Drugs List

Therapeutic Indications

Uses

Oral contraception - monophasic combined (standard dose oestrogen)

Administration

For oral administration.

Contraindications

Multiple risk factors for thromboembolic disease
Predisposition to thromboembolic disease
Abnormal liver function test
Acute pancreatitis
Breast cancer
Breastfeeding - until weaning or 6 months post partum
Cerebral ischaemia
Diabetes mellitus with vascular involvement
Endometrial hyperplasia
Focal migraine
Galactosaemia
Hepatic disorder
Hepatic neoplasm
Hepatitis with abnormal liver function
History of acute pancreatitis with hyperlipidaemia
History of breast cancer
History of hepatic neoplasm
History of hormone dependent neoplasm
History of thromboembolic disorder
Hormone dependent neoplasm
Ischaemic heart disease
Oestrogen dependent neoplasm
Pregnancy
Severe dyslipoproteinaemia
Severe hypertension
Undiagnosed gynaecological haemorrhage
Venous thromboembolism

Precautions and Warnings

Family history of thromboembolic disorder
Females over 35 years
History of chorea during pregnancy
Obesity
Prolonged immobilisation
Recent major surgery
Risk factor for oestrogen-dependent neoplasm
Tobacco smoking
Wearing of contact lenses
Abnormal mammography
Asthma
Atrial fibrillation
Cardiac valvulopathy
Cardiovascular disorder
Crohn's disease
Diabetes mellitus
Dyslipoproteinaemia
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hereditary angioneurotic oedema
History during pregnancy of pemphigoid gestationis
History of chloasma
History of cholelithiasis
History of cholestatic jaundice during pregnancy
History of haemolytic uraemic syndrome
History of hepatic disorder
History of migraine
History of oligomenorrhoea
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of secondary amenorrhoea
History of severe depression
History of steroid induced jaundice
Hyperlipidaemia
Hyperprolactinaemia
Hypertension
Hypoparathyroidism
Inflammatory bowel disease
Lactose intolerance
Malignant neoplasm
Multiple sclerosis
Non focal aura migraine
Otosclerosis
Recent trophoblastic disorder
Renal impairment
Severe depression
Sickle cell disease
Systemic lupus erythematosus

Assess family medical history prior to commencing treatment
Pre-treatment medical history and clinical examination
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Exclude pregnancy prior to initiation of treatment
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure
Increased risk of VTE during travel involving >5hr immobilisation
Vomiting or severe diarrhoea may impair efficacy
May affect results of some laboratory tests
May alter result of some lab tests-inform lab/redo 2months after OC stopped
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice, hepatitis or whole body itching
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if conditions likely to deteriorate in pregnancy worsen
Discontinue if depression worsens or recurs
Discontinue if epilepsy is exacerbated
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with sudden dysphasia or vertigo occurs
Discontinue if headache associated with sudden motor disturbances occurs
Discontinue if headache associated with syncope or collapse occurs
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if liver function tests become abnormal
Discontinue if severe pain in the calf of one leg occurs
Discontinue if sudden breathlessness (or cough with blood stained sputum)
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach occurs
Discontinue-first occurrence/worsening migraine/severe or frequent headache
Advise patient grapefruit products may increase plasma level
Advise patient concurrent St John's wort may reduce contraceptive effect
All contraceptive pills slightly increase the risk of breast cancer
Ensure patient is informed of risks of treatment
Treatment does not protect against risk of sexually transmitted disease
Women with a history of chloasma should avoid exposure to sun/UV light

Patients should be individually assessed before commencing combined 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.

The use of any combined hormonal contraceptive increases the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products may have up to twice this level of risk. The risk is greatest in the first year of use. There is also some evidence that the risk is increased when a combined hormonal contraceptive is restarted after a break in use of 4 weeks or more.

Combined hormonal contraceptives are contraindicated in patients with multiple risk factors for VTE and/or ATE. If the patient has more than one risk factor, it is possible that the increased risk is greater than the sum of the individual factors, in this case the total risk should be considered. If the risk outweighs the benefit then a combined hormonal contraceptive should not be prescribed.

Risk factors for venous thromboembolism
Obesity; prolonged immobilisation, major surgery (especially to the legs or pelvis), major trauma; family history of venous thromboembolism (especially at a relatively early age); cancer; systemic lupus erythematosus; haemolytic uraemic syndrome; chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), sickle cell disease and increasing age (particularly above 35 years).

