DIANE 35Action
The substance cyproterone acetate contained in Diane 35 inhibits the influence of androgens produced by the female system. So, you can cause disease or an increased production of androgens or a particular sensitivity to these hormones.
While Diana is 35, the function of an increase in sebaceous glands, which play an important role in the pathogenesis of acne andSeborrhea, is reduced. This leads - usually after 3-4 months of treatment - the healing of existing acne lesions. The excessive greasiness of hair and skin generally disappears earlier. Hair loss that often accompanies seborrhoea likewise diminishes.
fails, but the results will take several obvious, treatment with Diane 35 is indicated in women of childbearing age, which show mild forms of hirsutism, particularly in the slight increase in facial hairMonths of use.
Besides the effect described anti-androgen, cyproterone acetate has also a pronounced progestational action. Single-dose administration of cyproterone acetate would thus lead to poor circulation, which is avoided by its combination with ethinyl estradiol in Diane 35. This applies until the preparation is taken cyclically according to the instructions.
The contraceptive effect of Diane 35 is from the interplay of various factors, the most important of which are basedseen as the inhibition of ovulation and changes in cervical secretion. And the protection against pregnancy, estrogen / progestin combinations that are positive properties in addition to the negative attributes that can be useful in deciding on the method of contraception. The cycle is regular and the menstruation is often less painful and bleeding is lighter. This can lead to a reduction in the incidence of iron deficiency.
In addition to this, with the highest dosecombined oral contraceptives (COC) with 50 mcg of ethinyl estradiol, there are signs of a lower risk of fibrocystic breast tumors, ovarian cysts, pelvic inflammatory disease, ectopic pregnancy and endometrial and ovarian cancer. This can also apply to low-dose COC.
Pharmacokinetics
After oral administration, cyproterone acetate is completely absorbed over a wide dose range. The use of Diane 35 effects a maximum serum level of 15 ng cyproterone acetate / ml to 1.6Hours. Subsequently, serum levels of drugs in two stages of evaluation of half-life of 0.8 hours and 2.3 days marked decrease. The total clearance of cyproterone acetate from serum was 3.6 ml / min / kg. Cyproterone acetate is metabolized by different pathways including hydroxylations and conjugations. The main metabolite in human plasma is derived 15beta-hydroxy.
Some parts are unchanged dose of bile. Most of the dose is excreted as aUrine and bile in the ratio 03:07. The renal and biliary excretion was determined to continue with a half life of 1.9 days. The metabolites were eliminated from plasma at a similar rate (half-life of 1.7 days).
Cyproterone acetate is almost exclusively bound to plasma albumin. 3.5 to 4.0% of total drug spending levels are not associated. Because protein binding is non-specific changes of SHBG (sex hormone binding globulin binding) levels do not affect the pharmacokinetics of cyproterone acetate.
Thanksthe long terminal half-life disposal from plasma (serum) and the daily administration of cyproterone acetate accumulates during one treatment cycle. Mean maximum serum levels of drugs increased from 15 ng / ml (day 1) to 21 ng / ml and 24 ng / ml at the end of treatment cycles 1 and 3, respectively. The area under the concentration-time curve 2.2-fold (at the end of cycle 1) and 2.4 times (at the end of cycle 3). The steady-state conditions are reached after about 10 days. While long-termcyproterone acetate accumulates over treatment cycles of treatment by a factor of 2
The absolute bioavailability of cyproterone acetate is almost complete (88% of dose). The relative bioavailability of cyproterone acetate Diane 35 was 109%, compared to an aqueous microcrystalline suspension.
Ethinylestradiol
Oral ethinylestradiol is rapidly and completely absorbed. After taking Diane 35, the maximum levels of drug in the serum of 80 pg / ml are reached at 1.7Hours. 2 hours and 20 hours - the plasma levels of ethinyl estradiol in two phases characterized by half-life of a decline. are calculated from analytical reasons, these parameters only for higher doses.
For ethinyl estradiol and its apparent volume of distribution of about 5 l / kg and a metabolic clearance rate from plasma of about 5 ml / min / kg.
Ethinylestradiol is highly but not specifically bound to serum albumin. 2% of the drug levels are unbound. WhileAbsorption and first pass liver metabolism in ethinyl estradiol and a reduced bioavailability resulting variable. unchanged drug is not excreted. Ethinylestradiol metabolites are excreted through urine and bile in a ratio of 4:06 with a half-life of about one day.
Based on the half-life of terminal phase disposition from the plasma and the daily intake, plasma levels of steady-state after 3-4 days and are higher than 30 to 40% compared to a single dose. L 'relative bioavailability (reference: aqueous microcrystalline suspension) of ethinylestradiol from Diane 35 was almost complete.
The systemic availability of ethinyl estradiol may be affected in both directions by other drugs. There is no interaction with high doses of vitamin C. Ethinylestradiol induces the hepatic synthesis of SHBG (sex hormone binding globulin binding) and CBG (corticosteroid binding globulin), in continuous use. The extent of SHBG induction, however, dependsthe chemical structure and dose of progestin administered. During treatment with Diane 35 serum concentrations of SHBG of approximately 100 nmol / L to 300 nmol / l, and serum concentrations of CBG increased from approximately 50 mcg / ml to 95 mcg / ml.
Directions
For the treatment of androgen-dependent diseases in women, such as acne, especially pronounced forms and those that have seborrhea or by inflammation or formation accompanied by knots (Papulopustular acne, acne nodulocystica)androgenetic alopecia and mild forms of hirsutism. Diane 35 is also indicated for oral contraception in women with androgen-dependent diseases and for the treatment of polycystic ovary syndrome.
Dosage and administration
Diane 35 is to be taken regularly to achieve the therapeutic efficacy and the required contraceptive protection. The dosage of Diane 35 and Diane 35 ED is similar to standard therapy of most combined oral contraceptives. Sun Management itselfThe rules must be followed.
The improper use of Diane 35 and Diane 35 ED can cause bleeding between periods and impair the therapeutic safety and contraceptives.
