http___www.krenizdravo.com_korisno_upute_novynette-uputa-o-lijeku_1.xml
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Name of the medicinal product Qualitative and quantitative composition Pharmaceutical form Clinical particulars - 4.1 Therapeutic indications - 4.2 Posology and method of administration - 4.3 Contraindications - 4.4 Special warnings and precautions for use - 4.5 Interaction with other medicinal products and other forms of interaction - 4.6 Fertility, pregnancy and lactation - 4.7 Effects on ability to drive and use machines - 4.8 Undesirable effects - 4.9 Overdose Pharmacological properties - 5.1 Pharmacodynamic properties - 5.2 Pharmacokinetic properties - 5.3 Preclinical safety data Pharmaceutical particulars - 6.1 List of excipients - 6.2 Incompatibilities - 6.3 Shelf life - 6.4 Special precautions for storage - 6.5 Nature and contents of container - 6.6 Special precautions for disposal and other handling Marketing authorisation holder Marketing authorisation number(s) Date of first authorisation/renewal of the authorisation Date of revision of the text How to take QlairaTablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. Tablet taking is continuous. One tablet is to be taken daily for 28 consecutive days. Each subsequent pack is started the day after the last tablet of the previous wallet. Withdrawal bleeding usually starts during the intake of the last tablets of a wallet and may not have finished before the next wallet is started. In some women, the bleeding starts after the first tablets of the new wallet are taken. How to start Qlaira• No preceding hormonal contraceptive use (in the past month)Tablet-taking has to start on day 1 of the woman's natural cycle (i.e. the first day of her menstrual bleeding). • Changing from a combined hormonal contraceptive (combined oral contraceptive /COC), vaginal ring, or transdermal patchThe woman should start with Qlaira on the day after the last active tablet (the last tablet containing the active substances) of her previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Qlaira on the day of removal. • Changing from a progestogen-only method (progestogen-only pill, injection, implant) or from a progestogen-releasing intrauterine system (IUS) The woman may switch any day from the progestogen-only pill (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 be advised to additionally use a barrier method for the first 9 days of tablet-taking. • Following first-trimester abortion The woman may start immediately. When doing so, she needs not take additional contraceptive measures.• Following delivery or second-trimester abortion For breastfeeding women see section 4.6. 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 9 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period. Management of missed tabletsMissed (white) placebo tablets can be disregarded. However, they should be discarded to avoid unintentionally prolonging the interval between active-tablet taking. The following advice only refers to missed active tablets:If the woman is less than 12 hours late in taking any tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time. If she is more than 12 hours late in taking any tablet, contraceptive protection may be reduced. The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Depending on the day of the cycle on which the tablet has been missed (see chart below for details), back-up contraceptive measures (e.g. a barrier method such as a condom) have to be used according to the following principles:Not more than two tablets are to be taken on a given day. If a woman has forgotten to start a new wallet, or if she has missed one or more tablets during days 3 -9 of the wallet, she may already be pregnant (provided she has had intercourse in the 7 days before the oversight). The more tablets (of those with the two combined active ingredients on days 3 24) that are missed and the closer they are to the placebo tablet phase, the higher the risk of a pregnancy. If the woman missed tablets and subsequently has no withdrawal bleed at the end of the wallet /beginning of new wallet, the possibility of a pregnancy should be considered. Paediatric populationNo data available for use in adolescents below 18 years. Advice in case of gastro-intestinal disturbancesIn case of severe gastro-intestinal disturbances (e.g., vomiting or diarrhoea), absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after active tablet-taking, the next tablet should be taken as