Consumer medicine information

GyMiso

Misoprostol

BRAND INFORMATION

Brand name

GyMiso Tablets

Active ingredient

Misoprostol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using GyMiso.

What is in this leaflet

This leaflet answers some common questions about GyMiso® tablets. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given GyMiso® tablets against the expected benefits it will have for you.

If you have any concerns about being given this medicine, ask your doctor.

Keep this leaflet.

You may need to read it again.

What GyMiso® is used for

GyMiso® contains misoprostol. It belongs to a group of medicines called prostaglandins. It acts like prostaglandin E1. GyMiso® induces contractions of the smooth muscle and relaxation of the cervix. These properties help open the cervix and push out the contents of the uterus.

GyMiso® can therefore be used to terminate a pregnancy.

GyMiso® is recommended for the medical termination of pregnancy. It is recommended for use up to 49 days after your last menstrual period. It is given in combination with another medicine called mifepristone, which blocks progesterone, a hormone that is needed for pregnancy to continue.

Ask your doctor if you have any questions about why GyMiso® has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor’s prescription.

Before you are given GyMiso®

When you must not be given it

You should not be given GyMiso® if:

  • you are pregnant and wish to carry your pregnancy to term
  • you have any allergies to misoprostol, or any other prostaglandins or any of the other ingredients listed at the end of this leaflet

You should not be given a mifepristone tablet and GyMiso® tablets if:

  • you cannot take mifepristone or have any allergies to mifepristone
  • you suffer from chronic adrenal failure
  • you suffer from severe disease where it is necessary to take steroids (e.g. asthma uncontrolled by treatment)
  • you have known or suspected hypocoagulation diseases
  • you are on anticoagulant therapy

You should not be given a mifepristone tablet and GyMiso® tablets for termination of pregnancy up to 49 days since your last period if:

  • your pregnancy has not been confirmed by a pregnancy test or an ultrasound scan
  • the first day of your last period was more than 49 days ago
  • your doctor suspects an ectopic pregnancy (the egg is implanted outside the womb)

You should not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If this medicine is used after the expiry date it may not work as well.

If you are under 18 years of age, you should only take GyMiso® if advised to do so by your doctor.

There is limited information on the use of GyMiso® in adolescents less than 18 years of age.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you take GyMiso®

Tell your doctor if you have allergies to any other medicines, foods preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • heart or cardiovascular disease
  • epilepsy
  • asthma
  • kidney problems
  • liver problems
  • malnutrition
  • problems with your adrenal glands
  • anaemia
  • blood disorders which lead to difficulty in clotting
  • if you are taking anticoagulants
  • if you are taking corticosteroids including inhaled corticosteroids for the treatment of asthma
  • if you have an intra-uterine device (IUD), as this needs to be removed.

If you have not told your doctor about any of the above, tell him/her before you take mifepristone and GyMiso®.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket, health food shop, naturopath or herbalist.

Some medicines and GyMiso® may interfere with each other.

Different medicines may be affected by GyMiso®, or may affect how well it works. You may need to be given different amounts of your medicines, or you may need to be given different medicines.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while being treated with GyMiso®.

How GyMiso® is given

How much to take

Your doctor will tell you how many tablets you need to take and when to take them.

GyMiso® is usually taken 36 to 48 hours after you have taken mifepristone.. You will need to take four GyMiso® tablets (misoprostol 800 micrograms). These are taken either as four tablets in one dose, or as two tablets followed two hours later by another two tablets.

How to take GyMiso®

GyMiso® should be swallowed with water.

GyMiso® can also be taken by holding the tablet in your mouth, between the cheek and gum, for 30 minutes before swallowing any fragments with water.

It is recommended that GyMiso® should be taken on an empty stomach - 2 hours before or after a meal.

After you take GyMiso® tablets, you should stay at home and rest for 3 hours. Vaginal bleeding will occur and the pregnancy may be expelled within a few hours of taking GyMiso® or during the next few days. The bleeding lasts on average for 10 to 16 days and may be heavy.

It is very important that you have follow up with your doctor 14 to 21 days after you take mifepristone and GyMiso®, to ensure that the termination was complete, because incomplete termination will increase the risk of serious infection or bleeding.

