1. NAME OF THE MEDICINAL
Bemasive 150/20 microgram film-coated tablets.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 150 micrograms desogestrel and 20 micrograms ethinylestradiol.
For excipients see 6.1.
3. PHARMACEUTICAL FORM
Pale yellow tablets, round, biconvex with "RG" engraved on one side and "P9" on the other.
4.2 Dosage and administration
4.2.1 Taking Bemasive 150/20 microgram film-coated tablets
The tablets should be taken in the order established in the container, every day, about the same time of day. Take one tablet daily for 21 consecutive days. The next pack will begin after an interval of 7 days without treatment; during this rest interval withdrawal bleeding may occur. The bleeding usually starts on the 2nd or 3rd day after taking the last tablet and may not cease before you start taking the next pack.
4.2.2 How to start making Bemasive 150/20 microgram film-coated tablets
No previous decision of hormonal contraceptives (during the last month)
Taking tablets should be started the first day of normal menstrual cycle (ie, the first day that the woman has menstrual bleeding). Taking tablets can also start day 2-5, but during the first cycle is recommended the simultaneous use of a barrier method during the 7 early days of tablet-.
Switching from another oral contraceptive
The woman should start taking Bemasive the day after the normal rest interval or after placebo tablets of former oral contraceptive.
Product change progesterone (minipíldoras, injectable, implants)
Women can replace the mini-pill any day (case of an implant on the day of his retirement, if it is an injection when you have to administer the next injection)
After abortion in 1andr quarter
Taking tablets should begin immediately. In this case no additional contraceptive measures are necessary.
After delivery or abortion in the 2 nd quarter
For women who are breastfeeding - see section 4.6.
Women should be advised to start taking the oral contraceptive on days 21-28 after delivery or abortion in the 2 nd quarter. If you start taking the oral contraceptive later, should be advised the simultaneous use of a barrier method during the 7 early days of tablet taking. If a woman has had sex, pregnancy should be ruled out before you start taking the tablets, or must wait for her first menstrual.
4.2.3 Forget taking tablets
If you have forgotten to take the tablet during less than 12 hours, not reduced contraceptive protection. The woman should take the missed tablet as soon as you remember and take the remaining tablets in the usual way.
If you have forgotten to take the tablet during more 12 hours contraceptive protection may be reduced. If you forget to take tablets must consider the following two basic rules:
1. The continued taking tablets should not be interrupted for a period longer than 7 days.
2. Needed 7 days of uninterrupted tablet taking to achieve a sufficient suppression of the hypothalamic-pituitary-ovarian.
Accordingly, should be made the following recommendation for daily practice:
The woman should take the last missed tablet as soon as you remember, even if it means you have to take 2 tablets at once. Then, continue taking the tablets at the time of day used. During the 7 days following a method must be employed simultaneously barrier, not. a condom. If you have had sex in the 7 days preceding, should be considered pregnancy. The risk of pregnancy increases the more the tablets have been forgotten and the proximity to the regular period of rest from treatment.
The woman should take the last missed tablet as soon as you remember, even if it means you should take 2 both tablets. Then, continues to take tablets at the usual time of day. If the tablets have been taken correctly during the 7 days prior to forget taking the tablet, no further action is necessary to take contraceptive. Nevertheless, if this is not the case, or has forgotten to take over 1 compressed, Women should be advised to use another method of contraception for 7 days.
Due to the proximity of the rest period, the risk of reduced contraceptive protection is imminent. However, this risk can be prevented by adjusting the dosing regimen. Thus, no further action is necessary contraceptive if followed one of the two alternatives shown below, assuming that all tablets are taken correctly during the 7 days prior to forget taking the tablet. If this is not the case, Women should be advised to follow the first of the two alternatives and simultaneously use another method of contraception for the 7 days.
1. The user should take the last missed tablet as soon as you can even if it means you should take 2 both tablets. Then continue to take the tablets at the usual time of day. Start with the next pack immediately after taking the last tablet of the current pack, namely, no break between packs. It is unlikely that the user menstruating until the end of the second pack, but may experience spotting or breakthrough bleeding the days when you are taking the tablets.