Risk factors for arterial thromboembolism
Increasing age (particularly above 35 years); smoking; hypertension; obesity; family history of arterial thromboembolism (especially at a relatively early age); migraine; diabetes mellitus, valvular heart disease; atrial fibrillation; dyslipoproteinaemia and systemic lupus erythematosus

Should the patient develop symptoms of VTE or ATE, then the combined hormonal contraceptive should be discontinued.

Breast cancer
There is an increased risk of breast cancer with combined oral contraceptive (COC) use. Breast cancer is rare among women under 40 years of age whether or not they take COC. The most important risk factor for breast cancer in COC users is the age at which women discontinue the COC; the older the age at stopping the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

Pregnancy and Lactation

Pregnancy

Contraindicated during pregnancy.

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

Contraindicated during breastfeeding.

The use of these preparations may lead to reduction in the volume of milk produced and to a change in its composition. Very small amounts of the active substances may be excreted in the milk. Combined oral contraceptives should be avoided until weaning (or at least 6 months post partum). Oral progestogen-only pills are preferred.

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" bleeds (early cycles)
Abdominal pain
Absence of withdrawal bleeding
Breast enlargement
Breast secretion
Breast tenderness
Cervical erosion
Change in carbohydrate metabolism
Change in lipid metabolism
Change in vitamin metabolism
Changes in cervical secretion
Changes in libido
Changes in vaginal secretion
Chloasma
Cholelithiasis
Chorea
Contact lenses may irritate
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Disturbances of appetite
Fluid retention
Gastro-intestinal symptoms
Headache
Hepatic impairment
Hepatic tumours
Hypertension
Increased risk of breast cancer
Increased size of uterine fibroids
Irritability
Leg cramps
Menstrual bleeding decreased
Nausea
Nervousness
Photosensitivity
Post medication amenorrhoea
Pulmonary embolism
Skin reactions
Systemic lupus erythematosus
Thrombosis
Visual disturbances
Vomiting
Weight changes

Presentation

Tablets containing mestranol and norethisterone

Drugs List

Therapeutic Indications

Uses

Oral contraception - monophasic combined (standard dose oestrogen)

Dosage

Adults

Adolescents

Additional Dosage Information

Administration

For oral administration.

Contraindications

Multiple risk factors for thromboembolic disease
Predisposition to thromboembolic disease
Abnormal liver function test
Acute pancreatitis
Breast cancer
Breastfeeding - until weaning or 6 months post partum
Cerebral ischaemia
Diabetes mellitus with vascular involvement
Endometrial hyperplasia
Focal migraine
Galactosaemia
Hepatic disorder
Hepatic neoplasm
Hepatitis with abnormal liver function
History of acute pancreatitis with hyperlipidaemia
History of breast cancer
History of hepatic neoplasm
History of hormone dependent neoplasm
History of thromboembolic disorder
Hormone dependent neoplasm
Ischaemic heart disease
Oestrogen dependent neoplasm
Pregnancy
Severe dyslipoproteinaemia
Severe hypertension
Undiagnosed gynaecological haemorrhage
Venous thromboembolism

Precautions and Warnings

Family history of thromboembolic disorder
Females over 35 years
History of chorea during pregnancy
Obesity
Prolonged immobilisation
Recent major surgery
Risk factor for oestrogen-dependent neoplasm
Tobacco smoking
Wearing of contact lenses
Abnormal mammography
Asthma
Atrial fibrillation
Cardiac valvulopathy
Cardiovascular disorder
Crohn's disease
Diabetes mellitus
Dyslipoproteinaemia
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hereditary angioneurotic oedema
History during pregnancy of pemphigoid gestationis
History of chloasma
History of cholelithiasis
History of cholestatic jaundice during pregnancy
History of haemolytic uraemic syndrome
History of hepatic disorder
History of migraine
History of oligomenorrhoea
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of secondary amenorrhoea
History of severe depression
History of steroid induced jaundice
Hyperlipidaemia
Hyperprolactinaemia
Hypertension
Hypoparathyroidism
Inflammatory bowel disease
Lactose intolerance
Malignant neoplasm
Multiple sclerosis
Non focal aura migraine
Otosclerosis
Recent trophoblastic disorder
Renal impairment
Severe depression
Sickle cell disease
Systemic lupus erythematosus

