function is usually restored within 8 weeks after discontinuation. Diagnostic tests of pituitary gonadal function conducted during treatment and up to 8 weeks after discontinuation of therapy may be misleading.

Sneezing during or immediately after dosing may impair absorption of nafarelin. If sneezing occurs upon administration, repeating the dose, may be advisable.

If the use of a nasal decongestant is required at the time of nafarelin administration, administer 30 minutes after nafarelin dose.

Contains benzalkonium chloride which may cause contractions of the respiratory passage. It may cause oedema in the nasal mucosa, especially on long term use.

Pregnancy and Lactation

Pregnancy

Contraindicated as the safety in human pregnancy has not been established. Exclude pregnancy before commencing treatment.
Should pregnancy occur, therapy should be discontinued and the woman informed of the potential risk to foetal development.
Non hormonal barrier methods of contraception should be employed during therapy.

Animal studies in rats have shown dose related foetal mortality and a decrease in foetal weight when administered intramuscularly. These effects on rat foetal mortality are logical consequences of the alterations in hormonal levels brought about by nafarelin in this species.
Use of nafarelin in human pregnancy has not been studied.

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 14-17 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

Contraindicated as it is not known whether or to what extent nafarelin is secreted in the breast milk.

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

Counselling

Advise women of the need for non-hormonal barrier contraception during treatment.

Advise patients to administer other nasal preparations at least 30 minutes after nafarelin dose.

Advise patients to repeat dose if sneezing occurs during or immediately after dosing.

Advise patients to report new or worsening symptoms of depression to their doctor.

Side Effects

Hypersensitivity reactions
Dyspnoea
Chest pain
Urticaria
Rash
Pruritus
Hot flushes
Changes in libido
Vaginal dryness
Headache
Migraine
Emotional lability
Acne
Myalgia
Changes in breast size
Irritation of nasal mucosa
Palpitations
Depression
Ovarian cysts
Decrease in trabecular bone density
Increases in serum transaminases (reversible)
Increase in serum alkaline phosphatase (reversible)
Paraesthesia
Blurred vision
Alopecia
Weight gain
Weight loss
Insomnia
Hypertension
Hypotension
Rhinitis
Seborrhoea
Hirsutism
Arthralgia
Menopausal-like symptoms
Uterine haemorrhage
Oedema
Oestrogen deficiency

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: December 2012

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

Summary of Product Characteristics: Synarel Nasal Spray. Pharmacia Ltd. Revised July 2012.