2. May also be recommended to women stop taking tablets from the current pack. In this case you must leave a rest period of up 7 days, including the days when you forget to take tablets, and then continue with the next pack.
If a woman has forgotten to take the tablets and then having no menstruation in the first normal period of rest, should be considered a pregnancy.
4.2.4 Caution if vomiting or severe diarrhea
If vomiting or severe diarrhea occurs within 3-4 hours after taking the tablet, it may not be completely absorbed. Therefore, apply the precautions to forget taking tablets as described in paragraph
4.2.3.. If she does not want to change your usual dosage, should take (the) compressed
(s,en) extra needed another container.
4.2.5 As delay a withdrawal bleed
To delay the period, the woman should continue with another pack of Bemasive while resting period. The delay period may be extended as desired until the end of the second container. During the delay of menstruation a woman may experience breakthrough bleeding or spotting. Taking regular Bemasive resumes after the normal period 7 rest days.
To change the period to the next day of the week in which the woman is used under its current cycle, should be advised to shorten the next period of rest for the desired number of days. Shortening the rest period increases the risk of not having menstrual periods, and may have breakthrough bleeding and spotting while taking the tablets from the next pack (as when delaying the period)
Combined oral contraceptives should not be used under any of the following conditions. If it occurs for the first time any of the following conditions while taking oral contraceptives, its use should be stopped immediately.
– Venous thrombosis of the history of venous thrombosis (DVT, pulmonary embolism)
– Arterial thrombosis the history of arterial thrombosis (not. stroke, myocardial
myocardial) or prodromal symptoms (not. angina pectoris and transient ischemic attack)
– The presence of factor / is severe or multiple risk of arterial thrombosis:
– diabetes mellitus with vascular symptoms
– severe hypertension
– dyslipoproteinaemia serious
– Acquired the hereditary predisposition to thrombosis of the venous blood, such as APC resistance, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, anticoagulants lúpico)
– Presence or history of serious liver disease in which liver function values have not returned to normal.
– Present the history of liver tumors (benign or malignant).
– Known breast cancer, prior or suspected.
– Known or suspected malignancies sex steroid.
– Vaginal bleeding diagnosed in.
– History of migraine with focal neurological symptoms.
– Hypersensitivity to the active substances or any of the excipients of tablets coated Bemasive.
4.4 Warnings and precautions for use
If present some of the risk factors listed below, must be weighed against each individual case, the advantages of the use of oral contraceptives against the possible risks, and discuss it with women, before she decides whether to take the oral contraceptive. In case of worsening or if any of these risk factors, Women should consult with your doctor, to decide whether to discontinue the use of oral contraceptive.
1. Circulatory disturbances
Epidemiological studies indicate a relationship between oral contraceptive use and an increased risk of arterial and venous thrombosis and thromboembolic disease, como
Myocardial Infarction, transient ischemic attack, deep vein thrombosis and pulmonary embolism.
The use of any combined oral contraceptive carries an increased risk of venous thromboembolism (TEV) compared con el use. The increased risk of VTE is highest during the first year if the woman has never used a combined oral contraceptive. This increased risk is less than the risk of VTE associated with pregnancy which is estimated at 60 cases 100.000 pregnancies. VTE is fatal in 1-2% cases.
Several epidemiological studies have found that women using combined oral contraceptives ethinylestradiol, most with a dose of 30 g, and a progestin such as desogestrel have an increased risk of VTE compared to those using combined oral contraceptives containing less than 50 mcg of ethinyl estradiol and the progestin levonorgestrel.
For products containing 30 mu.g of ethinylestradiol in combination with desogestrel or gestodene, compared with those containing less than 50 micrograms of ethinyl estradiol and levonorgestrel, the overall relative risk of VTE is estimated in the range of 1,5 a,en 2,0. The incidence of VTE for levonorgestrel combined oral contraceptives with less than 50 μg of ethinyl estradiol are approximately 20 cases 100.000 women / year. To Bemasive the incidence is approximately 30-40 cases 100.000 women per year is, 10-20 Additional cases 100.000 woman-years of use. The relative risk impact on the number of additional cases could be the greatest in women during the first year of use of a combined oral contraceptive when the risk of VTE with all oral contraceptives is higher.