soon as possible. This tablet should be taken within 12 hours of the usual time of tablet-taking, if possible. If more than 12 hours elapse, the advice concerning missed tablets, as given in section 4.2 Management of missed tablets, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the corresponding tablet(s) needed from another pack. WarningsIf any of the conditions or risk factors mentioned below is present, the suitability of Qlaira 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 Qlaira should be discontinued. In case of suspected or confirmed VTE or ATE, CHC use should be discontinued. In case anticoagulant therapy is started, adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins). No epidemiological studies on the effects of estradiol/ estradiol valerate containing COC's exist. All the following warnings and precautions are derived from clinical and epidemiological data of ethinyl estradiol containing COCs. Whether these warning and precautions apply to Qlaira is unknown.• 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. It is not yet known how the risk with Qlaira compares with these lower risk products. The decision to use any product other than one known to have the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with CHCs, 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). Epidemiological studies in women who use low dose (<50 ug ethinylestradiol) combined hormonal contraceptives have found that out of 10,000 women between about 6 and 12 will develop a VTE in one year It is estimated that out of 10,000 women who use a levonorgestrel-containing CHC about 61 will develop a VTE in one year. It is not yet known how the risk of VTE with CHCs that contain dienogest in combination with estradiol compares with the risk with low dose levonorgestrel-containing CHCs. The number of VTEs per year with low dose CHCs 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. 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 VTEThe 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). Qlaira 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 VTEThere 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:o unilateral swelling of the leg and/or foot or along a vein in the lego pain or tenderness in the leg which may be felt only when standing or walkingo increased warmth in the affected leg; red or discoloured skin on the leg. Symptoms of pulmonary embolism (PE) can include:o sudden onset of unexplained shortness of breath or rapid breathingo sudden coughing which may be associated with haemoptysiso sharp chest paino severe light headedness or dizzinesso 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 ATEThe risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see table). Qlaira 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). Table: Risk factors for ATE Symptoms of ATEIn 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:o sudden numbness or weakness of the face, arm or leg, especially on one side of the bodyo sudden trouble walking, dizziness, loss of balance or coordinationo sudden confusion, trouble speaking or understandingo sudden trouble seeing in one or both eyeso sudden, severe or prolonged headache with no known causeo 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:o pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastboneo discomfort radiating to the back, jaw, throat, arm, stomacho feeling of being full, having indigestion or chokingo sweating, nausea, vomiting or dizzinesso extreme weakness, anxiety, or shortness of breatho rapid or irregular heartbeats.• TumoursAn increased risk of cervical cancer in long-term users of COCs (> 5 years) 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 behaviour and other factors such as human papilloma virus (HPV). 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. 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. 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. 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 taking COCs.• Other conditionsWomen with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of a COC then it is prudent for the physician to withdraw the COC and treat the hypertension. Where considered appropriate, COC 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 COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss. In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs. 