SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
1
SUMMARY OF PRODUCT CHARACTERISTICS
2 1. NAME OF THE MEDICINAL PRODUCT
Circlet, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Circlet contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol. The ring releases etonogestrel and ethinylestradiol at an average amount of 0.120 mg and 0.015 mg respectively per 24 hours, over a period of 3 weeks.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Vaginal delivery system.
Circlet is flexible, transparent, and colourless to almost colourless ring, with an outer diameter of 54 mm and a cross-sectional diameter of 4 mm.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Contraception.
Circlet is intended for women of fertile age. The safety and efficacy have been established in women aged 18 to 40 years.
The decision to prescribe Circlet should take into consideration the individual woman’s current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with Circlet compares with other combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.4).
4.2 Posology and method of administration
Posology
To achieve contraceptive effectiveness, Circlet must be used as directed (see ‘How to use Circlet’ and ‘How to start Circlet’).
Paediatric population The safety and efficacy of Circlet in adolescents under the age of 18 have not been studied.
Method of administration
HOW TO USE CIRCLET
The woman herself can insert Circlet in the vagina. The physician should advise the woman how to insert and remove Circlet. For insertion the woman should choose a position that is most comfortable for her, e.g. standing with one leg up, squatting, or lying down. Circlet should be compressed and inserted into the vagina until it feels comfortable. An optional alternative is to insert the ring using the
3 NuvaRing Applicator which is distributed separately. The NuvaRing Applicator may not be available in all countries. The exact position of Circlet in the vagina is not critical for the contraceptive effect of the ring (see Figures 1-4).
Once Circlet has been inserted (see ‘How to start Circlet’) it is left in the vagina continuously for 3 weeks. Advise women to regularly check for the presence of Circlet in the vagina (for example, before and after intercourse). If Circlet is accidentally expelled, the woman should follow the instructions given in section 4.2, ‘What to do if the ring is temporarily outside the vagina’ (for more information, see also section 4.4, ‘Expulsion’). Circlet must be removed after 3 weeks of use on the same day of the week as the ring was inserted. After a ring-free interval of one week a new ring is inserted (e.g. when Circlet is inserted on a Wednesday at about 22.00 h the ring should be removed again on the Wednesday 3 weeks later at about 22.00 h. The following Wednesday a new ring should be inserted). Circlet can be removed by hooking the index finger under the ring or by grasping the ring between the index and middle finger and pulling it out (Figure 5). The used ring should be placed in the sachet (keep out of the reach of children and pets) and discarded as described in section 6.6. The withdrawal bleed usually starts 2-3 days after removal of Circlet and may not have finished completely before the next ring insertion is due.
Use with other female vaginal barrier methods Circlet may interfere with the correct placement and position of certain female barrier methods, such as a diaphragm, cervical cap, or female condom. These contraceptive methods should not be used as back-up methods with Circlet.
Figure 1 Take Circlet out of the sachet
Figure 2 Compress the ring
Figure 3 Choose a comfortable position to insert the ring
4
Figure 4A Figure 4B Figure 4C Insert the ring into the vagina with one hand (Figure 4A), if necessary the labia may be spread with the other. Push the ring into the vagina until the ring feels co mfortable (Figure 4B). Leave the ring in place for 3 weeks (Figure 4C). Figure 5: Circlet can be removed by hooking the index finger under the ring or by grasping the ring between the index and middle finger and pulling it out.
HOW TO START CIRCLET
No hormonal contraceptive use in the preceding cycle Circlet has to be inserted on the first day of the woman's natural cycle (i.e. the first day of her menstrual bleeding). Starting on days 2-5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of Circlet use.
Changing from a combined hormonal contraceptive The woman should insert Circlet at the latest on the day following the usual tablet-free, patch-free or placebo tablet interval of her previous combined hormonal contraceptive.
If the woman has been using her previous method consistently and correctly and if it is reasonably certain that she is not pregnant she may also switch from her previous combined hormonal contraceptive on any day of the cycle.
The hormone-free interval of the previous method should never be extended beyond its recommended length.
Changing from a progestagen-only method (minipill, implant, or injection), or from a progestagen-releasing intrauterine system [IUS] The woman may switch on any day from the minipill (from an implant, or the IUS on the day of its removal, from an injectable when the next injection would be due) but should in all of these cases use an additional barrier method for the first 7 days of Circlet use.
Following first-trimester abortion The woman may start immediately. When doing so, she needs not to take additional contraceptive measures. If an immediate application is considered undesirable, the woman should follow the advice given for ‘No hormonal contraceptive use in the preceding cycle’. In the meantime, she should be advised to use an alternative contraceptive method.
Following delivery or second-trimester abortion For breast-feeding women, see section 4.6.
5 Women should be advised to start during the fourth week after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of Circlet use. However, if intercourse has already occurred, pregnancy should be excluded or the woman has to wait for her first menstrual period, before starting Circlet use.
DEVIATIONS FROM THE RECOMMENDED REGIMEN
Contraceptive efficacy and cycle control may be compromised if the woman deviates from the recommended regimen. To avoid loss of contraceptive efficacy in case of a deviation, the following advice can be given:
What to do in case of a lengthened ring-free interval
The woman should insert a new ring as soon as she remembers. A barrier method such as a male condom should be used in addition for the next 7 days. If intercourse took place during the ring-free interval, the possibility of a pregnancy should be considered. The longer the ring-free interval, the higher the risk of a pregnancy.
What to do if the ring was temporarily outside the vagina
Circlet should be left in the vagina for a continuous period of 3 weeks. If the ring is accidentally expelled, it can be rinsed with cool to lukewarm (not hot) water and should be reinserted immediately.
If Circlet has been out of the vagina for less than 3 hours contraceptive efficacy is not reduced. The woman should reinsert the ring as soon as possible, but at the latest within 3 hours.
If Circlet has been out of the vagina, or is suspected to have been out of the vagina for more than 3 hours during the 1st or 2nd week of use, contraceptive efficacy may be reduced. The woman should reinsert the ring as soon as she remembers. A barrier method such as a male condom should be used until Circlet has been in the vagina continuously for 7 days. The longer the time Circlet has been out of the vagina and the closer this is to the ring-free interval, the higher the risk of a pregnancy.
If Circlet has been out of the vagina, or is suspected to have been out of the vagina for more than 3 hours during the 3rd week of the three-week use period, contraceptive efficacy may be reduced. The woman should discard that ring, and one of the following two options should be chosen:
1. Insert a new ring immediately Note: Inserting a new ring will start the next three-week use period. The woman may not experience a withdrawal bleed from her previous cycle. However breakthrough spotting or bleeding may occur. 2. Have a withdrawal bleeding and insert a new ring no later than 7 days (7x24 hours) from the time the previous ring was removed or expelled. Note: This option should only be chosen if the ring was used continuously for the preceding 7 days.
If Circlet was out of the vagina for an unknown amount of time, the possibility of pregnancy should be considered. A pregnancy test should be performed prior to inserting a new ring.
What to do in case of lengthened ring-use
6 Although this is not the recommended regimen, as long as Circlet has been used for maximally 4 weeks, contraceptive efficacy is still adequate. The woman may maintain her one-week ring- free interval and subsequently insert a new ring. If Circlet has been left in place for more than 4 weeks, contraceptive efficacy may be reduced and pregnancy should be ruled out before inserting a new Circlet.
If the woman has not adhered to the recommended regimen and subsequently has no withdrawal bleed in the following ring-free interval, pregnancy should be ruled out before inserting a new Circlet.
HOW TO SHIFT PERIODS OR HOW TO DELAY A PERIOD
If in exceptional cases a period needs to be delayed, the woman may insert a new ring without having a ring-free interval. The next ring can be used for up to 3 weeks again. The woman may experience bleeding or spotting. Regular use of Circlet is then resumed after the usual one week ring-free interval.
To shift her period to another day of the week than the woman is used to with her current scheme, she can be advised to shorten her forthcoming ring-free interval by as many days as she likes. The shorter the ring-free interval, the higher the risk that she does not have a withdrawal bleed and will experience breakthrough bleeding and spotting during the use of the next ring.
4.3 Contraindications
(CHCs) should not be used in the following conditions. Should any of the conditions appear for the first time during the use of Circlet, it should be removed immediately.
Presence or risk of venous thromboembolism (VTE) o Venous thromboembolism - current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]). o Known hereditary or acquired predisposition for venous thromboembolism, such as APC- resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency. o Major surgery with prolonged immobilisation (see section 4.4). o A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4). Presence or risk of arterial thromboembolism (ATE) o Arterial thromboembolism - current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris). o Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA). o Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant). o History of migraine with focal neurological symptoms. o A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms severe hypertension severe dyslipoproteinaemia. Pancreatitis or a history thereof if associated with severe hypertriglyceridemia. Presence or history of severe hepatic disease as long as liver function values have not returned to normal. Presence or history of liver tumours (benign or malignant).