How is Diane 35
The tablets should be taken in the order on the package every day at the same time, add more liquid if necessary. One active tablet is taken daily for 21 consecutive days. Each additional package is started after an interval of 7 days or tablet-free period of 7 days of placebo tablets,during which withdrawal bleeding usually occurs. This usually starts 2-3 days after the last tablet and may not finish before the next pack is started.
How do I start Diane 35
No hormonal contraceptive use (last month)
Tablets Women's Day on 1 Start 's natural cycle (ie the first day of menstruation). As permitted on days 2-5, but during the first cycle a barrier method in addition to the first 7 days of recommendedTablets.
Changing from another combined oral contraceptive (COC)
The woman was with Diane 35 preferably on the day after the last active tablet of her previous COC, but not later than the day following the usual tablet-free interval or placebo tablet interval of the previous COC.
Changing from a progestogen-only methods (mini-pill, injection, implant)
The woman can go every day from the mini-pill (from a plant on the day of removal, from an injectable when the nextInjection would be due), but it should be recommended in all these cases, as well as a barrier method for the first 7 days of tablet intake.
After the abortion in the first quarter
The woman may start immediately. They do not need additional contraceptive measures.
Following delivery or abortion in the second quarter
Women should be advised to start the day 21-28 after delivery or abortion in the second quarter.
If later, the woman should be recommended in additionUse a barrier method for the first 7 days of tablet intake. However, if the relationship has already occurred, pregnancy should be before the actual use of Diane 35 are excluded or that the woman must wait for the first period.
How is Diane 35 ED
The tablets should be taken in the order on the package every day at the same time, add more liquid if necessary. One tablet will be taken every day. Each additional pack is started immediately after the last packet. While takingthe 7 placebo tablets a withdrawal bleed usually occurs.
How do I start Diane 35 ED
No hormonal contraceptive use (last month)
Tablets Women's Day on 1 Start 's natural cycle (ie the first day of menstruation). The first tablet should be selected from the red zone of the pack. Another method of contraception such as condoms or a diaphragm must be used for the first 14 days of taking the tablets.
Changing from another combinedoral contraceptive (COC)
The woman should start Diane 35 ED in red on the day after the last active tablet of her previous COC.
Changing from a progestogen-only methods (mini-pill, injection, implant)
The woman can go to every day from the mini-pill-(from a plant on the day of release from an injectable when the next injection would be due), but it should be recommended in all these cases, as well as being a barrier method for the first 14 daysTablets.
After the abortion in the first quarter
The woman may start immediately. They do not need additional contraceptive measures.
Following delivery or abortion in the second quarter
Women should be advised to start the day 21-28 after delivery or abortion in the second quarter.
If later, the woman must have, in addition to a barrier method for the first 14 days of taking the tablets. However, if the relationship has already occurred, pregnancy should beexcluded before the actual Diane 35ED use or the woman must wait for the first time.
Management of missed tablets
may contain errors in the recording of non-hormonal tablets in Diane 35ED be ignored.
If the user less than 12 hours late taking hormone tablet, is not affected. The woman, the tablet as soon as you remember, and must continue to take the tablets at the usual time.
If they take more than 12 hours latehormonal contraception pill can be reduced.
There are at particularly high risk of pregnancy if tablets are at the beginning or end of the pack lose. If tablets in the first week of taking hormonal tablets and the relationship has taken place are missed in the 7 days prior to the possibility of pregnancy should be considered.
The management of missed tablets can be guided by the following two basic rules:
The tablet-taking must never be interrupted for more than 7 days
7 daysuninterrupted tablet taking are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian.
These rules form the basis of information provided to patients in the leaflet.
additional contraceptive precautions
If you need additional contraceptive precautions, either:
* Don 't have sex
Use a hood as spermicide
Use a condom
Do not use the rhythm or temperature methods as extra contraceptive measures. This is because oral contraceptivesChange the usual menstrual cycle changes such as changes in temperature and cervical mucus.
The rule of 7 days
Continue to take your pills. They are not protected against pregnancy until you've taken your little hormone pill everyday for the next 7 days in a row. Use another method of contraception (other contraceptive precautions) such as condoms or not having sex for the next 7 days while taking the next 7 small hormone pills.
When there are fewer than 7 small hormone pills leftin the pack, finish the small hormone pills and go straight to the small hormone pills of the next pack. This means that you are not a gap between the small hormone pills and you miss the big non-hormonal pills if you have the package of 28 days. You can not have a period until the end of the next pack. This is not harmful.
Advice on vomiting
If you vomit within 3-4 hours after taking tablets, absorption may not be complete. If the woman does not change itsnormally required schedule, you have to take it further (s) from another pack.
The periods of change or how slow you have a period of
should be to delay a period the woman with hormonal tablets from another pack of Diane 35 and Diane 35 to continue without a range of non-hormonal tablets or tablets ED. The extension can be made as long as you want until the end of the second pack. During the extension of women with bleeding and spotting may.
To move thePeriods to another day of the week in which she has used her current show, advises them, shorten the interval following its compressed or omit the non-hormonal tablets Diane 35ED how many days they like to be. The shorter the interval, the greater the risk that they do not have a withdrawal bleeding and breakthrough bleeding and spotting during the second package (like a late period).
Application time
The length depends on the severity ofclinical features, in general, treatment should be carried out over several months.
It is recommended to be 35 or Diane Diane 35ED for at least another 3-4 cycles after the disappearance of symptoms. Should there be a recurrence weeks or months after discontinuation of tablet-taking, treatment with Diane 35 will be included again. A longer treatment may be recommended for the PCO syndrome.
Contraindications
The preparations containing estrogen / progestin combinations shouldare not used if the following conditions. If one of the conditions appear for the first time during use, the product should be stopped immediately.
* Thrombosis (venous or arterial) present or in history (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke).
Prodromi existing or thrombosis (eg transient ischemic attack, angina pectoris).
Diabetes mellitus with vascular changesParticipation.
The presence of severe or multiple risk factors (s) of venous or arterial thrombosis may also be a contraindication.
Presence or history of severe liver disease until liver function is not normalized.
