Drugs List

Therapeutic Indications

Uses

Contraception - injectable

Intended for short term contraception when a high level of efficacy independent of possible patient errors is required, for example:
Short term depot contraception for women whose partners undergo vasectomy, to prevent pregnancy until the vasectomy is effective.
Short term depot contraception for women immunised against rubella, to prevent pregnancy during the period of virus activity.

Administration

For intramuscular injection into the gluteal muscles.

No liquid should run back from the injection site as efficacy may be impaired.

At low temperatures the injection solution viscosity is high and this requires considerable injection pressure. It is therefore recommended that the ampoule is immersed in warm water before injection. A medium bore needle should be used and fastened securely to the syringe.

Contraindications

Suspected breast cancer
Suspected endometrial cancer
Abnormal liver function test
Breast cancer
Disorder of lipid metabolism
Endometrial cancer
Hepatic neoplasm
History of breast cancer
History of endometrial cancer
History of hepatic neoplasm
History of thromboembolic disorder
Hypertension
Porphyria
Pregnancy
Severe diabetes with vascular changes
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

History of ectopic pregnancy
Tobacco smoking
Breastfeeding
Diabetes mellitus
Hepatic impairment
History of cholestatic jaundice during pregnancy
History of depression
History of pruritus during pregnancy
Unilateral fallopian tube

Assess family medical history prior to commencing treatment
Administer injection slowly
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
If intra-abdominal haemorrhage consider liver tumour
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor antidiabetic drug treatment
Consider ectopic pregnancy if abdominal and menstrual disturbances occur
Increased risk of venous thromboembolism
May induce or enhance hepatic tumour development
May affect results of some laboratory tests
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if depression worsens or recurs
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if perceptual disturbances occur
Discontinue if significant rise in blood pressure occurs
Advise patient concurrent St John's wort may reduce contraceptive effect
Changes in menstrual bleeding patterns should be expected
Treatment does not protect against risk of sexually transmitted disease

Prior to first injection, investigations into underlying conditions causing undiagnosed vaginal bleeding should be carried out. In women over 40 after prolonged amenorrhoea, endometrial pathology should be excluded.

If bleeding has not occurred in the eight weeks following the first injection, the second injection must not be administered until pregnancy is excluded.

Women who use hormonal contraceptives are more likely to experience venous thromboembolism, arterial thrombosis, including cerebral and myocardial infarction, and subarachnoid haemorrhage. It should be noted that full recovery from such disorders may not always occur.

Norethisterone enantate may theoretically exacerbate porphyria and existing liver impairment.

Women with a history of a disease that is prone to worsen during pregnancy should be carefully observed during medication (for example idiopathic jaundice or severe pruritus of pregnancy). Consider discontinuing norethisterone enantate if the patient experiences a recurrence of cholestatic jaundice which occurred first during pregnancy or during previous use of sex steroids.
Coughing, dyspnoea and circulatory disturbances may occur during or immediately after injection. Injecting the solution very slowly can avoid these reactions.

Pregnancy and Lactation

Pregnancy

Norethisterone enantate is contraindicated during pregnancy.

Norethisterone enantate has slight androgenic activity. If a female foetus is exposed to this product after the first month of pregnancy, a virilising effect on the external genitalia of a female foetus cannot be totally ruled out on theoretical grounds.

Masculinisation of female foetuses has been reported when the mother has been administered norethisterone. For progestional agents, as a group, an increased incidence for cardiovascular defects and hypospadias has been reported (Briggs, 2015).

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

Use norethisterone enantate with caution during breastfeeding.

Norethisterone enantate does not appear to inhibit milk production, however traces appear in breast milk which although considered harmless to a healthy neonate, may theoretically impair bilirubin degradation, especially during the first week of life. Thus, if the mother has received norethisterone enantate, neonates with severe or persistent jaundice requiring treatment should not be breastfed.

LactMed suggests that during breastfeeding progestin-only contraceptives are considered to be the hormonal contraceptives of choice. Norethisterone does not adversely affect the composition of milk, the growth of the infant or the milk supply.

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

"Spotting" bleeding
Amenorrhoea
Bloating
Breakthrough bleeding
Breast discomfort
Depression
Dizziness
Headache
Hypersensitivity reactions
Injection site reactions
Menstrual disturbances
Nausea
Skin disorder
Skin reactions
Weight gain

Presentation

Injections of norethisterone enantate.

Drugs List

Therapeutic Indications

Uses

Contraception - injectable

Intended for short term contraception when a high level of efficacy independent of possible patient errors is required, for example:
Short term depot contraception for women whose partners undergo vasectomy, to prevent pregnancy until the vasectomy is effective.
Short term depot contraception for women immunised against rubella, to prevent pregnancy during the period of virus activity.