7 Known or suspected malignant conditions of the genital organs or the breasts, if sex steroid- influenced. Undiagnosed vaginal bleeding. Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 of Circlet
Circlet is contraindicated for concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see sections 4.4 and section 4.5).
4.4 Special warnings and precautions for use
WARNINGS
If any of the conditions or risk factors mentioned below is present, the suitability of Circlet should be discussed with the woman.
In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact her doctor to determine whether the use of Circlet should be discontinued.
1. Circulatory Disorders
Risk of venous thromboembolism (VTE)
The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products such as Circlet may have up to twice this level of risk. The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with Circlet, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use. There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more . In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a VTE over the period of one year. However, in any individual woman, the risk may be far higher, depending on her underlying risk factors (see below). It is estimated that out of 10,000 women who use a low dose CHC that contains levonorgestrel, about 61 will develop a VTE in one year. Inconsistent results on the risk of VTE with Circlet compared with CHCs that contain levonorgestrel have been found (with relative risk estimates ranging from no increase, RR=0.96, to an almost 2-fold increase, RR=1.90). This corresponds to between about 6 and 12 VTEs in a year out of 10,000 women who use Circlet. In both cases, the number of VTEs per year is fewer than the number expected in women during pregnancy or in the postpartum period. VTE may be fatal in 1-2 % of the cases.
1 Mid-point range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non- use of approximately 2.3 to 3.6
8 Number of VTE events per 10,000 women in one year
Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal,or retinal veins and arteries
Risk factors for VTE The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see table).
Circlet is contraindicated if a woman has multiple risk factors that put her at high risk of venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be considered. If the balance of benefits and risks is considered to be negative, a CHC should not be prescribed (see section 4.3).
Table: Risk factors for VTE Risk factor Comment Obesity (body mass index over 30 kg/m²) Risk increases substantially as BMI rises.
Particularly important to consider if other risk factors also present.
Prolonged immobilisation, major surgery, any In these situations it is advisable to discontinue use surgery to the legs or pelvis, neurosurgery, or of the patch/pill/ring (in the case of elective major trauma surgery at least four weeks in advance) and not resume until two weeks after complete Note: Temporary immobilisation including air remobilisation. Another method of contraception travel > 4 hours can also be a risk factor for VTE, should be used to avoid unintentional pregnancy. particularly in women with other risk factors. Antithrombotic treatment should be considered if Circlet has not been discontinued in advance.
Positive family history (venous thromboembolism If a hereditary predisposition is suspected, the
9 ever in a sibling or parent especially at a relatively woman should be referred to a specialist for early age, e.g. before 50) advice before deciding about any CHC use.
Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease
Increasing age Particularly above 35 years
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis. The increased risk of thromboembolism in pregnancy, and particularly the 6-week period of the puerperium, must be considered (for information on "Pregnancy and lactation" see section 4.6).
Symptoms of VTE (deep vein thrombosis and pulmonary embolism) In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include: - unilateral swelling of the leg and/or foot or along a vein in the leg; - pain or tenderness in the leg which may be felt only when standing or walking; - increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include: - sudden onset of unexplained shortness of breath or rapid breathing; - sudden coughing which may be associated with haemoptysis; - sharp chest pain; - severe light headedness or dizziness; - rapid or irregular heartbeat. Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.
Risk of arterial thromboembolism (ATE) Epidemiological studies have associated the use of CHCs with an increased risk for arterial thromboembolism (myocardial infarction) or for cerebrovascular accident (e.g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal.
Risk factors for ATE The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see table). Circlet is contraindicated if a woman has one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see section 4.3).
10 Table: Risk factors for ATE Risk factor Comment Increasing age Particularly above 35 years
Smoking Women should be advised not to smoke if they wish to use a CHC. Women over 35 who continue to smoke should be strongly advised to use a different method of contraception. Hypertension
Obesity (body mass index over 30 kg/m2) Risk increases substantially as BMI increases.
Particularly important in women with additional risk factors Positive family history (arterial thromboembolism If a hereditary predisposition is suspected, the ever in a sibling or parent especially at relatively woman should be referred to a specialist for early age, e.g. below 50) advice before deciding about any CHC use.
Migraine An increase in frequency or severity of migraine during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation.
Other medical conditions associated with Diabetes mellitus, hyperhomocysteinaemia, adverse vascular events valvular heart disease and atrial fibrillation, dyslipoproteinaemia and systemic lupus erythematosus.
Symptoms of ATE
In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.
Symptoms of a cerebrovascular accident can include: - sudden numbness or weakness of the face, arm or leg, especially on one side of the body; - sudden trouble walking, dizziness, loss of balance or coordination; - sudden confusion, trouble speaking or understanding; - sudden trouble seeing in one or both eyes; - sudden, severe or prolonged headache with no known cause; - loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of a myocardial infarction (MI) can include: - pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastbone; - discomfort radiating to the back, jaw, throat, arm, stomach; - feeling of being full, having indigestion or choking; - sweating, nausea, vomiting or dizziness; - extreme weakness, anxiety, or shortness of breath; - rapid or irregular heartbeats.
11 In case of suspected or confirmed VTE or ATE, CHC use should be discontinued. Adequate contraception should be initiated because of the teratogenicity of anti-coagulant therapy (coumarins).
2. Tumours
Epidemiological studies indicate that the long-term use of oral contraceptives displays a risk factor for the development of cervical cancer in women infected with human papillomavirus (HPV). However, there is still uncertainty about the extent to which this finding is influenced by confounding effects (e.g. differences in number of sexual partners or in use of barrier contraceptives). No epidemiological data on the risk of cervical cancer in users of Circlet are available (see ‘medical examination/consultation’). A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been reported in users of COCs. In isolated cases, these tumours have led to life-threatening intra- abdominal hemorrhages. Therefore, a hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal hemorrhage occur in women using Circlet.
3. ALT elevations
During clinical trials with patients treated for hepatitis C virus infections (HCV) with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequently in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.5).
4. Other conditions
Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using hormonal contraceptives. Although small increases in blood pressure have been reported in many women using hormonal contraceptives, clinically relevant increases are rare. A definitive relationship between hormonal contraceptive use and clinical hypertension has not been established. However, if a sustained clinically significant hypertension develops during the use of Circlet then it is prudent for the physician to suspend the use of the ring and treat the hypertension. Where considered appropriate, Circlet use may be resumed if normotensive values can be achieved with antihypertensive therapy. The following conditions have been reported to occur or deteriorate with both pregnancy and during the use of hormonal contraceptives, but the evidence of an association with its use is inconclusive: jaundice and / or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss. Exogenous oestrogens may induce or exacerbate symptoms of (hereditary) angioedema.
12 Acute or chronic disturbances of liver function may necessitate the discontinuation of the use of Circlet until markers of liver function return to normal. Recurrence of cholestatic jaundice and/ or pruritus related to cholestasis, which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of the ring. Although oestrogens and progestagens may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using hormonal contraception. However, diabetic women should be carefully monitored while using Circlet especially in the first months of use. New onset or deterioration of Crohn’s disease and ulcerative colitis has been reported to occur with the use of hormonal contraceptives, but the evidence of an association with its use is inconclusive. Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst using Circlet. If a woman has any of the following conditions she may not be able to insert Circlet correctly or may in fact lose the ring: prolapse of the uterine cervix, cystocele and/or rectocele, severe or chronic constipation. Very rarely it has been reported that Circlet is inadvertently inserted in the urethra and possibly ending up in the bladder. Therefore, incorrect positioning should be considered in the differential diagnosis in case of symptoms of cystitis. During the use of Circlet, women may occasionally experience vaginitis. There are no indications that the efficacy of Circlet is affected by the treatment of vaginitis, or that the use of Circlet affects the treatment of vaginitis (see section 4.5). Very rarely it has been reported that the ring adhered to vaginal tissue, necessitating removal by a healthcare provider. In some cases when the tissue had grown over the ring, removal was achieved by cutting the ring without incising the overlying vaginal tissue. Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
MEDICAL EXAMINATION/CONSULTATION
Prior to the initiation or reinstitution of Circlet use a complete medical history (including family history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a physical examination should be performed, guided by the contraindications (see section 4.3) and warnings (see section 4.4). It is important to draw a woman’s attention to the information on venous and arterial thrombosis, including the risk of Circlet compared with other CHCs, the symptoms of VTE and ATE, the known risk factors and what to do in the event of a suspected thrombosis.
The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given. The frequency and nature of examinations should be based upon established practice guidelines and be adapted to the individual woman.
Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
REDUCED EFFICACY
The efficacy of Circlet may be reduced in the event of non-compliance (section 4.2), or when concomitant medications that decrease the plasma concentration of ethinylestradiol and/or etonogestrel are used (section 4.5).
13 REDUCED CYCLE CONTROL
Irregular bleeding (spotting or breakthrough bleeding) may occur during the use of Circlet. If bleeding irregularities occur after previously regular cycles while Circlet has been used according to the recommended regimen, then non-hormonal causes should be considered, and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage.
In some women a withdrawal bleed may not occur during the ring-free interval. If Circlet has been used according to the instructions described in section 4.2, it is unlikely that the woman is pregnant. However, if Circlet has not been used according to these instructions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before use of Circlet is continued.
MALE EXPOSURE TO ETHINYLESTRADIOL AND ETONOGESTREL
The extent and possible pharmacological role of exposure of male sexual partners to ethinylestradiol and etonogestrel through absorption through the penis have not been examined.
BROKEN RINGS
On very rare occasions Circlet has been reported to get disconnected during use (see section 4.5). Vaginal injury associated with ring breakage has been reported. The woman is advised to remove the broken ring and reinsert a new ring as soon as possible and use a barrier method such as a male condom in addition for the next 7 days. The possibility of a pregnancy should be considered and the woman should contact her physician.
EXPULSION
Circlet has been reported to get expelled, for example if the ring has not been inserted properly, while removing a tampon, during sexual intercourse, or in case of severe or chronic constipation. Prolonged expulsion may lead to contraceptive failure and/or breakthrough bleeding. Therefore, to ensure efficacy the woman should be advised to regularly verify the presence of Circlet. (for example, before and after intercourse).
If Circlet is accidentally expelled and is left outside of the vagina for less than 3 hours contraceptive efficacy is not reduced. The woman should rinse the ring with cool to lukewarm (not hot) water and reinsert it as soon as possible, but at the latest within 3 hours.
If Circlet has been out of the vagina, or is suspected to have been out of the vagina for more than 3 hours contraceptive efficacy may be reduced. In that case, the applicable advice given in section 4.2 ‘What to do if the ring was temporarily outside the vagina’ should be followed.
4.5 Interaction with other medicinal products and other forms of interaction
INTERACTIONS WITH OTHER MEDICINAL PRODUCTS
Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Effects of other medicinal products on Circlet
14 Interactions can occur with drugs or herbal products that induce microsomal enzymes which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive failure.
Management Enzyme induction can already be observed after a few days of treatment. Maximum enzyme induction is generally seen within a few weeks. After the cessation of drug therapy, enzyme induction may be sustained for about 4 weeks.
Short-term treatment Women on treatment with enzyme-inducing drugs or herbal products should temporarily use a barrier method or another method of contraception in addition to Circlet. Note: Circlet should not be used with a diaphragm, cervical cap, or female condom. The barrier method must be used during the whole time of the concomitant drug therapy and for 28 days after its discontinuation. If concomitant drug administration runs beyond the 3 weeks of a ring-cycle, the next ring should be inserted immediately, without having the usual ring-free interval.
Long-term treatment In women on long-term treatment with hepatic enzyme-inducing active substances, another reliable, non-hormonal method of contraception is recommended.
The following interactions have been reported in the literature.
Substances increasing the clearance of combined hormonal contraceptives Interactions can occur with medicinal or herbal products that induce microsomal enzymes, specifically cytochrome P450 enzymes (CYP), which can result in increased clearance reducing plasma concentrations of sex hormones and may decrease the effectiveness of combined hormonal contraceptives, including Circlet. These products include phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, some HIV protease inhibitors (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz), and products containing the herbal remedy St. John’s wort.
Substances with variable effects on the clearance of combined hormonal contraceptives When co-administered with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g. nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and/or combinations with HCV medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of progestagens, including etonogestrel, or estrogen. The net effect of these changes may be clinically relevant in some cases.
Substances decreasing the clearance of combined hormonal contraceptives The clinical relevance of potential interactions with enzyme inhibitors remains unknown. Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of estrogens or progestogens, including etonogestrel.
There have been reports of ring breakage during concomitant use of intravaginal preparations, including, antimycotic, antibiotic and lubricant products (see section 4.4, ‘Broken Rings’). Based on pharmacokinetic data, vaginally administered antimycotics and spermicides are unlikely to affect the contraceptive efficacy and safety of Circlet.
Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
15 Pharmacodynamic interactions Concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, may increase the risk of ALT elevations (see sections 4.3 and 4.4). Therefore, Circlet users must switch to an alternative method of contraception (e.g., progestagen-only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen. Circlet can be restarted 2 weeks following completion of treatment with this combination drug regimen.
LABORATORY TESTS
The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins, (e.g. corticosteroid binding globulin and sex hormone binding globulin), lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.
INTERACTION WITH TAMPONS
Pharmacokinetic data show that the use of tampons has no effect on the systemic absorption of the hormones released by Circlet. On rare occasions Circlet might be expelled while removing a tampon (see advice for ‘What to do if the ring was temporarily outside the vagina’).
4.6 Fertility, pregnancy and lactation
Fertility Circlet is indicated for the prevention of pregnancy. If the woman wants to stop using Circlet because she wants to get pregnant, she is advised to wait until she has a natural period before trying to conceive as this will help her calculate when the baby is due.
Pregnancy Circlet is not indicated during pregnancy. If pregnancy occurs with Circlet in situ, the ring should be removed. Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were used inadvertently during early pregnancy.
A clinical study in a small number of women showed that despite the intravaginal administration, intrauterine concentrations of contraceptive steroids with Circlet are similar to the levels observed in COC users (see section 5.2). Clinical experience of the outcomes of pregnancies exposed to Circlet has not been reported.
The increased risk of VTE during the postpartum period should be considered when re-starting Circlet (see sections 4.2 and 4.4).
Breastfeeding Lactation may be influenced by oestrogens, as they may reduce the quantity and change the composition of breast milk. Therefore, the use of Circlet should generally not be recommended until the nursing mother has completely weaned her child. Small amounts of the contraceptive steroids and / or their metabolites may be excreted with the milk but there is no evidence that this adversely affects the infant’s health.
4.7 Effects on ability to drive and use machines
On the basis of the pharmacodynamic profile, Circlet has no or negligible influence on the ability to drive and use machines.
16
4.8 Undesirable effects
The most frequently reported undesirable effects in the clinical trials with Circlet were headache and vaginal infections and vaginal discharge, each reported by 5-6% of the women.
Description of selected adverse reactions An increased risk of arterial and venous thrombotic and thromboembolic events, including myocardial infarction, stroke, transient ischaemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in section 4.4.
Also other undesirable effects have been reported in women using CHCs: these are discussed in more detail in section 4.4.
Adverse drug reactions that have been reported in clinical trials, observational studies, or during postmarketing use with Circlet are listed in the Table below. The most appropriate MedDRA term to describe a certain adverse event is listed.
All adverse reactions are listed by system organ class and frequency; common ( 1/100 to < 1/10), uncommon ( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), and not known (cannot be estimated from the available data).
System Organ Common Uncommon Rare Not known1 Class Cervicitis, Infections and Vaginal infection Cystitis, Urinary infestations tract infection Hypersensitivity Immune system reactions, including disorders angioedema and anaphylaxis Metabolism and Increased nutrition appetite disorders Affect lability, Psychiatric Depression, Mood altered, disorders Libido decreased Mood swings Nervous system Headache, Dizziness, disorders Migraine Hypoaesthesia Visual Eye disorders disturbance Venous Vascular thromboembolism Hot flush disorders Arterial thromboembolism Abdominaldiste nsion, Gastrointestinal Abdominal pain, Diarrhoea, disorders Nausea Vomiting, Constipation Skin and Alopecia, Chloasma subcutaneous Acne Eczema, Urticaria tissue disorders Pruritus, Rash Musculoskeleta Back pain, l and Muscle spasms, connective Pain in extremity tissue disorders
17 System Organ Common Uncommon Rare Not known1 Class Dysuria, Renal and Micturition urinary urgency, disorders Pollakiuria Amenorrhoea, Galactorrhoea Penis disorders Breast discomfort, Breast enlargement, Breast mass, Cervical polyp, Coital bleeding, Dyspareunia, Ectropion of cervix, Breast Fibrocystic tenderness, Reproductive breast disease, Genital pruritus system and Menorrhagia, female, breast disorders Metrorrhagia, Dysmenorrhoea, Pelvic Pelvic pain, discomfort, Vaginal discharge Premenstrual syndrome, Uterine spasm, Vaginal burning sensation, Vaginal odour, Vaginal pain, Vulvovaginal discomfort, Vulvovaginal dryness Fatigue, General Irritability, disorders and Malaise, Vaginal ring site administration Oedema, tissue overgrowth site conditions Sensation of foreign body Blood pressure Investigations Weight increased increased Injury, Vaginal ring Vaginal injury poisoning and discomfort, Vaginal ring associated with ring procedural Vaginal ring complication breakage complications expelled 1) Listing of adverse events based on spontaneous reporting.