The epidemiological data for oral contraceptives containing desogestrel or gestodene combined with 20 the micrograms etinilestradiol, not suggest a lower risk of VTE than those containing 30 the micrograms etinilestradiol.
All this information should be considered when prescribing these COCs, and when it is advisable to choose a method (s,en) contraceptive (s,en).
Thrombosis in other blood vessels has been reported rarely in women taking oral contraceptives, not. hepatic veins and arteries, mesentéricas, renal or retinal. There is no agreement on whether the occurrence of these cases is related to oral contraceptive use.
Symptoms of venous or arterial thrombosis can include:
– unilateral leg pain unusual and / or swelling
– sudden severe pain in the chest, irradiated or not the left arm.
– sudden fatigue
– sudden attack of coughing
– any unusual headache, intense and prolonged
– sudden loss of vision, Partial total.
– slurred speech or aphasia
– with the collapse without focal seizure
– severe weakness or numbness suddenly affecting one side or one part of the body
– motor disorders
– abdomen "acute"
The risk of venous thromboembolic complications in women taking combined oral contraceptives increases with:
– historic familiar (venous thromboembolism in parents or siblings at a relatively early age). In case of suspected hereditary predisposition, Women should inform the specialist for advice, before deciding on the use of combined oral contraceptives.
– prolonged immobilization, major surgery, any operation in the legs or major trauma. In these situations, it is advisable to stop taking the oral contraceptive (in case of planned surgery, at least 4 weeks before de la intervención) and not reinstituted until 2 weeks after full mobilization. Antithrombotic therapy should be considered.
– obesity (body mass index greater than 30 kg/m2).
– there is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis.
The risk of arterial thromboembolic complications in women taking combined oral contraceptives increases with:
– smoking (be warned older women 35 years not to smoke if they want to use combined oral contraceptives)
– valvular heart
– atrial fibrillation
The presence of a serious risk factor or multiple risk factors for venous or arterial disease respectively, may also constitute a contraindication. You should also take into account the possibility of anticoagulant therapy. The combined oral contraceptive users should contact their physician if any signs of thrombosis. In case of suspicion or presence of thrombosis, should be discontinued the use of combined oral contraceptives. Should begin adequate contraception because of the teratogenicity of anticoagulant therapy (cumarinas)
During the postpartum period, should consider the increased risk of thromboembolism
(For more information, see section 4.6, "Pregnancy and lactation")
Other diseases that have been associated with circulatory disorders including diabetes mellitus, lupus erythematosus, HUS, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia. If an increase in the frequency or severity of migraine during oral contraceptive use (which can be a prodrome of cerebrovascular disorder) you should consider immediate discontinuation of.
In some epidemiological studies have reported an increased risk of cervical cancer in women in long-term treatment with oral contraceptives, but has not yet been sufficiently clarified that extent this finding may be influenced by the sexual behavior and other factors such as human papillomavirus (HPV).
A meta-analysis 54 Epidemiological studies have shown that women who use oral contraceptives have a slightly increased risk of breast cancer diagnosis. The increased risk gradually decreases during 10 years following the cessation of treatment with oral contraceptives. Since breast cancer is rare in women under 40 años, the increased number of cases of breast cancer diagnosed in women who are or have been on oral contraceptives is low, compared with the risk of breast cancer during their lifetime. These studies provide no evidence of a causal relationship. The observed pattern of increased risk may be due to earlier diagnosis of breast cancer in users of oral contraceptives, the biological effects of oral contraceptive or a combination of both. The breast cancer cases diagnosed in women taking oral contraceptives are likely to be clinically less advanced compared to breast cancer cases diagnosed in nonusers.
In rare cases, benign liver tumors have been reported in women taking oral contraceptives, and even more rarely malignant liver tumors. In some cases, these tumors may lead to intra-abdominal bleeding life-threatening. When there is pain in the upper abdomen, in case of liver or if signs of intraabdominal bleeding in women taking oral contraceptives should be considered a liver tumor as a differential diagnosis.
3. Other conditions
Women with hypertriglyceridemia or hereditary predisposition to it may have an increased risk of pancreatitis while taking oral contraceptives.