Presence or history of liver tumors (benign or malignant).
Known or suspected malignant conditions of the genitals or breasts, if sex steroid-influenced.
Undiagnosed vaginal bleeding.
Known /Suspected pregnancy.
Lactation
Hypersensitivity to any component of Diane 35
Diane 35 is not applied in men.
Warnings and Precautions
Clinical experience and epidemiological estrogen / progestin combinations such as Diane 35 is principally due to the combined oral contraceptives (COC) is based. Therefore, the following warnings apply for the use of COC for the 35th Diane
If any of the conditions / risk factors referred to below is available, the benefits of usingDiane 35 should against the potential risks for each woman weighed and discussed with the woman before deciding to use it. In case of deterioration, exacerbation or first appearance of the disease or risk factors should consult the doctor's wife. The physician must then decide whether its use should be suspended to decide.
Circulatory Problems
Epidemiological studies have suggested a link between the use of combined oral contraceptives and increased riskarterial disease and venous thrombotic and thromboembolic events, such as heart attack, stroke, deep vein thrombosis and pulmonary embolism. These events occur rarely.
Venous thromboembolism (VTE), which is deep vein thrombosis and / or pulmonary embolism may occur during the use of all COCs. The approximate incidence of VTE (mcg <50 EE), users of OCS with low dose of estrogen is up to 4 per 10 000 women years of 0.5 to 3 per 10,000 women years compared to non-OC users. But theIncidence of VTE, while COC significantly lower than the incidence associated with pregnancy (ie 6 years of 10 000 pregnant women).
Thrombosis is extremely rare has been reported to occur in other blood vessels, such as the hepatic veins, mesenteric, renal, or retinal artery in COC. There is consensus that the occurrence of these events is associated with the use of combined oral contraceptives.
Symptoms of venous or arterial thrombosis: unilateral leg pain and / orSwelling, sudden severe chest pain, whether it radiates to the left arm, shortness of breath, sudden onset of coughing, unusual, severe, prolonged headache, sudden partial or complete loss of vision, double vision, slurred speech or aphasia, dizziness , collapse with or without focal seizure, weakness or very marked numbness suddenly on one side or part of the body, motor disturbances, acute "belly.
The risk of thromboembolism (venous and / or arterial) increaseswith:
Age
Smoking (cigarettes smoked and with increasing age the risk further increases, especially in women over 35 years)
a positive family history (ie venous or arterial thromboembolism in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use.
Obesity (body mass index above 30 kg / m2 ²)
Dyslipoproteinemia
High Blood Pressure
Valvular heart diseaseDisease
Atrial fibrillation
prolonged immobilization, major surgery, surgery or severe trauma to the legs. In these situations it is advisable COC (in the case of elective surgery, at least four weeks before) and not until two weeks after the demobilization of repair.
There is no consensus on the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.
The increased risk of thromboembolism in the puerperium mustconsidered.
Other diseases that were adverse cardiovascular events, including diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, inflammatory bowel disease (Crohn's disease 'or ulcerative colitis) and sickle cell anemia.
An increase in the frequency or severity of migraine with COC use (the prodromal phase of a cerebrovascular event) may be grounds for immediate suspension of the COC.
Biochemical factors that mayof hereditary or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk / benefit, the physician should take into account the fact that appropriate treatment can reduce the associated risk of disease and the risk of thrombosis associatedPregnancy is higher than that associated with COC.
Cancer
An increased risk of cervical cancer in long-term users of combined oral contraceptives has been reported in some epidemiological studies, but there is still controversy about the extent to which this statement is confusing the effect of sexual behavior and other factors such as human papilloma virus (HPV).
A meta-analysis of 54 epidemiological studies that there is a slight increase in relative risk (RR = 1.24)breast cancer in women who are currently diagnosed with combined oral contraceptives. The increased risk gradually disappears during the 10 years from the termination of the COC. Because breast cancer is rare in women under 40 years, the number of breast cancers being diagnosed more and recent COC users is small compared to the overall risk of breast cancer. These studies provide no evidence of causation. The pattern of risk observed may be due to an early diagnosis ofBreast cancer in COC users, the biological effects of COCs or a combination of both. Breast cancer diagnosed in the number of users tend to be less advanced clinically diagnosed cancer in non-users.
In rare cases, benign and have been reported even more rarely, malignant liver tumors in users of combined oral contraceptives. In some cases, these tumors to life-threatening intra-abdominal haemorrhage resulted. A tumor of the liver should be considered in the differential diagnosis to consider when more seriousAbdominal pain, enlarged liver or signs of intra-abdominal bleeding in women, the COC.
Other conditions
Women with hypertriglyceridemia or a family history of it may be at increased risk of pancreatitis when using COCs.
Although small increases in blood pressure reported in many women taking combined oral contraceptives are clinically important rare. A relationship between the use of combined oral contraceptives and clinical hypertension has not been established. However, if a sustained clinicallysignificant hypertension develops during the use of a COC then withdraw to the doctor, the COC and the treatment of assay. Where considered appropriate, COC use may be continued if the values of blood pressure can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate use both pregnancy and COC, but the evidence of an association with COC use is inconclusive: jaundice and / or pruritus related to cholestasis, gallstoneEducation, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea s', herpes gestationis, otosclerosis, hearing loss.
Acute or chronic disturbances of liver function, elimination of COC use until markers of liver function requiring return to normal. Recurrence of cholestatic jaundice, which requires only occurs during pregnancy or previous use of sex hormones, the setting of the COC.
Although COCs may have an impact onperipheral insulin resistance and glucose tolerance, there is no evidence of the need to change the therapeutic regimen in diabetics using COCs. However, women with diabetes should be closely observed while taking COCs.
Crohn 's disease and ulcerative colitis have been associated with combined oral contraceptives.
Chloasma may occur occasionally, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to sunlight or UV light while takingKOK.
If women with hirsutism, symptoms have recently developed or increased substantially, the causes (androgen-producing tumor, adrenal enzyme defect) must be clarified by differential diagnosis.
Medical examination / consultation
A complete medical history and physical examination must be prior to the introduction or reintroduction of Diane 35, which are taken of contraindications and warnings. This should be repeated at least once a year for the use of Diane 35th Periodmedical evaluation is also important because contraindications (eg a transient ischemic attack, etc.) or risk factors (eg, family history of venous or arterial thrombosis) may appear for the first time the use of the 35th Diane The frequency and nature such evaluation should be individualized for each woman, but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests.
WomenIt should be noted that to protect the preparations such as Diane 35 does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced effectiveness
The efficacy of Diane 35 in the case of forgotten pills, vomiting or medications can be reduced.
Reduced cycle control
occurs with combinations of estrogen / progesterone, irregular bleeding (spotting or breakthrough bleeding) may, especially in the first months of use. Thus, the assessment of irregular bleedinguseful only after an adaptation phase of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes should be considered and appropriate diagnostic measures should be taken to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may occur during the interval of the tablets. If the COC has been taken under the proposed indications, it is unlikely that the woman is pregnant.Otherwise, however, the COC in this direction before the first missed withdrawal bleed or if two withdrawal bleeding are missed, pregnancy must be excluded before COC use had continued.
Pregnancy and lactation
Use in pregnancy
The administration of Diane 35 is contraindicated during pregnancy.
If you become pregnant during treatment with Diane 35, the production should be stopped immediately.
Use during lactation
The administration of Diane 35 is alsocontraindicated during lactation. Cyproterone acetate is transferred into the milk of lactating women. About 0.2% of the maternal dose will reach the newborn via milk corresponding to a dose of about 1 mcg / kg. During established lactation 0.02% of the daily dose of ethinyl estradiol mothers can be transmitted to baby through breast milk.
Effects on ability to drive and use machines
No effects observed.
Preclinical safety data
Systemic toxicity
Systemic tolerance in animalsStudies after oral administration repeatedly observed no signs of systemic intolerance may be prohibitive for use in humans at the required dosage of the information provided.
There are no animal-experimental studies on a possible sensitizing effect of cyproterone acetate and ethinyl estradiol were performed.
Embryo toxicity / teratogenicity
Investigations embryotoxic or teratogenic effects with the combination of both agents showed no effects indicativea general teratogenic effect following treatment during organogenesis before development of the external genitalia. The administration of cyproterone acetate during the hormone-sensitive ifferentiation of the genital organs (after approximately 45 days of pregnancy) may lead to signs of feminisation of male fetuses in the following higher doses. The observation of male infants who were exposed in utero to cyproterone acetate did not show any signs of feminisation. However, pregnancyContraindication to the use of the 35th Diane
Genotoxicity and carcinogenicity
Recognized first-line tests of genotoxicity gave negative results when conducted with cyproterone acetate. However, more tests showed that cyproterone acetate was capable of, with DNA (and an increase in DNA repair) in liver cells of rats and monkeys and in freshly isolated human hepatocytes, while no adducts DNA were detected in liver cells of dogs.
This DNA adduct formationprobably occurred at exposures that might occur with the recommended dose for cyproterone acetate. In the in vivo effects of cyproterone acetate treatment were the increased incidence of focal, possibly pre-neoplastic, liver lesions in which cellular enzymes were altered in female rats and an increased mutation rate in transgenic mice carrying a bacterial gene as target for the mutation.
Clinical experience and well-conducted epidemiological studies to date do not support aincreased incidence of liver tumors in humans. Even in the tumorigenicity of cyproterone acetate in rodents investigations show evidence of a specific tumorigenic potential. It should be noted, however, that sex steroids may be the growth of certain hormone-dependent tissues and tumors promote be worn.
Overall, the available information, objections to the use of Diane 35 in humans when used in accordance with the instructions for each show andrecommended dose.
Adverse effects
Serious side effects of Diane 35 is referred to in the contraindications and warnings and precautions sections.
The following side effects have been reported in users of Diane 35 and the association has been neither confirmed nor refuted:
* Breast tenderness, pain, discharge
Headache
Migraine
Changes in libido
depression
Contact lens intolerance
Nausea
Vomiting
Changes in vaginal
various skin diseases
Water retention
Change of weight
Hypersensitivity reaction.
Interaction
Interactions with other drugs that may cause increased clearance of sex hormones lead to breakthrough bleeding and failure of oral contraceptives. This confirms with hydantoins, barbiturates, primidone, carbamazepine and rifampicin; oxcarbamazepine, topiramate, felbamate and griseofulvin are also suspected. The mechanism of thisInteraction appears to be induction of liver enzymes on the properties of these drugs. Maximal enzyme induction is not generally for 2-3 weeks, but may be continued for at least 4 weeks after discontinuation of the drug.
Contraceptive failures have also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this effect is unclear.
Women in short-term treatment with one of the above classes of drugs or individual drugsneed to temporarily use a barrier method in addition to Diane 35, ie during the period of co-administration of drugs and for 7 days after their discontinuation. For women in rifampicin a barrier method should be the next Diane 35 should be used at the time of rifampicin administration and for 28 days after discontinuation. If co-administration of drugs through the end of Diane 35 tablets in the pack, Diana 35, the next pack without the usual startingTablet range.
In women, the long-term treatment with hepatic enzyme-inducing drug experts have recommended to increase the doses of contraceptive steroids. If a high dosage of birth control is not desirable or appears unsatisfactory or unreliable, for example in case of irregular bleeding, another method of contraception should be advised.
Laboratory tests
The use of preparations like Diane 35 can influence the results of some laboratory tests, including biochemical parameters ofLiver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, eg corticosteroid binding globulin and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal range.
Overdose
There are no reports of serious consequences of overdose.
Symptoms
Symptoms that may arise in this case are nausea, vomiting and vaginal in young girls, slightBleeding.
Treatment
There is no antidote and treatment should be symptomatic.
Pharmaceutical Precautions
Shelf life: 5 years
Special precautions for storage: under 25 ° C
Packaging unit
3 calendar days with 21 packs or 28 tablets.
Diane 35 tablets are available in blister strips containing funnel polyvinyl chloride film with counter sealing foil made of aluminum with heat sealable coating.
