Femoston 1/10mg

Femoston 1/10mg

estradiol

estradiol + dydrogesterone

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Abbott
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Contents
17β-estradiol (hemihydrate), dydrogesterone.
Description
Femoston 1/10 contains 14 white tablets, each containing 1 mg 17β-estradiol (as hemihydrate) and 14 grey tablets, each containing 1 mg 17β- estradiol (as hemihydrate) and 10 mg dydrogesterone.
Excipients/Inactive Ingredients: Tablet core (all tablets): Lactose monohydrate, hypromellose, maize starch, colloidal anhydrous silica, magnesium stearate.
Film-coating: White colouring agent (1mg tablets): Titanium dioxide (E171), hypromellose, Macrogol 400.
Grey colouring agent (1/10 mg tablets): Titanium dioxide (E171), iron oxide black (E172), polyvinyl alcohol, Macrogol 3350, talc.
Action
Pharmacotherapeutic Group: Genito urinary system and sex hormones, progestogens and oestrogens, sequential preparations. ATC Code: G03FB08.
Pharmacology: Pharmacodynamics: Estradiol: The active ingredient, 17β-estradiol, is chemically and biologically identical to endogenous human estradiol.
It substitutes for the loss of oestrogen production in menopausal women, and alleviates menopausal symptoms.
Oestrogens prevent bone loss following menopause or ovariectomy.
Dydrogesterone: Dydrogesterone is an orally-active progestogen having an activity comparable to parenterally administered progesterone.
As oestrogens promote the growth of the endometrium, unopposed oestrogens increase the risk of endometrial hyperplasia and cancer. The addition of a progestogen greatly reduces the oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised women.
Clinical trial Information: Relief of oestrogen-deficiency symptoms and bleeding patterns.
Relief of menopausal symptoms was achieved during the first few weeks of treatment.
Regular withdrawal bleeding occurred in 76% of the women with a mean duration of 5 days.
Withdrawal bleeding usually started at mean day 28 of the cycle. Break through bleeding and/or spotting appeared in 23% of the women during the first three months of therapy and in 15% of the women during months 10-12 of treatment. Amenorrhoea (no bleeding or spotting) occurred in 21% of the cycles during the first year of treatment.
Prevention of osteoporosis.
Oestrogen deficiency at menopause is associated with increase in bone turnover and a decline in bone mass. The effect of oestrogens on the bone mineral density is dose dependent.
Protection appears to be effective for as long as treatment is continued. After discontinuation of HRT, bone mass is lost at a rate similar to that in untreated women.
Evidence from the WHI trial and meta-analysed trials shows that current use of HRT, alone or in combination with a progestogen - given to predominantly healthy women - reduces the risk of hip, vertebral, and other osteoporotic fractures. HRT may also prevent fractures in women with low bone density and/or established osteoporosis, but the evidence for that is limited.
For Femoston 1/10 the increase in lumbar spine BMD was 5.2% ± 3.8% (mean ± SD), and the percentage of women with no change or an increase in lumbar spine BMD was 93.0%.
Femoston 1/10 also had an effect on hip BMD.
The increase after two years of treatment with Femoston 1/10 was 2.7% ± 4.2 % (mean ± SD) at femoral neck, 3.5% ± 5.0% (mean ± SD) at trochanter and 2.7%±6.7% (mean ± SD) at Wards triangle.
The percentage of women who maintained or gained BMD in the 3 hip areas after treatment with Femoston 1/10 was 67-78%.
Pharmacokinetics: Estradiol: Absorption: Absorption of estradiol is dependent on the particle size, micronized estradiol is readily absorbed from the gastrointestinal tract.
The following table provides the mean single dose pharmacokinetic parameters of estradiol (E2), estrone (E1) and estrone sulphate (E1S) for each dose of micronized estradiol. Data is presented as mean (SD). (See Table 1.)