It is recommended that you do not travel away from home during the time that you are bleeding so that you can visit your doctor or clinic if necessary.

In case of heavy and prolonged bleeding, you should contact your doctor immediately in order to schedule an appointment.

In rare cases, a termination can occur after you take mifepristone but before you take GyMiso®. It is essential that you are checked to confirm that a complete termination has occurred. If this occurs, you should contact your doctor immediately in order to schedule an appointment.

If you forget to take your dose of GyMiso®

Contact your doctor immediately if you forget to take GyMiso® tablets and it is greater than 48 hours after you have taken a mifepristone 200 mg tablet.

If you are given too much (overdose)

GyMiso® is given to you by your doctor. An overdose is not likely to occur. Ask your doctor if you have any concerns.

While you are being given GyMiso®

Things you must do

If you are pregnant

In some cases treatment with mifepristone and GyMiso® may not result in a termination of pregnancy.

You must keep all of your doctor’s appointments so that your progress can be checked. This is very important.

If treatment with mifepristone and GyMiso® does not work, a termination can be arranged using another method.

If treatment with mifepristone and GyMiso® does not work and you wish to keep your pregnancy, it is not known if mifepristone can cause harm to your baby. It is believed, though, that GyMiso® can cause harm to your baby. You need to tell your doctor or nurse about mifepristone and GyMiso® so that they can carefully monitor your pregnancy.

If you are Rhesus negative, the use of mifepristone and GyMiso® requires that your doctor will take measures to prevent Rhesus factor sensitization, along with the general measures taken during any pregnancy termination.

If you are breastfeeding

GyMiso® should not be taken if you are breastfeeding.

If you are taking other medicines

If you are about to be started on any new medicines, remind your doctor or pharmacist that you have recently been given mifepristone and GyMiso®.

Ask your doctor or pharmacist for advice before taking any medicine.

Tell any other doctors, dentists, and pharmacists who treat you that you have recently been given these medicines.

If you plan to become pregnant, tell your doctor that you have been given this medicine.

Your doctor can discuss with you the risks and benefits involved.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given mifepristone and GyMiso®.

Do not be alarmed by the following list of side effects, you may not experience any of them.

Tell your doctor if you notice any of the following and they worry you:

  • headache
  • vaginal bleeding which may be heavy or prolonged
  • spotting
  • cramps
  • breast tenderness
  • fainting
  • hot flushes, skin rashes or itching
  • side effects related to GyMiso® such as nausea, vomiting, diarrhoea, dizziness, abdominal discomfort, abdominal pain, cramps, fatigue and chills and/or fever.

Tell your doctor if you notice anything that is making you feel unwell.

Infection
Serious infections are very rare in a medical termination of pregnancy and can be potentially life threatening. If you have symptoms occurring more than 24 hours after taking misoprostol of ongoing abdominal pain, or feeling unwell, or feeling weak, with or without a fever you should contact your doctor without delay.

Bleeding
Vaginal bleeding usually starts a few hours after taking misoprostol tablets. Bleeding can occur for 10 to 16 days and it is usual for bleeding to be heavier than a normal period for 2 to 3 days. Contact your doctor immediately if you find you have very heavy bleeding and have soaked more than 2 pads per hour over 2 hours.

Other side effects not listed above may also occur in some people.

After being given GyMiso®

Storage

GyMiso® should be kept in a cool, dry place where the temperature stays below 25 degrees C. Store GyMiso® in the original packaging.

Keep GyMiso® where children cannot reach it.

GyMiso® should not be used after the expiry date printed on the pack. If this medicine is used after the expiry date it may not work as well.

Disposal

Any GyMiso® which is not used will be disposed of in a safe manner by your doctor or pharmacist.

Using contraceptives

It is possible for you to become pregnant again immediately after the pregnancy termination is completed. As some effects of mifepristone and GyMiso® may still be present, it is recommended that you avoid getting pregnant again before your next menstrual period after taking these medicines.

Product description

What it looks like

GyMiso® is presented in a box containing a blister pack of 4 white, round, flat tablets with ML on one side and 200 on the other. Each tablet contains 200 micrograms of misoprostol.

Ingredients

GyMiso® contains the active ingredient misoprostol plus hypromellose, microcrystalline cellulose, sodium starch glycollate, and hydrogenated castor oil.

