- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
For a full list of excipients, see section 6.1
|For termination of pregnancy, Mifegyne and the prostaglandin can only be prescribed and administered in accordance with the countries national laws and regulations.|
1- Medical termination of developing intra-uterine pregnancy.In sequential use with a prostaglandin analogue, up to 63 days of amenorrhea.
2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester.3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester).
4- Labour induction in foetal death in utero.In patients where prostaglandin or oxytocin cannot be used.
1- Medical termination of developing intra-uterine pregnancyThe method of administration will be as follows:• Up to 49 days of amenorrhea:600 mg of mifepristone (i.e. 3 tablets of 200 mg each) is taken in a single oral dose, followed 36 to 48 hours later, by the administration of a prostaglandin analogue; misoprostol 400 µg orally, or gemeprost 1 mg per vaginam.Alternatively, 200 mg of mifepristone can also be used in a single oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue gemeprost 1 mg per vaginam (see section 5.1. pharmacodynamic properties)• Between 50-63 days of amenorrhea600 mg of mifepristone (i.e. 3 tablets of 200 mg each) is taken in a single oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue gemeprost 1 mg per vaginam.Alternatively, 200 mg of mifepristone can also be used in a single oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue gemeprost 1 mg per vaginam (see section 5.1. pharmacodynamic properties)
2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester.200 mg of mifepristone (one tablet), followed 36 to 48 hours later (but not beyond) by surgical termination of pregnancy.
3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons600 mg of mifepristone (i.e. 3 tablets of 200 mg each) taken in a single oral dose, 36 to 48 hours prior to scheduled prostaglandin administration which will be repeated as often as indicated.
4- Labour induction in foetal death in utero600 mg of mifepristone (e.g. 3 tablets of 200 mg each) in a single oral daily dose, for two consecutive days.Labour should be induced by the usual methods if it has not started within 72 hours following the first administration of mifepristone.
IN ALL INDICATIONS- chronic adrenal failure,- hypersensitivity to the active substance or to any of the excipients,- severe asthma uncontrolled by therapy,- inherited porphyria.
In the indication: medical termination of developing pregnancy- pregnancy not confirmed by ultrasound scan or biological tests,- pregnancy beyond 63 days of amenorrhea,- suspected extra-uterine pregnancy,- contra-indication to the prostaglandin analogue selected.
In the indication: softening and dilatation of the cervix uteri prior to surgical termination of pregnancy:- pregnancy not confirmed by ultrasound scan or biological test,- pregnancy of 84 days of amenorrhea and beyond - suspected extra-uterine pregnancy.Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester)- contra-indications to the prostaglandin analogue selected
Labour induction in foetal death in uteroShould prostaglandin combination be required, refer to contra-indications to the prostaglandin analogue selected.
|In the absence of specific studies, Mifegyne is not recommended in patients with: - Renal failure - Hepatic failure - Malnutrition|
1- Medical termination of developing intra-uterine pregnancyThis method requires an active involvement of the woman who should be informed of the method's requirements:- the necessity to combine treatment with prostaglandin to be administered at a second visit,- the need for a follow-up visit (3rd visit) within 14 to 21 days after intake of Mifegyne in order to check for complete expulsion,- the possible failure of the method, leading to a pregnancy termination by another method.In the case of a pregnancy occurring with an intra-uterine device in situ, this device must be removed before administration of Mifegyne. The expulsion may take place before prostaglandin administration (in about 3% of cases). This does not preclude the control visit in order to check for the complete expulsion and the uterine vacuity.• Risks related to the method- FailuresThe non-negligible risk of failure, which occurs in 1.3 to 7.5 % of the cases, makes the control visit mandatory in order to check that the expulsion is completed. In rare case of non complete expulsion, a surgical revision may be necessary.The efficacy of the method decreases with parity, and consequently increasing age of the woman.- BleedingThe patient must be informed of the occurrence of prolonged vaginal bleeding (an average of about 12 days or more after Mifegyne intake) which may be heavy. Bleeding occurs in almost all cases and is not in anyway a proof of complete expulsion.The patient should be informed not to travel far away from the prescribing centre as long as complete expulsion has not been recorded. She will receive precise instructions as to whom she should contact and where to go, in the event of any problems emerging, particularly in the case of very heavy vaginal bleeding.
