Source: Health Products Regulatory Authority (ZA) Revision Year: 2021 Publisher: Ranbaxy Pharmaceuticals (Pty) Ltd, 14 Lautre Road, Stormill Ext.1, Roodepoort, Johannesburg
MEDABON CO should never be prescribed in the following situations:
In the absence of specific studies, caution is advised when MEDABON CO use is considered in patients with:
This method requires an active involvement of the woman who should be informed of the requirements of the method:
In the case of a pregnancy occurring with an intra-uterine device in situ, this device must be removed before administration of mifepristone.
The expulsion of the product of conception may take place before misoprostol administration (in 1 to 2% of cases). This does not preclude the follow-up visit in order to check that abortion is complete.
Before MEDABON CO is given to a woman who has undergone genital mutilation (FGM) a physical examination must be performed by a qualified trained medical professional to exclude any anatomical obstacles to medical abortion.
Because it is important to have access to appropriate medical care if an emergency develops, the treatment procedure should only be performed where the patient has access to medical facilities equipped to provide surgical treatment for incomplete abortion, or emergency blood transfusion or resuscitation during the period from the first visit until discharged by the administering qualified medical professional.
The non-negligible risk of failure, which occurs in 4,5-7,8% of the cases, makes the follow-up visit mandatory in order to check that abortion is complete. The patient should be informed that surgical treatment may be required to achieve completem abortion.
The patient must be informed of the occurrence of prolonged vaginal bleeding (an average of about 13 days after mifepristone intake, up to three weeks in some women). In a few cases, heavy bleeding may require surgical evacuation of the uterus. Bleeding is not in any way a proof of termination of pregnancy as it occurs also in most cases of failure.
The patient should be informed not to travel far away from the prescribing centre as long as complete expulsion has not been confirmed. She should receive precise instructions as to whom she should contact and where to go, in the event of any problems or emergency, particularly in the case of very heavy vaginal bleeding.
A follow-up visit must take place within a period of 14-21 days after administration of mifepristone to verify by the appropriate means (clinical examination, ultrasound scan, or beta-hCG measurement) that expulsion of the abortion has been completed and that vaginal bleeding has stopped or substantially reduced. In case of persistent bleeding (even light) beyond the follow-up visit, its disappearance should be checked a few weeks later. If an ongoing pregnancy is suspected, a further ultrasound scan may be required to evaluate its viability.
Persistence of vaginal bleeding at this point could signify incomplete abortion, or an unnoticed extra-uterine pregnancy, and appropriate investigation/treatment should be considered.
In the event of an ongoing pregnancy diagnosed at the follow-up visit, termination by another method should be proposed to the woman.
Since heavy bleeding requiring haemostatic curettage occurs in 0,2-1,8% of the cases during the medical method of pregnancy termination, special care should be given to patients with haemostatic disorders with hypocoagulability, or with anaemia. The decision to use the medical or the surgical method should be decided with specialised consultants according to the type of haemostatic disorder and the level of anaemia.
The genital tract is more susceptible to ascending infection when the cervix is dilated after abortion or childbirth. There are few data on the incidence of clinically significant pelvic infection after medical abortion, but it seems to be rare and probably occurs less often than after vacuum aspiration. Many of the symptoms of pelvic infection, such as pain, are often non-specific and hence precise diagnosis is difficult. In women with clinical signs such as pelvic pain, abdominal or adnexal tenderness, vaginal discharge and fever, a pelvic infection should be suspected and appropriate treatment should be given.
Cases of fatal or serious toxic shock caused by pathogens like Clostridium sordellii 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 vaginal administration of misoprostol tablets for oral use. It cannot be excluded that this infection may occur also with vaginal misoprostol as in MEDABON CO. Clinicians should be aware of this potentially fatal complication.
Pregnancy-related symptoms such as nausea and vomiting may increase after mifepristone and increase further after misoprostol administration, and they will weaken and disappear during the abortion process. Lower abdominal pain and cramping are the most common symptoms and they are related to misoprostol administration and the abortion process. If pain persists after expulsion of the products of conception, its origin should be investigated. Diarrhoea is the most common dose-related side effect related to misoprostol use which normally does not require treatment. Some women also report chills, shivering and/or temperature rise after misoprostol administration.
Regarding rhesus determination and prevention of rhesus allo-immunisation, the same general measures apply to the use of medical abortion as during any termination of pregnancy.
Any reproductive tract infections should be treated before the medical abortion regimen is administered.