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 (containing <0.05 mg ethinylestradiol). However, diabetic women should be carefully observed while taking COCs, particularly in the early stage of COC use. Worsening of endogenous depression, of epilepsy, of 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. Estrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. Patients with terminal renal insufficiency should be closely observed, since the level of circulating estrogens may be increased after administration of Qlaira. This medicinal product contains not more than 50 mg lactose per tablet. 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/consultationPrior to the initiation or reinstitution of Qlaira 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 contra-indications (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 Qlaira 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 hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases. Reduced efficacyThe efficacy of COCs may be reduced for example in the following events: missed active tablets (section 4.2), gastro-intestinal disturbances (section 4.2) during active tablet taking or concomitant medication (section 4.5). Cycle controlWith all COCs, 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. Based on patient diaries from a comparative clinical trial, the percentage of women per cycle experiencing intracyclic bleeding was 10 18 % for women using Qlaira. Users of Qlaira may experience amenorrhea although not being pregnant. Based on patient diaries, amenorrhea occurs in approximately 15% of cycles. If Qlaira has been taken according to the directions described in Section 4.2, it is unlikely that the woman is pregnant. If Qlaira has not been taken according to these directions prior to the first missed withdrawal bleed or if the withdrawal bleeding is missed in two consecutive cycles, pregnancy must be ruled out before Qlaira use is continued. 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. 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 PregnancyQlaira should not be used during pregnancy. If pregnancy occurs during use of Qlaira, further intake should be stopped. However, extensive epidemiological studies with ethinylestradiol containing COCs 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 taken inadvertently during pregnancy. Animal studies do not indicate a risk for reproductive toxicity (see section 5.3). The increased risk of VTE during the postpartum period should be considered when re-starting Qlaira (see section 4.2 and 4.4). BreastfeedingLactation may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs 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. These amounts may affect the child. FertilityQlaira is indicated for the prevention of pregnancy. For information on return to fertility, see section 5.1. Description of selected adverse reactionsAn 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 section 4.4. Occurrence of amenorrhea and intracyclic bleeding based on patient diaries is summarized in section 4.4 Cycle control. The following serious adverse events have been reported in women using COCs, which are discussed in section 4.4 Special warning and precautions for use:- Venous thromboembolic disorders;- Arterial thromboembolic disorders;- Hypertension;- Liver tumours; - Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn's disease, ulcerative colitis, epilepsy, migraine, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice;- Chloasma;- Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.- In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema. The frequency of diagnosis of breast cancer is very slightly increased among COC 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 sections 4.3 and 4.4. In addition to the above mentioned adverse reactions, erythema nodosum, erythema multiforme, breast discharge and hypersensitivity have occurred under treatment with ethinylestradiol containing COCs. Although these symptoms were not reported during the clinical studies performed with Qlaira, the possibility that they also occur under treatment cannot be ruled out. Reporting of suspected adverse reactionsReporting 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. AbsorptionOrally administered dienogest is rapidly and almost completely absorbed. Maximal serum concentrations of 90.5ng/ml are reached at about 1 hour after oral administration of the Qlaira tablet containing 2 mg estradiol valerate + 3 mg dienogest. Bioavailability is about 91 %. The pharmacokinetics of dienogest is dose-proportional within the dose range of 1 8 mg. Concomitant food intake has no clinically relevant effect on the rate and extent of dienogest absorption. DistributionA relatively high fraction of 10% of circulating dienogest is present in the free form, with approx. 