Nomegestrol and estradiol oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of nomegestrol acetate and estradiol.
Drugs List
Therapeutic Indications
Uses
Oral contraception - oestrogen and progestogen
Dosage
Adults
One tablet for twenty eight consecutive days.
Each pack begins with twenty four white active tablets which are followed by four yellow placebo tablets. Subsequent packs are started immediately after the previous pack is completed, regardless of the presence or absence of withdrawal bleeding. Withdrawal bleeding usually starts on day two to three after intake of the last white tablet and may not have finished before the next pack is started.
Starting the tablets
No preceding hormonal contraceptive use (in the past month)
Tablet-taking has to start on day one of the woman's natural cycle (i.e. the first day of her menstrual bleeding). No additional contraceptive measures are necessary.
Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring or transdermal patch)
The woman should start with active tablets preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC. Where a vaginal ring or transdermal patch has been used, the woman should start tablet taking preferably on the day of removal, but at the latest when the next application would have been due.
Changing from a progestogen-only-method (mini pill, implant, injectable) or from a hormone-medicated Intra Uterine system (IUS)
The woman may switch any day from the mini pill and active tablet taking should be started on the next day. An implant or IUS may be removed any day, and active tablet taking should be started on the day of its removal. When changing from an injectable contraceptive, active tablets should be started on the day when the next injection would have been due. In all of these cases, the woman should be advised to additionally use a barrier method until she has completed 7 days of uninterrupted active tablet-taking.
Following first trimester abortion
The woman may start immediately. No additional contraceptive measures are necessary.
Following delivery (not breastfeeding) or second-trimester abortion
The woman should be advised to start between day twenty one and twenty eight after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method until she has completed 7 days of uninterrupted active tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.
Additional Dosage Information
Missed tablets
Less than 24 hours late
Contraceptive protection is not affected. Take the missed tablet as soon as remembered and further tablets at the usual time.
More than 24 hours late
Contraceptive protection may be reduced. There is a higher risk of pregnancy if tablets are missed near the end of the 24 active white tablets, than if tablets are missed in the first 7 days.
Day 1 to 7
Take the missed tablet as soon possible, even if this means taking 2 tablets at the same time. Further tablets should be taken at the usual time. Barrier contraception should be used for the next 7 days and pregnancy should be considered if intercourse took place in the preceding 7 days.
Day 8 to 17
Take the missed tablet as soon possible, even if this means taking 2 tablets at the same time. Further tablets should be taken at the usual time. Provided in the preceding 7 days the tablets have been taken correctly, no additional contraceptive measures are required. However, if more than 1 tablet has been missed, barrier contraception should be used for the next 7 days.
Day 18 to 24
By adjusting the tablet intake schedule, reduced contraceptive protection can still be prevented. There is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed tablet all tablets have been taken correctly. If this is not the case then first option should be followed and extra contraceptive precautions used for the next 7 days:
- The last missed tablet should be taken as soon as remembered, even if this means taking 2 tablets at the same. Further tablets should be taken at the usual time until all active tablets are used up. The placebo tablets should be discarded and the next pack taken straight away.
- The remaining active tablets in the pack should be discontinued. The placebo tablets should then be taken for a maximum of 3 days, so that the total number of tablets missed is no more than 4. The next blister pack should then be started.
Day 25 to 28 (placebo tablet phase)
Contraceptive protection is not reduced. The remaining placebo tablets should be discarded to avoid prolonging the placebo tablet phase and the next pack should be started.
Contraindications
Major surgery with prolonged post-operative immobilisation
Multiple risk factors for thromboembolic disease
Predisposition to thromboembolic disease
Abnormal liver function test
Acute pancreatitis
Breastfeeding - until weaning or 6 months post partum
Cerebrovascular disorder
Diabetes mellitus with vascular involvement
Focal migraine
Galactosaemia
Hepatic neoplasm
History of acute pancreatitis with hyperlipidaemia
History of hepatic neoplasm
History of hormone dependent neoplasm
History of pancreatitis
History of thromboembolic disorder
Hormone dependent neoplasm
Ischaemic heart disease
Porphyria
Pregnancy
Severe dyslipoproteinaemia
Severe hypertension
Undiagnosed gynaecological haemorrhage
Venous thromboembolism
Precautions and Warnings
Body mass index above 30kg per square metre
Family history of thromboembolic disorder
Females over 35 years
Prolonged immobilisation
Recent major surgery
Risk factor for oestrogen-dependent neoplasm
Tobacco smoking
Atrial fibrillation
Diabetes mellitus
Dyslipoproteinaemia
Endometriosis
Epileptic disorder
Glucose-galactose malabsorption syndrome
Haemolytic uraemic syndrome
Hereditary angioneurotic oedema
History during pregnancy of pemphigoid gestationis
History of chloasma
History of cholelithiasis
History of cholestatic jaundice during pregnancy
History of migraine
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of severe depression
History of steroid induced jaundice
Hyperlipidaemia
Hyperprolactinaemia
Hypertension
Inflammatory bowel disease
Lactose intolerance
Malignant neoplasm
Non focal aura migraine
Recent trophoblastic disorder
Severe depression
Sickle cell disease
Sydenham's chorea
Systemic lupus erythematosus
Uterine fibroids
Valvular heart disease
Assess family medical history prior to commencing treatment
Exclude oestrogen dependent neoplasm before 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
Breakthrough bleeding should be investigated
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Increased risk of VTE with immobility greater than 4 hrs (including travel)
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 headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with syncope or collapse occurs
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if hypertension develops
Discontinue if liver function tests become abnormal
Discontinue if severe pain in the calf of one leg occurs
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
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.
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
Nomegestrol with estradiol is contraindicated during pregnancy.
Before starting treatment, pregnancy must be excluded. The preparation should be withdrawn immediately if pregnancy occurs while taking oral contraception. Accidental administration during pregnancy does not require termination of the pregnancy or additional diagnostic studies.
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.
Lactation
Nomegestrol with estradiol is 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 six months post partum). Oral progestogen-only pills are preferred.
Counselling
Advise patients to take the tablets at the same time each day (preferably in the evening).
Advise patients that taking St Johns Wort may reduce contraceptive efficacy.
Advise patient that consuming grapefruit products may increase plasma level of the drug.
Severe gastrointestinal disturbances (vomiting or diarrhoea)
If severe gastrointestinal disturbances occur, absorption may not be complete and additional contraceptive measures should be taken.
If vomiting occurs within 3 to 4 hours after tablet-taking, a new tablet should be taken as soon as possible. If more than 24 hours elapse, the advice concerning missed tablets is applicable. If the user does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) from another pack.
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.
Advise patient to seek advice from a healthcare professional if unprotected sex has occurred 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.
Advise patient to seek urgent medical attention if symptoms of venous thromboembolism or arterial thromboembolism occur.
Side Effects
"Spotting" bleeds (early cycles)
Abdominal distension
Absence of withdrawal bleeding
Acne
Alopecia
Attention disturbances
Breast enlargement
Breast pain
Breast swelling
Breathlessness
Cardiovascular accident
Cerebrovascular accident
Cervical erosion
Change in lipid metabolism
Changes in cervical secretion
Changes in libido
Chest pain
Chloasma
Cholecystitis
Cholelithiasis
Chorea
Collapse
Contact lenses may irritate
Cough (with blood stained sputum)
Decreased glucose tolerance
Depression
Disturbances of appetite
Dry mouth
Dry skin
Dryness of eyes
Dyspareunia
Fluid retention
Galactorrhoea
Headache
Hepatic tumours
Hot flushes
Hunger
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypertrichosis
Increased risk of breast cancer
Increased risk of cervical cancer
Increases in hepatic enzymes
Intermenstrual bleeding
Irritability
Menorrhagia
Menstrual bleeding decreased
Metrorrhagia
Migraine
Mood changes
Motor disturbances
Nausea
Numbness
Oedema
Pain in calf
Pancreatitis
Pelvic pain
Post medication amenorrhoea
Premenstrual-like syndrome
Pruritus
Pulmonary embolism
Seborrhoea
Sensation of heaviness
Skin reactions
Systemic lupus erythematosus
Thrombosis
Uterine cramps
Vaginal discomfort
Vaginal dryness
Vaginal odour
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: October 2019
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.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of product characteristics: Zoely 2.5/1.5 mg film-coated tablets. Merck Sharp & Dohme Limited. Revised January 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 02 October 2019
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