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Distribution: Oestrogens can be found either unbound or bound. About 98-99% of the estradiol dose binds to plasma proteins, from which about 30-52% on albumin and about 46-69% on the sex hormone-binding globulin (SHBG).
Metabolism: Following oral administration, estradiol is extensively metabolised. The major unconjugated and conjugated metabolites are estrone and estrone sulphate. These metabolites can contribute to the oestrogen activity, either directly or after conversion to estradiol. Estrone sulphate may undergo enterohepatic circulation.
Elimination: In urine, the major compounds are the glucuronides of estrone and estradiol. The elimination half-life is between 10-16 h.
Oestrogens are secreted in the milk of nursing mothers.
Dose and time dependencies: Following daily oral administration of Femoston, estradiol concentrations reached a steady-state after about five days.
Generally, steady state concentrations appeared to be reached within 8 to 11 days of dosing.
Dydrogesterone: Absorption: Following oral administration, dydrogesterone is rapidly absorbed with a Tmax between 0.5 and 2.5 hours. The absolute bioavailability of dydrogesterone (oral 20 mg dose versus 7.8 mg intravenous infusion) is 28 %.
The following table provides the mean steady state pharmacokinetic parameters of dydrogesterone (D) and dihydrodydrogesterone (DHD). Data is presented as mean (SD). (See Table 2.)