The substance cyproterone acetate contained in Diane 35 inhibits the influence of androgens produced by the female system. So, you can cause disease or an increased production of androgens or a particular sensitivity to these hormones.
While Diana is 35, the function of an increase in sebaceous glands, which play an important role in the pathogenesis of acne andSeborrhea, is reduced. This leads - usually after 3-4 months of treatment - the healing of existing acne lesions. The excessive greasiness of hair and skin generally disappears earlier. Hair loss that often accompanies seborrhoea likewise diminishes.
fails, but the results will take several obvious, treatment with Diane 35 is indicated in women of childbearing age, which show mild forms of hirsutism, particularly in the slight increase in facial hairMonths of use.
Besides the effect described anti-androgen, cyproterone acetate has also a pronounced progestational action. Single-dose administration of cyproterone acetate would thus lead to poor circulation, which is avoided by its combination with ethinyl estradiol in Diane 35. This applies until the preparation is taken cyclically according to the instructions.
The contraceptive effect of Diane 35 is from the interplay of various factors, the most important of which are basedseen as the inhibition of ovulation and changes in cervical secretion. And the protection against pregnancy, estrogen / progestin combinations that are positive properties in addition to the negative attributes that can be useful in deciding on the method of contraception. The cycle is regular and the menstruation is often less painful and bleeding is lighter. This can lead to a reduction in the incidence of iron deficiency.
In addition to this, with the highest dosecombined oral contraceptives (COC) with 50 mcg of ethinyl estradiol, there are signs of a lower risk of fibrocystic breast tumors, ovarian cysts, pelvic inflammatory disease, ectopic pregnancy and endometrial and ovarian cancer. This can also apply to low-dose COC.
Pharmacokinetics
After oral administration, cyproterone acetate is completely absorbed over a wide dose range. The use of Diane 35 effects a maximum serum level of 15 ng cyproterone acetate / ml to 1.6Hours. Subsequently, serum levels of drugs in two stages of evaluation of half-life of 0.8 hours and 2.3 days marked decrease. The total clearance of cyproterone acetate from serum was 3.6 ml / min / kg. Cyproterone acetate is metabolized by different pathways including hydroxylations and conjugations. The main metabolite in human plasma is derived 15beta-hydroxy.
Some parts are unchanged dose of bile. Most of the dose is excreted as aUrine and bile in the ratio 03:07. The renal and biliary excretion was determined to continue with a half life of 1.9 days. The metabolites were eliminated from plasma at a similar rate (half-life of 1.7 days).
Cyproterone acetate is almost exclusively bound to plasma albumin. 3.5 to 4.0% of total drug spending levels are not associated. Because protein binding is non-specific changes of SHBG (sex hormone binding globulin binding) levels do not affect the pharmacokinetics of cyproterone acetate.
Thanksthe long terminal half-life disposal from plasma (serum) and the daily administration of cyproterone acetate accumulates during one treatment cycle. Mean maximum serum levels of drugs increased from 15 ng / ml (day 1) to 21 ng / ml and 24 ng / ml at the end of treatment cycles 1 and 3, respectively. The area under the concentration-time curve 2.2-fold (at the end of cycle 1) and 2.4 times (at the end of cycle 3). The steady-state conditions are reached after about 10 days. While long-termcyproterone acetate accumulates over treatment cycles of treatment by a factor of 2
The absolute bioavailability of cyproterone acetate is almost complete (88% of dose). The relative bioavailability of cyproterone acetate Diane 35 was 109%, compared to an aqueous microcrystalline suspension.
Ethinylestradiol
Oral ethinylestradiol is rapidly and completely absorbed. After taking Diane 35, the maximum levels of drug in the serum of 80 pg / ml are reached at 1.7Hours. 2 hours and 20 hours - the plasma levels of ethinyl estradiol in two phases characterized by half-life of a decline. are calculated from analytical reasons, these parameters only for higher doses.
For ethinyl estradiol and its apparent volume of distribution of about 5 l / kg and a metabolic clearance rate from plasma of about 5 ml / min / kg.
Ethinylestradiol is highly but not specifically bound to serum albumin. 2% of the drug levels are unbound. WhileAbsorption and first pass liver metabolism in ethinyl estradiol and a reduced bioavailability resulting variable. unchanged drug is not excreted. Ethinylestradiol metabolites are excreted through urine and bile in a ratio of 4:06 with a half-life of about one day.
Based on the half-life of terminal phase disposition from the plasma and the daily intake, plasma levels of steady-state after 3-4 days and are higher than 30 to 40% compared to a single dose. L 'relative bioavailability (reference: aqueous microcrystalline suspension) of ethinylestradiol from Diane 35 was almost complete.
The systemic availability of ethinyl estradiol may be affected in both directions by other drugs. There is no interaction with high doses of vitamin C. Ethinylestradiol induces the hepatic synthesis of SHBG (sex hormone binding globulin binding) and CBG (corticosteroid binding globulin), in continuous use. The extent of SHBG induction, however, dependsthe chemical structure and dose of progestin administered. During treatment with Diane 35 serum concentrations of SHBG of approximately 100 nmol / L to 300 nmol / l, and serum concentrations of CBG increased from approximately 50 mcg / ml to 95 mcg / ml.
Directions
For the treatment of androgen-dependent diseases in women, such as acne, especially pronounced forms and those that have seborrhea or by inflammation or formation accompanied by knots (Papulopustular acne, acne nodulocystica)androgenetic
Dosage and administration
Diane 35 is to be taken regularly to achieve the therapeutic efficacy and the required contraceptive protection. The dosage of Diane 35 and Diane 35 ED is similar to standard therapy of most combined oral contraceptives. Sun Management itselfThe rules must be followed.
The improper use of Diane 35 and Diane 35 ED can cause bleeding between periods and impair the therapeutic safety and contraceptives.
How is Diane 35
The tablets should be taken in the order on the package every day at the same time, add more liquid if necessary. One active tablet is taken daily for 21 consecutive days. Each additional package is started after an interval of 7 days or tablet-free period of 7 days of placebo tablets,during which withdrawal bleeding usually occurs. This usually starts 2-3 days after the last tablet and may not finish before the next pack is started.
How do I start Diane 35
No hormonal contraceptive use (last month)
Tablets Women's Day on 1 Start 's natural cycle (ie the first day of menstruation). As permitted on days 2-5, but during the first cycle a barrier method in addition to the first 7 days of recommendedTablets.
Changing from another combined oral contraceptive (COC)
The woman was with Diane 35 preferably on the day after the last active tablet of her previous COC, but not later than the day following the usual tablet-free interval or placebo tablet interval of the previous COC.
Changing from a progestogen-only methods (mini-pill, injection, implant)
The woman can go every day from the mini-pill (from a plant on the day of removal, from an injectable when the nextInjection would be due), but it should be recommended in all these cases, as well as a barrier method for the first 7 days of tablet intake.
After the abortion in the first quarter
The woman may start immediately. They do not need additional contraceptive measures.
Following delivery or abortion in the second quarter
Women should be advised to start the day 21-28 after delivery or abortion in the second quarter.
If later, the woman should be recommended in additionUse a barrier method for the first 7 days of tablet intake. However, if the relationship has already occurred, pregnancy should be before the actual use of Diane 35 are excluded or that the woman must wait for the first period.
How is Diane 35 ED
The tablets should be taken in the order on the package every day at the same time, add more liquid if necessary. One tablet will be taken every day. Each additional pack is started immediately after the last packet. While takingthe 7 placebo tablets a withdrawal bleed usually occurs.
How do I start Diane 35 ED
No hormonal contraceptive use (last month)
Tablets Women's Day on 1 Start 's natural cycle (ie the first day of menstruation). The first tablet should be selected from the red zone of the pack. Another method of contraception such as condoms or a diaphragm must be used for the first 14 days of taking the tablets.
Changing from another combinedoral contraceptive (COC)
The woman should start Diane 35 ED in red on the day after the last active tablet of her previous COC.
Changing from a progestogen-only methods (mini-pill, injection, implant)
The woman can go to every day from the mini-pill-(from a plant on the day of release from an injectable when the next injection would be due), but it should be recommended in all these cases, as well as being a barrier method for the first 14 daysTablets.
After the abortion in the first quarter
The woman may start immediately. They do not need additional contraceptive measures.
Following delivery or abortion in the second quarter
Women should be advised to start the day 21-28 after delivery or abortion in the second quarter.
If later, the woman must have, in addition to a barrier method for the first 14 days of taking the tablets. However, if the relationship has already occurred, pregnancy should beexcluded before the actual Diane 35ED use or the woman must wait for the first time.
Management of missed tablets
may contain errors in the recording of non-hormonal tablets in Diane 35ED be ignored.
If the user less than 12 hours late taking hormone tablet, is not affected. The woman, the tablet as soon as you remember, and must continue to take the tablets at the usual time.
If they take more than 12 hours latehormonal contraception pill can be reduced.
There are at particularly high risk of pregnancy if tablets are at the beginning or end of the pack lose. If tablets in the first week of taking hormonal tablets and the relationship has taken place are missed in the 7 days prior to the possibility of pregnancy should be considered.
The management of missed tablets can be guided by the following two basic rules:
The tablet-taking must never be interrupted for more than 7 days
7 daysuninterrupted tablet taking are required to achieve adequate suppression of the hypothalamic-pituitary-ova
These rules form the basis of information provided to patients in the leaflet.
additional contraceptive precautions
If you need additional contraceptive precautions, either:
* Don 't have sex
Use a hood as spermicide
Use a condom
Do not use the rhythm or temperature methods as extra contraceptive measures. This is because oral contraceptivesChange the usual menstrual cycle changes such as changes in temperature and cervical mucus.
The rule of 7 days
Continue to take your pills. They are not protected against pregnancy until you've taken your little hormone pill everyday for the next 7 days in a row. Use another method of contraception (other contraceptive precautions) such as condoms or not having sex for the next 7 days while taking the next 7 small hormone pills.
When there are fewer than 7 small hormone pills leftin the pack, finish the small hormone pills and go straight to the small hormone pills of the next pack. This means that you are not a gap between the small hormone pills and you miss the big non-hormonal pills if you have the package of 28 days. You can not have a period until the end of the next pack. This is not harmful.
Advice on vomiting
If you vomit within 3-4 hours after taking tablets, absorption may not be complete. If the woman does not change itsnormally required schedule, you have to take it further (s) from another pack.
The periods of change or how slow you have a period of
should be to delay a period the woman with hormonal tablets from another pack of Diane 35 and Diane 35 to continue without a range of non-hormonal tablets or tablets ED. The extension can be made as long as you want until the end of the second pack. During the extension of women with bleeding and spotting may.
To move thePeriods to another day of the week in which she has used her current show, advises them, shorten the interval following its compressed or omit the non-hormonal tablets Diane 35ED how many days they like to be. The shorter the interval, the greater the risk that they do not have a withdrawal bleeding and breakthrough bleeding and spotting during the second package (like a late period).
Application time
The length depends on the severity ofclinical features, in general, treatment should be carried out over several months.
It is recommended to be 35 or Diane Diane 35ED for at least another 3-4 cycles after the disappearance of symptoms. Should there be a recurrence weeks or months after discontinuation of tablet-taking, treatment with Diane 35 will be included again. A longer treatment may be recommended for the PCO syndrome.
Contraindications
The preparations containing estrogen / progestin combinations shouldare not used if the following conditions. If one of the conditions appear for the first time during use, the product should be stopped immediately.
* Thrombosis (venous or arterial) present or in history (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke).
Prodromi existing or thrombosis (eg transient ischemic attack, angina pectoris).
Diabetes mellitus with vascular changesParticipation.
The presence of severe or multiple risk factors (s) of venous or arterial thrombosis may also be a contraindication.
Presence or history of severe liver disease until liver function is not normalized.
Presence or history of liver tumors (benign or malignant).
