Ethinylestradiol with norelgestromin transdermal
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Transdermal patches containing ethinylestradiol and norelgestromin
Drugs List
Therapeutic Indications
Uses
Combined oestrogen/progestogen contraceptive - transdermal patch
Dosage
Adults
Contraception should begin on the first day of menstruation. A single patch is applied and worn for 7 days. The day the first patch is applied (day 1) determines the subsequent change days. The patch is changed on the same day of each of the following weeks (days 8 and 15) and the start of the next cycle. Day 22 marks the start of the patch-free week
If a patch is first applied on a day other than the first day of the menstrual cycle, a non-hormonal contraceptive should be used concurrently for the first 7 days.
Switching from a combined oral contraceptive
If there is no withdrawal bleeding within 5 days of the last active tablet, exclude pregnancy before starting treatment with the patches. If more than 7 days have elapsed since the last active tablet, advise the woman to consult her doctor before starting treatment as ovulation may have occurred.
Changing from a progestogen-only method
The first patch may be applied on any day (minipill) or the day of removal of an implant, or the day the next injection is due. A non-hormonal method of contraception should be used for the first 7 days.
Following abortion or miscarriage
The first patch may be applied on any day following abortion or miscarriage before 20 weeks gestation. An additional method of contraception is not needed if treatment is started immediately, but note that ovulation may occur within 10 days of abortion or miscarriage.
Following abortion of miscarriage at or after 20 weeks gestation, treatment may start either on the 21st day post-abortion or miscarriage, or on the first day of the first spontaneous menstruation, whichever occurs first.
Following delivery
If not breastfeeding, treatment should start no sooner than 4 weeks after delivery. If started later, an additional method of non-hormonal contraception should be used for the first 7 days. If intercourse has already occurred, exclude pregnancy or wait for the first spontaneous menstrual period to start treatment.
Additional Dosage Information
Only one patch is to be used at any one time.
Under no circumstances should there be more than a 7 day patch-free interval between dosing cycles. If there are more than 7 patch-free days, the user may not be protected against conception and a non-hormonal contraceptive must then be used concurrently for the next 7 days. The risk of ovulation increases with each day beyond the recommended contraceptive-free period.
Patch change day is missed in the middle of the cycle (week 2 day 8 or week 3 day 15)
Delayed by up to 48 hours
The patient should apply a new patch immediately and the next patch should be applied on the usual change day. No additional contraception is required if the patch was worn correctly in the preceding 7 days.
Delayed by more than 48 hours
The patient may not be protected from pregnancy. The patient should stop the current contraceptive cycle and start a new four week cycle by immediately applying a new patch. This will now be the new change day for the new cycle and additional non-hormonal contraception must be used for the next 7 days.
Delayed at the end of the cycle (week 4 day 22)
The patch should be removed as soon as possible and the next cycle should begin on the usual change day. No additional contraception is required.
Detached patch
If a patch becomes partially or completely detached, insufficient delivery of medicinal product occurs.
Patch remains partly detached for less than 24 hours
The patch should be re-applied to the same place or replaced immediately with a new patch.
No additional contraception is necessary, and the next patch should be applied on the usual change day.
Patch remains partly detached for more than 24 hours (or if the user is unsure when the patch became detached)
The patient may not be protected from pregnancy. The patient should stop the current cycle and start a new cycle immediately by applying a new patch. This will now be a new change day and additional non-hormonal contraception is required for the next 7 days.
If a patch is no longer sticky it should not be reapplied. Additional adhesives or bandages should not be used to hold the patch in place.
Change day adjustment
If a patient wishes to postpone a menstrual period for one cycle it is acceptable to apply another patch at the beginning of week 4 (day 22), therefore not observing the patch free interval. Breakthrough bleeding or spotting may occur at this point. A patch free interval of 7 days should be observed after 6 consecutive weeks of patch wearing, and following this normal application can be resumed.
Change days can be adjusted if required. The current treatment cycle should be completed, with the third patch being removed on the correct day. During the patch free week a new change day may be selected by applying the first patch of the new cycle on the desired day. Under no circumstances should there be more than 7 patch free days. If there is a shorter patch free interval breakthrough bleeding is more likely during the subsequent cycle.
