Ethinylestradiol with norethisterone oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Tablets containing ethinylestradiol and norethisterone
Drugs List
Therapeutic Indications
Uses
Oral contraception - oestrogen and progestogen
Dosage
Adults
Regardless of the preparation, tablet-taking should be initiated on the first day of menstruation. If menstruation has already started then the first tablet may be taken up to and including day 5 of the menstrual cycle, in this case additional (non-hormonal) contraceptive precautions are required for the first 7 days. One tablet to be taken daily at the same time (preferably evening) without interruption for 21 days, followed by a break of 7 days. Subsequent packs are started after the 7 tablet-free day interval. Sequential preparation should be taken in the order directed on the package.
After childbirth (not breastfeeding) or 2nd trimester abortion or miscarriage Tablet taking can start 21 days after a vaginal delivery provided that the patient is fully ambulant and there are no puerperal complications (increased risk of thrombosis if started earlier). If the tablets are started later than 21 days after delivery, alternative (non-hormonal) methods of contraception are required for the first 7 days of tablet-taking. Since the first post-partum ovulation may precede the first bleeding, another method of contraception should be used in the interval between childbirth and the first course of tablets. If unprotected intercourse has taken place during this period, then pregnancy should be excluded or the woman should wait for her first menstrual period before tablet taking may commence. After 1st trimester abortion or miscarriage After a first trimester abortion or miscarriage, oral contraception may be started immediately in which case no additional contraceptive precautions are required. Changing from a combined oral contraceptive pill All active tablets in the current previous combined oral contraceptive pack should be finished. The first new tablet should be taken the next day, or at the latest the day after usual tablet-free (or placebo) period. No additional contraceptive precautions are required. Any inactive tablets should be discarded. Changing from a combined hormonal contraceptive vaginal ring or transdermal patch The first tablet should be taken on the day of removal, but no later than when the next application would have been due. Changing from a progestogen-only pill The first tablet may be taken on any day, additional (non-hormonal) contraceptive precautions should be taken for the first 7 days of tablet-taking. If the tablet is taken on the first day of menstruation no additional contraception is required. Changing from a progestogen implant, injection or intrauterine system (IUS) The first tablet should be taken on the day the implant or IUS is due for removal or the next injection is due. Additional (non-hormonal) contraceptive precautions should be taken for the first 7 days of tablet-taking.
Additional Dosage Information
Missed tablets
It is important to bear in mind that the critical time for loss of protection is when a tablet is omitted at the beginning or end of a cycle (and therefore the tablet-free interval is lengthened). A missed tablet is defined as being 12 hours or more late. Advise patients that missing tablets or starting the pack late may make the tablet less effective. The missed tablet should be taken as soon as remembered, even if this means taking 2 tablets at the same time. The remaining tablets in the pack should be taken at the usual time and the next pack should be started as soon as the current pack is finished i.e. no tablet-free interval. A non-hormonal method of contraception is required for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of pregnancy should be considered If two or more tablets are missed (i.e. more than 48 hours late) anywhere in the pack, then the patient should: Take last missed tablet as soon as remembered, even if it means taking 2 tablets at the same time and leave any earlier missed tablets. Continue taking the rest of the pack as usual and use an additional (non-hormonal) method of contraception for the next 7 days. Emergency contraception may be needed. The next pack of tablets may be needed to be taken without a break. Emergency Contraception 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. Diarrhoea and vomiting Vomiting up to 4 hours after taking a dose or severe diarrhoea can interfere with absorption and limit effectiveness. Another tablet should be taken as soon as possible. If more than 12 hours� elapse from the usual time of tablet-taking then the missed tablet advice should be taken. Additional precautions should therefore be used during and for 7 days after recovery. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.