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Distribution: After intravenous administration of dydrogesterone the steady-state volume of distribution is approximately 1400 L. Dydrogesterone and DHD are more than 90% bound to plasma proteins.
Metabolism: Following oral administration, dydrogesterone is rapidly metabolized to DHD. The levels of the main active metabolite 20 α-dihydrodydrogesterone (DHD) peak about 1.5 hours post dose. The plasma levels of DHD are substantially higher as compared to the parent drug. The AUC and Cmax ratios of DHD to dydrogesterone are in the order of 40 and 25, respectively. Mean terminal half lives of dydrogesterone and DHD vary between 5 to 7 and 14 to 17 hours, respectively. A common feature of all metabolites characterised is the retention of the 4,6 diene-3-one configuration of the parent compound and the absence of 17α-hydroxylation. This explains the lack of oestrogenic and androgenic effects of dydrogesterone.
Elimination: After oral administration of labeled dydrogesterone, on average 63% of the dose is excreted into the urine. Total plasma clearance is 6.4 L/min. Within 72 hours excretion is complete. DHD is present in the urine predominantly as the glucuronic acid conjugate.
Dose and time dependencies: The single and multiple dose pharmacokinetics are linear in the oral dose range 2.5 to 10 mg. Comparison of the single and multiple dose kinetics shows that the pharmacokinetics of dydrogesterone and DHD are not changed as a result of repeated dosing. Steady state was reached after 3 days of treatment.
Indications/Uses
Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women at least 6 months since last menses.
Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis.
Elderly population: The experience in treating women older than 65 years is limited.
Dosage/Direction for Use
For oral use.
Treatment commences with one white tablet daily for the first 14 days followed by one grey tablet daily for the next 14 days, as directed on the 28 day calendar pack.
Femoston 1/10 should be taken continuously without a break between packs.
For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration (see also Precautions) should be used.
Patients changing from another continuous sequential or cyclical preparation should complete the 28 day cycle and then change to Femoston 1/10.
Patients changing from a continuous combined preparation may start therapy at any time.
Depending on the clinical response, the dosage can subsequently be adjusted.
If a dose has been forgotten, it should be taken as soon as possible. If more than 12 hours have elapsed, treatment should be continued with the next tablet without taking the forgotten tablet.
The likelihood of breakthrough bleeding or spotting may be increased.
Femoston 1/10 can be taken irrespective of food intake.
Paediatric population: There is no relevant indication for the use of Femoston 1/10 in the paediatric population.
Overdosage
Both estradiol and dydrogesterone are substances with low toxicity. Symptoms such as nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue, and withdrawal bleeding could occur in cases of overdosing. It is unlikely that any specific symptomatic treatment will be necessary. Aforementioned information is also applicable for overdosing in children.
Contraindications
Known past or suspected breast cancer.
Known or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer).
Known or suspected progestogen-dependent neoplasms (e.g. meningioma).
Undiagnosed genital bleeding.
Untreated endometrial hyperplasia.
Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism).
Known thrombophilic disorders (e.g. protein C, protein S or antithrombin deficiency, see Precautions).
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction).
Acute liver disease, or a history of liver disease, as long as the liver function tests have failed to return to normal.
Porphyria.
Known hypersensitivity to the active substances or to any of the excipients.
Special Precautions
For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.
Evidence regarding the risks associated with HRT in the treatment of premature menopause is limited. Due to the low level of absolute risk in younger women, however, the balance of benefits and risks for these women may be more favourable than in older women.
Medical examination and follow-up: Before initiating or re-instituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see Breast cancer as follows). Investigations, including appropriate imaging tools, e.g. mammography should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Conditions which need supervision: If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with Femoston 1/10, in particular: Leiomyoma (uterine fibroids) or endometriosis; Risk factors for thromboembolic disorders (see as follows); Risk factors for oestrogen dependent tumours, e.g. 1st degree heredity for breast cancer; Hypertension; Liver disorders (e.g. liver adenoma); Diabetes mellitus with or without vascular involvement; Cholelithiasis; Migraine or (severe) headache; Systemic lupus erythematosus; A history of endometrial hyperplasia (see as follows); Epilepsy; Asthma; Otosclerosis.
Reasons for immediate withdrawal of therapy: Therapy should be discontinued in case a contraindication is discovered and in the following situations: Jaundice or deterioration in liver function; Significant increase in blood pressure; New onset of migraine-type headache; Pregnancy.
Breast cancer: The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogen-progestogen and possibly also oestrogen-only HRT, that is dependent on the duration of taking HRT.
Combined oestrogen-progestogen therapy: The randomised placebo-controlled trial, the Women's Health Initiative study (WHI), and epidemiological studies are consistent in finding an increased risk of breast cancer in women taking combined oestrogen-progestogen for HRT that becomes apparent after about 3 years (see Adverse Reactions).
Oestrogen-only therapy: The WHI trial found no increase in the risk of breast cancer in hysterectomised women using oestrogen-only HRT. Observational studies have mostly reported a small increase in risk of having breast cancer diagnosed that is substantially lower than that found in users of oestrogen-progestogen combinations (see Adverse Reactions).
The excess risk becomes apparent within a few years of use but returns to baseline within a few (at most five) years after stopping treatment.
HRT, especially oestrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Endometrial hyperplasia and carcinoma: In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased when oestrogens are administered alone for prolonged periods. The reported increase in endometrial cancer risk among oestrogen-only users varies from 2- to 12-fold greater compared with non-users, depending on the duration of treatment and oestrogen dose (see Adverse Reactions). After stopping treatment risk may remain elevated for at least 10 years.
The addition of a progestogen cyclically for at least 12 days per month/28 day cycle or continuous combined oestrogen-progestogen therapy in non-hysterectomised women can prevent the excess risk associated with oestrogen-only HRT.
Breakthrough bleeding and spotting may occur during the first months of treatment. If breakthrough bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Ovarian cancer: Ovarian cancer is much rarer than breast cancer.
Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only or combined oestrogen-progestogen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping. Some other studies, including the WHI trial suggest that use of combined HRTs may be associated with a similar, or slightly smaller, risk (see Adverse Reactions).
Venous thromboembolism: HRT is associated with a 1.3-3 fold risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of HRT than later (see Adverse Reactions).
Patients with known thrombophilic states have an increased risk of VTE and HRT may add to this risk. HRT is therefore contraindicated in these patients (see Precautions).
Generally recognised risk factors for VTE include: use of oestrogens, older age, major surgery, prolonged immobilisation, obesity (BMI > 30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE), and cancer. There is no consensus about the possible role of varicose veins in VTE.
As in all postoperative patients, prophylactic measures need be considered to prevent VTE following surgery. If prolonged immobilisation is to follow elective surgery temporarily stopping HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is completely mobilised.
In women with no personal history of VTE but with a first degree relative with a history of thrombosis at young age, screening may be offered after careful counselling regarding its limitations (only a proportion of thrombophilic defects are identified by screening).
If a thrombophilic defect is identified which segregates with thrombosis in family members or if the defect is "severe" (e.g. antithrombin, protein S, or protein C deficiencies or a combination of defects) HRT is contraindicated.
Women already on chronic anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic-symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
Coronary artery disease (CAD): There is no evidence from randomised controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined oestrogenprogestogen or oestrogen-only HRT.
Combined oestrogen-progestogen therapy: The relative risk of CAD during use of combined oestrogen-progestogen HRT is slightly increased. As the baseline absolute risk of CAD is strongly dependent on age, the number of extra cases of CAD due to oestrogen-progestogen use is very low in healthy women close to menopause, but will rise with more advanced age.
Oestrogen-only: Randomised controlled data found no increased risk of CAD in hysterectomised women using oestrogen-only therapy.
Ischaemic Stroke: Combined oestrogen-progestogen and oestrogen-only therapy are associated with an up to 1.5-fold increase in risk of ischaemic stroke. The relative risk does not change with age or time since menopause. However, as the baseline risk of stroke is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age (see Adverse Reactions).
Other conditions: Oestrogens may cause fluid retention and therefore patients with cardiac or renal dysfunction should be carefully observed.
Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.
Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biological active hormone concentrations are unchanged.
Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1antitrypsin, ceruloplasmin).
HRT use does not improve cognitive function. There is some evidence of increased risk of probable dementia in women who start using continuous combined or oestrogen-only HRT after the age of 65.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This oestrogen-progestogen combination treatment is not contraceptive.
Important information about the ingredients: Femoston 1/10 contains lactose monohydrate. If the patient has been told by the doctor that he/she has an intolerance to some sugars, especially lactose, contact the doctor before taking this medicinal product.
Effects on ability to drive and use machines: Femoston 1/10 has no or negligible influence on the ability to drive and use machines.
Use In Pregnancy & Lactation
Femoston 1/10 is not indicated during pregnancy. If pregnancy occurs during medication with Femoston 1/10 treatment should be withdrawn immediately.
The results of most epidemiological studies to date relevant to inadvertent fetal exposure to combinations of oestrogens with progestogens indicate no teratogenic or foetotoxic effect.
There are no adequate data from the use of estradiol/dydrogesterone in pregnant women.
Lactation: Femoston 1/10 is not indicated during lactation.
Adverse Reactions
Inform the doctor about undesirable effects when using this medicine.
The most commonly reported adverse drug reactions of patients treated with estradiol/dydrogesterone in clinical trials are headache, abdominal pain, breast pain/tenderness and back pain.
The following undesirable effects have been observed with the frequencies indicated as follows during clinical trials (n=4929): The frequencies of study related side effects are ranked according to the following: very common (more than 1 cases in 10 treated patients); common (from 1 to 10 cases in 100 treated patients); uncommon (from 1 to 10 cases in 1000 treated patients); very rare (from 1 to 10 cases in 10000 treated patients).
Infections and infestations: Common: Vaginal candidiasis.
Neoplasms benign, malignant and unspecified: Uncommon: Increase in size of leiomyoma.
Immune system disorders: Uncommon: Hypersensitivity.
Psychiatric disorders: Common: Depression, nervousness.
Uncommon: Influence on libido.
Nervous system disorders: Very common: Headache.
Common: Migraine, dizziness.
Cardiac disorders: Rare: Myocardial infarction.
Vascular disorders: Uncommon: Venous thromboembolism*.
Gastrointestinal disorders: Very common: Abdominal pain.
Common: Nausea, vomiting, flatulence.
Hepatobiliary disorders: Uncommon: Abnormal hepatic function, occasionally with jaundice, asthenia or malaise, and abdominal pain, Gallbladder disorders.
Skin and subcutaneous tissue disorders: Common: Allergic skin reactions (e.g. rash, urticaria, pruritus).
Rare: Angioedema, vascular purpura.
Musculoskeletal and connective tissue disorders: Very common: Back pain.
Reproductive system and breast disorders: Very common: Breast pain/tenderness.
Common: Menstrual disorders (including postmenopausal spotting, metrorrhagia, menorrhagia, oligo/amenorrhoea, irregular menstruation, dysmenorrhoea), pelvic pain, cervical discharge.
Uncommon: Breast enlargement, premenstrual syndrome.
General disorders and administration site reactions: Common: Asthenic conditions (asthenia, fatigue, malaise), peripheral oedema.
Investigations: Common: Increased weight.
Uncommon: Decreased weight.
* see further information as follows
Breast cancer risk: An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined oestrogen-progestogen therapy for more than 5 years.
Any increased risk in users of oestrogen-only therapy is substantially lower than that seen in users of oestrogen-progestogen combinations.
The level of risk is dependent on the duration of use (see Precautions).
Results of the largest randomised placebo-controlled trial (WHI-study) and largest epidemiological study (MWS) are presented. (See Tables 3 and 4.)


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Click on icon to see table/diagram/image


Endometrial cancer risk: Postmenopausal women with a uterus: The endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT.
In women with a uterus, use of oestrogen-only HRT is not recommended because it increases the risk of endometrial cancer (see Precautions).
Depending on the duration of oestrogen-only use and oestrogen dose, the increase in risk of endometrial cancer in epidemiology studies varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.
Adding a progestogen to oestrogen-only therapy for at least 12 days per cycle can prevent this increased risk. In the Million Women Study the use of five years of combined (sequential or continuous) HRT did not increase the risk of endometrial cancer (RR of 1.0 (0.8-1.2)).
Ovarian cancer: Use of oestrogen-only or combined oestrogen-progestogen HRT has been associated with a slightly increased risk of having ovarian cancer diagnosed (see Precautions).
A meta-analysis from 52 epidemiological studies reported an increased risk of ovarian cancer in women currently using HRT compared to women who have never used HRT (RR 1.43, 95% CI 1.31-1.56). For women aged 50 to 54 years taking 5 years of HRT, this results in about 1 extra case per 2000 users. In women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period.
Risk of venous thromboembolism: HRT is associated with a 1.3-3-fold increased relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of using HRT (see Precautions). Results of the WHI studies are presented: See Table 5.


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Risk of coronary artery disease: The risk of coronary artery disease is slightly increased in users of combined oestrogen-progestogen HRT over the age of 60 (see Precautions).
Risk of ischaemic stroke: The use of oestrogen-only and oestrogen-progestogen therapy is associated with an up to 1.5 fold increased relative risk of ischaemic stroke. The risk of haemorrhagic stroke is not increased during use of HRT.
This relative risk is not dependent on age or on duration of use, but as the baseline risk is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age (see Precautions). (See Table 6.)


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Other adverse reactions have been reported in association with oestrogen/progestogen treatment (including estradiol/dydrogesterone): Neoplasms benign, malignant and unspecified: Oestrogen dependent neoplasms both benign and malignant, e.g. endometrial cancer, ovarian cancer. Increase in size of progestogen dependent neoplasms, e.g. meningioma.
Blood and lymphatic system disorders: Haemolytic anaemia.
Immune system disorders: Systemic lupus erythematosus.
Metabolism and nutrition disorders: Hypertriglyceridemia.
Nervous system disorders: Probable dementia, chorea, exacerbation of epilepsy.
Eye disorders: Steepening of corneal curvature, contact lenses intolerance.
Vascular disorders: Arterial thromboembolism.
Gastrointestinal disorders: Pancreatitis (in women with pre-existing hypertriglyceridemia).
Skin and subcutaneous tissue disorders: Erythema multiforme, erythema nodosum, chloasma or melasma, which may persist when drug is discontinued.
Musculoskeletal and connective tissue disorders: Leg cramps.
Renal and urinary disorders: Urinary incontinence.
Reproductive system and breast disorders: Fibrocystic breast disease, uterine cervical erosion.
Congenital, familial and genetic disorders: Aggravated porphyria.
Investigations: Total thyroid hormones increased.
Drug Interactions
No interaction studies have been performed.
The efficacy of oestrogens and progestogens might be impaired: The metabolism of oestrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically the P450 enzymes 2B6, 3A4, 3A5, 3A7, such as anticonvulsants (e.g. phenobarbital, carbamazepine, phenytoin) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong inhibitors of CYP450 3A4, A5, A7, by contrast, exhibit inducing properties when used concomitantly with steroid hormones.
Herbal preparations containing St. John's Wort (Hypericum perforatum) may induce the metabolism of oestrogens and progestogens via the CYP450 3A4 pathway.
Clinically, an increased metabolism of oestrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile.
Oestrogens might interfere with the metabolism of other drugs: Oestrogens per se may inhibit CYP450 drug-metabolising enzymes via competitive inhibition.
This is in particular to be considered for substrates with a narrow therapeutic index, such as: tacrolimus and cyclosporine A (CYP450 3A4, 3A3); fentanyl (CYP450 3A4); theophylline (CYP450 1A2).
Clinically this may lead to an increased plasma level of the affected substances up to toxic concentrations. Thus, careful drug monitoring for an extended period of time might be indicated and a dosage decrease of tacrolimus, fentanyl, cyclosporin A and theophylline may be necessary.
Caution For Usage
Incompatibilities: Not applicable.
Further information: Any unused product or waste material should be disposed of in accordance with local requirements.
The information in this monograph is limited. For further information, please contact the doctor or pharmacist.
Storage
Shelf life and storage conditions: 3 years.
Do not store above 30°C.
Store in the original package.
ATC Classification
G03FA14 - dydrogesterone and estrogen ; Belongs to the class of progestogens and estrogens in fixed combinations.
Presentation/Packing
FC tab [14's (round, white, bears the inscription "379" on one side) + 14's (round, grey, bears the inscription "379" on one side)] 28's.
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