Assess family medical history prior to commencing treatment
Pre-treatment medical history and clinical examination
Contains lactose
Resume use only after 2wks full ambulation from surgery/immobilisation
Exclude pregnancy prior to initiation of treatment
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure
Increased risk of VTE during travel involving >5hr immobilisation
Vomiting or severe diarrhoea may impair efficacy
May affect results of some laboratory tests
May alter result of some lab tests-inform lab/redo 2months after OC stopped
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice, hepatitis or whole body itching
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if conditions likely to deteriorate in pregnancy worsen
Discontinue if depression worsens or recurs
Discontinue if epilepsy is exacerbated
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with sudden dysphasia or vertigo occurs
Discontinue if headache associated with sudden motor disturbances occurs
Discontinue if headache associated with syncope or collapse occurs
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if liver function tests become abnormal
Discontinue if severe pain in the calf of one leg occurs
Discontinue if sudden breathlessness (or cough with blood stained sputum)
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach occurs
Discontinue-first occurrence/worsening migraine/severe or frequent headache
Advise patient grapefruit products may increase plasma level
Advise patient concurrent St John's wort may reduce contraceptive effect
All contraceptive pills slightly increase the risk of breast cancer
Ensure patient is informed of risks of treatment
Treatment does not protect against risk of sexually transmitted disease
Women with a history of chloasma should avoid exposure to sun/UV light

Patients should be individually assessed before commencing combined 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.

The use of any combined hormonal contraceptive increases the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products may have up to twice this level of risk. The risk is greatest in the first year of use. There is also some evidence that the risk is increased when a combined hormonal contraceptive is restarted after a break in use of 4 weeks or more.

Combined hormonal contraceptives are contraindicated in patients with multiple risk factors for VTE and/or ATE. If the patient has more than one risk factor, it is possible that the increased risk is greater than the sum of the individual factors, in this case the total risk should be considered. If the risk outweighs the benefit then a combined hormonal contraceptive should not be prescribed.

Risk factors for venous thromboembolism
Obesity; prolonged immobilisation, major surgery (especially to the legs or pelvis), major trauma; family history of venous thromboembolism (especially at a relatively early age); cancer; systemic lupus erythematosus; haemolytic uraemic syndrome; chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), sickle cell disease and increasing age (particularly above 35 years).

Risk factors for arterial thromboembolism
Increasing age (particularly above 35 years); smoking; hypertension; obesity; family history of arterial thromboembolism (especially at a relatively early age); migraine; diabetes mellitus, valvular heart disease; atrial fibrillation; dyslipoproteinaemia and systemic lupus erythematosus

Should the patient develop symptoms of VTE or ATE, then the combined hormonal contraceptive should be discontinued.

Breast cancer
There is an increased risk of breast cancer with combined oral contraceptive (COC) use. Breast cancer is rare among women under 40 years of age whether or not they take COC. The most important risk factor for breast cancer in COC users is the age at which women discontinue the COC; the older the age at stopping the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

Pregnancy and Lactation

Pregnancy

Contraindicated during pregnancy.

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

Contraindicated during breastfeeding.

The use of these preparations may lead to reduction in the volume of milk produced and to a change in its composition. Very small amounts of the active substances may be excreted in the milk. Combined oral contraceptives should be avoided until weaning (or at least 6 months post partum). Oral progestogen-only pills are preferred.

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 on the appropriate course of action if a tablet is missed during the cycle.

Inform patients that if they experience any of the symptoms of thrombosis (pain in calf, sudden breathlessness, prolonged headache, visual disturbances, weakness) they should seek medical advice

Women should be advised of the small increased risk of developing breast cancer before oral contraception is started.

Advise patient that consuming grapefruit products may increase plasma level of the drug.

Advise patients that taking St Johns Wort may reduce contraceptive efficacy.

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

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" bleeds (early cycles)
Abdominal pain
Absence of withdrawal bleeding
Breast enlargement
Breast secretion
Breast tenderness
Cervical erosion
Change in carbohydrate metabolism
Change in lipid metabolism
Change in vitamin metabolism
Changes in cervical secretion
Changes in libido
Changes in vaginal secretion
Chloasma
Cholelithiasis
Chorea
Contact lenses may irritate
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Disturbances of appetite
Fluid retention
Gastro-intestinal symptoms
Headache
Hepatic impairment
Hepatic tumours
Hypertension
Increased risk of breast cancer
Increased size of uterine fibroids
Irritability
Leg cramps
Menstrual bleeding decreased
Nausea
Nervousness
Photosensitivity
Post medication amenorrhoea
Pulmonary embolism
Skin reactions
Systemic lupus erythematosus
Thrombosis
Visual disturbances
Vomiting
Weight changes

Effects on Laboratory Tests

A large number of laboratory tests may be affected by combined oral contraceptives, predominantly by the oestrogenic component. These include:
Biochemical parameters of thyroid, hepatic, adrenal and renal function;
Plasma levels of carrier proteins and lipid/lipoprotein fractions;
Parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.
Changes generally remain within the normal laboratory range.

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: January 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: Norinyl-1 tablets. Pfizer Limited. Revised August 2016