90% being bound non-specifically to albumin. Dienogest does not bind to the specific transport proteins SHBG and CBG. The volume of distribution at steady state (Vd,ss) of dienogest is 46 l after the intravenous administration of 85 µg 3H-dienogest. MetabolismDienogest is nearly completely metabolized by the known pathways of steroid metabolism (hydroxylation, conjugation), mainly by CYP3A4. The pharmacologically inactive metabolites are excreted rapidly resulting in dienogest as the major fraction in plasma accounting for approximately 50% of circulating dienogest derived compounds. The total clearance following the intravenous administration of 3H-dienogest was calculated as 5.1 l/h. EliminationThe plasma half-life of dienogest is approximately 11 hours. Dienogest is extensively metabolized and only 1% of drug is excreted unchanged. The ratio of urinary to fecal excretion is about 3:1 after oral administration of 0.1 mg/kg. Following oral administration, 42% of the dose is eliminated within the first 24 h and 63% within 6 days by renal excretion. A combined 86% of the dose is excreted by urine and feces after 6 days. Steady-State ConditionsPharmacokinetics of dienogest are not influenced by SHBG levels. Steady state is reached after 3 days of the same dosage of 3 mg dienogest in combination with 2 mg estradiol valerate. Trough, maximum and average dienogest serum concentrations at steady state are 11.8 ng/ml, 82.9 ng/ml and 33.7 ng/ml, respectively. The mean accumulation ratio for AUC (0-24h) was determined to be 1.24.• Estradiol valerate AbsorptionAfter oral administration estradiol valerate is completely absorbed. Cleavage to estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites estrone and estriol. Maximal serum estradiol concentrations of 70.6 pg/ml are reached between 1.5 and 12 hours after single ingestion of the tablet containing 3 mg estradiol valerate on Day 1. MetabolismThe valeric acid undergoes very fast metabolism. After oral administration approximately 3% of the dose is directly bioavailable as estradiol. Estradiol undergoes an extensive first-pass effect and a considerable part of the dose administered is already metabolized in the gastrointestinal mucosa. Together with the presystemic metabolism in the liver, about 95 % of the orally administered dose becomes metabolized before entering the systemic circulation. The main metabolites are estrone, estrone sulfate and estrone glucuronide. DistributionIn serum 38 % of estradiol is bound to SHBG, 60 % to albumin and 2-3 % circulate in free form. Estradiol can slightly induce the serum concentrations of SHBG in a dose-dependent manner. On day 21 of the treatment cycle, SHBG was approximately 148% of the baseline, it decreased to about 141% of the baseline by day 28 (end of placebo phase). An apparent volume of distribution of approximately 1.2 l/kg was determined after iv. administration. EliminationThe plasma half-life of circulating estradiol is about 90 min. After oral administration, however, the situation differs. Because of the large circulating pool of estrogen sulfates and glucuronides, as well as enterohepatic recirculation, the terminal half-life of estradiol after oral administration represents a composite parameter which is dependent on all of these processes and is in the range of about 13-20 h. Estradiol and its metabolites are mainly excreted in urine, with about 10% being excreted in the stool. Steady-state conditionsPharmacokinetics of estradiol are influenced by SHBG levels. In young women, the measured estradiol plasma levels are a composite of the endogenous estradiol and the estradiol generated from Qlaira. During the treatment phase of 2 mg estradiol valerate + 3 mg dienogest, maximum and average estradiol serum concentrations at steady state are 66.0 pg/ml and 51.6 pg/ml, respectively. Throughout the 28 day cycle, stable minimum estradiol concentrations were maintained and ranged from 28.7 pg/ml to 64.7 pg/ml. Special PopulationsPharmacokinetics of Qlaira was not investigated in patients with impaired renal or liver function. Bayer plc Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why? Active ingredients Legal categories This site uses cookies. By continuing to browse the site you are agreeing to our policy on the use of cookies. Continue