Hormone-dependent tumours (e.g. liver tumours, breast cancer) have been reported in association with CHC use. For further information see section 4.4.
On very rare occasions Circlet has been reported to get disconnected during use (see sections 4.4 and 4.5).
Interactions Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with hormonal contraceptives (see section 4.5).
18 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9 Overdose
There have been no reports of serious deleterious effects from an overdose of hormonal contraceptives. Symptoms that may occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment should be symptomatic.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other gynecologicals, Intravaginal contraceptives, vaginal ring with progestagen and oestrogen, ATC code: G02BB01
Mechanism of action Circlet contains etonogestrel and ethinylestradiol. Etonogestrel is a 19-nortestosterone-derived progestagen and binds with high affinity to progesterone receptors in the target organs. Ethinylestradiol is an oestrogen widely used in contraceptive products. The contraceptive effect of Circlet is based on various mechanisms, the most important of which is the inhibition of ovulation.
Clinical efficacy and safety Clinical studies were performed worldwide (US, EU, and Brazil) in women between the ages of 18 and 40 years. The contraceptive efficacy appeared to be at least comparable with that known for combined oral contraceptives. The following table shows the Pearl Indices (number of pregnancies per 100 woman years of use) found in the clinical studies with Circlet.
Analysis Method Pearl Index 95 % CI No of Cycles ITT (user + method 0.96 0.64 – 1.39 37,977 failure) PP (method failure) 0.64 0.35 – 1.07 28,723
With the use of higher-dosed COCs (0.05 mg ethinylestradiol) the risk of endometrial and ovarian cancer is reduced. Whether this also applies to a lower-dosed contraceptive like Circlet remains to be determined.
BLEEDING PATTERN
A large comparative study with 150/30 µg levonorgestrel/ethinylestradiol OC (n= 512 vs n= 518) evaluating vaginal bleeding characteristics over 13 cycles showed low incidences of breakthrough spotting or bleeding for Circlet (2.0-6.4%). Furthermore, vaginal bleeding was exclusively restricted to the ring-free interval for most subjects (58.8-72.8%).
EFFECTS ON BONE MINERAL DENSITY
The effects of Circlet (n=76) on bone mineral density (BMD) were studied in comparison to a non- hormonal intrauterine device (IUD) (n=31) in women over a period of two years. No adverse effects on bone mass have been observed.
19
Paediatric population The safety and efficacy of Circlet in adolescents under the age of 18 have not been studied.
5.2 Pharmacokinetic properties
Etonogestrel
Absorption Etonogestrel released by Circlet is rapidly absorbed by the vaginal mucosa. Maximum serum concentrations of etonogestrel of approximately 1,700 pg/mL are reached at about 1 week after insertion. Serum concentrations show small fluctuations and slowly decrease to approximately 1,600 pg/mL after 1 week, 1,500 pg/mL after 2 weeks and 1,400 pg/mL after 3 weeks of use. Absolute bioavailability is approximately 100%, which is higher than after oral administration. Cervical and intrauterine etonogestrel levels were measured in a small number of women using Circlet or an oral contraceptive containing 0.150 mg desogestrel and 0.020 mg ethinylestradiol. The observed levels were comparable.
Distribution Etonogestrel is bound to serum albumin and to sex hormone binding globulin (SHBG). The apparent volume of distribution of etonogestrel is 2.3 L/kg.
Biotransformation Etonogestrel is metabolized by the known pathways of steroid metabolism. The apparent clearance from serum is about 3.5 L/h. No direct interaction was found with the co-administered ethinylestradiol.
Elimination Etonogestrel serum levels decrease in two phases. The terminal elimination phase is characterized by a half-life of approximately 29 hours. Etonogestrel and its metabolites are excreted at a urinary to biliary ratio of about 1.7:1. The half-life of metabolite excretion is about 6 days.
Ethinylestradiol
Absorption Ethinylestradiol released by Circlet is rapidly absorbed by the vaginal mucosa. Maximum serum concentrations of about 35 pg/mL are reached 3 days after insertion and decrease to 19 pg/mL after 1 week, 18 pg/mL after 2 weeks and 18 pg/mL after 3 weeks of use. The monthly systemic ethinylestradiol exposure (AUC0-∞) with Circlet is 10.9 ng.h/mL. Absolute bioavailability is approximately 56%, which is comparable with oral administration of ethinylestradiol. Cervical and intrauterine ethinylestradiol levels were measured in a small number of women using Circlet or an oral contraceptive containing 0.150 mg desogestrel and 0.020 mg ethinylestradiol. The observed levels were comparable.
Distribution Ethinylestradiol is highly but non-specifically bound to serum albumin. An apparent volume of distribution of about 15 L/kg was determined.
Biotransformation Ethinylestradiol is primarily metabolized by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed. These are present as free metabolites and as sulphate and glucuronides conjugates. The apparent clearance is about 35 L/h.
20 Elimination Ethinylestradiol serum levels decrease in two phases. The terminal elimination phase is characterized by a large individual variation in half-life, resulting in a median half-life of approximately 34 hours. Unchanged ethinylestradiol is not excreted; ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 1.3:1. The half-life of metabolite excretion is about 1.5 days.
Special populations
Paediatric population The pharmacokinetics of Circlet in healthy postmenarcheal female adolescents under the age of 18 have not been studied.
Effect of renal impairment No studies were performed to evaluate the effect of renal disease on the pharmacokinetics of Circlet.
Effect of hepatic impairment No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of Circlet. However, steroid hormones may be poorly metabolized in women with impaired liver function.
Ethnic groups No formal studies were performed to assess pharmacokinetics in ethnic groups.
5.3 Preclinical safety data
Non-clinical data with ethinylestradiol and etonogestrel reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction, other than those already known for humans.
Environmental Risk Assessment (ERA) Environmental risk assessment studies have shown that 17α-ethinylestradiol and etonogestrel may pose a risk to surface water organisms (see section 6.6).
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Ethylene vinylacetate copolymer, 28% vinylacetate; ethylene vinylacetate copolymer, 9% vinylacetate; magnesium stearate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
40 months.
21 6.4 Special precautions for storage
Prior to dispensing: 3 years, store in a refrigerator (2 °C - 8 °C).
At the time of dispensing: The dispenser places a date of dispensing on the packaging. The product should be inserted no later than 4 months from the date of dispensing, but in all cases prior to the expiry date, whichever comes first.
After dispensing: 4 months, store below 30°C.
Store in the original package in order to protect from light and moisture.
6.5 Nature and contents of container
Sachet containing one Circlet. The sachet is made of aluminum foil with an inner layer of low-density polyethylene and an outer layer of polyethylene terephthalate (PET). It is reclosable and waterproof. The sachet is packed in a printed cardboard box together with the package leaflet. Each box contains 1 or 3 rings. Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
See section 4.2. The dispenser has to indicate the date of dispensing on the packaging. It is recommended for the 3-rings presentation to indicate this date on the ply carton as well as on the sachet. Circlet should be inserted no later than 4 months from the date of dispensing, but in all cases prior to the expiry date, which ever comes first. After removal, Circlet should be replaced in the reclosable sachet and disposed of with the normal household waste in a manner that avoids accidental contact with others. This medicinal product may pose a risk to the environment (see section 5.3). Circlet should not be flushed down the toilet. Any unused (expired) rings should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
[To be completed nationally]
8. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
[To be completed nationally]
10. DATE OF REVISION OF THE TEXT
[To be completed nationally]
22
23
LABELLING
24
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
OUTER CARTON, Circlet 0.120 mg/0.015 mg per 24 hours, vaginal delivery system
1. NAME OF THE MEDICINAL PRODUCT
Circlet, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system etonogestrel / ethinylestradiol
2. STATEMENT OF ACTIVE SUBSTANCE(S)
Daily release of etonogestrel and ethinylestradiol: 0.120 mg and 0.015 mg, respectively (for 3 weeks). 1 ring contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol.
3. LIST OF EXCIPIENTS
Excipients: Ethylene vinylacetate copolymer 28% vinylacetate Ethylene vinylacetate copolymer 9% vinylacetate Magnesium stearate
4. PHARMACEUTICAL FORM AND CONTENTS
Vaginal delivery system
1 sachet containing 1 ring for vaginal use 3 sachets containing each 1 ring for vaginal use
5. METHOD AND ROUTE(S) OF ADMINISTRATION
Vaginal use Read the package leaflet before use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
For the dispenser: When Circlet is dispensed to the patient, fill in the box on the packaging. Circlet should be used either within 4 months from the date of dispensing or before the expiry date, whichever comes first.
