Eloine 3 mg FC tablets

u2022 Oral contraceptive.

u2022 Treatment of moderate acne vulgaris in women seeking oral contraception.

u2022 Treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who have chosen oral contraception as their method of birth control. The efficacy of ELOINE for PMDD was not assessed beyond 3 cycles. ELOINE has not been evaluated for treatment of premenstrual syndrome (PMS).

Method of administration: Oral use. ELOINE, when taken correctly, has a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly. Tablets must be taken in the order directed on the package, at about the same time every day, with some liquid if needed. One tablet is taken daily for 28 days. Each subsequent pack is started the day after the last intake of the previous pack. A withdrawal bleed usually starts on day 2 to 3 after starting the placebo tablets (white tablets in the last row) and may not be finished before the next pack is started.

How to start ELOINE:

No preceding hormonal contraceptive use (in the past month): Tablet-taking has to start on day 1 of the womanu2019s natural cycle (i.e. the first day of her menstrual bleeding). Starting on days 2 to 5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.

Changing from a combined hormonal contraceptive (combined oral contraceptive), vaginal ring or transdermal patch: The woman should start with ELOINE preferably on the day after the last active tablet of her previous combined oral contraceptive, but at the latest on the day following the usual tablet-free or inactive tablet interval of her previous combined oral contraceptive. In case a vaginal ring or transdermal patch has been used, the woman should start using ELOINE preferably on the day of removal, but at the latest when the next application would have been due.

Changing from a progestogen-only method (minipill, injection, implant) or from a progestogen-releasing intrauterine system: The woman may switch any day from the minipill, from an implant or the intrauterine system on the day of its removal and from an injectable when the next injection would be due, but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking.

Following first-trimester abortion: The woman may start immediately. When doing so, she need not take additional contraceptive measures.

Following delivery or second-trimester abortion: For breastfeeding women see u201cPregnancy and lactationu201d. Women should be advised to start at day 21 to 28 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 tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of ELOINE use or the woman has to wait for her first menstrual period.

Combined oral contraceptives such as ELOINE should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during treatment with ELOINE, the product should be stopped immediately.

• Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.
• Presence or history of prodromata of a thrombosis (e.g. transient ischaemic attack, angina pectoris).
• History of migraine with focal neurological symptoms.
• Diabetes mellitus with vascular involvement.
• The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis (see u201cWarningsu201d).
• Severe hepatic disease as long as liver function values have not returned to normal.
• Severe renal insufficiency or acute renal failure with a creatinine clearance of < 30 ml/min.
• Presence or history of liver tumours (benign or malignant).
• Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts).
• Undiagnosed vaginal bleeding.
• Known or suspected pregnancy.
• Hypersensitivity to the active substances or to any of the excipients.

Circulatory disorders: Epidemiological studies have suggested an association between the use of ELOINE and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. The risk of VTE is highest during the first year of use. This increased risk is present after initially starting ELOINE or restarting (following a 4 week or greater pill free interval) the same or a different combined oral contraceptive. Data from a large, prospective 3-armed cohort study suggest that this increased risk is mainly present during the first 3 months. Overall the risk for venous thromboembolism (VTE) in users of low estrogen dose combined oral contraceptives is two to threefold higher than for non-users of combined oral contraceptives who are not pregnant.

VTE may be life-threatening or may have a fatal outcome. Venous thromboembolism, manifesting as deep venous thrombosis and/or pulmonary embolism, may occur. The occurrence of thrombosis has been reported in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in ELOINE users. Arterial thromboembolic events may be life-threatening or may have a fatal outcome. The risk of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident increases with:

• age;
• smoking (with heavier smoking and increasing age the risk increases further, especially in women over 35 years of age);
• a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any combined oral contraceptive use;
• obesity (body mass index over 30 kg/mu00b2);
• dyslipoproteinaemia;
• hypertension;
• migraine;
• valvular heart disease;
• atrial fibrillation;
• prolonged immobilisation, major surgery, any surgery to the legs, or major trauma.

In these situations it is advisable to discontinue combined oral contraceptive use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation. The increased risk of thromboembolism in the puerperium must be considered (see u201cPregnancy and lactationu201d). Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease. An increase in frequency or severity of migraine during ELOINE use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the ELOINE.

Biochemical factors that may be indicative of a hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyperhomocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

Tumours: The most important risk factor for cervical cancer is persistent human papilloma virus infection. Some epidemiological studies have indicated that long-term use of ELOINE may further contribute to an increased risk of cervical cancer. 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 ELOINE. The excess risk gradually disappears during the course of the 10 years after cessation of ELOINE use. Benign liver tumours and, even more rarely, malignant liver tumours have been reported in users of ELOINE. In isolated cases, these tumours have led to life-threatening intraabdominal haemorrhages. A hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intraabdominal haemorrhage occur in women taking ELOINE.

Other conditions: Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using combined oral contraceptives such as ELOINE. Small increases in blood pressure have been reported in many women taking ELOINE and clinically relevant increases may occur. If a sustained clinically significant hypertension develops during the use of ELOINE then it is prudent for the medical practitioner to withdraw ELOINE and treat the hypertension. The occurrence or deterioration of the following conditions have been reported with ELOINE use: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenhamu2019s chorea; herpes gestationis; otosclerosis-related hearing loss. In women with hereditary angioedema exogenous oestrogens such as ELOINE may induce or exacerbate symptoms of angioedema. Acute or chronic disturbances of liver function may necessitate the discontinuation of ELOINE. Recurrence of cholestatic jaundice which first occurred during pregnancy or previous use of sex steroids necessitates the discontinuation of ELOINE. ELOINE may have an effect on peripheral insulin resistance and glucose tolerance. Hence diabetic women should be carefully observed while taking ELOINE. Crohnu2019s disease and ulcerative colitis have been associated with combined oral contraceptive such as ELOINE. Chloasma may 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 taking ELOINE.