|A follow-up visit must take place within a period of 14 to 21 days after administration of Mifegyne to verify by the appropriate means (clinical examination, ultrasound scan, and beta-hCG measurement) that expulsion has been completed and that vaginal bleeding has stopped. In case of persistent bleeding (even light) beyond the control visit, its disappearance should be checked within a few days.If an ongoing pregnancy is suspected, a further ultrasound scan may be required to evaluate its viability.|
2- Softening and dilatation of the cervix uteri prior to surgical pregnancy terminationFor the full efficacy of therapy, the use of Mifegyne must be followed, 36 to 48 hours later and not beyond, by surgical termination.• Risks related to the method- BleedingThe woman will be informed of the risk of vaginal bleeding which may be heavy, following intake of Mifegyne. She should be informed of the risk of abortion prior to surgery (although minimal): she will be informed on where to go in order to check for the completeness of expulsion, or in any case of emergency.Since heavy bleeding requiring curettage occurs in about 1% of patients, special care should be given to patients with haemostatic disorders, hypocoagulability, or severe anaemia.- Other risksThey are those of the surgical procedure.
3- In all instancesThe use of Mifegyne requires rhesus determination and hence the prevention of rhesus allo-immunisation as well as other general measures taken usually during any termination of pregnancy.During clinical trials, pregnancies occurred between embryo expulsion and the resumption of menses.To avoid potential exposure of a subsequent pregnancy to mifepristone, it is recommended that conception be avoided during the next menstrual cycle. Reliable contraceptive precautions should therefore commence as early as possible after mifepristone administration.
Precautions for use
1- In all instancesIn case of suspected acute adrenal failure, dexamethasone administration is recommended. 1 mg of dexamethasone antagonises a dose of 400 mg of mifepristone. Due to the antiglucocorticoid activity of mifepristone, the efficacy of long-term corticosteroid therapy, including inhaled corticosteroids in asthmatic patients, may be decreased during the 3 to 4 days following intake of Mifegyne. Therapy should be adjusted. A decrease of the efficacy of the method can theoretically occur due to the antiprostaglandin properties of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin (acetyl salicylic acid). Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.
2- Medical termination of developing intra-uterine pregnancyRare but serious cardiovascular accidents have been reported following the intra muscular administration of prostaglandin analogue. For this reason, women with risk factors for cardiovascular disease or established cardiovascular disease should be treated with caution.
Method of prostaglandin administrationDuring intake and for three hours following the intake, the patient should be monitored in the treatment centre, in order not to miss possible acute effects of prostaglandin administration. The treatment centre must be equipped with adequate medical facilities.On discharge from the treatment centre all women should be provided with appropriate medications as necessary and be fully counselled regarding the likely signs and symptoms she may experience and have direct access to the treatment centre by telephone or local access.
3- For the sequential use of Mifegyne - Prostaglandin, whatever the indicationThe precautions related to the prostaglandin used should be followed where relevant.
LactationMifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, no data is available. Consequently, mifepristone use should be avoided during breast-feeding.
Nervous system disorders
Very common:- Nausea, vomiting, diarrhoea (these gastro intestinal effects related to prostaglandin use are frequently reported).
Common:- Cramping, light or moderate.
Skin and subcutaneous tissue disorders
Uncommon- Hypersensitivity: Skin rashes uncommon (0.2%).
Rare- Single cases of urticaria, erythroderma, erythema nodosum, toxic epidermal necrolysis have also been reported.
Very rare- Angioedema
Infections and infestationsCommon:- Infection following abortion. Suspected or confirmed infections (endometritis, pelvic inflammatory disease) have been reported in less than 5% of women.
Very rare:- Very rare cases of serious or fatal toxic shock caused by pathogens like Clostridium sordellii endometritis or Escherichia coli, presenting with or without fever or other obvious symptoms of infection, have been reported after medical abortion with the use of 200 mg mifepristone followed by non authorised vaginal administration of misoprostol tablets for oral use. Clinicians should be aware of this potentially fatal complication (see section 4.4. special warnings and special precautions for use).
Uncommon:- Hypotension (0.25%)
General disorders and administration site conditions
Rare:- malaise, vagal symptoms (hot flushes, dizziness, chills), fever.
Reproductive system and breast disorders
Very common:- Very common uterine contractions or cramping (10 to 45%) in the hours following prostaglandin intake.
Common:- Heavy bleeding occurs in about 5% of the cases and may require haemostatic curettage in up to 1.4% of the cases.
Rare:- During induction of second trimester termination of pregnancy or labour induction for foetal death in utero during the third trimester, uterine rupture has been uncommonly reported after prostaglandin intake. The reports occurred particularly in multiparous women or in women with a caesarean section scar.
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