Known or suspected malignant conditions of the genitals or breasts, if sex steroid-influenced.
Undiagnosed vaginal bleeding.
Known /Suspected pregnancy.
Lactation
Hypersensitivity to any component of Diane 35
Diane 35 is not applied in men.
Warnings and Precautions
Clinical experience and epidemiological estrogen / progestin combinations such as Diane 35 is principally due to the combined oral contraceptives (COC) is based. Therefore, the following warnings apply for the use of COC for the 35th Diane
If any of the conditions / risk factors referred to below is available, the benefits of usingDiane 35 should against the potential risks for each woman weighed and discussed with the woman before deciding to use it. In case of deterioration, exacerbation or first appearance of the disease or risk factors should consult the doctor's wife. The physician must then decide whether its use should be suspended to decide.
Circulatory Problems
Epidemiological studies have suggested a link between the use of combined oral contraceptives and increased riskarterial disease and venous thrombotic and thromboembolic events, such as heart attack, stroke, deep vein thrombosis and pulmonary embolism. These events occur rarely.
Venous thromboembolism (VTE), which is deep vein thrombosis and / or pulmonary embolism may occur during the use of all COCs. The approximate incidence of VTE (mcg <50 EE), users of OCS with low dose of estrogen is up to 4 per 10 000 women years of 0.5 to 3 per 10,000 women years compared to non-OC users. But theIncidence of VTE, while COC significantly lower than the incidence associated with pregnancy (ie 6 years of 10 000 pregnant women).
Thrombosis is extremely rare has been reported to occur in other blood vessels, such as the hepatic veins, mesenteric, renal, or retinal artery in COC. There is consensus that the occurrence of these events is associated with the use of combined oral contraceptives.
Symptoms of venous or arterial thrombosis: unilateral leg pain and / orSwelling, sudden severe chest pain, whether it radiates to the left arm, shortness of breath, sudden onset of coughing, unusual, severe, prolonged headache, sudden partial or complete loss of vision, double vision, slurred speech or aphasia, dizziness , collapse with or without focal seizure, weakness or very marked numbness suddenly on one side or part of the body, motor disturbances, acute "belly.
The risk of thromboembolism (venous and / or arterial) increaseswith:
Age
Smoking (cigarettes smoked and with increasing age the risk further increases, especially in women over 35 years)
a positive family history (ie venous or arterial thromboembolism in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use.
Obesity (body mass index above 30 kg / m2 ²)
Dyslipoproteinemia
High Blood Pressure
Valvular heart diseaseDisease
Atrial fibrillation
prolonged immobilization, major surgery, surgery or severe trauma to the legs. In these situations it is advisable COC (in the case of elective surgery, at least four weeks before) and not until two weeks after the demobilization of repair.
There is no consensus on the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.
The increased risk of thromboembolism in the puerperium mustconsidered.
Other diseases that were adverse cardiovascular events, including diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, inflammatory bowel disease (Crohn's disease 'or ulcerative colitis) and sickle cell anemia.
An increase in the frequency or severity of migraine with COC use (the prodromal phase of a cerebrovascular event) may be grounds for immediate suspension of the COC.
Biochemical factors that mayof hereditary or acquired predisposition to venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk / benefit, the physician should take into account the fact that appropriate treatment can reduce the associated risk of disease and the risk of thrombosis associatedPregnancy is higher than that associated with COC.
Cancer
An increased risk of cervical cancer in long-term users of combined oral contraceptives has been reported in some epidemiological studies, but there is still controversy about the extent to which this statement is confusing the effect of sexual behavior and other factors such as human papilloma virus (HPV).
A meta-analysis of 54 epidemiological studies that there is a slight increase in relative risk (RR = 1.24)breast cancer in women who are currently diagnosed with combined oral contraceptives. The increased risk gradually disappears during the 10 years from the termination of the COC. Because breast cancer is rare in women under 40 years, the number of breast cancers being diagnosed more and recent COC users is small compared to the overall risk of breast cancer. These studies provide no evidence of causation. The pattern of risk observed may be due to an early diagnosis ofBreast cancer in COC users, the biological effects of COCs or a combination of both. Breast cancer diagnosed in the number of users tend to be less advanced clinically diagnosed cancer in non-users.
In rare cases, benign and have been reported even more rarely, malignant liver tumors in users of combined oral contraceptives. In some cases, these tumors to life-threatening intra-abdominal haemorrhage resulted. A tumor of the liver should be considered in the differential diagnosis to consider when more seriousAbdominal pain, enlarged liver or signs of intra-abdominal bleeding in women, the COC.
Other conditions
Women with hypertriglyceridemia or a family history of it may be at increased risk of pancreatitis when using COCs.
Although small increases in blood pressure reported in many women taking combined oral contraceptives are clinically important rare. A relationship between the use of combined oral contraceptives and clinical hypertension has not been established. However, if a sustained clinicallysignificant hypertension develops during the use of a COC then withdraw to the doctor, the COC and the treatment of assay. Where considered appropriate, COC use may be continued if the values of blood pressure can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate use both pregnancy and COC, but the evidence of an association with COC use is inconclusive: jaundice and / or pruritus related to cholestasis, gallstoneEducation, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea s', herpes gestationis, otosclerosis, hearing loss.
Acute or chronic disturbances of liver function, elimination of COC use until markers of liver function requiring return to normal. Recurrence of cholestatic jaundice, which requires only occurs during pregnancy or previous use of sex hormones, the setting of the COC.
Although COCs may have an impact onperipheral insulin resistance and glucose tolerance, there is no evidence of the need to change the therapeutic regimen in diabetics using COCs. However, women with diabetes should be closely observed while taking COCs.
Crohn 's disease and ulcerative colitis have been associated with combined oral contraceptives.
Chloasma may occur occasionally, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to sunlight or UV light while takingKOK.
If women with hirsutism, symptoms have recently developed or increased substantially, the causes (androgen-producing tumor, adrenal enzyme defect) must be clarified by differential diagnosis.
