DIANE 35
Oral Contraceptives /Acne Treatment Preparations
Acne Papulopustulosa, Acne Nodulosistika
INDICATION
Provide
additional benefits for diseases that depend on androgens in women such
as acne, especially those accompanied by sebore or inflammatory or form
nodes (acne papulopustulosa, acne nodulosistika), alopecia (hair loss)
androgenetic, mild forms of hirsutism (excessive hair growth on the
female pattern hair growth in males).
PACKAGING
Tablets 21 PCS
DOSE
1 tablet a day from the first day of the cycle for 21 days followed by a period of rest for 7 days.
Taken with food
Not used for pregnancy Or Lactation
Manufacturer
|
|
Cyproterone acetate, ethinyl
estradiol.
|
|
Oral contraception; acne in
patients on contraceptives.
|
|
Diane-35 is to be taken
regularly in order to achieve the therapeutic efficacy and the required
contraceptive protection. The dose regimen is similar to the usual regimen of
most of the combined oral contraceptives. Thus, the same administration rules
must be considered. Combined oral contraceptives when taken correctly, have a
failure rate of approximately 1% per year. The failure rate may increase when
pills are missed or taken incorrectly. The irregular intake of Diane-35 can
lead to intermenstrual bleedings and could deteriorate the therapeutic and
contraceptive reliability.
Taking Diane-35: Tablets must be taken in the order directed on the package everyday at about the same time with some liquid as needed. 1 tab is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet-free interval, during which time a withdrawal bleed usually occurs. This usually starts on days 2-3 after the last tablet and may not have finished before the next pack is started. Starting on Diane-35: No Preceding Hormonal Contraceptive Use (in the past month): Tablet-taking has to start on day 1 of the woman's natural cycle (ie, the 1st day of her menstrual bleeding). Starting on days 2-5 is allowed, but during the 1st cycle, a barrier method is recommended in addition for the first 7 days of tablet-taking. Changing from a Combined Oral Contraceptive (COC): The woman should start with Diane-35 preferably on the day after the last active tablet of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC. Changing from a Progestogen-Only Method (minipill, injection, implant) or from a Progestogen-Releasing Intrauterine System (IUS): The woman may switch any day from the minipill (from an implant or the IUS on the day of its removal, from an injectable when the next injection would be due), but should, in all of these cases, be advised to additionally use a barrier method for the first 7 days of tablet-taking. Following 1st-Trimester Abortion: The woman may start immediately. When doing so, she need not take additional contraceptive measures. Following Delivery or 2nd-Trimester Abortion: For breastfeeding women, see Use in pregnancy & lactation under Contraindications. Women should be advised to start at days 21-28 after delivery or 2nd-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of Diane-35 use or the woman has to wait for her 1st menstrual period. Management of Missed Tablets: If the user is <12 hrs late in taking any tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time. If she is >12 hrs late in taking any tablet, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules: Tablet-taking must never be discontinued for >7 days; and 7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-ovarian axis. Accordingly, the following advice can be given in daily practice: Week 1: The user should take the last missed tablet as soon as she remembers, even if this means taking 2 tabs at the same time. She then continues to take tablets at her usual time. In addition, a barrier method eg, a condom, should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the regular tablet-free interval, the higher the risk of a pregnancy. Week 2: The user should take the last missed tablet as soon as she remembers, even if this means taking 2 tabs at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the 1st missed tablet, there is no need to use extra contraceptive precautions. However, if this is not the case or if she missed >1 tab, the woman should be advised to use extra precautions for 7 days. Week 3: The risk of reduced reliability is imminent because of the forthcoming tablet-free interval. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following 2 options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the 1st missed tablet, the woman has taken all tablets correctly. If this is not the case, the woman should be advised to follow the first of these 2 options and to use extra precautions for the next 7 days as well. The user should take the last missed tablet as soon as she remembers, even if this means taking 2 tabs at the same time. She then continues to take tablets at her usual time. The next pack must be started as soon as the current pack is finished ie, no gap should be left between packs. The user is unlikely to have a withdrawal bleed until the end of the 2nd pack, but she may experience spotting or breakthrough bleeding on tablet-taking days. The woman may also be advised to discontinue tablet-taking from the current pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack. If the woman missed tablets and subsequently has no withdrawal bleed in the first normal tablet-free interval, the possibility of pregnancy should be considered. Advice in Case of Gastrointestinal Disturbances: In case of severe gastrointestinal disturbances, absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hrs after tablet-taking, the advice concerning missed tablets, as given under Management of Missed Tablets, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) needed from another pack. Shifting Periods or Delaying a Period: To delay a period, the woman should continue with another pack of Diane-35 without a tablet-free interval. The extension can be carried on for as long as wished until the end of the 2nd pack. During the extension, the woman may experience breakthrough-bleeding or spotting. Regular intake of Diane-35 is then resumed after the usual 7-day tablet-free interval. To shift her periods to another day of the week than the woman is used to with her current scheme, she can be advised to shorten her forthcoming tablet-free interval by as many days as she likes. The shorter the interval, the higher the risk that she does not have a withdrawal bleed and will experience breakthrough-bleeding and spotting during the 2nd pack (just as when delaying a period). Length of Use: The length of use depends on the severity of the clinical picture; in general, treatment should be carried out over several months. It is recommended to take Diane-35 for at least another 3-4 cycles after the signs have subsided. Should there be a recurrence, weeks or months after discontinuation of tablet-taking, treatment with Diane-35 may be resumed. |
|
There have been no reports of
serious deleterious effects from overdose. Symptoms that may occur in this
case are nausea, vomiting and, in young girls, slight vaginal bleeding. There
are no antidotes and further treatment should be symptomatic.
|
|
Preparations containing
estrogen/progestogen combinations should not be used in the presence of any
of the following conditions. Should any of the conditions appear for the
first time during their use, Diane-35 should be stopped immediately.
Presence or a history of venous or arterial thrombotic/thromboembolic events (eg, deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident. Presence or history of prodromi 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 severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see Warnings). Pancreatitis or a history thereof if associated with severe hypertriglyceridemia. Presence or history of severe hepatic disease as long as liver function values have not returned to normal. Presence or history of liver tumors (benign or malignant). Known or suspected sex steroid-influenced malignancies (eg, of the genital organs or the breasts). Undiagnosed vaginal bleeding. Hypersensitivity to the active substances or to any of the excipients of Diane-35. Diane-35 is not for use in men. Use in pregnancy & lactation: The administration of Diane-35 is contraindicated during pregnancy. If pregnancy occurs during medication with Diane-35, the preparation must be withdrawn immediately. The administration of Diane-35 is also contraindicated 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 maternal dose of ethinylestradiol could be transferred to the newborn via milk. |
|
If any of the following
conditions/risk factors are present, the benefits of the use of Diane-35
should be weighed against the possible risks for each individual woman and
discussed with the woman before she decides to start using it. In the event
of aggravation, exacerbation or first appearance of any of these conditions
or risk factors, the woman should contact her physician. The physician should
then decide on whether use of Diane-35 should be discontinued.
