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Etonogestrel with ethinylestradiol vaginal


Vaginal ring containing etonogestrel and ethinylestradiol.

The release rate is approximately 120 micrograms etonogestrel and 15 micrograms ethinylestradiol per 24 hours, over a period of 3 weeks.

Drugs List

  • etonogestrel 120microgram/24hour and ethinylestradiol 15microgram/24hour vaginal ring
  • NUVARING 120microgram+15microgram/24hour vaginal ring
  • SYRENIRING 120microgram+15microgram/24hour vaginal ring
  • Therapeutic Indications


    Combined hormonal contraceptive - intra-vaginal



    One ring to be inserted into the vagina and to be worn continuously for 3 weeks, followed by a ring-free interval of 1 week.

    The ring should be removed exactly 3 weeks after it is inserted.

    Starting therapy
    No preceding hormonal contraceptive use
    The ring should be inserted on the first day of the menstrual cycle.

    Therapy may be initiated on days 2 to 5 of the menstrual cycle. Additional barrier contraception should be used for 7 days during the first cycle.

    Changing from a combined hormonal contraceptive
    The ring should be inserted at the latest on the first day following the usual hormone-free interval of her previous hormonal contraceptive. The hormone-free interval of the previous contraceptive should not extend beyond its recommended length.

    If the patient has been using the previous contraceptive method consistently and correctly and if it is reasonably certain that the patient is not pregnant, the patient may switch therapy from the previous combined contraceptive on any day of the cycle.

    Changing from a progestagen-only method (minipill, implant or injection) or from a progestagen-releasing intrauterine system (IUS)
    Patients taking the minipill may switch therapy on any day of the cycle. Patients using an IUS or implant should insert the ring on the day of the removal of the previous contraceptive device. Patients receiving progestagen injection should insert the ring on the day in which the next injection would be due.

    When switching from a progestagen-only method to the etonogestrel and ethinylestradiol vaginal ring, the first 7 days of therapy should be supported by additional barrier contraception.

    Following first-trimester abortion
    Treatment may begin immediately. If the ring is inserted immediately following the procedure, no additional contraceptive measures are necessary. If immediate insertion of the vaginal ring is not considered desirable, the advice given for 'no preceding hormonal contraceptive use' should be followed and an alternative contraceptive used in the intervening period.

    Following delivery or second-trimester abortion
    Patients should be advised to initiate therapy during the fourth week after delivery or second-trimester abortion. If therapy is started after this time, additional barrier contraception should be recommended for the following 7 days. If intercourse has already occurred, pregnancy should be excluded or the patient must wait for her first menstrual period before initiating therapy with the vaginal ring.

    Additional Dosage Information

    It is recommended that the patient regularly checks to verify presence of the ring. Should the ring be accidentally expelled, the patient should follow the instructions given below.

    Deviations from the recommended regimen
    Contraceptive efficacy and cycle control may be compromised if the patient deviates from the recommended regimen. If the patient does not adhere to the recommended dosage and does not experience a withdrawal bleed following a ring-free interval, pregnancy should be ruled out before continuing therapy. Should the circumstances below occur, the following advice may be given:

    Lengthened ring-free interval
    The patient should insert the new ring as soon as she remembers. A barrier method of contraception such as a male condom should be used for the following 7 days. If intercourse took place during the ring-free interval, pregnancy should be considered. Risk of pregnancy increases with the length of the ring-free interval.

    Ring temporarily outside vagina
    Should the ring be accidentally expelled during the 3 week dosage period, it may be rinsed with cool or lukewarm (not hot) water and reinserted immediately.

    If the ring has been out of the vagina for less than 3 hours, contraceptive efficacy is not reduced. The patient should reinsert the ring as soon as possible, within 3 hours of it being expelled.

    If the ring has or is suspected to have been outside of the vagina for greater than 3 hours during the first or second week of use, contraceptive efficacy may be reduced. The patient should rinse and reinsert the ring as soon as she remembers. Additional barrier contraception such as a male condom is recommended until the ring has been constantly inside the vagina for 7 days. The greater the time in which the ring has been outside of the vagina, the higher the risk of pregnancy.

