Drugs List

Therapeutic Indications

Uses

Oral contraception - progestogen only

Contraindications

Acute hepatic disorder
Breast cancer
Cerebrovascular disorder
Chronic hepatic disorder
Coronary arteriosclerosis
Disorder of lipid metabolism
Galactosaemia
Hepatic neoplasm
History of breast cancer
History of cholestatic jaundice during pregnancy
History of hormone dependent neoplasm
History of pruritus during pregnancy
History of thromboembolic disorder
History of thrombophlebitis
Ischaemic heart disease
Porphyria
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Females over 35 years
History of pre-eclampsia
Obesity
Tobacco smoking
Wearing of contact lenses
Abnormal liver function test
Asthma
Breastfeeding
Cardiac disorder
Diabetes mellitus
Epileptic disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
History of hepatic impairment
History of migraine
History of severe depression
Hypercholesterolaemia
Hypertension
Impaired carbohydrate tolerance
Lactose intolerance
Recent trophoblastic disorder
Renal disorder

Treatment does not prevent risk of transmission of HIV
Assess family medical history prior to commencing treatment
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure before starting treatment
If intra-abdominal haemorrhage consider liver tumour
If pregnancy occurs possibility of ectopic pregnancy should be considered
If upper abdominal complaints/liver enlargement consider liver tumour
Investigate persistent or recurrent vaginal bleeding
May induce or enhance hepatic tumour development
Vomiting or severe diarrhoea may impair efficacy
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if hypertension develops
Discontinue if symptoms of cerebrovascular accident occur
Discontinue if symptoms of deep vein thrombosis occur
Discontinue if symptoms of pulmonary embolism occur
Discontinue of symptoms of myocardial infarction occur
Advise patient concurrent St John's wort may reduce contraceptive effect
Advise patient to discontinue therapy if any disturbances of vision occur
All contraceptive pills slightly increase the risk of breast cancer
Changes in menstrual bleeding patterns should be expected
Ensure patient is informed of risks of treatment

Patients should be individually assessed before commencing oral contraceptives and at regular intervals thereafter. Assessment should include personal and family history which should then guide physical examination. Parameters to be measured should include blood pressure, weight and body mass index (BMI) and if judged appropriate by the clinician, breast, abdominal examination, pelvic examination and cervical cytology. Specific attention should be given to conditions associated with increased risk of adverse events including migraine and cardiovascular risk factors such as obesity, smoking, hypertension, thrombophilia, hyperlipidaemia and previous venous thromboembolism.

Progestogen-only oral contraceptives may offer less protection against ectopic pregnancy, than against intrauterine pregnancy.

When discontinuing norethisterone during periods of immobilisation or surgery, each woman should be individually considered with regard to the nature of the operation, the duration of immobilisation, the presence of additional risk factors and the likelihood of unwanted conception.

Pregnancy and Lactation

Pregnancy

Norethisterone is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of norethisterone during pregnancy.

Female foetus have undergone masculinisation after maternal use of norethisterone (Briggs, 2015).

Pregnancy must be excluded before starting treatment and the preparation should be withdrawn immediately if pregnancy occurs while taking oral contraception.

It has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations, such as cardiovascular defects, eye and ear anomalies and increased frequency of Down's syndrome, although other studies have failed to support these findings. The possibility cannot be excluded, but it is certain that if a risk exists at all, it is very small.

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 with caution during breastfeeding.

The contraceptives of choice during breastfeeding are the pure gestagens. There are no well established hormonal contraceptives that would require breastfeeding to be interrupted (Schaefer, 2015).

Briggs (2015) suggests that norethisterone may cause a dose dependant suppression in milk production, which may lead to lower infant weight gain. It is advised to use the lowest possible dose of norethisterone, monitor infant weight and gain and consider nutritional supplements if necessary.

LactMed notes that some evidence indicates that norethisterone may offer protection against bone mineral density loss whilst breastfeeding. LactMed also suggests that norethisterone does not adversely affect the composition/supply of milk or the growth of the nursing infant. There are limited consistent physical or mental differences that have been found in infants whose mothers were using norethisterone.

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
Benign hepatic adenomata
Breakthrough bleeding
Breast discomfort
Changes in libido
Depression
Disturbances of appetite
Dizziness
Fatigue
Gastro-intestinal symptoms
Headache
Hypertension
Increased risk of breast cancer
Irregular menstruation
Menorrhagia
Migraine
Nausea
Nervousness
Rash
Skin disorder
Vomiting
Weight changes

Presentation

Oral formulations of norethisterone

Drugs List

Therapeutic Indications

Uses

Oral contraception - progestogen only

Dosage

Adults

Additional Dosage Information

Contraindications

Acute hepatic disorder
Breast cancer
Cerebrovascular disorder
Chronic hepatic disorder
Coronary arteriosclerosis
Disorder of lipid metabolism
Galactosaemia
Hepatic neoplasm
History of breast cancer
History of cholestatic jaundice during pregnancy
History of hormone dependent neoplasm
History of pruritus during pregnancy
History of thromboembolic disorder
History of thrombophlebitis
Ischaemic heart disease
Porphyria
Pregnancy
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Females over 35 years
History of pre-eclampsia
Obesity
Tobacco smoking
Wearing of contact lenses
Abnormal liver function test
Asthma
Breastfeeding
Cardiac disorder
Diabetes mellitus
Epileptic disorder
Gall bladder disorder
Glucose-galactose malabsorption syndrome
History of hepatic impairment
History of migraine
History of severe depression
Hypercholesterolaemia
Hypertension
Impaired carbohydrate tolerance
Lactose intolerance
Recent trophoblastic disorder
Renal disorder