Circulatory Disorders: Epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases eg, myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These events occur rarely. Venous thromboembolism (VTE), manifesting as deep venous thrombosis and/or pulmonary embolism, may occur during the use of all COCs. The approximate incidence of VTE in users of low estrogen dose (<0.05 mg EE) OCs is up to 4 per 10,000 woman years compared to 0.5-3 per 10,000 woman years in non-OC users. The incidence of VTE associated with pregnancy is 6 per 10,000 pregnant woman years. Extremely rarely, thrombosis has been reported to occur in other blood vessels eg, hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs. Symptoms of venous or arterial thrombotic/thromboembolic events, or of a cerebrovascular accident can include: Unilateral leg pain and/or swelling; sudden severe pain in the chest, whether or not it radiates to the left arm; sudden breathlessness; sudden onset of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without focal seizure; weakness or very marked numbness suddenly affecting one side or one part of the body; motor disturbances; "acute" abdomen. The risk of venous or arterial thrombotic/thromboembolic events, or of a cerebrovascular accident increases with: Age; smoking (with heavier smoking and increasing age the risk further increases, especially in women >35 years); a positive family history (ie, venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use; obesity (body mass index >30 kg/m2), dyslipoproteinemia; hypertension; migraine; valvular heart disease; atrial fibrillation; prolonged immobilization, major surgery, any surgery to the legs or major trauma. In these situations, it is advisable to discontinue COC use (in the case of elective surgery, at least 4 weeks in advance) and not to resume until 2 weeks after complete remobilization. There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism. The increased risk of thromboembolism in the puerperium must be considered (see Use in pregnancy & lactation under Contraindications). Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease. An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC. Biochemical factors that may be indicative of hereditary or acquired predisposition for 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 considering 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 low dose COCs (<0.05 mg EE). Tumors: An increased risk of cervical cancer in long-term users of COCs has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behavior and other factors eg, human papilloma virus (HPV). A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR=1.24) of having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women <40 years, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer. These studies do not provide evidence for causation. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users. In rare cases, benign liver tumors, and even more rarely, malignant liver tumors have been reported in users of COCs. In isolated cases, these tumors have led to life-threatening intra-abdominal hemorrhages. A hepatic tumor should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal hemorrhage occur in women taking COCs. Other Conditions: Women with hypertriglyceridemia or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of a COC, then it is prudent for the physician to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy. The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: Jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs. Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using low dose COCs (containing <0.05 mg EE). However, diabetic women should be carefully observed while taking COCs. Crohn's disease and ulcerative colitis have been associated with COC use. Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking COCs. If in women suffering from 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 should be taken prior to
the initiation or reinstitution of Diane-35, guided by the contraindications
(see Contraindications) and warnings (see Warnings), and should be repeated
periodically. Periodic medical assessment is also of importance because
contraindications (eg, a transient ischemic attack, etc) or risk factors (eg,
a family history of venous or arterial thrombosis) may appear for the first
time during the use of Diane-35. The frequency and nature of these
assessments should be based on established practice guidelines and be adapted
to the individual woman but should generally include special reference to
blood pressure, breasts, abdomen and pelvic organs, including cervical
cytology.
Women should be advised that preparations eg, Diane-35, do not protect against HIV infections (AIDS) and other sexually transmitted diseases. Reduced Efficacy: The efficacy of Diane-35 may be reduced in the event of eg, missed tablets (see Management of Missed Tablets under Dosage & Administration), gastrointestinal disturbances (see Advice in Case of Gastrointestinal Disturbances under Dosage & Administration) or concomitant medication (see Interactions). Reduced Cycle Control: With estrogen/progestogen combinations, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about 3 cycles. If bleeding irregularities persist or occur after previously regular cycles, then nonhormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage. In some women, withdrawal bleeding may not occur during the tablet-free interval. If the COC has been taken according to the directions described under Dosage & Administration, it is unlikely that the woman is pregnant. However, if the COC has not been taken according to these directions prior to the 1st missed withdrawal bleed or if 2 withdrawal bleeds are missed, pregnancy must be ruled out before COC use is continued. Effects on the Ability to Drive or Operate Machinery: No observed effects. |
|
The administration of Diane-35
is contraindicated during pregnancy. If pregnancy occurs during medication
with Diane-35, the preparation must be withdrawn immediately.
The administration of Diane-35 is also contraindicated 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 maternal dose of ethinylestradiol could be transferred to the newborn via milk. |
|
The most serious undesirable
effects associated with the use of COCs are listed under Warnings.
Other side effects that have been reported in patients taking of Diane-35 but for which the association has been neither confirmed nor refuted are: Breast: Tenderness, pain, enlargement, secretion. Central Nervous System: Headache, migraine, changes in libido, depressive mood/mood changes. Gastrointestinal Tract: Nausea, vomiting and other gastrointestinal complaints. Skin: Various skin disorders (eg, rash, erythema nodosum, erythema multiforme). Urogenital: Changes in vaginal secretion. Eyes: Contact lens intolerance. Others: Fluid retention, change in body weight, hypersensitivity reaction. |
|
Interactions between
estrogen/progestogen combination like Diane-35 and other drugs may lead to
breakthrough bleeding and/or contraceptive failure. The following
interactions have been reported in the literature.