    If the ring has or is suspected to have been outside for more than 3 hours during the third week of use, contraceptive efficacy may be reduced. The patient should discard the ring and either:
    1. Insert a new ring immediately. Doing so will restart the three-week period. The patient may not experience a withdrawal bleed during these three weeks but breakthrough spotting or bleeding may occur.
    2. Have a withdrawal bleed and insert a new ring no later than 7 days from the time of removal of the previous ring. This option is not recommended if that patient has not used the ring continuously for 7 days prior to removal.

    Lengthened ring use
    If the period of use of the ring does not exceed 4 weeks, contraceptive efficacy is still adequate. The patient may maintain their 1 week ring-free interval and subsequently insert a new ring. Should the ring be used for more than 4 weeks, contraceptive efficacy may be compromised and pregnancy should be ruled out before inserting a new ring.

    To shift a period
    If a period needs to be delayed, the patient may insert a new ring without having a ring-free interval. The next ring may be used for up to 3 weeks again. The patient may experience bleeding or spotting. Following these 3 weeks, the usual 1 week free interval should be taken and regular use of the vaginal ring should resume.

    If a patient wishes to shift her period to another day of the week, she can be advised to shorten her forthcoming ring-free interval by as many days as required. The shorter the ring-free interval, the higher the risk that she would not have a withdrawal bleed and therefore experience breakthrough bleeding and spotting during the use of the next ring.


    Major surgery
    Predisposition to thromboembolic disease
    Prolonged immobilisation
    Abnormal liver function test
    Cerebrovascular accident
    Diabetes mellitus with vascular involvement
    Focal migraine
    Hepatic neoplasm
    History of acute pancreatitis with hyperlipidaemia
    History of cerebrovascular accident
    History of hepatic neoplasm
    History of hormone dependent neoplasm
    History of myocardial infarction
    History of thromboembolic disorder
    Hormone dependent neoplasm
    Myocardial infarction
    Oestrogen dependent neoplasm
    Severe dyslipoproteinaemia
    Severe hepatic impairment
    Severe hypertension
    Transient ischaemic attack
    Undiagnosed gynaecological haemorrhage

    Precautions and Warnings

    Body mass index above 30kg per square metre
    Family history of thromboembolic disorder
    Females over 35 years
    Severe trauma
    Tobacco smoking
    Atrial fibrillation
    Chronic inflammatory bowel disease
    Diabetes mellitus
    Familial hypertriglyceridaemia
    Haemolytic uraemic syndrome
    History of angioedema
    History of chloasma
    History of cholestatic jaundice during pregnancy
    History of herpes gestationis
    History of pregnancy-related deterioration in otosclerosis
    History of pruritus during pregnancy
    Malignant neoplasm
    Sickle cell disease
    Sydenham's chorea
    Systemic lupus erythematosus
    Valvular heart disease

    Assess family medical history prior to commencing treatment
    Exclude oestrogen dependent neoplasm before treatment
    Pre-treatment medical history and clinical examination
    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
    Advise patient of thromboembolic symptoms and to report them if they occur
    Advise patient to seek medical advice if unable to remove device
    Increased risk of VTE with immobility greater than 4 hrs (including travel)
    May affect results of some laboratory tests
    Discontinue 4 - 6 weeks before major surgery
    Discontinue at first signs of jaundice, hepatitis or whole body itching
    Discontinue if first occurrence or worsening of migraine/severe headache
    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 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 thromboembolism occurs
    Interrupt therapy if severe hypertension requiring medical treatment occurs
    Advise patient grapefruit products may increase plasma level
    Advise patient concurrent St John's wort may reduce contraceptive effect
    Female: Do not use with female barrier contraception
    Advise patient of slight increased risk of breast cancer
    Treatment does not protect against risk of sexually transmitted disease
    Women with a history of chloasma should avoid exposure to sun/UV light

    Assessment of patient prior to starting hormonal contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications, precautions and warnings for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

    Patients with the following conditions may not be able to insert the ring or may lose the ring: prolapse of the uterine cervix, cystocele and/or rectocele, severe or chronic constipation.

    If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures (which may include curettage) are indicated to exclude malignancy or pregnancy.

    Pregnancy and Lactation


    Etonogestrel with ethinylestradiol is contraindicated in pregnancy.

    Therapy with the etonogestrel and ethinylestradiol ring should be discontinued in the event of pregnancy.