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NOVYNETTE- uputa o lijeku » pravilo 7 dana, doziranje, nuspojave Sastav Jedna filmom tableta sadržava 0,020 mg etinilestradiola i 0,150 mg dezogestrela. Pomoćne tvari: laktoza hidrat, krumpirov škrob, povidon, stearatna kiselina, silicijev dioksid, koloidni, bezvodni, magnezijev stearat, ά-tokoferol, boja kinolin žuta (E 104), hipromeloza, makrogol 6000, propilenglikol. Farmaceutski oblik i veličina pakovanja Filmom obložena tableta. 21 (1×21) filmom obložena tableta u blisteru (PVC/PVDC//Al), u kutiji Farmakoterapijska skupina i djelovanje Pripravci koji djeluju na urogenitalni sustav i spolni hormoni; Spolni hormoni i ostali pripravci koji djeluju na spolni sustav; Progestageni i estrogeni, fiksne kombinacije. Način i mjesto izdavanja Na recept, u ljekarni. Terapijske indikacije Oralna kontracepcija. Kontraindikacije – Trudnoća ili sumnja na trudnoću (koja se još ne može isključiti) ili dojenje. – Umjerena do teška hipertenzija – Hiperlipoproteinemija – Arterijska tromboza prisutna ili u anamnezi (npr. infarkt miokarda, cerebrovaskularni akcident). – Usto, prisutnost više od jednoga faktora rizika za arterijsku bolest. – Potvrđena venska tromboembolija u anamnezi (VTE); Idiopatska VTE u obiteljskoj anamnezi. Drugi poznati faktori rizika za nastanak VTE. – Šećerna bolest s krvožilnim komplikacijama – Teška jetrena bolest, kolestatska žutica ili hepatitis (akutni virusni ili nevirusni), ili te bolesti u anamnezi, ako se rezultati testova jetrene funkcije nisu vratili na normalne vrijednosti, te 3 mjeseca nakon što se utvrdi da testovi jetrene funkcije pokazuju normalne vrijednosti; anamneza žutice u trudnoći ili žutice uslijed uporabe steroida, kronična obiteljska nehemolitična žutica i Dubin-Johnsonov sindrom, tumori jetrenih stanica i porfirija. – Kolelitijaza – Poznati tumori koji ovise o estrogenu ili sumnja na njih, hiperplazija endometrija; nedijagnosticirano vaginalno krvarenje. – Sistemski eritematozni lupus ili ta bolest u anamnezi. – U anamnezi tijekom trudnoće ili ranije uporabe steroida: – teški pruritus – pemfigoid gestationis – žutica – manifestacija ili pogoršanje otoskleroze – Preosjetljivost na bilo koji sastojak Novynette tableta Mjere opreza Ako je prisutna bilo koja od niže navedenih bolesti, liječnik će za svaku ženu pojedinačno procijeniti kolika je korist od uporabe kombiniranih oralnih kontraceptiva (engl. COC) u odnosu na moguće rizike, te isto s njom razmotriti, prije nego što ona odluči da će ga početi koristiti. Pacijenticu treba biti pod strogim nadzorom. U slučaju agravacije, pogoršanja ili pojave bilo koje od tih bolesti ili faktora rizika dok pacijentica uzima pilulu, uporabu pilule valja prekinuti, koristiti alternativne nehormonske metode kontracepcije (ne metode određivanja sigurnih dana ili temperature), te bez odlaganja zatražiti savjet liječnika. – Poremećaji koagulacije. – Druge bolesti povezane s povećanim rizikom od kardiovaskularnih bolesti kao što je latentno ili očito zatajenje srca, renalna disfunkcija, ili ta stanja u anamnezi. – Epilepsija ili to stanje u anamnezi. – Migrena ili to stanje u anamnezi. – Kolelitijaza u anamnezi. – Prisutnost bilo kojeg faktora rizika za nastanak tumora ovisnih o estrogenu; ginekološki poremećaji osjetljivi na estrogen, kao što su fibromiomi maternice i endometrioza (Vidi niže navedeni tekst; Pilula i karcinom). – Šećerna bolest. – Teška depresija ili ta bolest u anamnezi. Ako je ona popraćena poremećajem metabolizma triptofana, primjena vitamina B6 mogla bi imati terapijsku vrijednost. – Hemoglobinopatija srpastih stanica, jer pod određenim okolnostima, npr. tijekom infekcija ili anoksije, pripravci koji sadrže estrogen mogu izazvati tromboembolijski proces u pacijentica s tom bolešću. – Ako rezultati testova jetrene funkcije postanu abnormalni, valja prekinuti uporabu. Pilula i tromboza Neka epidemiološka ispitivanja navode na zaključak da postoji povezanost između uporabe kombiniranih oralnih kontraceptiva i povećanog rizika od arterijskih i venskih trombotičnih i tromboembolijskih bolesti, kao što je infakrt miokarda, moždani udar, duboka venska tromboza i pulmonarna embolija. Ti događaji rijetko nastupaju. Dokazano je da postoji povećani rizik od razvoja venske tromboembolije (engl.VTE) povezano s uporabom oralnih kontraceptiva. Prekomjerni rizik od VTE najveći je tijekom prve godine, kada žena po prvi put koristi neki kombinirani oralni kontraceptiv. Manji