Hepatic Metabolism: Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones (eg, phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and products containing St. John's wort). Interference with Enterohepatic Circulation: Some clinical reports suggest that enterohepatic circulation of estrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (eg, penicillins, tetracyclines). Women on treatment with any of these drugs should temporarily use a barrier method in addition to Diane-35, or choose another method of contraception. With microsomal enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after discontinuation. If the period during which the barrier method is used runs beyond the end of the tablets in the Diane-35 pack, the next pack should be started without the usual tablet-free interval. Estrogen/progestogen combinations like Diane-35 may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may be affected (eg, cyclosporin). Note: The prescribing information of concomitant medications should be consulted to identify potential interactions. Laboratory Tests: The use of preparations eg, Diane-35, may influence the results of certain laboratory tests, including biochemical parameters of liver, 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 laboratory range. |
|
Each tablet contains
cyproterone acetate 2 mg and ethinylestradiol 0.035 mg. It also contains the
following excipients: Lactose monohydrate, maize starch, povidone 25,000,
magnesium stearate, sucrose, povidone 700,000, macrogol 6000, calcium
carbonate precipitated, talc, glycerol 85%, titanium dioxide, yellow ferric
oxide pigment, red ferric oxide pigment and montanglycol wax.
|
|
Pharmacology: Cyproterone acetate inhibits the influence of
the androgens which are also produced by the female organism. It is thus
possible to treat diseases, the cause of which is either an increased
production of androgens or a particular sensitivity to these hormones.
While Diane-35 is being taken, the increased sebaceous gland function, which plays an important role in the development of acne and seborrhea, is reduced. This leads, usually after 3-4 months of therapy, to the healing of existing acne efflorescences. The excessive greasiness of the hair and skin generally disappears earlier. The loss of hair which frequently accompanies seborrhea likewise diminishes. Treatment with Diane-35 is indicated in women of childbearing age who exhibit mild forms of hirsutism, and in particular, in slightly increased facial hair; results do not, however, become apparent until after several months of use. Apart from the described antiandrogen effect, cyproterone acetate has also a pronounced progestational action. The sole administration of cyproterone acetate would thus lead to cycle disturbances, which are avoided by its combination with ethinylestradiol in Diane-35. This holds true as long as Diane-35 is taken cyclically according to the instructions. The contraceptive effect of Diane-35 is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in the cervical secretion. In addition to protection against pregnancy, estrogen/progesterone combinations have positive adverse properties (see Adverse Reactions). The cycle is more regular and the menstruation is often less painful, and bleeding is lighter. The latter may result in a decrease in the occurrence of iron deficiency. Apart from this, there is evidence of a reduced risk of endometrial and ovarian cancer. Furthermore, the higher dosed COCs (EE 0.05 mg) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower-dosed COCs remains to be confirmed. Pharmacokinetics: Cyproterone Acetate: Absorption: Orally administered cyproterone acetate is rapidly and completely absorbed. Peak serum concentrations of 15 ng/mL are reached at about 1.6 hrs after single ingestion. Bioavailability is about 88%. Distribution: Cyproterone acetate is almost exclusively bound to serum albumin. Only 3.5-4% of the total serum drug concentrations are present as free steroid. The ethinylestradiol-induced increase in SHBG does not influence the serum protein-binding of cyproterone acetate. The apparent volume of distribution of cyproterone acetate is about 986±437 L. Metabolism: Cyproterone acetate is almost completely metabolized. The main metabolite in plasma was identified as 15β-OH-CPA, which is formed via the cytochrome P-450 enzyme CYP3A4. The clearance rate from serum is about 3.6 mL/min/kg. Elimination: Cyproterone acetate serum levels decrease in 2 phases which are characterized by half-lives of about 0.8 hr and about 