During clinical trials, pregnancies have occurred between abortion and the resumption of menses. To avoid potential exposure of a subsequent pregnancy to mifepristone, it is recommended that unprotected sexual intercourse be avoided until the appearance of the first menses after the abortion. Reliable contraceptive methods should therefore be started as early as possible after misoprostol administration.
In 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 mifepristone. Therapy should be adjusted.
A decrease of the efficacy of the method can theoretically occur due to the antiprostaglandin properties of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin (acetyl salicylic acid). Limited evidence suggests that co-administration of NSAIDs on the day of misoprostol administration does not adversely influence the effects of mifepristone or misoprostol and does not reduce the clinical efficacy of medical termination of pregnancy.
Serious cardiovascular accidents have been reported following the intramuscular administration of prostaglandin analogue. For this reason, women with risk factors for cardiovascular disease or established cardiovascular disease should be treated with caution.
During 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 misoprostol administration.
On discharge from the treatment centre the woman 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.
No interaction studies have been performed in view of the single dose administration. On the basis of mifepristone’s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampicin, dexamethasone, St John’s wort and certain anticonvulsants (phenytoin, phenobarbital and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone).
Based on in vitro inhibition information, co-administration of mifepristone may lead to an increase in serum levels of medicines that are CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Therefore, caution should be exercised when mifepristone is administered with medicines that are CYP3A4 substrates and have narrow therapeutic range, such as ciclosporin, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl and quinidine, or some medicines used during general anaesthesia.
Antacids containing magnesium may worsen misoprostol-induced diarrhoea.
MEDABON CO is indicated for the termination of pregnancy and has no other use during pregnancy.
The abortifacient effect of mifepristone precludes the proper assessment of any teratogenic effect of the molecule.
With sub-abortive doses, isolated cases of malformations are observed in rabbits, but not in rats or mice, and are too few to be considered significant, or attributable to mifepristone.
In humans, the few reported cases of malformations do not allow a causality assessment for mifepristone alone or associated to prostaglandin. Therefore, data are too limited to determine whether the molecule is a human teratogen.
Animal studies have not evidenced teratogenicity of misoprostol but have shown its fetotoxicity at high doses.
There are currently no relevant clinical data that suggest the possible occurrence of malformation after the vaginal use of misoprostol during pregnancy. However, in a few cases where misoprostol was self-administered (orally or vaginally) in order to induce an abortion, the following deleterious effects of misoprostol have been suggested: malformations of limbs, of fetus movements and of cranial nerves (hypomimia, abnormalities in suckling, deglutition, and eye movements). To date, a risk of malformation cannot be excluded.
Consequently:
Mifepristone is a lipophilic compound and is therefore likely to be excreted in the mother’s breast milk. However, no data are available. Misoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and excreted in breast milk, and could cause undesirable effects such as diarrhoea in nursing infants. Consequently, mothers taking MEDABON CO should not breastfeed their infants (see section 4.3).
No studies on the effects on the ability to drive and use machines have been performed. Mifepristone and misoprostol (as contained in MEDABON CO) may cause dizziness, which could have an effect on the ability to drive and use machines.
Less frequent: Cases of serious or fatal toxic and septic shock (caused by Clostridium sordelli or Escherichia coli) which can be with or without fever or other obvious symptoms of infection have been reported. Clinicians should be aware of this potentially fatal complication (see section 4.4).
Less frequent: Hypotension.
Frequent: Stomach cramping (light or moderate). Nausea, vomiting, diarrhoea (these gastrointestinal effects are related to misoprostol use).
Less frequent: Hypersensitivity (skin rashes), urticaria, erythroderma, erythema nodosum, epidermal necrolysis.
Frequent: Uterine contractions or cramping (up to 70 to 80%) in the hours following misoprostol intake. Heavy bleeding occurs in up to 5% of the cases and may require haemostatic curettage and blood transfusion in up to 1,8% of the cases.
Less frequent: Infection following abortion: suspected or confirmed infections (endometritis, pelvic inflammatory disease) have been reported in less than 1% of women.
Less frequent: Headaches, malaise, vagal symptoms (hot flushes, dizziness, chills have been reported) and fever.
Less frequent: Uterine rupture has been reported after prostaglandin intake for induction of termination of second trimester pregnancy or labour induction for fetal death in utero in the third trimester. Uterine ruptures occurred particularly in multiparous women or in women with a caesarean section scar.
Reporting suspected adverse reactions after authorisation of MEDABON CO is important. It allows continued monitoring of the benefit/risk balance of MEDABON CO. Health care providers are asked to report any suspected adverse reactions via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8
Not applicable.
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