Medical examination/consultation: A complete medical history and physical examination should be taken prior to the initiation or reinstitution of ELOINE use, guided by the u201cContra-indicationsu201d and u201cWarningsu201d, and should be repeated periodically. Periodic medical assessment is also of importance because contra-indications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of ELOINE. The frequency and nature of these assessments should be based on established practice guidelines and be adapted to the individual woman, but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests. Women should be advised that ELOINE does not protect against HIV infections (AIDS) and other sexually transmitted diseases (STDs). Women should be advised that additional barrier contraceptive measures are needed to prevent transmission of STDs and HIV infection.

Interactions between ELOINE and other medicines may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

Hepatic metabolism: Interactions can occur with medicines that induce microsomal enzymes, which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St Johnu2019s Wort). Also, HIV protease (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and combinations of them, have been reported to potentially affect hepatic metabolism.

Interference with enterohepatic circulation: Some clinical reports suggest that enterohepatic circulation of oestrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines). Women on treatment with any of these medicines should temporarily use a barrier method in addition to ELOINE or choose another method of contraception. With microsomal enzyme-inducing medicines, the barrier method should be used during the time of concomitant medicine administration and for 28 days after their discontinuation. Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after discontinuation. If the period during which the barrier method is used runs beyond the end of the active tablets in the ELOINE pack, the inactive tablets should be omitted and the next pack of ELOINE should be started with the active tablets in the white section (i.e. without the usual inactive tablet interval).

The main metabolites of drospirenone in human plasma are generated without involvement of the cytochrome P450 system. Inhibitors of this enzyme system are therefore unlikely to influence the metabolism of drospirenone. ELOINE may affect the metabolism of certain other medicines. Accordingly, plasma and tissue concentrations either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine). Based on in vitro inhibition studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin and midazolam as marker substrates, an interaction of drospirenone at doses of 3 mg with the metabolism of other medicines is unlikely.

Other interactions: There is a potential for an increase in serum potassium in women taking ELOINE with other medicines that may increase serum potassium levels. Such medicines include angiotensin-II-receptor antagonists, potassium-sparing diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone (combined with estradiol) with an ACE inhibitor or indomethacin, no clinically or statistically significant differences in serum potassium concentrations were observed. No formal interaction studies were carried out with tuberculosis or HIV treatments. Note: The package insert information of concomitant medications should be consulted to identify potential interactions.

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 lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range. Drospirenone causes an increase in plasma renin activity and plasma aldosterone induced by its mild antimineralocorticoid activity.

ELOINE is not indicated during pregnancy. If pregnancy occurs during treatment with ELOINE, further intake should be stopped. The use of ELOINE is not recommended during breastfeeding. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk.

No studies on the effects on the ability to drive and use machines have been performed. No effects on ability to drive and use machines have been observed in users of combined oral contraceptives such as ELOINE.

The frequencies of adverse reactions (ARs) reported in clinical trials with drospirenone/ethinylestradiol are summarised in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (u2265 1/10), common (u2265 1/100 to < 1/10), uncommon (u2265 1/1 000 to < 1/100) and rare (u2265 1/10 000 to < 1/1 000).

* including breast tenderness ** including vaginal discharge *** bleeding irregularities usually subside during continued treatment

The most appropriate MedDRA term to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well. The following serious adverse events have been reported in women using combined oral contraceptives, which are discussed in the u201cWarningsu201d section:

• venous thromboembolic disorders;
• arterial thromboembolic disorders;
• cerebrovascular accidents;
• hypertension;
• hyperkalaemia (in patients with renal impairment and pre-treatment upper reference range serum potassium levels);
• hypertriglyceridaemia;
• changes in glucose tolerance or effect on peripheral insulin resistance;
• liver tumours (benign and malignant);
• liver function disturbances;
• chloasma;
• in women with hereditary angioedema exogenous oestrogens as contained in ELOINE may induce or exacerbate symptoms of angioedema;
• occurrence or deterioration of: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenhamu2019s chorea; herpes gestationis; otosclerosis-related hearing loss, Crohnu2019s disease, ulcerative colitis, cervical cancer.

The frequency of diagnosis of breast cancer is slightly increased among oral contraceptives users. Causation with combined oral contraceptives use is unknown. For further information, see sections u201cContra-indicationsu201d and u201cWarningsu201d.

The following adverse reactions have been identified worldwide during post approval use of ELOINE: Immune system disorder: hypersensitivity. Psychiatric disorder: altered mood. Eye disorder: contact lens intolerance. Gastrointestinal disorders: abdominal pain, diarrhoea. Skin and subcutaneous tissue disorders: rash, urticarial, erythema nodosum, erythema multiforme. Reproductive system and breast disorders: breast enlargement.

On the basis of general experience with combined oral contraceptives, symptoms that may occur in case of taking an overdose of active tablets are: nausea; vomiting; and, in young girls, slight vaginal bleeding. Treatment should be symptomatic and supportive.