2.3-3.3 days. Cyproterone acetate is partly excreted in unchanged form. Its metabolites are excreted at a urinary-to-biliary ratio of about 1:2. The half-life of metabolite excretion is about 1.8 days. Steady-State Conditions: Cyproterone acetate pharmacokinetics are not influenced by SHBG levels. Following daily ingestion, drug serum levels increase about 2.5-fold reaching steady-state conditions during the second half of a treatment cycle. Ethinylestradiol: Absorption: Orally administered ethinylestradiol is rapidly and completely absorbed. Peak serum concentrations of about 71 pg/mL are reached at 1.6 hrs. During absorption and first-liver passage, ethinylestradiol is metabolized extensively, resulting in a mean oral bioavailability of about 45% with a large interindividual variation of about 20-65%. Distribution: Ethinylestradiol is highly but nonspecifically bound to serum albumin (approximately 98%), and induces an increase in the serum concentrations of SHBG. An apparent volume of distribution of about 2.8-8.6 L/kg was determined. Metabolism: Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. It is primarily metabolized by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed, and these are present as free metabolites and as conjugates with glucuronides and sulfate. The clearance rate was reported to be about 2.3-7 mL/min/kg. Elimination: Ethinylestradiol serum levels decrease in 2 disposition phases characterized by half-lives of about 1 hr and 10-20 hrs, respectively. Unchanged drug is not excreted, ethinylestradiol metabolites are excreted at a urinary-to-biliary ratio of 4:6. The half-life of metabolite excretion is about 1 day. Steady-State Conditions: Steady-state conditions are reached during the second half of a treatment cycle when serum drug levels are higher by 60% as compared to single dose. |
|
G03HB01 - cyproterone and
estrogen ; Belongs to the class of antiandrogen preparations in
combination with estrogens. Used to counter androgenic activities.
|
|
G
|
|
Tab (coated) 21's.
|
source:
http://www.mims.com/indonesia/drug/info/diane%2035/?type=full#UseInPregnancyLactation
Cyproterone + Ethinylestradiol
Available Brands
|
·
Diane 35
·
Neynna
|
Indications |
Listed
in Dosage.
|
Dosage |
Adult : PO Acne; Hirsutism; Oral
contraception Each tab contains
cyproterone acetate 2 mg and ethinylestradiol 35 mcg: First treatment course:
1 tab/day for 21 days starting on first day of menstruation. Subsequent
courses: 1 tab once daily taken at the same time for 21 days after 7 tab-free
days.
|
Dosage Details |
Oral
Acne, Hirsutism, Oral contraception
Adult: Available
preparation:
Cyproterone acetate 2 mg and ethinylestradiol 35 mcg First treatment course: 1 tab once daily taken at the same time for 21 days starting on 1st day of menstruation. Subsequent courses: 1 tab once daily taken at the same time for 21 days after 7 tab-free days. Discontinue therapy 3-4 cycles after symptoms have resolved. |
Hepatic Impairment |
Contraindicated.
|
Contraindications |
Current or history of cerebrovascular accident, breast cancer,
venous or arterial thrombotic or thromboembolic events (e.g. DVT, pulmonary
embolism, MI) including risk factors. DM w/ vascular symptoms, severe HTN and
dyslipoproteinaemia, undiagnosed vaginal bleeding, history of migraine w/
focal neurological symptoms. Hepatic impairment (e.g. hepatic tumour, severe
cirrhosis, viral hepatitis). Pregnancy and lactation. Concomitant use w/
ombitasvir, paritaprevir, ritonavir, dasabuvir.
|
Special Precautions |
Patient w/ history of DM w/ mild vascular symptoms or mild
nephropathy, retinopathy or neuropathy, CV diseases (e.g. adequately
controlled HTN), hereditary angioedema, fibrocystic disease of the breast,
uterine fibroids, migraine, clinical depression, connective tissue disease
(e.g. synovitis, SLE, rheumatoid arthritis), porphyria and chloasma,
hypertriglyceridemia, familial defects of lipoprotein metabolism,
malabsorption syndrome. Smokers, obese, or surgical patients. Renal
impairment.
|
Adverse Drug Reactions |
Significant: Worsening of migraine w/o focal neurological symptoms;
risk or worsening of renal dysfunction, jaundice, pruritus associated w/
cholestasis, gallstone formation, SLE, herpes gestations,
otosclerosis-related hearing loss, loss of vision, diplopia, proptosis,
sickle cell anaemia, induction or exacerbation of angioedema, acute or
chronic hepatic function disturbances. Rarely, thrombosis in other blood
vessels (e.g. renal, hepatic, mesenteric, cerebral or retinal veins and arteries),
benign hepatic tumours.