Treatment does not prevent risk of transmission of HIV
Assess family medical history prior to commencing treatment
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Do breast & pelvic exam. before & during treatment if clinically indicated
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure before starting treatment
If intra-abdominal haemorrhage consider liver tumour
If pregnancy occurs possibility of ectopic pregnancy should be considered
If upper abdominal complaints/liver enlargement consider liver tumour
Investigate persistent or recurrent vaginal bleeding
May induce or enhance hepatic tumour development
Vomiting or severe diarrhoea may impair efficacy
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice
Discontinue if first occurrence or worsening of migraine/severe headache
Discontinue if hypertension develops
Discontinue if symptoms of cerebrovascular accident occur
Discontinue if symptoms of deep vein thrombosis occur
Discontinue if symptoms of pulmonary embolism occur
Discontinue of symptoms of myocardial infarction occur
Advise patient concurrent St John's wort may reduce contraceptive effect
Advise patient to discontinue therapy if any disturbances of vision occur
All contraceptive pills slightly increase the risk of breast cancer
Changes in menstrual bleeding patterns should be expected
Ensure patient is informed of risks of treatment

Patients should be individually assessed before commencing oral contraceptives and at regular intervals thereafter. Assessment should include personal and family history which should then guide physical examination. Parameters to be measured should include blood pressure, weight and body mass index (BMI) and if judged appropriate by the clinician, breast, abdominal examination, pelvic examination and cervical cytology. Specific attention should be given to conditions associated with increased risk of adverse events including migraine and cardiovascular risk factors such as obesity, smoking, hypertension, thrombophilia, hyperlipidaemia and previous venous thromboembolism.

Progestogen-only oral contraceptives may offer less protection against ectopic pregnancy, than against intrauterine pregnancy.

When discontinuing norethisterone during periods of immobilisation or surgery, each woman should be individually considered with regard to the nature of the operation, the duration of immobilisation, the presence of additional risk factors and the likelihood of unwanted conception.

Pregnancy and Lactation

Pregnancy

Norethisterone is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of norethisterone during pregnancy.

Female foetus have undergone masculinisation after maternal use of norethisterone (Briggs, 2015).

Pregnancy must be excluded before starting treatment and the preparation should be withdrawn immediately if pregnancy occurs while taking oral contraception.

It has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations, such as cardiovascular defects, eye and ear anomalies and increased frequency of Down's syndrome, although other studies have failed to support these findings. The possibility cannot be excluded, but it is certain that if a risk exists at all, it is very small.

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 with caution during breastfeeding.

The contraceptives of choice during breastfeeding are the pure gestagens. There are no well established hormonal contraceptives that would require breastfeeding to be interrupted (Schaefer, 2015).

Briggs (2015) suggests that norethisterone may cause a dose dependant suppression in milk production, which may lead to lower infant weight gain. It is advised to use the lowest possible dose of norethisterone, monitor infant weight and gain and consider nutritional supplements if necessary.

LactMed notes that some evidence indicates that norethisterone may offer protection against bone mineral density loss whilst breastfeeding. LactMed also suggests that norethisterone does not adversely affect the composition/supply of milk or the growth of the nursing infant. There are limited consistent physical or mental differences that have been found in infants whose mothers were using norethisterone.

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 patients that taking St John's Wort may reduce contraceptive efficacy.

Advise patients to take the tablets at the same time each day (preferably in the evening).

Advise patient to seek advise at first indications of pregnancy.

Advise patient to discontinue therapy if any disturbances of vision occur.

If unprotected sexual intercourse has taken place in the previous 7 days and two or more tablets have been missed (i.e. more than 48 hours late) in the first week of a pack, emergency contraception may be needed. Advise the patient to seek guidance from a contraception clinic, family doctor or a pharmacist.

When additional contraceptive precautions are required, advise patients either not to have sex or to use a cap plus spermicide, or for her partner to use a condom. Rhythm methods are not advisable as the pill disrupts the usual cyclical changes associated with the natural menstrual cycle.

Side Effects

"Spotting" bleeding
Amenorrhoea
Benign hepatic adenomata
Breakthrough bleeding
Breast discomfort
Changes in libido
Depression
Disturbances of appetite
Dizziness
Fatigue
Gastro-intestinal symptoms
Headache
Hypertension
Increased risk of breast cancer
Irregular menstruation
Menorrhagia
Migraine
Nausea
Nervousness
Rash
Skin disorder
Vomiting
Weight changes

Effects on Laboratory Tests

Laboratory technicians should be made aware of patients who are receiving oral contraception, so that any effects on the above tests can be taken into consideration.

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: April 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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.

Joint Formulary Committee. British National Formulary. 72nd ed. London: BMJ Group and Pharmaceutical Press; 2016.

Summary of Product Characteristics: Noriday Tablets. Pfizer Ltd. Revised February 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: 15 March 2017