    No detectable risk is known regarding the use of etonogestrel and ethinylestradiol during pregnancy. However, ethinylestradiol is considered high risk during pregnancy and human studies have shown an increased risk of birth defects. Oestrogens as a group have shown an increased risk for eye and ear abnormalities, Down's syndrome and cardiovascular defects. However separate studies to re-evaluate this evidence have failed to support these claims.

    Inadvertent use of combined hormonal contraceptives during pregnancy is not cause for termination or invasive diagnostic procedures.

    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 ( ) or if this is unavailable at the backup site ( ).


    Use etonogestrel with ethinylestradiol with caution in breastfeeding.

    Oestrogens may decrease the milk composition and milk production of nursing mothers. Ethinylestradiol is excreted in milk in small amounts and may suppress lactation at doses higher than 30 micrograms/day, since the ring releases on average 15 micrograms/day suppression is unlikely. There have been reports of breast enlargement in the infants of mothers taking hormonal contraceptives containing ethinylestradiol.

    Studies on the effects of etonogestrel on lactation report no statistically significant differences in infant illness or growth rates. No difference was found in milk volume, or in the content of lactose, protein or fat. Etonogestrel is excreted in milk in small amounts.

    The use of non-hormonal contraceptive methods is preferred during breastfeeding. It is not recommended to initiate combined hormonal contraceptives until 6 weeks postpartum. During 6 weeks and 6 months postpartum the potential suppression of lactation usually outweighs the advantages of combined hormonal contraceptives. Progestin-only contraceptives are preferred over combined hormonal contraceptives.

    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


    Patients should be advised that side effects such as dizziness and visual disturbances may affect ability to operate or drive machinery.

    Patients should be advised on the correct method of inserting and removing the vaginal ring.

    Advise patient to seek medical advice if unable to remove the vaginal ring.

    Advise patients of procedures to follow if dosing regimen is not kept or if the ring is broken.

    Advise the patient that the vaginal ring does not provide protection from sexually transmitted diseases.

    Advise the patient to contact their physician in case of possible symptoms of thrombosis.

    Advise patient temporary immobilisation, including air travel greater than 4 hours, can be a risk factor for venous thromboembolism.

    Patients should be advised to report any increase in headache frequency or onset of focal symptoms.

    Advise patient of the slight increased risk of breast cancer.

    Women with a history of chloasma should avoid exposure to sun/UV light.

    Advise patient that concurrent use of St John's wort may reduce contraceptive effect.

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

    Side Effects

    Abdominal distension
    Abdominal pain
    Arterial thrombosis
    Back pain
    Breakthrough bleeding
    Breast enlargement
    Breast pain
    Breast tenderness
    Cervical erosion
    Cervical polyp
    Emotional lability
    Extremity pain
    Fibrocystic breast changes
    Genital pruritus
    Hepatic tumours
    Hot flushes
    Hypersensitivity reactions
    Increased appetite
    Increased risk of breast cancer
    Mood changes
    Muscle spasm
    Pelvic pain
    Postcoital bleeding
    Premenstrual symptoms
    Reduced libido
    Sensation of foreign body
    Urinary tract infections
    Urinary urgency
    Uterine spasm
    Vaginal discharge
    Vaginal discomfort
    Vaginal dryness
    Vaginal odour
    Vaginal pain
    Vaginal ring site tissue overgrowth
    Venous thrombosis
    Visual disturbances
    Vulvovaginal burning
    Vulvovaginal infections
    Weight gain


    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 ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last full review: September 2015

    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.

    Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

    Summary of Product Characteristics: NuvaRing 0.12 mg /0.015 mg per 24 hours, vaginal delivery system. Merck Sharp & Dohme Ltd. Revised January 2018.

    Summary of Product Characteristics: SyreniRing 0.12 mg /0.015 mg per 24 hours, vaginal delivery system. Crescent Pharma Limited. Revised July 2017.

    NICE Evidence Services Available at: Last accessed: 07 February 2019

    UK Drugs in Lactation Advisory Service.
    Available at:
    Last accessed: 21 September 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Etonogestrel. Last revised: 08 September 2015
    Last accessed: 17 September 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Ethinyl Estradiol. Last revised: 10 March 2015
    Last accessed: 17 September 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Contraceptives, Oral, Combined. Last revised: 05 May 2015
    Last accessed: 17 September 2015

    The Norwegian Porphyria Centre (NAPOS).
    Available at:
    Last revised: 16 April 2010
    Last accessed: 21 September 2015

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