Rigevidon

Composition: Each tablet contains ethinylestradiol 0.03 mg and levonorgestrel 0.15 mg.
Excipients/Inactive Ingredients: Each tablet contains 33 mg of lactose monohydrate and 22.46 mg of sucrose.
Core: colloidal anhydrous silica, magnesium stearate, talc, maize starch, lactose monohydrate.
Coating: sucrose, talc, calcium carbonate, titanium dioxide (E171), copovidone K90, Macrogol 6000, colloidal anhydrous silica, povidone K30, carmellose sodium.

Pharmacotherapeutic group: Progestogens and estrogens, fixed combinations. ATC code: G03AA07.
Pharmacology: Pharmacodynamics: Combined, estrogen-progestogen mini-pill.
Pearl index: 0.1 per cent women years.
The contraceptive efficacy of Rigevidon arises from 3 complementary actions: at the hypothalamic-pituitary axis by means of inhibition of ovulation; at the cervical mucus which becomes impermeable to migration of spermatozoids; at the endometrium, which becomes inappropriate for implantation.
Pharmacokinetics: Levonorgestrel: Absorption: Levonorgestrel is rapidly and completely absorbed after oral administration of Rigevidon. The bioavailability is approximately 100% and levonorgestrel is not subject to first-pass metabolism.
Distribution: Levonorgestrel is to a large extent bound to albumin and SHBG (Sex Hormon Binding Globulin) in plasma.
Biotransformation: Metabolism is mainly by reduction of the △4-3-oxo group and hydroxylation at the positions 2α, 1β and 16β, followed by conjugation. The majority of the metabolites circulating in the blood are sulphates of 3α, 5β-tetrahydro-levonorgestrel, while excretion mainly takes place as glucuronides. Some of the original levonorgestrel is also circulating as 17β-sulphate. Metabolic clearance is subject to marked inter-individual variation which may partly explain the wide variation in the concentrations of levonorgestrel observed among patients.
Elimination: Levonorgestrel is eliminated with a mean T_½ of approximately 36 hours at steady state. Levonorgestrel and its metabolites are primarily excreted in the urine (40%-68%) and approximately 16%-48% is excreted in the faeces.
Ethinylestradiol: Absorption: Ethinylestradiol is rapidly and completely absorbed, and peak plasma levels are reached after 1.5 hours. Following presystemic conjugation and first-pass metabolism, the absolute bioavailability is 60%. The area under curve and C_max may over time be expected to increase slightly.
Distribution: Ethinylestradiol is to 98.8% bound to plasma proteins, almost entirely to albumin.
Biotransformation: Ethinylestradiol undergoes presystemic conjugation both in the small intestinal mucosa and in the liver. Hydrolysis of the direct conjugates of ethinylestradiol by the intestinal flora gives ethinylestradiol, which can be re-absorbed, thereby creating an enterohepatic circulation. The primary route of metabolism of ethinylestradiol is cytochrome P-450-mediated hydroxylation, where the primary metabolites are 2-OH-ethinylestradiol and 2-methoxy-ethinylestradiol. 2-OH-ethinylestradiol is further metabolised to chemically reactive metabolites.
Elimination: Ethinylestradiol disappears from plasma with a T_½ of approximately 29 hours (26-33 hours), plasma clearance varies from 10-30 l/hour. The excretion of conjugates of ethinylestradiol and its metabolites takes place via urine and faeces (ratio 1:1).
Toxicology: Preclinical safety data: Acute toxicity of ethinylestradiol and levonorgestrel is low. Because of marked species differences preclinical results possess a limited predictive value for the application of estrogens in humans.
In experimental animals estrogens displayed an embryolethal effect already at relatively low doses; malformations of the urogenital tract and feminisation of male fetuses were observed. Levonorgestrel displayed a virilising effect in female fetuses. Reproduction toxicology studies in rats, mice and rabbits revealed no hint for teratogenicity beyond the effect on sexual differentiation.
Preclinical data based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenic potential revealed no particular human risks beyond those discussed in other sections of the CCDS.