25
For person dispensing Date dispensed: To be used before:
8. EXPIRY DATE
EXP
9. SPECIAL STORAGE CONDITIONS
Prior to dispensing to the patient, store at 2 – 8C. After dispensing to the patient, Circlet can be stored for up to 4 months at temperatures below 30C.
Store in the original package in order to protect from light and moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE circlet
26
17. UNIQUE IDENTIFIER – 2D BARCODE
2D barcode carrying the unique identifier included.
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
PC: {number} SN: {number} NN: {number}
27
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
SACHET, Circlet 0.120 mg/0.015 mg per 24 hours, vaginal delivery system
1. NAME OF THE MEDICINAL PRODUCT
Circlet, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system etonogestrel / ethinylestradiol
2. STATEMENT OF ACTIVE SUBSTANCE(S)
1 ring contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol.
3. PHARMACEUTICAL FORM AND CONTENTS
Vaginal delivery system 1 ring for vaginal use
4. OTHER SPECIAL WARNING(S), IF NECESSARY
For person dispensing Date dispensed: To be used before:
Open here
5. EXPIRY DATE
EXP:
6. SPECIAL STORAGE CONDITIONS
Store in the original package in order to protect from light and moisture. Store below 30C. Use within 4 months after dispensing but before the expiry date on the package.
7. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
8. BATCH NUMBER
28
Lot:
29
PACKAGE LEAFLET
30 Package leaflet: Information for the user
Circlet, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system Etonogestrel/Ethinylestradiol
Important things to know about combined hormonal contraceptives (CHCs):
They are one of the most reliable reversible methods of contraception if used correctly. They slightly increase the risk of having a blood clot in the veins and arteries, especially in the first year or when restarting a combined hormonal contraceptive following a break of 4 or more weeks. Please be alert and see your doctor if you think you may have symptoms of a blood clot (see section 2 “Blood clots”).
Read all of this leaflet carefully before you start using Circlet because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor, or pharmacist. This medicine has been prescribed for you only. Do not pass it on to others. It may harm them. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet 1. What Circlet is and what it is used for 2. What you need to know before you use Circlet 2.1 When you should not use Circlet 2.2 Warnings and precautions Blood clots Cancer 2.3 Children and adolescents 2.4 Other medicines and Circlet Laboratory tests 2.5 Pregnancy and breast-feeding 2.6 Driving and using machines 3. How to use Circlet 3.1 How to insert and remove Circlet 3.2 Three weeks in, one week out 3.3 When to start with the first ring 3.4 What to do if… Your ring is accidentally expelled from the vagina Your ring has temporarily been out of the vagina Your ring breaks You have inserted more than one ring You have forgotten to insert a new ring after the ring-free interval You have forgotten to remove the ring You have missed a menstrual period You have unexpected bleeding You want to change the first day of your menstrual period You want to delay your menstrual period 3.5 When you want to stop using Circlet 4. Possible side effects 5. How to store Circlet 6. Contents of the pack and other information What Circlet contains
31 What Circlet looks like and contents of the pack Marketing Authorisation Holder and Manufacturer
1. What Circlet is and what it is used for
Circlet is a contraceptive vaginal ring used to prevent pregnancy. Each ring contains a small amount of two female sex hormones – etonogestrel and ethinylestradiol. The ring slowly releases these hormones into the blood circulation. Because of the low amount of hormones that is released, Circlet is considered a low-dose hormonal contraceptive. Since Circlet releases two different types of hormones it is a so-called combined hormonal contraceptive.
Circlet works just like a combined contraceptive pill (the Pill) but instead of taking a pill every day, the ring is used for 3 weeks in a row. Circlet releases two female sex hormones that prevent the release of an egg cell from the ovaries. If no egg cell is released you cannot become pregnant.
2. What you need to know before you use Circlet
General notes Before you start using Circlet you should read the information on blood clots in section 2. It is particularly important to read the symptoms of a blood clot – see section 2 “Blood clots”.
In this leaflet, several situations are described where you should stop using Circlet, or where Circlet may be less reliable. In such situations you should not have intercourse or you should take extra non- hormonal contraceptive precautions – such as using a male condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because Circlet alters the monthly changes of the body temperature and of the cervical mucus.
Circlet, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any other sexually transmitted disease.
2.1 When you should not use Circlet
You should not use Circlet if you have any of the conditions listed below. If you do have any of the conditions listed below, you must tell your doctor. Your doctor will discuss with you what other form of birth control would be more appropriate.
if you have (or have ever had) a blood clot in a blood vessel of your legs (deep vein thrombosis, DVT), your lungs (pulmonary embolus, PE) or other organs; if you know you have a disorder affecting your blood clotting - for instance, protein C deficiency, protein S deficiency, antithrombin – III deficiency, Factor V Leiden or antiphospholipid antibodies; if you need an operation or if you are off your feet for a long time (see section ‘Blood clots’); if you have ever had a heart attack, or a stroke; if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may be a first sign of a heart attack) or transient ischaemic attack (TIA – temporary stroke symptoms); if you have any of the following diseases that may increase your risk of a clot in the arteries: – severe diabetes with blood vessel damage – very high blood pressure – a very high level of fat in the blood (cholesterol or triglycerides) – a condition known as hyperhomocysteinaemia if you have (or have ever had) a type of migraine called ‘migraine with aura’; if you have (had) inflammation of the pancreas (pancreatitis) associated with high levels of fat in your blood.
32 if you have (had) severe liver disease and your liver is not yet working normally. if you have (had) a benign or malignant tumour in the liver. if you have (had), or if you may have, cancer of the breast or the genital organs. if you have any unexplained vaginal bleeding. if you are allergic to ethinylestradiol or etonogestrel, or any of the other ingredients of this medicine (listed in section 6).
If any of these conditions appear for the first time while using Circlet, remove the ring immediately and contact your doctor. In the meantime, use non-hormonal contraceptive measures.
Do not use Circlet if you have hepatitis C and are taking medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see also section 2.4 ‘Other medicines and Circlet’).
2.2 Warnings and precautions
When should you contact your doctor? Seek urgent medical attention – if you notice possible signs of a blood clot that may mean you are suffering from a blood clot in the leg (i.e. deep vein thrombosis), a blood clot in the lung (i.e. pulmonary embolism), a heart attack or a stroke (see ‘Blood clots’ section below). For a description of the symptoms of these serious side effects please go to “How to recognise a blood clot”.
Tell your doctor if any of the following conditions apply to you. If the condition develops, or gets worse while you are using Circlet, you should also tell your doctor. if a close relative has or has ever had breast cancer; if you have epilepsy (see section 2.4: ‘Other medicines and Circlet’); if you have liver disease (for instance jaundice) or gallbladder disease (for instance gallstones); if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease); if you have systemic lupus erythematosus (SLE - a disease affecting your natural defense system); if you have haemolytic uraemic syndrome (HUS - a disorder of blood clotting causing failure of the kidneys); if you have sickle cell anaemia (an inherited disease of the red blood cells); if you have elevated levels of fat in the blood (hypertriglyceridaemia) or a positive family history for this condition. Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas); if you need an operation, or you are off your feet for a long time (see in section 2 ‘Blood clots’); if you have just given birth you are at an increased risk of blood clots. You should ask your doctor how soon after delivery you can start using Circlet; if you have an inflammation in the veins under the skin (superficial thrombophlebitis); if you have varicose veins; if you have a condition that occurred for the first time or worsened during pregnancy or previous use of sex hormones (e.g. hearing loss, porphyria [a disease of the blood], herpes gestationis [skin rash with vesicles during pregnancy], Sydenham’s chorea [a disease of the nerves in which sudden movements of the body occur], hereditary angioedema [you should see your doctor immediately if you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives together with difficulty breathing]; if you have (or have ever had) chloasma (yellowish-brown pigment patches, so called ‘pregnancy patches’, particularly on the face). If so, avoid too much exposure to the sun or ultraviolet light;
33 if you have a medical condition that makes it difficult to use Circlet – for example, if you are constipated, have a prolapse of the uterine cervix or have pain during intercourse; if you have an urgent, frequent, burning, and/or painful urination, and cannot locate the ring in the vagina. These symptoms may indicate accidental placement of Circlet into the urinary bladder.
BLOOD CLOTS
Using a combined hormonal contraceptive such as Circlet increases your risk of developing a blood clot compared with not using one. In rare cases a blood clot can block blood vessels and cause serious problems.
Blood clots can develop in veins (referred to as a ‘venous thrombosis’, ‘venous thromboembolism’ or VTE) in the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE).
Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects or, very rarely, they may be fatal.
It is important to remember that the overall risk of a harmful blood clot due to Circlet is small.
HOW TO RECOGNISE A BLOOD CLOT
Seek urgent medical attention if you notice any of the following signs or symptoms.
Are you experiencing any of these signs? What are you possibly suffering from?
swelling of one leg or along a vein in the leg or foot especially when Deep vein thrombosis accompanied by: pain or tenderness in the leg which may be felt only when standing or walking increased warmth in the affected leg change in colour of the skin on the leg e.g. turning pale, red or blue
sudden unexplained breathlessness or rapid breathing; Pulmonary embolism sudden cough without an obvious cause, which may bring up blood; sharp chest pain which may increase with deep breathing; severe light headedness or dizziness; rapid or irregular heartbeat; severe pain in your stomach;
If you are unsure, talk to a doctor as some of these symptoms such as coughing or being short of breath may be mistaken for a milder condition such as a respiratory tract infection (e.g. a ‘common cold’).
Symptoms most commonly occur in one eye: Retinal vein thrombosis immediate loss of vision or (blood clot in the eye) painless blurring of vision which can progress to loss of vision
chest pain, discomfort, pressure, heaviness Heart attack
34 sensation of squeezing or fullness in the chest, arm or below the breastbone; fullness, indigestion or choking feeling; upper body discomfort radiating to the back, jaw, throat, arm and stomach; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats
sudden weakness or numbness of the face, arm or leg, especially on Stroke one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure.
Sometimes the symptoms of stroke can be brief with an almost immediate and full recovery, but you should still seek urgent medical attention as you may be at risk of another stroke.
swelling and slight blue discolouration of an extremity; Blood clots blocking severe pain in your stomach (acute abdomen). other blood vessels
BLOOD CLOTS IN A VEIN
What can happen if a blood clot forms in a vein? The use of combined hormonal contraceptives has been connected with an increase in the risk of blood clots in the vein (venous thrombosis). However, these side effects are rare. Most frequently, they occur in the first year of use of a combined hormonal contraceptive. If a blood clot forms in a vein in the leg or foot it can cause a deep vein thrombosis (DVT). If a blood clot travels from the leg and lodges in the lung it can cause a pulmonary embolism. Very rarely a clot may form in a vein in another organ such as the eye (retinal vein thrombosis).
When is the risk of developing a blood clot in a vein highest? The risk of developing a blood clot in a vein is highest during the first year of taking a combined hormonal contraceptive for the first time. The risk may also be higher if you restart taking a combined hormonal contraceptive (the same product or a different product) after a break of 4 weeks or more.
After the first year, the risk gets smaller but is always slightly higher than if you were not using a combined hormonal contraceptive.
When you stop using Circlet your risk of a blood clot returns to normal within a few weeks.
What is the risk of developing a blood clot? The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you are taking.
The overall risk of a blood clot in the leg or lung (DVT or PE) with Circlet is small. Out of 10,000 women who are not using any combined hormonal contraceptive and are not pregnant, about 2 will develop a blood clot in a year.
35 Out of 10,000 women who are using a combined hormonal contraceptive that contains levonorgestrel, norethisterone, or norgestimate, about 5-7 will develop a blood clot in a year. Out of 10,000 women who are using a combined hormonal contraceptive that contains norelgestromin, or etonogestrel such as Circlet, between about 6 and 12 women will develop a blood clot in a year. The risk of having a blood clot will vary according to your personal medical history (see “Factors that increase your risk of a blood clot” below). Risk of developing a blood clot in a year Women who are not using a combined hormonal pill/patch/ring About 2 out of 10,000 women and are not pregnant Women using a combined hormonal contraceptive pill containing About 5-7 out of 10,000 women levonorgestrel, norethisterone or norgestimate Women using Circlet About 6-12 out of 10,000 women
Factors that increase your risk of a blood clot in a vein The risk of a blood clot with Circlet is small but some conditions will increase the risk. Your risk is higher: if you are very overweight (body mass index or BMI over 30 kg/m2); if one of your immediate family has had a blood clot in the leg, lung or other organ at a young age (e.g. below the age of about 50). In this case you could have a hereditary blood clotting disorder; if you need to have an operation, or if you are off your feet for a long time because of an injury or illness, or you have your leg in a cast. The use of Circlet may need to be stopped several weeks before surgery or while you are less mobile. If you need to stop using Circlet ask your doctor when you can start using it again; as you get older (particularly above about 35 years); if you gave birth less than a few weeks ago.
The risk of developing a blood clot increases the more conditions you have. Air travel (>4 hours) may temporarily increase your risk of a blood clot, particularly if you have some of the other factors listed. It is important to tell your doctor if any of these conditions apply to you, even if you are unsure. Your doctor may decide that Circlet needs to be stopped. If any of the above conditions change while you are using Circlet, for example a close family member experiences a thrombosis for no known reason, or you gain a lot of weight, tell your doctor.
BLOOD CLOTS IN AN ARTERY
What can happen if a blood clot forms in an artery? Like a blood clot in a vein, a clot in an artery can cause serious problems. For example, it can cause a heart attack or a stroke.
Factors that increase your risk of a blood clot in an artery
It is important to note that the risk of a heart attack or stroke from using Circlet is very small but can increase:
with increasing age (beyond about 35 years); if you smoke. When using a combined hormonal contraceptive like Circlet you are advised to stop smoking. If you are unable to stop smoking and are older than 35 your doctor may advise you to use a different type of contraceptive; if you are overweight;
36 if you have high blood pressure; if a member of your immediate family has had a heart attack or stroke at a young age (less than about 50). In this case you could also have a higher risk of having a heart attack or stroke; if you, or someone in your immediate family, have a high level of fat in the blood (cholesterol or triglycerides); if you get migraines, especially migraines with aura; if you have a problem with your heart (valve disorder, disturbance of the rhythm called atrial fibrillation); if you have diabetes.
If you have more than one of these conditions or if any of them are particularly severe, the risk of developing a blood clot may be increased even more. If any of the above conditions change while you are using Circlet, for example, you start smoking, a close family member experiences a thrombosis for no known reason, or you gain a lot of weight, tell your doctor.
Cancer
The information given below was obtained in studies with combined oral contraceptives and it may also apply to Circlet. Information about vaginal administration of contraceptive hormones (as in Circlet) is not available.
Breast cancer has been found slightly more often in women using combined pills, but it is not known whether this is caused by the treatment. For example, it may be that tumours are found more in women on combined pills because they are examined by the doctor more often. The increased occurrence of breast cancer becomes gradually less after stopping the combined pill.
It is important to regularly check your breasts and you should contact your doctor if you feel any lump. You should also tell your doctor if a close relative has, or ever had breast cancer (see section 2.2 ‘Warnings and precautions’).
In rare cases, benign liver tumours, and in even fewer cases malignant liver tumours have been reported in pill users. Contact your doctor if you have unusual severe abdominal pain. For users of the combined Pill it has been reported that cancer of the endometrium (the lining of the womb) and cancer of the ovaries occur less frequently. This may also be the case for Circlet but this has not been confirmed.
Psychiatric disorders
Some women using hormonal contraceptives including Circlet have reported depression or depressed mood. Depression can be serious and may sometimes lead to suicidal thoughts. If you experience mood changes and depressive symptoms contact your doctor for further medical advice as soon as possible.
2.3 Children and adolescents
The safety and efficacy of Circlet in adolescents under the age of 18 have not been studied.
2.4 Other medicines and Circlet
Always tell your doctor which medicines or herbal products you are already using. Also tell any other doctor or dentist (or the pharmacist) who prescribes another medicine that you use Circlet. They can tell you if you need to take additional contraceptive precautions (for example, male condoms) and if so, for how long, or, whether the use of another medicine you need must be changed.
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Some medicines – can have an influence on the blood levels of Circlet; – can make it less effective in preventing pregnancy; – can cause unexpected bleeding.
These include medicines used for the treatment of: epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate); tuberculosis (e.g. rifampicin); HIV infection (e.g. ritonavir, nelfinavir, nevirapine, efavirenz); Hepatitis C virus infection (e.g. boceprevir, telaprevir); other infectious diseases (e.g. griseofulvin); high blood pressure in the blood vessels of the lungs (bosentan); depressive moods (the herbal remedy St. John’s wort).
If you are taking medicines or herbal products that might make Circlet less effective, a barrier contraceptive method should also be used (for example, a male condom). Since the effect of another medicine on Circlet may last up to 28 days after stopping the medicine, it is necessary to use the additional barrier contraceptive method for that long. Note: Do not use Circle with a diaphragm, cervical cap, or female condom.