Although slight increases have been reported blood pressure in women taking oral contraceptives, increases are rare in clinically relevant blood. Only in these rare cases is warranted immediate discontinuation of the oral contraceptive. Not established the relationship between oral contraceptive use and clinical hypertension. If during oral contraceptive use in pre-existing hypertension, constant elevated values of blood pressure or a significant increase in blood pressure does not respond adequately to antihypertensive therapy, discontinue therapy with oral contraceptive. Where considered appropriate, can resume oral contraceptives once they have reached normal blood pressure by antihypertensive therapy.
It has been reported that the following conditions may occur or have been aggravated during pregnancy and oral contraceptive use, but the evidence regarding the use of oral contraceptives is not conclusive: Jaundice and / or pruritus associated with cholestasis; stone formation; porphyria; lupus erythematosus; Hemolytic uremic syndrome; Sydenham chorea; herpes gestationis; loss of hearing due to otosclerosis.
Acute or chronic disorders of liver function may require discontinuation of oral contraceptives, until the parameters have normalized liver function. Recurrent cholestatic jaundice and / or itching associated cholestasis, that can occur in early pregnancy or previous use of sex hormones, requires discontinuation of oral contraceptives.
Although oral contraceptives may influence the peripheral insulin resistance and glucose tolerance, indication that there is no need to change the therapeutic regimen in diabetics using oral contraceptives. However, should be monitored closely for them during oral contraceptive use.
Have been associated with the use of combined oral contraceptives, Crohn's disease, endogenous depression, epilepsy and ulcerative colitis.
Chloasma may occur occasionally, particularly in women with a history of chloasma during pregnancy. Women with a tendency to chloasma should avoid exposure to sunlight or ultraviolet radiation whilst taking oral contraceptives.
4.4.2 Medical examination / consultation
Before starting or resuming the use of Bemasive must obtain a complete medical history
(including family history) and pregnancy must be excluded.
Blood pressure should be measured and should have a physical exam, with reference to the contraindications (º 4.3) and warnings (4.4.).
Also women should be informed that the prospectus carefully read and follow the advice that provides the same. The frequency and nature of examinations should be based on established practices and guidelines should be adapted to each individual woman.
Women should be informed that oral contraceptives do not protect against HIV infection (PAGE) or other sexually transmitted diseases.
4.4.3 Reduced efficacy
The effect of oral contraceptives may be reduced if you forget to take the tablets (º 4.2.3), the intense vomiting diarrhea (º 4.2.4) the concomitant administration of drugs otros (º 4.5.1)
4.4.4 Reduced cycle control
Irregular bleeding may occur (spotting and breakthrough bleeding), outlet associated with any oral contraceptive, particularly during the first months. Therefore evaluate the occurrence of irregular bleeding is only relevant after an adaptation period of approximately 3 cycles.
If irregular bleeding persist or occur after previously regular cycles, Non-hormonal causes should be considered and appropriate precautions should be taken to rule out malignancy or pregnancy. This may include curettage.
Some women do not menstruate during the period of rest from treatment. If you have taken the oral contraceptive under the instructions described in paragraph 4.2, is unlikely that the woman is pregnant. Yes, however, oral contraceptive has not been taken according to the instructions before the disappearance of menstruation, or if not taken two periods, pregnancy should be ruled out before continuing oral contraceptive taking.
Do not use the herb St. John (Hypericum perforatum) while taking Bemasive, because of the risk of decreased plasma concentrations and reduced clinical effects of tablets Bemasive (see 4.5 Interactions).
4.5 Interaction with other medicinal products and other forms of interaction
Drug interactions that result in increased clearance of sex hormones could cause breakthrough bleeding and contraceptive failure.
It has been established with hydantoins, barbiturates, primidona, carbamazepine and rifampin. They are also suspected oxcarbazepine, topiramate, felbamato, griseofulvin nevirapine y. The mechanism of this interaction appears to be based on the properties of induction of hepatic enzymes of these drugs. Maximal enzyme induction is not usually seen until 2-
3 weeks after starting treatment, but it may persist for at least 4 weeks after discontinuation.
It has also been reported contraceptive failure with antibiotics such as ampicillin and tetracycline. This mechanism of action has not been elucidated.
Women subjected to short-term treatment (a week) with any of the drugs included in the groups described above, should temporarily use a barrier method in addition to the oral contraceptive, ie, during the simultaneous making of another drug and for 7 days after the cessation of collection of the same. Women who are taking rifampin should use a barrier method in addition to the oral contraceptive, during the period of treatment with rifampicin and during 28 days after discontinuation of treatment with rifampicin. If the other drugs taken simultaneously exceed the number of tablets of oral contraceptive package, women should begin the next pack of oral contraceptive without observing the usual rest period.
Experts recommend increasing the dose of contraceptive steroids in women undergoing long-term treatment with drugs that induce hepatic enzymes. Another contraceptive method should be recommended if it is not advisable to high doses of contraceptive steroids or high dose is inadequate or unsafe, not. in case of irregular bleeding.
Hierba de San Juan (Hypericum perforatum): should not be taken concurrently with this medication, and that could potentially lead to a loss of contraceptive effect. Have been reported breakthrough bleeding and unwanted pregnancies. This is due to the grass-inducing effect of S. Juan on drug metabolizing enzymes. The inducing effect may persist for at least 2 weeks after cessation of treatment with St. John's wort.
Concomitant administration of ritonavir with a fixed combination of oral contraception leads to a reduction 41% the mean AUC of ethinyl estradiol, for what should be considered an increase in the dose of oral contraceptives containing ethinyl estradiol or alternative contraceptive measures.
4.5.2 Laboratory analysis
The use of contraceptive steroids may influence the results of certain lab tests, biochemical parameters including liver function, thyroid, adrenal y renal; plasma levels of transport proteins, not. corticosteroid fractions bound to globulins and lipid / lipoprotein; metabolism parameters carbohydrates and coagulation parameters and fibrinolysis. The changes usually remain within normal reference values of laboratory.
4.6 Pregnancy and lactation
Bemasive is not indicated in pregnancy.
If pregnancy occurs, Bemasive treatment should be stopped immediately. Nevertheless, large epidemiological studies have shown an increased risk of malformations in children born to women who have taken oral contraceptives before pregnancy, or teratogenic effects after oral contraceptive involuntary intake in early pregnancy.
Lactation may be influenced by oral contraceptive use because they can reduce the quantity and change the composition of breast milk, hence, generally not be recommended to use oral contraceptives final completion of breastfeeding. Small amounts of the contraceptive steroids and / or its metabolites may be excreted with the milk during use of combined oral contraceptives. These amounts can affect a child.
4.7 Effects on ability to drive and use machines
No effects were observed on the ability to drive and use machines.
4.8 Adverse Reactions
For serious adverse reactions in women taking oral contraceptives, see section
4.4 “Warnings and precautions for use”.
There is an increased risk of VTE in all women using a
COC. For information about the differences in risk between oral contraceptives, see section 4.4..
While using Bemasive described the following adverse reactions:
|Organ, systems||Myouand frequent|
Dysmenorrhea PMS breast pain
Dizziness Headache Nervousness Depression Libido
Have been reported following serious adverse reactions in women using combination oral contraceptives are discussed in section 4.4. Warnings and precautions for use ":
– Venous thromboembolism;
– Arterial Thromboembolism;
– Liver tumors;
– Occurrence or deterioration of conditions for which no conclusive relationship has been established with the use of oral contraceptives: Crohn's disease, ulcerative colitis, epilepsy, migraine, endometriosis, mioma uterino, porphyria, Systemic Lupus Erythematosus, herpes gestationis, Sydenham chorea, Hemolytic uremic syndrome, cholestatic jaundice;
No serious adverse effects have been reported after overdose. Symptoms that may occur related to overdose: nausea, vomiting, in young girls, slight vaginal bleeding. No antidote exists, and if necessary should be given symptomatic treatment.
5. Pharmacological properties
Pharmacotherapeutic group: Systemic hormonal contraceptive
ATC code: G 03 AA 09
The contraceptive action of oral contraceptives is based on the interaction of different factors, of which the most important is the inhibition of ovulation and endometrial changes.