je od rizika koji je povezan s trudnoćom, koji je procijenjen kao 60 slučajeva na 100.000 trudnoća. Neka su epidemiološka ispitivanja zabilježila da u žena koje upotrebljavaju kombinirane oralne kontraceptive koji sadrže desogestrel ili gestoden (takozvane pilule treće generacije), postoji veći rizik od VTE, nego u onih koje upotrebljavaju pilule što sadrže levonorgestrel (takozvane pilule druge generacije). Rizik od tromboembolije (venske i/ili arterijske) povećava se s: – dobi – pušenjem (rizik se to povećava što je pušenje jače, a dob starija, osobito u žena starijih od 35 godina) – pozitivnom obiteljskom anamnezom (t.j. je li u brata, sestre ili roditelja u relativno mladoj dobi, ikada postojala venska ili arterijska tromboembolija). Ako se sumnja na nasljednu predispoziciju, ženu valja uputiti specijalisti radi savjetovanja, prije nego što se odluči za uporabu bilo kojeg kombiniranog oralnog kontraceptiva (COC) – pretilosti (indeks tjelesne mase veći od 30kg/m2 ) – dislipoproteinemijom – hipertenzijom – valvularnom bolesti srca – fibrilacijom atrija – diabetesom – dugotrajnijom imobilizacijom, većim kirurškim zahvatom, svakim operacijskim zahvatom na nogama, ili težom ozljedom. U tim se situacijama preporuča prekinuti uporabu kombiniranog oralnog kontraceptiva (u slučaju elektivnog operacijskog zahvata, barem četiri tjedna prije njega), a nastaviti ga uzimati tek dva tjedna nakon što se postigne potpuna pokretljivost. Nema usklađenog mišljenja o mogućoj ulozi varikoznih vena i tromboflebitisa površinskih vena kod venske tromboembolije. Liječnik mora uzeti u obzir povećani rizik od tromboembolije u puerperiju. Druga medicinska stanja koja se povezuju sa štetnim vaskularnim događajima, uključuju diabetes mellitus, sistemski eritematozni lupus, uremijski hemolitični sindrom, kroničnu upalnu bolest crijeva (Crohnova bolest ili ulcerativni kolitis), te bolest srpastih stanica. Povećanje učestalosti ili intenziteta migrene tijekom uporabe COC-a (što može prethoditi cerebrovaskularnom događaju) može biti razlogom za trenutačan prekid uporabe COC-a. Znakovi i simptomi tromoboembolije mogu uključivati: – iznenadnu jaku bol u prsima, bez obzira da li se širi u lijevu ruku; – iznenadno pomanjkanje daha; – svaku neuobičajenu jaku, dugotrajnu glavobolju, osobito ako se javlja prvi put ili postaje sve gora, ili je povezana s bilo kojim od slijedećih simptoma: – nenadani parcijalni ili potpuni gubitak vida ili diplopija – afazija – vertigo – jaki napad nesvjestice – kolaps sa žarišnom epilepsijom ili bez nje – slabost ili vrlo izražena neosjetljivost koja iznenada zahvaća jednu stranu ili jedan dio tijela – motorički poremećaji – jaka bol u potkoljenici jedne noge – “akutni” abdomen. Pilula i karcinom Uporaba oralnih kontraceptiva koji sadrže estrogen, može ubrzati rast postojećih tumora koji ovise o spolnim steroidima. Zbog toga je uporaba tih oralnih kontraceptiva kontraindicirana u bolesnica s takvim tumorima. U brojnim epidemiološkim ispitivanjima praćen je rizik pojave karcinoma jajnika, endometrija, cerviksa i dojke u žena koje koriste kombinirane oralne kontraceptive. Jasno je dokazano da kombinirani oralni kontraceptivi nude stvarnu zaštitu i od raka jajnika i od raka endometrija. Povećani rizik od cervikalnog karcinoma u dugoročnih korisnica kombiniranih oralnih kontraceptiva zabilježen je u nekim ispitivanjima, no i dalje postoji kontroverza o stupnju u kojem se to može pripisati učincima spolnog ponašanja i drugim faktorima. Meta-analiza iz 54 epidemiološka ispitivanja zabilježila je da postoji nešto povećani relativni rizik (RR = 1,24) da će se rak dojke dijagnosticirati u žena koje sada koriste kombinirane oralne kontraceptive (COC). Zapaženi model povećanog rizika može biti zbog ranije dijagnoze raka dojke u korisnica kombiniranih oralnih kontraceptiva, zbog njihovih bioloških učinaka, ili zbog kombinacije ovo dvoje. Veća je vjerojatnost da će dodatni slučajevi raka dojke koji su dijagnosticirani u sadašnjih COC korisnica, ili u žena koje su ih koristile tijekom posljednjih deset godina, biti lokalizirani u dojci, nego oni u žena koje nikada nisu koristile kombinirane oralne kontraceptive. Rak dojke je rijedak među ženama mlađim od 40 godina, bez odbzira da li uzimaju COC. Dok se taj osnovni rizik povećava s dobi, veliki broj dijagnoza raka dojke u žena koje sada koriste ili su nedavno koristile COC, je malen u odnosu na opći rizik od raka dojke. Najvažniji faktor rizika raka dojke u korisnica COC-a jest dob u kojoj žene