Medical examination / consultation
A complete medical history and physical examination must be prior to the introduction or reintroduction of Diane 35, which are taken of contraindications and warnings. This should be repeated at least once a year for the use of Diane 35th Periodmedical evaluation is also important because contraindications (eg a transient ischemic attack, etc.) or risk factors (eg, family history of venous or arterial thrombosis) may appear for the first time the use of the 35th Diane The frequency and nature such evaluation should be individualized for each woman, but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests.
WomenIt should be noted that to protect the preparations such as Diane 35 does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced effectiveness
The efficacy of Diane 35 in the case of forgotten pills, vomiting or medications can be reduced.
Reduced cycle control
occurs with combinations of estrogen / progesterone, irregular bleeding (spotting or breakthrough bleeding) may, especially in the first months of use. Thus, the assessment of irregular bleedinguseful only after an adaptation phase of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes should be considered and appropriate diagnostic measures should be taken to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may occur during the interval of the tablets. If the COC has been taken under the proposed indications, it is unlikely that the woman is pregnant.Otherwise, however, the COC in this direction before the first missed withdrawal bleed or if two withdrawal bleeding are missed, pregnancy must be excluded before COC use had continued.
Pregnancy and lactation
Use in pregnancy
The administration of Diane 35 is contraindicated during pregnancy.
If you become pregnant during treatment with Diane 35, the production should be stopped immediately.
Use during lactation
The administration of Diane 35 is alsocontraindicated during lactation. Cyproterone acetate is transferred into the milk of lactating women. About 0.2% of the maternal dose will reach the newborn via milk corresponding to a dose of about 1 mcg / kg. During established lactation 0.02% of the daily dose of ethinyl estradiol mothers can be transmitted to baby through breast milk.
Effects on ability to drive and use machines
No effects observed.
Preclinical safety data
Systemic toxicity
Systemic tolerance in animalsStudies after oral administration repeatedly observed no signs of systemic intolerance may be prohibitive for use in humans at the required dosage of the information provided.
There are no animal-experimental studies on a possible sensitizing effect of cyproterone acetate and ethinyl estradiol were performed.
Embryo toxicity / teratogenicity
Investigations embryotoxic or teratogenic effects with the combination of both agents showed no effects indicativea general teratogenic effect following treatment during organogenesis before development of the external genitalia. The administration of cyproterone acetate during the hormone-sensitive ifferentiation of the genital organs (after approximately 45 days of pregnancy) may lead to signs of feminisation of male fetuses in the following higher doses. The observation of male infants who were exposed in utero to cyproterone acetate did not show any signs of feminisation. However, pregnancyContraindication to the use of the 35th Diane
Genotoxicity and carcinogenicity
Recognized first-line tests of genotoxicity gave negative results when conducted with cyproterone acetate. However, more tests showed that cyproterone acetate was capable of, with DNA (and an increase in DNA repair) in liver cells of rats and monkeys and in freshly isolated human hepatocytes, while no adducts DNA were detected in liver cells of dogs.
This DNA adduct formationprobably occurred at exposures that might occur with the recommended dose for cyproterone acetate. In the in vivo effects of cyproterone acetate treatment were the increased incidence of focal, possibly pre-neoplastic, liver lesions in which cellular enzymes were altered in female rats and an increased mutation rate in transgenic mice carrying a bacterial gene as target for the mutation.
Clinical experience and well-conducted epidemiological studies to date do not support aincreased incidence of liver tumors in humans. Even in the tumorigenicity of cyproterone acetate in rodents investigations show evidence of a specific tumorigenic potential. It should be noted, however, that sex steroids may be the growth of certain hormone-dependent tissues and tumors promote be worn.
Overall, the available information, objections to the use of Diane 35 in humans when used in accordance with the instructions for each show andrecommended dose.
Adverse effects
Serious side effects of Diane 35 is referred to in the contraindications and warnings and precautions sections.
The following side effects have been reported in users of Diane 35 and the association has been neither confirmed nor refuted:
* Breast tenderness, pain, discharge
Headache
Migraine
Changes in libido
depression
Contact lens intolerance
Nausea
Vomiting
Changes in vaginal
various skin diseases
Water retention
Change of weight
Hypersensitivity reaction.
Interaction
Interactions with other drugs that may cause increased clearance of sex hormones lead to breakthrough bleeding and failure of oral contraceptives. This confirms with hydantoins, barbiturates, primidone, carbamazepine and rifampicin; oxcarbamazepine, topiramate, felbamate and griseofulvin are also suspected. The mechanism of thisInteraction appears to be induction of liver enzymes on the properties of these drugs. Maximal enzyme induction is not generally for 2-3 weeks, but may be continued for at least 4 weeks after discontinuation of the drug.
Contraceptive failures have also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this effect is unclear.
Women in short-term treatment with one of the above classes of drugs or individual drugsneed to temporarily use a barrier method in addition to Diane 35, ie during the period of co-administration of drugs and for 7 days after their discontinuation. For women in rifampicin a barrier method should be the next Diane 35 should be used at the time of rifampicin administration and for 28 days after discontinuation. If co-administration of drugs through the end of Diane 35 tablets in the pack, Diana 35, the next pack without the usual startingTablet range.
In women, the long-term treatment with hepatic enzyme-inducing drug experts have recommended to increase the doses of contraceptive steroids. If a high dosage of birth control is not desirable or appears unsatisfactory or unreliable, for example in case of irregular bleeding, another method of contraception should be advised.
Laboratory tests
The use of preparations like Diane 35 can influence the results of some laboratory tests, including biochemical parameters ofLiver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, eg corticosteroid binding globulin and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal range.
Overdose
There are no reports of serious consequences of overdose.
Symptoms
Symptoms that may arise in this case are nausea, vomiting and vaginal in young girls, slightBleeding.
Treatment
There is no antidote and treatment should be symptomatic.
Pharmaceutical Precautions
Shelf life: 5 years
Special precautions for storage: under 25 ° C
Packaging unit
3 calendar days with 21 packs or 28 tablets.
Diane 35 tablets are available in blister strips containing funnel polyvinyl chloride film with counter sealing foil made of aluminum with heat sealable coating.