Nervous: Mood alterations. GI: Abdominal pain, nausea, vomiting, diarrhoea. Endocrine: Decreased libido, wt gain, breast pain, tenderness and hypertrophy. Dermatologic: Rash, urticaria. Others: Fluid retention. Potentially Fatal: Rarely, increased risk of venous and arterial thromboembolism, malignant hepatic tumours leading to intra-abdominal haemorrhage. |
Monitoring Parameters |
Assess
personal and family medical history prior to start of treatment and at
regular intervals thereafter. Include BP and breast, abdominal and pelvic
examinations including cervical cytology. Periodically evaluate the need to
continue treatment. Evaluate hypothalamic-pituitary function in women w/
persistent amenorrhoea following discontinuation of therapy.
|
Overdosage |
Symptoms:
Nausea, vomiting and withdrawal bleeding. Management: Symptomatic treatment.
|
Drug Interactions |
Increased exposure w/ hepatic enzyme inhibitors (e.g.
ketoconazole, verapamil, clarithromycin). Decreased exposure w/ hepatic
enzyme inducers (e.g. phenytoin, rifampicin, topiramate). Increased exposure
of ciclosporin. Decreased exposure of lamotrigine.
Ethinylestradiol: Increased exposure w/ etoricoxib. Decreased exposure w/ antibacterials (e.g. penicillins, tetracyclines). Potentially Fatal: Increased ALT levels (>5 times the upper limit of normal) w/ concomitant use of ombitasvir, paritaprevir, ritonavir and dasabuvir w/ or w/o ribavirin. |
Food Interaction |
Increased exposure w/ grapefruit juice. Decreased exposure w/
St. John’s wort.
|
Lab Interference |
May
interfere w/ tests for lipids, glucose tolerance, coagulation factors,
binding proteins.
|
Mechanism of Action |
Description: Cyproterone and Ethinylestradiol decreases androgen synthesis
by negative feedback mechanism and by inhibition of androgen-synthesising
enzymes. It also inhibits ovulation, reduces receptivity of endometrium to
implantation, and thickens cervical mucus to form a barrier to sperm, thereby
inhibiting conception.
Pharmacokinetics: Absorption: Cyproterone: Completely absorbed from the GI tract. Absolute bioavailability: 88%. Time to peak plasma concentration: 1.6 hr. Ethinylestradiol: Rapidly and completely absorbed from the GI tract. Absolute bioavailability: Approx 60%. Time to peak plasma concentration: 1.7 hr. Distribution: Enters breast milk. Ethinylestradiol: Volume of distribution: 5 L/kg. Plasma protein binding: 98.5% mainly to albumin. Metabolism: Cyproterone: Extensively metabolised via hydroxylation and conjugation by CYP3A4 enzyme to several metabolites including 15β-hydroxy cyproterone acetate. Ethinylestradiol: Metabolised mainly via aromatic hydroxylation to hydroxylated and methylated metabolites as free metabolites and as glucuronide and sulfate conjugates. Excretion: Cyproterone: Via urine and bile (mainly as metabolites; some as unchanged drug). Elimination half-life: 1.9 days. Ethinylestradiol: Via urine and bile, as metabolites. Elimination half-life: Approx 1 day. |
Storage |
Store
between 15-30°C. Protect from light.
Wear gloves during receiving, unpacking, and placing in storage. |
MIMS Class |
|
ATC Classification |
G03HB01
cyproterone and estrogen
Belongs to the class of antiandrogen preparations in combination with
estrogens. Used to counter androgenic activities.
|