prekidaju uporabu COC-a; što je žena starija kada prestaje s primjenom, to se više dijagnosticira rak dojke. Trajanje uporabe je manje važno, a prekomjerni rizik postupno nestaje tijekom 10 godina nakon prekida primjene COC-a, tako da izgleda da za 10 godina više nije prekomjeran. S korisnicom valja razmotriti moguće povećanje rizika od raka dojke, te ga procijeniti u odnosu na koristi od kombiniranih oralnih kontraceptiva, uzimajući u obzir dokaz da nude stvarnu zaštitu od rizika od razvoja nekih drugih oblika raka (npr. rak jajnika i endometrija). U rijetkim su slučajevima u dugoročnih korisnica oralnih kontraceptiva zabilježeni maligni tumori jetre. Benigni se tumori jetre također povezuju s uporabom oralnih kontraceptiva. Na tumor jetre valja pomišljati u diferencijalnoj dijagnozi, kada se javi bol u gornjemu dijelu abdomena, kada je jetra povećana ili postoje znakovi intraabdominalnog krvarenja. Smanjena pouzdanost Kada se Novynette tablete uzimaju prema uputama za uporabu, gotovo da ne postoji vjerojatnost da će doći do trudnoće. No, pod slijedećim se okolnostima može smanjiti pouzdanost oralnih kontraceptiva. Zaboravljene tablete Pod uvjetom da je manje od 12 sati zakasnila uzeti tabletu, pacijentica je treba uzeti čim se sjeti. Slijedeće tablete treba uzimati u uobičajeno vrijeme. Novynette će tijekom toga ciklusa još uvijek pružati kontraceptivnu zaštitu. Ako je s uzimanjem jedne ili više tableta zakasnila više od 12 sati, onda slijedećih 7 dana neće biti zaštićena. Ako se jedna ili više tableta zaborave duže od 12 sati, kontraceptivna će zaštita biti smanjena. Pacijentica treba uzeti posljednju tabletu koju je zaboravila, čak i onda ako to znači da mora uzeti dvije tablete u jednome danu, a nakon toga nastaviti uzimati tablete u normalno vrijeme. Slijedećih se 7 dana trebaju primjenjivati dodatne kontraceptivne mjere opreza, a pacijentica se treba pridržavati “Pravila 7 dana”. Ako se nakon uzimanja tablete javi povraćanje ili proljev, postoji mogućnost nedostatne aporpcije. Ako simptomi nestanu unutar 12 sati od uzimanja tablete, pacijentica treba uzeti dodatnu tabletu iz rezervnog pakovanja, te nastaviti, kao obično, uzimati tablete iz starog pakovanja. No, ako simptomi ustraju duže od tih 12 sati, dodatne su kontraceptivne mjere opreza potrebne za svaki spolni odnos tijekom trajanja želučanih i crijevnih tegoba, te tijekom slijedećih 7 dana (liječnik mora uputiti pacijenticu da se pridržava “Pravila 7 dana”). Ako pacijentica uzima određene druge lijekove Ako pacijentica uzima bilo koji od lijekova koji su navedeni u poglavlju “Interakcije”, liječnik je treba uputiti da se pridržava “Pravila 7 dana”: PRAVILO 7 DANA - Ako pacijentica zaboravi jednu tabletu dulje od 12 sati. - Ako pacijentica povraća ili ima proljev dulje od 12 sati. - Ako pacijentica uzima bilo koji od lijekova koji su navedeni pod naslovom Interakcije. - Pacijentica treba nastaviti uzimati tablete na uobičajeni način, te: - slijedećih 7 dana mora provoditi dodatne kontraceptivne mjere opreza - ALI – ako potroši sve tablete iz tekućeg pakovanja prije isteka tih 7 dana, mora započeti koristiti slijedeće pakovanje čim potroši sve tablete iz tekućeg pakovanja; t.j. između dva pakovanja ne smije ostavljati razmak. (Time se spriječava produžena stanka u uzimanju tableta, koja može povećati rizik od toga da jajnici otpuste jajašce i da se na taj način smanji kontraceptivna zaštita.) - Pacijentica neće imati menstruaciju sve dok ne potroši tablete iz 2 pakovanja, no to joj neće naškoditi, a ako dođe do oskudnog krvarenja u dane kada uzima tablete, to nije ništa ozbiljno. Ako se nakon nekoliko mjeseci uzimanja Novynette tableta iznenada pojavi točkasto ili probojno krvarenje (koje tijekom prethodnih ciklusa nije uočeno), ili izostane abrupcijsko krvarenje, kontraceptivna zaštita može biti smanjena. Ako ne nastupi abrupcijsko krvarenje, a nije se desio niti jedan od gore navedenih događaja, postoji velika vjerojatnost da nije riječ o trudnoći, a uporaba oralnog kontraceptiva može se nastaviti sve do kraja slijedećeg pakovanja. (Ako na kraju drugog ciklusa ne dođe do abrupcijskog krvarenja, treba prekinuti uzimati tablete i isključiti trudnoću, prije nego što se može nastaviti s korištenjem oralnog kontraceptiva.) No, ako je abrupcijsko krvarenje izostalo, a nastupio je bilo koji od gore spomenutih događaja, valja prekinuti uzimati tablete, te isključiti trudnoću, prije nego što se može ponovno uvesti uporaba oralnog kontraceptiva. Ovaj članak ima više stranica: