Yasmin 3mg/0.03mg 21 tabs, Drospirenone, Ethinyl Estradiol
THIS IS A BRAND MEDICATION
Oral contraceptive with antimineralocorticoid and antiandrogenic effects also beneficial for women with retention of hormone and the resulting symptoms and for women with acne and seborrhea.
Pharmacokinetics in Humans:
Pharmacodynamics: The contraceptive effect of COCs is based on the interaction of various factors, the most important of which is inhibition of ovulation and changes in cervical secretion. In addition to protection against pregnancy, COCs have several positive properties which, together with the negative properties (see Precautions and Adverse Effects) may be useful in choosing a method of birth control. The cycle is more regular, menstruation is often less painful and less intense bleeding. The latter may reduce the incidence of iron deficiency.
Drospirenone has beneficial properties in addition to contraception. Drospirenone has antimineralocorticoid activity that can prevent weight gain and other symptoms caused by fluid retention.
Compensates for the sodium retention caused by estrogen, which results in a very good tolerance, and has positive effects on premenstrual syndrome. In combination with ethinyl estradiol, drospirenone exhibits favorable lipid profile with increased HDL. Drospirenone exerts antiandrogenic activity, which produces a positive effect on the skin and reducing acne lesions and sebum production. In addition, drospirenone does not counteract the increase in SHBG induced by ethinylestradiol which is useful for binding and inactivation of endogenous androgens.
Drospirenone has no androgenic activity of all, estrogen, glucocorticoid and antiglucocorticoid. This, together with antimineralocorticoid and antiandrogen properties, gives a Biochemical and pharmacological profile very similar to the natural hormone progesterone. There is also evidence of reduced risk of endometrial cancer and ovarian cancer.
It has also been shown that higher dose COCs (0.05 mg ethinyl estradiol) reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Has yet to confirm whether this also applies to low-dose COCs.
Absorption: Administered orally, drospirenone is rapidly absorbed and almost completely. With a single administration of the drug reach maximum concentration in serum of about 37 ng / ml within 1-2 hours.
The absolute bioavailability is between 76 and 85%. Concomitant food intake does not affect bioavailability.
Distribution: Drospirenone binds to serum albumin and binds to sex hormone-binding globulin (sex hormone binding globulin, SHBG) or corticosteroid binding globulin (corticoid binding globulin, CBG). Only 3% to 5% of the total concentrations of drug are present in serum free steroid and 95-97% is bound to albumin nonspecifically.
Increased SHBG induced ethinylestradiol not affect the binding of drospirenone to serum proteins. The apparent volume of distribution of drospirenone is from 3.7-4.2 l / kg.
Metabolism Drospirenone is metabolized completely. In plasma, the major metabolites are the acid form of drospirenone, which is generated by opening the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, the two are formed without the intervention of P-450 . According to in vitro, drospirenone is metabolized to a lesser extent by cytochrome P-450 3A4.
The rate of elimination from serum is 1.2-1.5 ml / min / kg. When administered acutely drospirenone together with ethinylestradiol, there was no direct interaction.
Elimination: The serum levels of drospirenone decrease in two phases. The terminal elimination phase is characterized by a half life of approximately 31 hours. Drospirenone is not excreted in unchanged form. Drospirenone metabolites are excreted in bile and urine in a proportion of 1.2 to 1.4. The half-life of excretion of metabolites in urine and feces is approximately 1.7 days.
Steady-state conditions: The pharmacokinetics of drospirenone is not influenced by the concentration of SHBG.
After daily administration, serum drug concentrations increase two to three times, reaching steady state conditions during the second half of the treatment cycle.
Effects of renal impairment: Serum levels of steady-state drospirenone in women with mild compromise of renal function (creatinine clearance CLcr of 50-80 ml / min) are comparable to those of women with normal renal function (CLcr> 80 ml / min). Serum drospirenone levels were on average 37% higher in women with moderate compromise of kidney function (CrCl 30-50 ml / min) compared with those obtained in women with normal renal function. Drospirenone treatment was well tolerated by all groups.
Treatment with drospirenone showed no clinically significant effect on serum potassium.
Effects of liver involvement: In women with moderate compromise liver function (Child-Pugh B), the mean profiles of serum concentration-time drospirenone were comparable with those of women with normal liver function during the phases of absorption / distribution, Cmax similar values.
The reduction in serum drospirenone during the terminal disposition phase was approximately 1.8 times higher in volunteers with moderate compromise liver function, compared with volunteers with normal hepatic function. A decrease of approximately 50% in the apparent oral clearance (CL / f) in volunteers with moderate liver impairment, compared with those volunteers with normal hepatic function.
The observed decline in drospirenone clearance in volunteers with moderate compromise of liver function compared with healthy volunteers, did not result in an apparent difference in serum potassium between the 2 groups of volunteers. Even in the presence of diabetes and concomitant treatment with spironolactone (two factors that may predispose the patient to hyperkalemia), there was an increase in serum potassium levels above the upper limit of normal. Based on the results of this study can conclude that the combination ethinylestradiol / spironolactone is well tolerated in patients with mild or moderate liver impairment (Child-Pugh B).
Ethnic groups: The effect of ethnicity on the pharmacokinetics of drospirenone and ethinyl estradiol after oral single and repeated to young, healthy women, both Caucasian and Japanese. The results showed that ethnic differences between Japanese and Caucasian women had no clinically relevant effect on the pharmacokinetics of drospirenone and ethinyl estradiol.
Absorption: Ethinylestradiol is rapidly and completely absorbed after oral administration. Maximum serum concentrations are reached approximately 54-100 pg / ml after 1-2 hours. During absorption and first liver passage, ethinylestradiol is metabolized extensively, resulting in a mean oral bioavailability of 45%, with a large interindividual variation of about 20-65%.
Concomitant food intake reduced the bioavailability of ethinyl estradiol by approximately 25% of the subjects, whereas there was no change in others.
Distribution: Ethinylestradiol is highly but non-specifically to serum albumin (approximately 98%) and induces an increase in serum SHBG. The calculated apparent volume of distribution of ethinylestradiol is 2.8-8.6 l / kg.
Metabolism Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver.
Ethinylestradiol is primarily metabolized by aromatic hydroxylation but with formation of various hydroxylated and methylated metabolites, which are present as free metabolites and as conjugates with glucuronide and sulfate. Has reported a clearance rate of between 2.3 and 7.0 ml / min / kg.
Elimination: The serum concentrations of ethinyl estradiol decrease in two disposition phases characterized by half-lives of 1 hour and 10-20 hours respectively.
Ethinylestradiol is not removed intact, the proportion of urinary excretion: biliary metabolites of ethinylestradiol is 4:6. The half-life of metabolite excretion is about 1 day.
Steady-state conditions: The conditions for the steady state is reached during the second half of a cycle of treatment, when serum drug concentrations are higher in 40-110%, compared with those obtained with a single dose.
CONTRAINDICATIONS You should not use oral contraceptives (COCs) in the presence of any of the situations listed below. You must immediately stop using the prepared if any of them for the first time during his employment:
• Presence or history of thrombotic / thromboembolic arterial or venous (eg deep vein thrombosis, pulmonary embolism, myocardial infarction) or stroke.
• Presence or history of prodrome of a thrombosis (eg transient ischemic attack, angina pectoris).
• History of migraine with focal neurological symptoms.
• Diabetes mellitus with vascular involvement.
• The presence of a serious risk factor or multiple risk factors for arterial or venous thrombosis may also constitute a contraindication (see Precautions).
• Presence or history of pancreatitis associated with hypertriglyceridemia.
• Presence or history of severe liver disease while the liver function values â€‹â€‹have not returned to normal.
• severe renal insufficiency or acute renal failure.
• Presence or history of liver tumors (benign or malignant).
• known or suspected neoplasms, influenced by sex steroids (eg of the genital organs or the breasts).
• Vaginal bleeding undiagnosed.
• Known or suspected pregnancy thereof.
• Hypersensitivity to the active substances or any of the excipients.
Warnings: If you present any of the conditions or risk factors listed below, one must assess the risk / benefit of COCs for each individual woman and discussed with her before you decide to start using them. In case of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact your doctor who will decide whether to discontinue the use of COCs.
Circulatory Disorders Epidemiological studies have suggested an association between the use of COCs and an increased risk of thrombotic and thromboembolic diseases, arterial and venous, as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These events are rare.
During the use of all COCs, you may receive venous thromboembolism (VTE), manifesting as deep venous thrombosis and / or pulmonary embolism. The risk of venous thromboembolism is highest during the first year a woman ever uses a COC. The approximate incidence of VTE in users of COCs with low estrogen dose (<0.05 mg ethinylestradiol) is up to 4 per 10,000 woman years compared to 0.5 to 3 per 10,000 women-years in women not using COCs. The incidence of VTE associated with pregnancy is 6 per 10,000 pregnant woman years.
There have been extremely rare cases of thrombosis in other blood vessels, eg hepatic veins and arteries, mesenteric, renal, cerebral or retinal, in COC users. There is no consensus on whether the occurrence of these events is associated with the use of COCs.
Symptoms of thrombotic / thromboembolic events or arterial venous stroke may include: pain and / or swelling in one leg, sudden severe chest pain which may radiate to left arm or not sudden dyspnea, cough home Sudden, unusual headaches, intense and prolonged, sudden loss of vision, partial or complete, diplopia, slurred speech or aphasia, dizziness, collapse with or without focal seizures, weakness or very marked numbness suddenly affecting one side or a body part, movement disorders, abdomen "acute".
The risk of thrombotic / thromboembolic venous or arterial stroke increases with the following:
- Smoking (with heavier smoking and increasing age the risk increases, especially in women over 35 years).
- Family history positive (eg, venous or arterial thromboembolism in a sibling or parent at a relatively early age). If you suspect a hereditary predisposition, the woman should be referred to a specialist before deciding about any COC use.
- Obesity (BMI over 30 kg/m2).
- Valvular heart disease.
- Atrial Fibrillation.
- Prolonged immobilisation, major surgery, any surgery to the legs or major trauma. In these circumstances it is advisable to discontinue COC use (in case of elective surgery at least four weeks in advance) and not resume until two weeks after they complete remobilisation.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.
It should take into account the increased risk of thromboembolism in the puerperium (see Restrictions on use during pregnancy and lactation).
Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be grounds for immediate suspension of the AOC.
Biochemical factors that may indicate a hereditary or acquired predisposition for venous or arterial thrombosis include resistance to activated protein C (APC) resistance, hyperhomocysteinaemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When considering the risk / benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with use of low-dose COCs (<0.05 mg ethinylestradiol).
Tumors: The most important risk factor for developing cervical cancer is persistent infection with human papilloma virus (HPV). Some epidemiological studies have indicated that long-term use of COCs may further contribute to this increased risk but there continues to what extent this finding is attributable to confounding factors, eg cervical screening and sexual behavior, including use of barrier contraceptives.
A meta-analysis of 54 epidemiological studies 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 10 years following the suspension of the AOC. Since breast cancer is rare in women under 40 years, the overdiagnosis of breast cancer in current users and recent COC is small relative to the overall risk of breast cancer. These studies provide evidence for causation.
The observed pattern of increased risk may be due to a diagnosis of breast cancer earlier in COC users, the biological effects of COCs or a combination of both. Breast cancers diagnosed in women using COCs on occasion tend to be less advanced clinical point of view than those diagnosed in never-users.
In COC users have been observed in rare cases benign liver tumors, and even more rarely, malignant in rare cases have caused bleeding in the abdominal cavity with danger to the life of the patient. Consideration should be given a liver tumor in the differential diagnosis of women taking COCs and severe upper abdominal pain, enlarged liver or signs of intraabdominal bleeding.