The tablets do not contain gluten, lactose, tartrazine or any azo dyes.

Supplier

GyMiso® is supplied in Australia by:
MS Health
Suite 129, 135 Cardigan Street, Carlton
VIC 3053, Australia

MS Health Nurse After-care Telephone Service: 1300 515 883 (24 hours)

Licensed from Linepharma (France)

Australian registration number:
AUST R 188015

This leaflet was prepared on 21 January 2013.

Copyright. All rights reserved.

BRAND INFORMATION

Brand name

GyMiso Tablets

Active ingredient

Misoprostol

Schedule

S4

 

Name of the medicine

Misoprostol.

Excipients.

Hypromellose, microcrystalline cellulose, sodium starch glycollate type A and hydrogenated castor oil.

Description

Molecular formula: C22H38O5. MW: 382.5. CAS: 59122-46-2. Each tablet contains 200 micrograms of misoprostol as a 1% dispersion of misoprostol hypromellose. Misoprostol is a clear, colourless or yellowish oily liquid.

Pharmacology

Pharmacodynamic properties.

Pharmacotherapeutic group.

Other gynaecological medicines: prostaglandins. ATC code: G02AD06.
Misoprostol is a synthetic analogue of prostaglandin E1. At the recommended dosages, misoprostol induces contractions of the smooth muscle fibers in the myometrium and relaxation of the uterine cervix. The uterotonic properties of misoprostol should facilitate cervical opening and evacuation of intrauterine debris.
In the event of an early termination of pregnancy, the combination of GyMiso used in a sequential regimen after mifepristone leads to an increase in the success rate and accelerates the expulsion of the conceptus.
Pharmacodynamic studies in early pregnancy have found an increase in uterine tone around 8 minutes after oral and 40 minutes after buccal misoprostol, with sustained contractions achieved by a mean of around 90 minutes and uterine activity peaking prior to 5 hours. Following oral administration uterine activity rises earlier than other routes, but is lower overall. Pretreatment with mifepristone has previously been shown to increase uterine contractility in response to misoprostol.

Pharmacokinetic properties.

Absorption.

When administered orally, misoprostol is rapidly absorbed and metabolized. Peak concentrations around 1.1 nanogram/mL were reached about 15 minutes after a 400 microgram dose in the fasting state. Plasma concentrations of its main degradation metabolite, misoprostol acid, reach their peak of 2-2.5 nanogram/mL after a 2 microgram/kg oral dose within approximately 30 minutes and rapidly decline thereafter. As a result, uterine contractility increases and then plateaus after about one hour. Absorption is almost complete, measured at levels between 64-73% from urinary data. While not compared directly with oral administration, buccal administration has been found to result in peak concentrations comparable to those following vaginal administration, which have been found in turn to be lower and later than those for oral administration.

Distribution.

Serum protein binding of labeled misoprostol acid was studied in man and was similar in young (81-88%) and elderly (81-89%) subjects. Accumulation in erythrocytes was not seen.

Metabolism and excretion.

Metabolism of misoprostol to misoprostol acid is rapid with no intact misoprostol found in plasma consistent with an in vitro half-life of 6.4 minutes for de-esterification of misoprostol in human plasma at 37°C. Elimination of misoprostol and its metabolites is also rapid with a plasma elimination half-life of 35 minutes.
The liver is the primary site of metabolism and between 1-4% of misoprostol acid is excreted in the urine.
Misoprostol has no known drug interactions. No induction of the hepatic cytochrome P450 enzyme system has been observed.