Contraindications
Family history of thromboembolic disorder
Multiple risk factors for thromboembolic disease
Predisposition to thromboembolic disease
Abnormal liver function test
Atherogenic lipid profile
Breast cancer
Breastfeeding - until weaning or 6 months post partum
Cerebral ischaemia
Female genital neoplasm
Focal migraine
Galactosaemia
Hepatic neoplasm
History of breast cancer
History of hormone dependent neoplasm
History of thromboembolic disorder
Hyperlipidaemia
Ischaemic heart disease
Oestrogen dependent neoplasm
Porphyria
Pregnancy
Severe hypertension
Undiagnosed gynaecological haemorrhage
Venous thromboembolism
Precautions and Warnings
Females over 35 years
History of chorea during pregnancy
Obesity
Prolonged immobilisation
Recent major surgery
Risk factor for oestrogen-dependent neoplasm
Tobacco smoking
Asthma
Atrial fibrillation
Cardiac valvulopathy
Cardiovascular disorder
Depression
Diabetes mellitus
Dyslipoproteinaemia
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
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 migraine
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of severe depression
History of steroid induced jaundice
Hyperprolactinaemia
Hypertension
Inflammatory bowel disease
Lactose intolerance
Multiple sclerosis
Non focal aura migraine
Otosclerosis
Recent trophoblastic disorder
Renal impairment
Sickle cell disease
Systemic lupus erythematosus
Uterine fibroids
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
Exclude oestrogen dependent neoplasm before treatment
Pre-treatment medical history and clinical examination
Contains lactose
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain sucrose
Resume use only after 2wks full ambulation from surgery/immobilisation
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Monitor patients with a history of depression and/or suicide attempts
Advise patients/carers to seek medical advice if changes in behaviour/mood
Increased risk of VTE during travel involving >5hr immobilisation
Vomiting or severe diarrhoea may impair efficacy
May affect results of some laboratory tests
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 if depression worsens or recurs
Discontinue if epilepsy is exacerbated
Discontinue if hypertension develops
Discontinue if liver function tests become abnormal
Discontinue if sudden, severe pain in stomach occurs
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 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
Ethinylestradiol with norethisterone is contraindicated in 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
Ethinylestradiol with norethisterone is contraindicated in breastfeeding. The use of this preparation 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 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). Advise patient that consuming grapefruit products may increase plasma level of the drug.
Advise patients/carers to seek medical advice if changes in behaviour/ mood.
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 patient to get advice from contraception clinic, family doctor or a pharmacist about this. 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
Aphasia
Breast enlargement
Breast pain
Breast secretion
Breast tenderness
Breathlessness
Candidiasis
Cardiovascular accident
Cerebrovascular accident
Changes in cervical secretion
Changes in libido
Chest pain
Chloasma
Cholelithiasis
Cholestatic jaundice
Chorea
Coagulation disorders
Collapse
Contact lenses may irritate
Cough (with blood stained sputum)
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Diplopia
Endometriosis (aggravation of)
Epileptic seizures
Erythema multiforme
Erythema nodosum
Fainting
Fluid retention
Headache
Hepatic impairment
Hepatic tumours
Hypertension
Increased blood pressure
Increased risk of breast cancer
Increased risk of cervical cancer
Increased size of uterine fibroids
Intermenstrual bleeding
Menstrual bleeding decreased
Migraine
Mood changes
Motor disturbances
Nausea
Numbness
Pain in calf
Photosensitivity
Post medication amenorrhoea
Pulmonary embolism
Rash
Skin reactions
Suppression of lactation post-partum
Systemic lupus erythematosus
Thrombosis
Vertigo
Visual disturbances
Vomiting
Weakness
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. Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas. Summary of Product Characteristics: Brevinor Tablets. Pfizer Limited. Revised April 2019. Summary of Product Characteristics: Loestrin 20. Galen Limited. Revised February 2019.
Summary of Product Characteristics: Loestrin 30. Galen Limited. Revised February 2019.
Summary of Product Characteristics: Norimin Tablets. Pfizer Limited. Revised April 2019.
Summary of Product Characteristics: Synphase Tablets. Pfizer Limited. Revised April 2019.
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