In case of minor skin irritation
If patch use results in uncomfortable irritation, a new patch may be applied to a new location until the next change day.
Administration
For application to clean, dry intact healthy skin on the buttock, abdomen, upper outer arm or upper torso where it will not be rubbed by tight clothing.
It should not be applied to the breasts or to skin that is red, irritated or broken.
Consecutive patches should be applied to a different place to minimise potential irritation, although the same anatomic site may be used.
The patch should be pressed firmly until the edges stick well.
Contraindications
History of chorea during pregnancy
Predisposition to arterial disease
Predisposition to venous thromboembolism
Suspected endometrial cancer
Suspected oestrogen dependent neoplasm
Abnormal liver function test
Angina
Breast cancer
Breastfeeding
Cholestatic jaundice
Dyslipoproteinaemia
Familial conjugated hyperbilirubinaemias
Focal migraine
Hepatic adenoma
Hepatic disorder
Hepatic neoplasm
History of cerebrovascular accident
History of thromboembolic disorder
Infective hepatitis
Myocardial infarction
Oestrogen dependent neoplasm
Pregnancy
Protein C deficiency disease
Protein S deficiency disease
Recent cerebrovascular accident
Severe diabetes with vascular changes
Severe hypertension
Thrombosis
Transient cerebral ischaemic attack without headache
Transient ischaemic attack
Undiagnosed gynaecological haemorrhage
Precautions and Warnings
Body mass index above 30kg per square metre
Family history of thromboembolic disorder at a young age
Major surgery
Prolonged immobilisation
Severe trauma
Smokers over 35 years - increased risk of cardiovascular events
Tobacco smoking
Activated protein C resistance
Atrial fibrillation
Cardiovascular disorder
Chloasma
Diabetes mellitus
Epileptic disorder
Familial hypertriglyceridaemia
Gall bladder disorder
Haemolytic uraemic syndrome
History of depression
History of herpes gestationis
History of migraine
Hyperprolactinaemia
Hypertension
Hypertriglyceridaemia
Inflammatory bowel disease
Otosclerosis
Porphyria
Renal impairment
Severe depression
Sickle cell disease
Sydenham's chorea
Systemic lupus erythematosus
Thrombophilia
Valvular heart disease
Assess family medical history prior to commencing treatment
Exclude breast cancer before treatment
No evidence that transdermal patch safer than combined oral contraceptives
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
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Monitor blood pressure
Advise patient of thromboembolic symptoms and to report them if they occur
Increased risk of VTE during travel involving >5hr immobilisation
May affect results of some laboratory tests
Discontinue 4 weeks prior to major elective 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 significant rise in blood pressure 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
Ensure patient is informed of risks of treatment
Women with a history of chloasma should avoid exposure to sun/UV light
'Spotting' or heavier 'breakthrough' bleeding sometimes occur during the initial months of use, and normally cease spontaneously. Medication should be continued even if irregular bleeding occurs, If irregular bleeding is persistent, appropriate diagnostic measures to exclude an organic cause are indicated and may include curettage. This also applies in the case of spotting which occurs at irregular intervals in several consecutive cycles or which occurs for the first time after long term use of hormonal contraceptives. If the patch has not been applied as directed, or if two withdrawal bleeds have been missed, exclude pregnancy before further treatment.
Pregnancy and Lactation
Pregnancy
Ethinylestradiol with norelgestromin is contraindicated in pregnancy.
Should pregnancy occur, treatment should be discontinued immediately.
Oestrogens have been associated with cardiovascular defects, eye and ear abnormalities and hypospadias in the newborn when having been exposed to these in the womb. However, some studies have failed to find a relationship with cardiovascular defects and non-genital malformations. Down's syndrome has also been associated with oestrogens as a group.
Development alterations in the psychosexual performance of boys have been attributed to exposure to estradiol and progestogen in the womb. Males which have been exposed to estradiol and progestogen have demonstrated a trend to have less heterosexual characteristics and fewer masculine interests than males which have not been exposed to these hormones prenatally. Studies in animals have shown reproductive toxicity.
Schaeffer (2007) states that the accidental use of oral contraceptives in early pregnancy does not require either termination or additional diagnostic studies.
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 norelgestromin is contraindicated in breastfeeding.
Estradiol has been used to suppress postpartum breast engorgement in patients who do not desire to breastfeed. Oestrogenic agents demonstrate lower infant weight gain, decreased milk production and decreased composition of nitrogen and protein content of human milk. Even though the extent of these changes is low, the changes in milk production and composition may be of nutritional importance in malnourished mothers. Because of the reasons mentioned above the use of this medication should be avoided until the breastfeeding mother has completely weaned her child. Although small amounts of the active ingredients pass into breast milk, studies have shown that the level is too low to be of significance to the infant.
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 the use to follow the dosage instructions exactly in order to provide maximum contraceptive effectiveness. The user should check daily to ensure the patch is firmly in position.
Make-up, creams lotions, powders or other topical products should not be applied to the skin where the patch is situated or where it will be placed.
Advise women that hormonal contraception does not protect against HIV infection or other sexually transmitted diseases.
Users should be informed of the symptoms of thrombosis and advised to contact their physician immediately should symptoms of a possible thrombosis occur.
Advise users to read the manufacturers product information thoroughly.
Advise patients to report any changes in their breasts to their physician.
Advise patient to avoid use of St John's Wort as this may impair contraceptive efficacy.
Chloasma may occur and users with a tendency to chloasma or who have experienced chloasma gravidarum should avoid exposure to the sun or to ultraviolet light. Chloasma may be irreversible.
Advise patient that consuming grapefruit products may increase plasma level of the drug.
Side Effects
Abdominal pain
Abnormal liver function
Acne
Aggression
Allergic reaction
Alopecia
Anger
Anxiety
Application site reaction
Asthenia
Blood glucose disturbances
Breast changes
Breast pain
Cardiovascular accident
Cervical changes
Changes in libido
Chloasma
Cholecystitis
Cholelithiasis
Colitis
Contact dermatitis
Contact lenses may irritate
Crying
Depression
Diarrhoea
Dizziness
Dysmenorrhoea
Elevation of liver enzymes
Emotional lability
Enlarged abdomen
Fatigue
Fibrocystic breast changes
Fluid retention
Gallstones
Headache
Hypercholesterolaemia
Hypertension
Hypertriglyceridaemia
Increased risk of breast cancer
Increased risk of cervical cancer
Insomnia
Insulin resistance
Jaundice
Malaise
Malignant hepatic neoplasm
Menstrual disturbances
Migraine
Muscle spasm
Myocardial infarction
Nausea
Non-puerperal lactation
Oedema
Pain
Paraesthesia
Pruritus
Pulmonary embolism
Skin disorder
Skin reactions
Systemic lupus erythematosus
Taste disturbances
Thrombophlebitis
Thrombosis
Uterine fibroids
Uterine spasm
Vaginal haemorrhage
Visual disturbances
Vomiting
Vulvovaginal infections
Weight changes
Effects on Laboratory Tests
Some endocrine and hepatic function tests, and blood components may be affected by hormonal contraceptives.
Increased prothrombin and factors VII, VIII, IX and X, decreased anti-thrombin III, decreased protein S, increased noradrenaline induced platelet aggregability.
Increased thyroid binding globulin leading to increased circulating total thyroid hormone, as measured by protein bound iodine, T4 by column or radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated thyroid binding globulin, free T4 concentration is unaltered.
Other binding proteins may be elevated in the serum.
Sex hormone-binding globulins are increased and result in elevated levels of total circulating endogenous sex steroids. However free or biologically active levels of sex steroids either decrease or remain the same.
High-density lipoprotein (HDL-C), total cholesterol (Total-C), low-density lipoprotein (LDL-C) and triglycerides may all increase slightly, while LDL-C/HDL-C ratio may remain unchanged.
Glucose tolerance may be decreased.
Serum folate levels may be reduced by hormonal contraception. This is potentially significant for women who become pregnant shortly after discontinuing hormonal contraception. All women are advised to take a folic acid supplement peri-conceptually.
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 ).
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [May 27, 2014]].
Summary of Product Characteristics: Evra ransdermal patch. Janssen Cilag Ltd. Revised January 2014.
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