Oral contraception.
The decision to prescribe Rigevidon tablets should take into consideration the individual woman's current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with Rigevidon tablets compares with other combined hormonal contraceptives (CHCs) (see Contraindications and Precautions).

Posology: Route of administration: Oral.
How to use Rigevidon: Tablets must be taken orally in the order directed on the blister package at about the same time every day, with some liquid if necessary.
One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7 day tablet-free interval, during which time a withdrawal bleed usually occurs. Withdrawal bleeding will usually start on the 2nd or 3rd day after the last tablet has been taken and it may not have stopped, before the next blister pack is started.
How to start the use of Rigevidon: No preceding hormonal contraceptive use in the past month: Tablet-taking is started on day 1 of the woman's natural cycle (= the first day of menstrual bleeding).
Changing from another combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring or transdermal patch): Take the first tablet the day after the dose of the last active tablet of the previous contraceptive or, at the latest, the day after the usual period of stopping the tablets.
In case of vaginal ring or transdermal patch, take the first tablet the day of removal or at the latest the day scheduled for application of the new device or ring.
Changing from a progestogen-only method (progestogen-only or mini-pills, injection, implant or from a progestogen-releasing intrauterine system (IUS)): Switching from the mini-pill can be performed at any time in the cycle and Rigevidon tablet should be commenced the day after stopping.
Switching from an implant or IUS should occur on the day of removal and for an injectable contraceptive on the day scheduled for the new injection. In all cases, using an additional method of contraception for the 7 first days of treatment is recommended.
After abortion in 1st trimester: The woman may start the tablet intake immediately. In this case, it is not necessary to take further contraceptive precautions.
After delivery or abortion in 2nd trimester: The woman should be advised to start on day 21-28 after delivery in non-lactating women or abortion in the 2nd trimester, because there is an increased risk of thromboembolic disorders during the postpartum period. If starting later than this, the woman should be advised to use a concomitant barrier method during the first 7 days of tablet intake. However, if the woman already had intercourse, pregnancy must be excluded, before starting the tablets, or should wait for the first menstrual bleeding.
In case of breast-feeding: See Use in Pregnancy & Lactation.
Missed tablets: If the woman has forgotten tablet intake for less than 12 hours, the contraceptive protection is not reduced. The woman should take the tablet as soon as remembered, and the remaining tablets should be taken at the usual time.
If the delay exceeds 12 hours, the contraceptive protection may be reduced. Handling of missed active tablets may be managed by the following two basic rules: 1. Tablets should never be delayed for longer than 7 days.
2. Seven days of uninterrupted tablet taking is required to maintain adequate suppression of the hypothalamus-pituitary-ovarian-axis.
Thus, the following advice may be given in daily practice: Week 1: The woman should take the last missed tablet as soon as remembered, even if this means taking 2 tablets at the same time. Hereafter, continue taking the tablets at the usual time point. The woman should use a barrier method concomitantly, e.g. a condom, for the next 7 days. If intercourse has taken place during the previous 7 days, the possibility of pregnancy must be considered. The more forgotten tablets, and the closer to the usual hormone-free interval this takes place, the greater the risk of pregnancy.
Week 2: The woman should take the last missed tablet as soon as remembered, even if this means taking 2 tablets at the same time. Hereafter, continue taking the tablets at the usual time point. Provided that the tablets have been taken correctly during the 7 days preceding the first missed tablet, it is not necessary to take further contraceptive precautions. However, if this is not the case, or if more than 1 tablet has been forgotten, the woman should be advised to additionally use a barrier method (such as a condom) for 7 days.
Week 3: The risk of contraceptive failure is imminent because of the ensuing hormone-free interval. The reduced contraceptive protection may, however, be prevented by adjusting the tablet intake. Therefore, by following one of the following two alternatives, it is not necessary to take further contraceptive precautions, provided that all tablets have been taken correctly during the 7 days preceding the first missed tablet. If this is not the case, the woman should be advised to follow the first of the two alternatives. Additionally a barrier method (such as a condom) should be used concomitantly for the next 7 days.
1. The woman should take the last missed tablet as soon as remembered, even if this means taking 2 tablets at the same time. Thereafter, continue to take the tablets at the usual time point. The woman should start on the next blister pack immediately after taking the last tablet in the current blister pack, i.e. there will be no hormone-free interval between the blister packs. A withdrawal bleeding is unlikely until the end of the second blister pack, but may experience spotting or break through bleeding on the days tablets are being taken.
2. The woman may also be advised to stop taking tablets from the current blister pack. In this case, the woman should keep a hormone-free interval of up to 7 days, including the days the tablets that were forgotten to take, and thereafter continue with the next blister pack.
If the woman has missed tablets and does not get a withdrawal bleeding during the first, normal hormone-free interval, the possibility of pregnancy must be considered.
Advice in case of gastro-intestinal disturbances: In case of severe gastro-intestinal symptoms (e.g. vomiting or diarrhoea), absorption of the active ingredients may not be complete and additional contraceptive measures should be taken.
If vomiting or severe diarrhoea occurs within 3 to 4 hours after taking a tablet, a new tablet should be taken as a replacement as soon as possible. The new tablet should be taken if possible within 12 hours of the usual dose time.
If more than 12 hours elapse, the same instructions as those provided for missed tablets should apply (see "Missed tablets" as previously mentioned).
If the woman does not wish to modify the normal tablet-taking schedule, additional tablets from another blister pack should be taken.
How to delay or shift a withdrawal bleeding: In order to delay a withdrawal bleeding, the woman should continue the next blister pack of Rigevidon, after taking the last tablet in the current pack, without a hormone-free interval. The extension can be carried on for as long as desired until the end of the second blister pack. During the extension the woman may experience break through bleeding or spotting. Regular intake of Rigevidon is resumed after the usual 7 days hormone-free interval.
To shift withdrawal bleeding to another day of the week, rather than the one the woman is used to with the present tablet intake, the woman may be advised to shorten the forthcoming hormone-free interval by as many days as desired. The shorter the interval, the greater the risk that the woman will not have a withdrawal bleeding and will not have breakthrough bleeding or spotting during the second blister pack (which is also the case when delaying a period). It is important to emphasise that the hormone-free interval should not be extended.