Bemasive is a combined oral contraceptive, with ethinyl estradiol and progestin desogestrel. Ethinylestradiol is a well known estrogen synthesis.
Desogestrel is a synthetic progestogen. After oral administration, has potent inhibitory activity of ovulation, strong progestational activity and weak anti-estrogenic activity, not have estrogenic activity, and an activity androgenic / anabolic very weak.
The risk of ovarian and endometrial cancer is reduced with the use of higher doses of combined oral contraceptive (50 the micrograms etinilestradiol). Need to confirm if this also applies to low-dose combined oral contraceptives.
After oral administration of Bemasive, desogestrel is rapidly absorbed and transformed into 3- ceto-desogestrel. The peak plasma level achieved after 1,5 hours. The absolute bioavailability of 3-keto-desogestrel is 62-81%.
The 3-keto-desogestrel has a plasma protein binding 95,5-99%, binding primarily to albumin and SHBG. Increased SHBG ethinylestradiol induced influences the binding percentage and distribution of 3-keto-desogestrel in plasma proteins. Result, the concentration of 3-keto-desogestrel slowly increased during treatment, until it reaches steady state 3-13 days.
Phase I metabolism include hydroxylation of desogestrel catalyzed by cytochrome P-450 and subsequent dehydrogenation C3. The active metabolite 3-keto-desogestrel is then reduced, degradation products are conjugated with sulfate and glucuronide. Animal studies indicate that enterohepatic circulation is not relevant to the activity of desogestrel gestagenic.
The 3-keto-desogestrel is eliminated with a mean half-life of approximately 31 hours (24-38 hours), The plasma clearance varies between 5,0-9,5 l / hour. Desogestrel and its metabolites are excreted through urine and feces, as the free steroid conjugates. The ratio of elimination in urine or faeces is 1,5:1.
At steady state serum level of 3-keto-desogestrel rises two or three times.
Ethinylestradiol is rapidly absorbed and peak plasma levels are achieved after 1,5 hours. Following the conjugation presystemic and first pass metabolism, Absolute bioavailability of 60%. The AUC and Cmax are expected to increase slightly over time.
Ethinylestradiol has a plasma protein binding 98,8%, joining almost exclusively to albumin.
Ethinylestradiol is subject to presystemic conjugation in the mucosa of the small intestine and liver. Hydrolysis of direct conjugates of ethinyl estradiol released by the intestinal flora can be reabsorbed ethinylestradiol, enterohepatic circulation, thereby producing. The route
major metabolic hydroxylation of ethinyl estradiol is mediated by cytochrome P-450, in which major metabolites 2-OH-EE and 2-methoxy-EE. He 2-OH-EE is metabolized later chemically active metabolites.
Ethinylestradiol disappears from plasma with a half-life of approximately 29 hours (26-33 hours), plasma clearance ranges 10-30 l / hour. The conjugates of ethinyl estradiol and its metabolites are excreted through urine and feces (relationship 1:1).
Steady state is reached after 3-4 days, when the serum level of the drug is approximately 30 a 40% higher than after administration of a single dose.
5.3 Preclinical safety data
Toxicological studies have shown no other effects that can be explained based on the hormonal profile Bemasive.
6.1 Excipients ratio
In the compressed: Potato Starch; stearic acid; a-tocoferol; lactose monohydrate; magnesium stearate; colloidal anhydrous silica; povidone K 30; quinoline yellow E 104.
In coating: Hipromelosa; macrogol 600; propylene glycol.
6.4 Special precautions for storage No conservar a temperatura superior a 30 º C. Store in original container.
6.5 Nature and contents of container
Blisters de Aluminio-PVC/PVDC, Blister PVC / PVDC enveloped in aluminum blisters Aluminum-PP envelope with Aluminum, containing 21 tablets or 3 x 21 tablets.
6.6 Instructions for use and handling
No special requirements.
7. HOLDER MARKETING AUTHORIZATION
LABORATORIOS GYNEA, SL. Columbus, 5
08184 Palau-Solita i Plegamans
8. NUMBER marketing authorization
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
10. DATE OF REVISION OF THE TEXT