Circlet may influence the effect of other medicines, e.g. - medicines containing ciclosporin - the anti-epileptic lamotrigine (this could lead to an increased frequency of seizures)
Do not use Circlet if you have Hepatitis C and are taking medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir as this may cause increases in liver function blood test results (increase in ALT liver enzyme).
Your doctor will prescribe another type of contraceptive prior to the start of treatment with these medicinal products.
Circlet can be restarted approximately 2 weeks after completion of this treatment. See section 2.1 ‘When you should not use Circlet’.
Ask your doctor or pharmacist for advice before taking any medicine.
You can use tampons while using Circlet. Insert Circlet before inserting a tampon. You should be careful when removing a tampon to be sure that the ring is not accidentally pulled out. If the ring does come out, simply rinse the ring in cool to lukewarm water and immediately reinsert it.
Ring breakage has occurred when also using a vaginal product such as lubricant or treatment for infection (see section 3.4 ‘What to do if…Your ring breaks’). Using spermicides or vaginal yeast products will not reduce the contraceptive efficacy of Circlet.
Laboratory tests
If you are having any blood or urinary test, tell your health care professional that you are using Circlet as it may affect the results of some tests.
38 2.5 Pregnancy and breast-feeding
Circlet must not be used by women who are pregnant, or who think they may be pregnant. If you get pregnant while using Circlet you should remove the ring and contact your doctor.
If you want to stop Circlet because you want to get pregnant, see section 3.5 ‘When you want to stop using Circlet’.
Circlet is not usually recommended for use during breast-feeding. If you wish to use Circlet while breast-feeding, please seek the advice of your doctor.
2.6 Driving and using machines
Circlet is unlikely to affect your ability to drive or use machines.
3. How to use Circlet
You can insert and remove Circlet yourself. Your doctor will tell you when to start using Circlet for the first time. The vaginal ring must be put in on the correct day in your monthly cycle (see section 3.3 ‘When to start with the first ring’) and left in place for 3 weeks in a row. Regularly check that Circlet is in your vagina (for example, before and after intercourse) to ensure that you are protected from pregnancy.After the third week, you take Circlet out and have a one week break. You will usually have your monthly period during this ring-free interval
While using Circlet, you should not use certain female barrier contraceptive methods, such as a vaginal diaphragm, cervical cap, or female condom. These contraceptive barrier methods should not be used as your back-up method of birth control because Circlet may interfere with the correct placement and position of a diaphragm, cervical cap, or female condom. You can however use a male condom as an extra barrier contraceptive method.
3.1 How to insert and remove Circlet
1. Before inserting the ring, check that it is not out of date (see section 5 ‘How to store Circlet’). 2. Wash your hands before inserting or removing the ring. 3. Choose the position for inserting that is most comfortable to you, like standing with one leg up, squatting, or lying down. 4. Remove Circlet from its sachet. 5. Hold the ring between your thumb and index finger, press the opposite sides together and insert the ring into the vagina (see Figures 1– 4). Alternatively, you may choose to use the NuvaRing Applicator (not included with Circlet) to help you insert the ring. The NuvaRing Applicator may not be available in all countries. When Circlet is in place you should not feel anything. If you feel uncomfortable, gently change the position of Circlet (e.g., push the ring a bit farther into the vagina) until it is comfortable. The exact position of the ring inside the vagina is not important. 6. After 3 weeks you remove Circlet from the vagina. You can do this by hooking your index finger under the front rim of the ring or by grasping the rim and pulling it out (see Figure 5). If you locate the ring in your vagina, but are unable to remove it, you should contact your doctor. 7. Dispose of the used ring with the normal household waste, preferably inside the reclosable sachet. Do not flush Circlet down the toilet.
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Figure 1 Take Circlet out of the sachet
Figure 2 Compress the ring
Figure 3 Choose a comfortable position to insert the ring
Figure 4A Figure 4B Figure 4C Insert the ring into the vagina with one hand (Figure 4A), if necessary the labia may be spread with the other. Push the ring into the vagina until the ring feels comfortable (Figure 4B). Leave the ring in place for 3 weeks (Figure 4C). Figure 5 Circlet can be removed by hooking the index finger under the ring or by grasping the ring between the index and middle finger and pulling it out.
3.2 Three weeks in, one week out
1. Starting with the day you put it in, the vaginal ring must be left in place without interruption for 3 weeks. 2. After 3 weeks you remove the ring on the same day of the week and at approximately the same time as it was put in. For example, if you put Circlet in on a Wednesday at about 22.00 h, you should remove the ring 3 weeks later, on Wednesday, at about 22.00 h. 3. After you have removed the ring, you do not use a ring for 1 week. During this week a vaginal bleed should occur. Usually this starts 2–3 days after removal of Circlet. 4. Start a new ring exactly after the 1 week interval (again on the same day of the week and approximately the same time), even if you have not stopped bleeding.
40 If the new ring is inserted more than 3 hours too late, the protection from pregnancy may be reduced. Follow the instructions in section 3.4 ‘What to do if…You have forgotten to insert a new ring after the ring-free interval’.
If you use Circlet as described above, your vaginal bleed will take place every month on roughly the same days.
3.3 When to start with the first ring
You have not used a hormonal contraceptive during the last month Insert the first Circlet on the first day of your natural cycle (i.e. the first day of your menstrual period). Circlet starts working straight away. You don’t need to take any other contraceptive precautions. You can also start Circlet between day 2 and day 5 of your cycle, but if you have sexual intercourse during the first 7 days of Circlet use make sure that you also use an additional contraceptive method (such as a male condom). You only have to follow this advice when you use Circlet for the first time.
You have used a combined Pill during the last month Start using Circlet at the latest the day following the tablet-free period of your present Pill. If your Pill pack also contains inactive tablets, start Circlet at the latest on the day after the last inactive tablet. If you are not sure which tablet this is, ask your doctor or pharmacist. Never extend the hormone-free interval of your current Pill pack beyond its recommended length. If you have used the Pill consistently and correctly and if you are sure that you are not pregnant, you can also stop taking the Pill on any day of your current Pill pack and start using Circlet immediately.
You have used a transdermal patch during the last month Start using Circlet at the latest the day following your usual patch-free break. Never extend the patch-free break beyond its recommended length. If you have used the patch consistently and correctly and if you are sure that you are not pregnant, you can also stop using the patch on any day and start using Circlet immediately.
You have used a minipill (progestagen-only pill) during the last month. You can stop taking the minipill any day and start Circlet the next day, at the same time you would normally have taken your pill. But make sure you also use an additional contraceptive method (such as a male condom) for the first 7 days of ring use.
You have used an injectable or implant or a progestagen-releasing intrauterine device (IUD) during the last month. Start using Circlet when your next injection is due or on the day that your implant or your progestagen-releasing IUD is removed. But make sure you also use an additional contraceptive method (such as a male condom) for the first 7 days of ring use.
After having a baby. If you have just had a baby, your doctor may tell you to wait until after your first normal period before you start using Circlet. Sometimes it is possible to start sooner. Your doctor will advise you. If you are breast-feeding and want to use Circlet, you should discuss this first with your doctor.
After a miscarriage or an abortion. Your doctor will advise you.
41 3.4 What to do if…
Your ring is accidentally expelled from the vagina
Circlet may accidentally be expelled from the vagina – for example, if it has not been inserted properly, while removing a tampon, during sexual intercourse, during constipation, or if you have a prolapse of the womb. Therefore, you should regularly check whether the ring is still in your vagina (for example, before and after intercourse).
Your ring has temporarily been out of the vagina
Circlet might still protect you from getting pregnant, but this depends on how long it has been out of your vagina.
If the ring has been out of the vagina for: less than 3 hours, it will still protect you from pregnancy. You should rinse the ring with cold to lukewarm water (do not use hot water) and put the ring back in as soon as possible but only if the ring has been out of the vagina for less than 3 hours. more than 3 hours during the 1st and 2nd week, it may not protect you from pregnancy. You should rinse the ring with cold to lukewarm water (do not use hot water) and put the ring back in the vagina as soon as you remember, and leave the ring in place without interruption for at least 7 days. Use a male condom if you have sexual intercourse during these 7 days. If you are in your 1st week, and you had sexual intercourse during the past 7 days, there is a possibility you may be pregnant. In that case contact your doctor. more than 3 hours in the 3rd week it may not protect you from pregnancy. You should discard that ring and choose between one of the following two options: 1 – Insert a new ring immediately This will start the next three-week use period. You may not have your period, but breakthrough bleeding and spotting may occur. 2 – Do not insert the ring again. Have your period first and insert a new ring no later than 7 days from the time the previous ring was removed or fell out. You should only choose this option if you have used Circlet continuously during the previous 7 days. unknown amount of time, you may not be protected from pregnancy. Perform a pregnancy test and consult your doctor prior to inserting a new ring.
Your ring breaks
Very rarely Circlet may break. Vaginal injury associated with ring breakage has been reported. If you notice that your Circlet has broken, discard it and start with a new ring as soon as possible. Use extra contraceptive precautions (e.g. a male condom) during the next 7 days. If you had sexual intercourse before you noticed the ring breakage, please contact your doctor.
You have inserted more than one ring
There have been no reports of serious harmful effects due to an overdose of the hormones in Circlet. If you have accidentally inserted more than one ring, you may feel sick (nausea) or have vomiting or vaginal bleeding. Remove excess rings and contact your doctor if these symptoms persist.
You have forgotten to insert a new ring after the ring-free interval
If your ring-free interval was longer than 7 days, put a new ring as soon as you remember. Use extra contraceptive precautions (such as a male condom) if you have sexual intercourse during the next
42 7 days. If you had sexual intercourse in the ring-free interval, there is a possibility you may be pregnant. In that case contact your doctor immediately. The longer the ring-free interval, the higher the risk that you have become pregnant.
You have forgotten to remove the ring
If your ring has been left in place for between 3 and 4 weeks, it will still protect you from pregnancy. Have your regular ring-free interval of one week and subsequently insert a new ring. If your ring has been left in place for more than 4 weeks there is a possibility of becoming pregnant. Contact your doctor before you start with a new ring.
You have missed a menstrual period
You have followed the instructions for Circlet If you have missed a menstrual period but you followed the instructions for Circlet, and have not used other medicines, it is very unlikely that you are pregnant. Continue to use Circlet as usual. If you miss your menstrual period twice in a row, however, you may be pregnant. Tell your doctor immediately. Do not start the next Circlet until your doctor has checked you are not pregnant.
If you have not followed the instructions for Circlet If you have missed a menstrual period and you did not follow the instructions, and you do not have your expected period in the first normal ring-free interval, you may be pregnant. Contact your doctor before you start with a new Circlet.
You have unexpected bleeding
While using Circlet, some women have unexpected vaginal bleeding between menstrual periods. You may need to use sanitary protection. In any case, leave the ring in the vagina and continue to use the ring as normal. If the irregular bleeding continues, becomes heavy or starts again, tell your doctor.
You want to change the first day of your menstrual period.
If you follow the instructions for Circlet, your menstrual period (withdrawal bleed) will begin in the ring- free interval. If you want to change the day it starts, you can make the ring-free interval shorter (but never longer!).
For example, if your period usually begins on a Friday, you can change this to a Tuesday (3 days earlier) from next month onwards. Simply insert your next ring 3 days earlier than usual.
If you make your ring-free interval very short (for example, 3 days or less), you may not have your usual bleeding. You may have spotting (drops or flecks of blood) or breakthrough bleeding while using the next ring.
If you are not sure how to proceed, contact your doctor for advice.
You want to delay your menstrual period
Although it is not the recommended regimen, delay of your menstrual period (withdrawal bleed) is possible by inserting a new ring immediately after removing the current ring, with no ring-free interval between rings. You can leave the new ring inserted for up to a maximum of 3 weeks. You may experience spotting (drops or flecks of blood) or breakthrough bleeding while using this new ring. When
43 you want your period to begin, just remove the ring. Have your regular ring free interval of one week and subsequently insert a new ring.
You can ask your doctor for advice before deciding to delay your menstrual period.
3.5 When you want to stop using Circlet
You can stop using Circlet any time you want.
If you do not want to become pregnant, ask your doctor about other methods of birth control.
If you stop using Circlet because you want to get pregnant, you should wait until you have had a natural period before trying to conceive. This helps you calculate when the baby will be due.
4. Possible side effects
Like all medicines, Circlet can cause side effects, although not everybody gets them. If you get any side effect, particularly if severe or persistent, or have any change to your health that you think may be due to Circlet, please talk to your doctor.
An increased risk of blood clots in your veins (venous thromboembolism (VTE)) or blood clots in your arteries (arterial thromboembolism (ATE)) is present for all women taking combined hormonal contraceptives. For more detailed information on the different risks from taking combined hormonal contraceptives, please see section 2, “What you need to know before you use Circlet”.
If you are allergic to one of the ingredients of Circlet (hypersensitivity) you may experience the following symptoms (frequency unknown): angioedema and/or anaphylaxis [swollen face, lips, tongue and/or throat and/or difficulty swallowing] or hives together with difficulty breathing. If this happens, remove Circlet and contact your doctor immediately.
Users of Circlet have reported the following side effects.
Common may affect up to 1 in 10 women abdominal pain, feeling sick (nausea) yeast infection of the vagina (such as ‘thrush’); discomfort in the vagina due to the ring; genital itching; secretion from the vagina headache or migraine; depressive moods; lower sex drive breast pain; pelvic pain; painful menstrual periods acne weight gain the ring falling out
Uncommon may affect up to 1 in 100 women disturbed vision; dizziness swollen abdomen; vomiting, diarrhoea or constipation feeling tired, unwell or irritable; mood changes; mood swings extra fluid in the body (oedema) bladder or urinary tract infection difficulty or pain when passing urine; strong desire or need to pass urine; passing urine more often problems during intercourse, including pain, bleeding or partner feeling the ring increased blood pressure
44 increased appetite back pain; muscle spasms; pain in legs or arms less sensitive skin sore or larger breasts; fibrocystic breast disease (cysts in the breasts which may become swollen or painful) inflammation of the cervix; cervical polyps (growths in the cervix); rolling outward of the margin of the cervix (ectropion) changes to menstrual periods (e.g. periods can be heavy, long, irregular or stop altogether); pelvic discomfort; premenstrual syndrome; spasm of the uterus vaginal infection (fungal and bacterial); burning feeling, smell, pain, discomfort or dryness in the vagina or vulva hair loss, eczema, itching, rash or hot flushes.
Rare: may affect up to 1 in 1,000 women harmful blood clots in a vein or artery, for example: o in a leg or foot (i.e. DVT) o in a lung (i.e. PE) o heart attack o stroke o mini-stroke or temporary stroke-like symptoms, known as a transient ischaemic attack (TIA) o blood clots in the liver, stomach/intestine, kidneys or eye. The chance of having a blood clot may be higher if you have any other conditions that increase this risk. (See section 2 for more information on the conditions that increase risk for blood clots and the symptoms of a blood clot.) breast discharge
Not known (cannot be estimated from the available data) chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face) penis discomfort of the partner (such as irritation, rash, itching) inability to remove ring without medical assistance (e.g., because of adherence to vaginal wall) vaginal injury associated with ring breakage
Breast cancer and liver tumours have been reported in users of combined hormonal contraceptives. For more information, see section 2.2 Warnings and precautions, Cancer.
Very rarely Circlet may break. For more information, see section 3.4 What to do if…Your ring breaks.
Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store Circlet
Keep Circlet out of the sight and reach of children. If you discover that a child has been exposed to the hormones from Circlet, ask your doctor for advice.
Store below 30C. Store in the original package in order to protect from light and moisture.
45 Do not use a Circlet if it was dispensed to you more than 4 months ago. The dispensing date is stated on the carton and sachet.
Do not use Circlet after the expiry date which is stated on the carton and sachet.
Do not use Circlet if you notice a colour change in the ring or any visible signs of deterioration.
Dispose of the used ring with the normal household waste, preferably inside the reclosable sachet. Do not flush Circlet down the toilet. As with other medicines, do not throw away unused or outdated rings via wastewater or household waste. Ask your pharmacist how to throw away any unused rings no longer required. These measures will help protect the environment.
6. Contents of the pack and other information
What Circlet contains The active substances are: etonogestrel (11.7 mg) and ethinylestradiol (2.7 mg) The other ingredients are: ethylene vinylacetate copolymers (28% and 9% vinylacetate) (a type of plastic that will not dissolve in the body) and magnesium stearate.
Etonogestrel and ethinylestradiol are released from the ring at a rate of 0.120 mg/day and 0.015 mg/day, each for 3 weeks.
What Circlet looks like and contents of the pack Circlet is a flexible, transparent, colourless to almost colourless ring, 54 mm wide.
Each ring is packed in a reclosable foil sachet. The sachet is packed in a cardboard box together with this package leaflet. Each box contains 1 or 3 rings. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
[To be completed nationally]
{Name and address} <{tel}> <{fax}> <{e-mail}>
Manufacturer: N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands.
This medicinal product is authorised in the Member States of the EEA under the following name: Circlet 0.120 mg/0.015 mg per 24 hours, vaginal delivery system Belgium, Germany, Greece, Hungary, Luxembourg, The Netherlands, Poland, Portugal, Slovak Republic, Spain.
This leaflet was last revised in month YYYY.
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