Symptoms of overdose of oral contraceptive have been reported in adults, adolescents and children aged 12 and under. Symptoms of overdose can manifest by nausea, vomiting, breast pains, dizziness, abdominal pains, drowsiness/fatigue and vaginal bleeding in young girls. There is no antidote and treatment should only be symptomatic.

Combined oral contraceptives (COCs) are not to be used in the presence of any of the conditions listed as follows. Should any of the conditions appear for the first time during COC use, the product must be stopped immediately.
Presence or risk of venous thromboembolism (VTE): Venous thromboembolism - current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]); 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; Major surgery with prolonged immobilisation (see Precautions); A high risk of venous thromboembolism due to the presence of multiple risk factors (see Precautions).
Presence or risk of arterial thromboembolism (ATE): Arterial thromboembolism - current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris); Cerebrovascular disease - current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA); Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid antibodies (anticardiolipin-antibodies, lupus anticoagulant).
History of migraine with focal neurological symptoms; A high risk of arterial thromboembolism due to multiple risk factors (see Precautions) or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms; severe hypertension; severe dyslipoproteinaemia.
Severe hepatic disease, current or previous, as long as liver function values have not returned to normal.
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.
Hypersensitivity to the active substances levonorgestrel, ethinylestradiol or to any of the excipients of Rigevidon tablets.
Rigevidon is contraindicated for concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see Precautions and Interactions).

Warnings: If any of the conditions/risk factors mentioned as follows is present, the benefits of combined oral contraception use should be weighed against the possible risks for each individual and discussed with the woman before deciding to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors the woman should contact a physician. The physician should then decide on whether COC use should be discontinued.
Circulatory disorders: Risk of venous thromboembolism (VTE): The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) (such as deep vein thrombosis and pulmonary embolism) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. The decision to use Rigevidon tablets should be taken after a discussion with the woman to ensure understanding of the risk of VTE with Rigevidon tablets, how current risk factors influence this risk, and that 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 as follows).
Out of 10,000 women who use a levonorgestrel containing COC about 6¹ will develop VTE in one year. VTE may be fatal in 1% to 2% of the cases.
¹ Mid-point of 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.
Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in contraceptive pill users.
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 1).
Rigevidon tablets is contraindicated if a woman has multiple risk factors that puts the patient at high risk of venous thrombosis (see Contraindications). 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 the 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 Contraindications). (See Table 1.)

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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 see Use in Pregnancy & Lactation).
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 the patient 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 2). Rigevidon tablet is contraindicated if a woman has one serious or multiple risk factors for ATE that puts the woman at high risk of arterial thrombosis (see Contraindications). 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 the total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see Contraindications). (See Table 2.)

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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 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.
Tumours: Cervical cancer: An increased risk of cervical cancer in long-term users of COCs has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behavior and other factors such as human papilloma virus (HPV).
Breast cancer: A meta-analysis of 54 epidemiological studies showed 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. These studies do not provide evidence for causation.
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. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
Liver tumours: In rare cases, benign liver tumors, and even more rarely, malignant liver tumors have been reported in users of COCs. In isolated cases, these tumors have led to life-threatening intra-abdominal hemorrhages. A hepatic tumor should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal hemorrhage occur in women taking COCs.
Other conditions: Hypertriglyceridaemia: Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
Hypertension: Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. Only in these rare cases an immediate discontinuation of COC use is justified. If, during the use of a COC in preexisting hypertension, constantly elevated blood pressure values or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the COC must be withdrawn. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
Liver conditions: The occurrence of acute or chronic liver abnormalities may require the discontinuation of the COC until the liver parameters return to normal.
Angioedema: In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Glucose intolerance/diabetes: Although COCs 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 low-dose COCs. However, diabetic women should be carefully monitored, particularly in the early stage of COC use.
Others: The following conditions have been reported to occur or deteriorate during both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss.
Recurrence of cholestatic jaundice and/or cholestasis-related pruritus which occurred during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs.
Some cases of worsening of endogenous depression, epilepsy, Crohn's disease and of ulcerative colitis has been reported during COC use.
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 taking COCs.
Special attention should be paid to patients with hyperprolactinaemia.
Excipients with known effects: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose free diet should take this amount into consideration.
Medical examination/consultation: Prior to the initiation or reinstitution of ethinylestradiol/levonorgestrel 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 Contraindications) and warnings (see previously mentioned). It is important to draw a woman's attention to the information on venous and arterial thrombosis, including the risk of ethinylestradiol/levonorgestrel 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 on established practice guidelines and be adapted to the individual woman.
Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases (STD).
Reduced efficacy: The efficacy of combined oral contraceptives may be reduced in the event of missed tablets (see Dosage & Administration) vomiting or diarrhoea (see Dosage & Administration) or concomitant medication (see Interactions).
Reduced cycle control: With all combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about 3 cycles.
If bleeding irregularities persist or occur after previously regular cycles, 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 withdrawal bleeding may not occur during the tablet-free interval. If the COC has been taken according to the directions described in Dosage & Administration it is unlikely that the woman is pregnant. However, if the COC has not been taken according to these directions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before COC use is continued.
ALT elevations: During clinical trials with patients treated for hepatitis C virus infections (HCV) with the 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 frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs). Patients who are taking ethinylestradiol-containing medicinal products must switch to an alternative method of contraception (e.g. progestin only contraception or non-hormonal methods) prior to initiating ombitasvir/paritaprevir/ritonavir and dasubuvir therapy. (See Contraindications and Interactions).
Effects on ability to drive and use machines: Rigevidon have no effects or negligible influence on the ability to drive and use machines.

Pregnancy: Rigevidon is not indicated during pregnancy. If the woman becomes pregnant while using ethinylestradiol/levonorgestrel tablets, further intake must be stopped. 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 at unintentional intake of contraceptive pills in early pregnancy. The increased risk of VTE during the postpartum period should be considered when re-starting Rigevidon tablets (see Dosage & Administration and Precautions).
Breastfeeding: Lactation may be influenced by contraceptive pills as they may reduce the amount of breast milk and change its composition. Thus, the use of combined oral contraceptives should generally not be recommended until the nursing mother has weaned the child off breast milk. Small amounts of the contraceptive steroids and/or their metabolites may be excreted in breast milk. These amounts may affect the child. If the woman wishes to breastfeed, another means of contraception should be proposed.

The following adverse effects have been reported during use of ethinylestradiol/levonorgestrel. (See Table 3.)

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Description of selected adverse reactions: An increased risk of arterial and venous thrombotic and thrombo-embolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in Precautions.
The following serious adverse events have been reported in women using COCs, which are discussed in Precautions: Venous thromboembolic disorders; Arterial thromboembolic disorders; Hypertension; Liver tumours; Crohn's disease, ulcerative colitis, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice.
The frequency of diagnosis of breast cancer is slightly increased among OC-users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with COC use is unknown. For further information, see Contraindications and Precautions.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Interactions: Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with oral contraceptives (see Interactions).
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.

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Pharmacodynamic interactions: Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations (see Contraindications and Precautions). Therefore, Rigevidon 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. Rigevidon can be restarted 2 weeks following completion of treatment with this combination drug regimen.
Pharmacokinetic interactions: Effects of other medicinal products on Rigevidon tablets: Interactions can occur with drugs 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. Maximal 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 should temporarily use a barrier method or another method of contraception in addition to the COC. The barrier method must be used during the whole time of the concomitant drug therapy and for 28 days after its discontinuation.
If the drug therapy runs beyond the end of the tablets in the COC pack containing 21 tablets, the next COC pack should be started right after the previous one without the usual tablet-free interval.
Long-term treatment: In women on long-term treatment with enzyme-inducing active substances, another reliable, nonhormonal, method of contraception is recommended.
The following interactions have been reported in the literature: Substances increasing the clearance of COCs (diminished efficacy of COCs by enzyme-induction), e.g.: Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and HIV medication ritonavir, nevirapine and efavirenz and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate and products containing the herbal remedy St. John's Wort (Hypericum perforatum).
Substances with variable effects on the clearance of COCs: When co-administered with COCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of estrogen or progestins. The net effect of these changes may be clinically relevant in some cases.
Therefore, the prescribing information of concomitant HIV/HCV medications should be consulted to identify potential interactions and any related recommendations. In case of any doubt, an additional barrier contraceptive method should be used by women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor therapy.
Effects of Rigevidon tablets on other medicinal products: Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
Other forms of interaction: Troleandomycin: Troleandomycin may increase the risk of intrahepatic cholestasis during coadministration with COCs.
Modafinil: Risk of reduction of contraceptive efficacy during the treatment and a cycle after discontinuation of the treatment with modafinil, because of its enzyme inducer potential.
Use normodosed oral contraceptives or another contraceptive method.
Vemurafenib: Risk of reduction of estrogen and progestogen concentrations, with a consequent risk of lack of efficacy.
Perampanel: For perampanel doses greater or equal to 12 mg/d: risk of reduced contraceptive efficacy.
Preferably use another contraceptive method, especially mechanical.
Rufinamide: Moderate reduction in ethinylestradiol concentrations. Preferably use another contraceptive method, especially mechanical.
Etoricoxib: Increased concentrations of ethinylestradiol with etoricoxib.
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 blood coagulation and fibrinolysis. The changes generally remain within the normal laboratory range.

Store below 30°C.
Shelf-life: 2 years.

Oral Contraceptives

G03AA07 - levonorgestrel and ethinylestradiol ; Belongs to the class of progestogens and estrogens in fixed combinations. Used as systemic contraceptives.

C