Dosage

Adults

Administration

For intramuscular injection into the gluteal muscles.

No liquid should run back from the injection site as efficacy may be impaired.

At low temperatures the injection solution viscosity is high and this requires considerable injection pressure. It is therefore recommended that the ampoule is immersed in warm water before injection. A medium bore needle should be used and fastened securely to the syringe.

Contraindications

Suspected breast cancer
Suspected endometrial cancer
Abnormal liver function test
Breast cancer
Disorder of lipid metabolism
Endometrial cancer
Hepatic neoplasm
History of breast cancer
History of endometrial cancer
History of hepatic neoplasm
History of thromboembolic disorder
Hypertension
Porphyria
Pregnancy
Severe diabetes with vascular changes
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

History of ectopic pregnancy
Tobacco smoking
Breastfeeding
Diabetes mellitus
Hepatic impairment
History of cholestatic jaundice during pregnancy
History of depression
History of pruritus during pregnancy
Unilateral fallopian tube

Assess family medical history prior to commencing treatment
Administer injection slowly
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
If intra-abdominal haemorrhage consider liver tumour
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor antidiabetic drug treatment
Consider ectopic pregnancy if abdominal and menstrual disturbances occur
Increased risk of venous thromboembolism
May induce or enhance hepatic tumour development
May affect results of some laboratory tests
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if depression worsens or recurs
Discontinue if first appearance of migraine or severe or frequent headache
Discontinue if perceptual disturbances occur
Discontinue if significant rise in blood pressure occurs
Advise patient concurrent St John's wort may reduce contraceptive effect
Changes in menstrual bleeding patterns should be expected
Treatment does not protect against risk of sexually transmitted disease

Prior to first injection, investigations into underlying conditions causing undiagnosed vaginal bleeding should be carried out. In women over 40 after prolonged amenorrhoea, endometrial pathology should be excluded.

If bleeding has not occurred in the eight weeks following the first injection, the second injection must not be administered until pregnancy is excluded.

Women who use hormonal contraceptives are more likely to experience venous thromboembolism, arterial thrombosis, including cerebral and myocardial infarction, and subarachnoid haemorrhage. It should be noted that full recovery from such disorders may not always occur.

Norethisterone enantate may theoretically exacerbate porphyria and existing liver impairment.

Women with a history of a disease that is prone to worsen during pregnancy should be carefully observed during medication (for example idiopathic jaundice or severe pruritus of pregnancy). Consider discontinuing norethisterone enantate if the patient experiences a recurrence of cholestatic jaundice which occurred first during pregnancy or during previous use of sex steroids.
Coughing, dyspnoea and circulatory disturbances may occur during or immediately after injection. Injecting the solution very slowly can avoid these reactions.

Pregnancy and Lactation

Pregnancy

Norethisterone enantate is contraindicated during pregnancy.

Norethisterone enantate has slight androgenic activity. If a female foetus is exposed to this product after the first month of pregnancy, a virilising effect on the external genitalia of a female foetus cannot be totally ruled out on theoretical grounds.

Masculinisation of female foetuses has been reported when the mother has been administered norethisterone. For progestional agents, as a group, an increased incidence for cardiovascular defects and hypospadias has been reported (Briggs, 2015).

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

Use norethisterone enantate with caution during breastfeeding.

Norethisterone enantate does not appear to inhibit milk production, however traces appear in breast milk which although considered harmless to a healthy neonate, may theoretically impair bilirubin degradation, especially during the first week of life. Thus, if the mother has received norethisterone enantate, neonates with severe or persistent jaundice requiring treatment should not be breastfed.

LactMed suggests that during breastfeeding progestin-only contraceptives are considered to be the hormonal contraceptives of choice. Norethisterone does not adversely affect the composition of milk, the growth of the infant or the milk supply.

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

"Spotting" bleeding
Amenorrhoea
Bloating
Breakthrough bleeding
Breast discomfort
Depression
Dizziness
Headache
Hypersensitivity reactions
Injection site reactions
Menstrual disturbances
Nausea
Skin disorder
Skin reactions
Weight gain

Effects on Laboratory Tests

Raised plasma cortisol may occur, although there have been no clinical indications of adrenocortical function impairment.
Studies of the blood coagulation system have shown a decreased recalcification time and decreased thromboplastin time (Quick's test).

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: October 2018

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Noristerat 200mg, solution for intramuscular injection. Bayer plc. Revised August 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 19 October 2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Norethindrone Last revised: 02 March 2017
Last accessed: 18 October 2018