Other entities: In patients with renal impairment may be limited capacity to excrete potassium. In a clinical study, drospirenone intake showed no effect on serum potassium concentration in patients with mild or moderate. One can only assume is a theoretical risk of hyperkalemia in patients whose serum potassium level before treatment is at the upper limit of reference, and also using potassium sparing drugs.
Women with hypertriglyceridemia or a family history thereof, may be at increased risk of pancreatitis when using COCs.
Although small increases have been reported in blood pressure in women taking COCs, few cases of clinical relevance. Antimineralocorticoid effect of drospirenone may counteract the increase in blood pressure induced by ethinylestradiol observed in normotensive women using other COCs.
However, if there is a sustained clinically significant hypertension when using AOC, it is prudent for the physician to withdraw the COC and treat hypertension. When appropriate, you can restart the AOC if antihypertensive treatment achieved normal pressure values.
Although not shown conclusively that there is an association has been reported that the following occur or deteriorate with both pregnancy and COC use: jaundice and / or pruritus related to cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea, herpes gestationis, hearing loss associated with otosclerosis.
In women with hereditary angioedema, administration of exogenous estrogens may induce or exacerbate symptoms of angioedema.
The 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 has been presented for the first time during pregnancy or during 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 that is necessary to alter the therapeutic regimen in diabetics using low-dose COCs (containing <0.05 mg ethinylestradiol). However, diabetic women taking COCs must be carefully observed.
Has been associated with COC use Crohn's disease and ulcerative colitis.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to sunlight or ultraviolet radiation whilst taking COCs.
Examination / medical consultation prior to the initiation or reinstitution of COC is necessary to obtain a medical history and physical examination, guided by the contraindications and warnings, and these should be repeated periodically. Also important is the periodic medical evaluation, they may appear contraindications (eg a transient ischemic attack, etc.) or risk factors (eg, family history of venous or arterial thrombosis) for the first time during use of COCs.
The frequency and nature of these assessments should be based on established practice and adapt to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology.
It should warn women that oral contraceptives do not protect against HIV infection (AIDS) or other sexually transmitted diseases.
Reduced efficacy: The efficacy of COCs may be reduced for example, if a woman forgets to take the tablets (see DOSAGE AND ADMINISTRATION, Conduct to follow if you miss taking a tablet), in case of gastrointestinal disorders (see Dosage and administration, advice in case of gastrointestinal disorders) or are taking concomitant medications (see Interactions and other genus).
Reduced cycle control: All AOC can lead to irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, we must consider non-hormonal causes and appropriate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage.
It is possible that some women do not produce withdrawal bleeding during the tablet-free interval active. If you have taken the COC following the instructions described in Dosage and administration, it is unlikely that the woman is pregnant. However, if the COC has not taken following these instructions before the first withdrawal bleed that is missing or if there are two withdrawal bleeds are missed in a row, pregnancy should be ruled out before continuing to use COCs.
Use in Pregnancy and Lactation: YASMIN ® is not indicated during pregnancy. If a woman becomes pregnant while taking YASMIN ®, discontinue administration.
However, epidemiological studies on a large scale have not revealed an increased risk of birth defects in children of mothers who used COCs prior to pregnancy or teratogenic effect when COCs were taken inadvertently during early pregnancy.
The available data on the use of Yasmin ® during pregnancy are limited to draw conclusions about the negative effects of Yasmin ® on pregnancy, health of the fetus or newborn. There are still no relevant epidemiological data.
Lactation may be influenced by COCs as they may reduce the amount of milk and alter its composition and therefore should not be recommended in general the use of COCs until the mother has completely weaned. Small amounts of contraceptive steroids and / or its metabolites can be eliminated by milk.
ADVERSE REACTIONS: The most serious side effects associated with oral contraceptive use cited in General Precautions.
Other side effects have been reported in COC users, but for which the association has not been confirmed nor refuted are:
Organ or system
(≥ 1/1, 000 and <1/100)
Intolerance to contact lenses
Nausea, abdominal pain
Metabolism and nutrition
Nervous system disorders
Depressed mood, mood changes
And breast disorders of the reproductive system
Tenderness and pain
in the breast
Vaginal discharge, discharge from the breast
Skin and subcutaneous tissue
Erythema nodosum, erythema multiforme
* Record the most appropriate MedDRA term (version 7.0) to describe a certain adverse reaction. Not logged synonyms or related conditions, but should also be taken into account.
In women with hereditary angioedema, administration of exogenous estrogens may induce or exacerbate symptoms of angioedema.
DRUG INTERACTIONS AND OTHER GENDER: Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and / or oral contraceptive failure. Have the following interactions in the literature.
Hepatic metabolism: inter-actions may occur with drugs that induce microsomal enzymes, resulting in an increased clearance of sex hormones (eg phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and products containing Hypericum perforatum (St. John's wort).
Also reported that protease inhibitors (eg, ritonavir) and non-nucleoside HIV reverse transcriptase (eg, nevirapine), and combinations thereof, may potentially affect hepatic metabolism.
Interference with enterohepatic circulation: Some clinical reports suggest that enterohepatic circulation of estrogens may decrease when administered some antibiotics, which may reduce ethinylestradiol concentrations (eg penicillins, tetracyclines).
Women treated with either of these drugs should temporarily use a barrier method in addition to the COC or choose another method. With drugs that induce microsomal enzymes, the barrier method should be used during the period of concomitant drug administration and for 28 days of suspension. Women treated with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after his suspension. If the period during which the barrier method used is longer than that of the tablets of the COC pack, will start the next pack of COCs without leaving the usual tablet-free interval.
The main metabolites of drospirenone in human plasma are generated without the participation of cytochrome P-450. It is therefore unlikely that inhibitors of this enzyme system affecting metabolism of drospirenone.
Oral contraceptives may interfere with the metabolism of certain drugs. Accordingly, plasma and tissue concentrations may increase (eg cyclosporin) or decrease (eg lamotrigine).
According to inhibition studies in vitro and in vivo interaction studies conducted with voluntary users of omeprazole, simvastatin and midazolam as marker substrates, it is unlikely an interaction between drospirenone 3 mg with the metabolism of other drugs.
Other interactions: There is a theoretical possibility of increased serum potassium in women taking YASMIN ® with other drugs that may increase serum potassium levels. Such drugs include receptor antagonists of angiotensin II, potassium-sparing diuretics and aldosterone antagonists. However, studies evaluating the interaction between drospirenone (combined with estradiol) with an ACE inhibitor or indomethacin, there were no clinically or statistically significant differences in serum potassium concentrations.
Note: Please consult the prescribing information of concomitant medications to identify possible interactions.
CHANGES IN THE LABORATORY TEST RESULTS: The use of contraceptive steroids may affect the results of certain lab tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, for example, corticosteroid binding globulin and lipid / lipoprotein fractions, parameters of the metabolism of carbohydrates and parameters of coagulation and fibrinolysis.
Generally, the changes remain within normal limits of the laboratory. Drospirenone produces an increase in plasma renin activity and aldosterone plasma induced by mild antimineralocorticoid activity.
PRECAUTIONS IN RELATION TO EFFECTS OF CARCINOGENESIS, MUTAGENESIS, Impairment of Fertility: Preclinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity . However, consider that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.
DOSAGE AND ADMINISTRATION:
How to take YASMIN ®: If taken properly, COCs have a failure rate of approximately 1% per year.
Name of Medicine: Yasmin 24 / 4
Comparable patent medicine: Yasmin 24 / 4
Active ingredient: Drospirenone / Ethinylestradiol
Concentration: 3 mg / 0.02 mg
Box with 28 pills
Made in: Germany