Clinical Trials

Clinical efficacy of early medical abortion is defined as complete abortion without surgical intervention, regardless of the reason for the intervention, which may include continuing pregnancy, missed or incomplete abortion, prolonged or heavy vaginal bleeding or a woman's request.
A study of 966 patients with pregnancies up to 63 DA, randomized to 200 mg mifepristone followed 24-36 hours later by 800 micrograms of misoprostol orally or buccally, reported efficacy rates of 91.3% for the oral and 96.2% for the buccal group (RR 0.95, 95%CI 0.92-0.98, p = 0.003). When patients at 43-49 days gestation were considered, efficacy rates were not significantly different according to route of administration, 94.7% for the oral and 96.4% for the buccal group. This study allowed a repeat dose of misoprostol if abortion had not occurred by 7 to 14 days.
Clinical trials have reported efficacy rates varying from 89-98% with oral misoprostol in doses of 400 to 800 micrograms 24-48 hours after mifepristone. Varying results are likely due in part to varying follow-up and intervention practices. Some studies reported higher efficacies when a repeat dose of misoprostol was offered at a varying time interval (1-14 days) after the first dose.
For patients up to 49 days gestation clinical trials have consistently reported efficacy rates of at least 93% using 800 micrograms misoprostol orally in single or divided doses or 800 micrograms buccally 24-48 hours after 200 mg mifepristone, when a follow-up dose could be used.
Most studies that have reported mifepristone and oral misoprostol regimens in women after 49 days gestation have found significantly lower efficacy rates at later gestations, often less than 90%; for this reason oral misoprostol should not be used in medical abortion regimens after 49 days gestation. Such a decline has not been observed using buccal misoprostol to 63 days.

Indications

GyMiso is indicated in females of childbearing age for the medical termination of a developing intrauterine pregnancy in sequential combination with a mifepristone 200 mg tablet, up to 49 days of gestation.
The prescriber must ensure that consent and treatment of the patient is in accordance with the appropriate state or territory legislation.

Contraindications

Known hypersensitivity to misoprostol (or any prostaglandin) or to any of the excipients.
Contraindication to medical abortion (see product information of Mifepristone Linepharma 200 mg tablet) including: known or suspected hypocoagulation diseases, treatment with anticoagulants; uncertainty about pregnancy age; suspected ectopic pregnancy; contraindication to mifepristone.

Precautions

Misoprostol (or mifepristone) should not be administered if an intrauterine contraceptive device is present: it should be removed first.
Because of its abortive properties, GyMiso should not be used by a woman with a viable pregnancy and who intends to carry that pregnancy to term. Uterine hyperstimulation and rupture have been reported beyond the first trimester when much lower dosage of misoprosotol may be required.
Rare serious cardiovascular accidents have been reported following administration of prostaglandins including misoprostol. For this reason women with risk factors for cardiovascular disease or established cardiovascular disease should be treated with caution.
Epileptic seizures have been reported with prostaglandins and prostaglandin analogues administered by routes other than oral and this possibility should be borne in mind in patients with a history of epilepsy.
Bronchospasm may occur with some prostaglandins and prostaglandin analogues. The possibility should be borne in mind in patients with a history of asthma.

Special warnings and precautions for use.

Special warnings and precautions for use related to the combination of GyMiso with Mifepristone Linepharma, should also be followed (see Mifepristone Linepharma 200 mg tablet product information).

Medical termination of a developing intrauterine pregnancy.

Ectopic pregnancy should be excluded and gestation confirmed prior to medical abortion.
This method requires the involvement of the woman who should be informed of the requirements of the medical method, which involves the following.
The necessity to combine treatment with Mifepristone Linepharma.
The need for follow-up within 14 to 21 days after intake of Mifepristone Linepharma and GyMiso in order to confirm that the abortion is complete.
The nonnegligible risk of failure (see Clinical Trials) of the medical method which may require termination by another method.
On discharge from the treatment centre all women should be provided with appropriate medications as necessary and be fully counseled regarding the likely signs and symptoms she may experience and have direct access to the treatment centre by telephone or local access.
The following risks related to the medical method must be taken into account and explained to the woman.

Failures.

The nonnegligible risk of failure, which occurs in up to 7% of cases, makes follow-up mandatory in order to check that the expulsion is completed. Up to 49 days about 1% will have continuing pregnancies, the rest needing curettage for other reasons.

Bleeding.

The patient must be informed of the occurrence of prolonged vaginal bleeding (an average of 10 to 16 days after Mifepristone Linepharma and GyMiso intake) which may be heavy. Bleeding occurs in almost all cases and is not in any way proof of complete expulsion. Persistent bleeding can be the consequence of incomplete expulsion. Bleeding can be large enough to necessitate a blood transfusion and to lead to a significant decrease in haemoglobin levels.
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.
Follow-up must take place within a period of 14 to 21 days after administration of Mifepristone Linepharma and GyMiso to verify by the appropriate means (clinical examination, ultrasound scan, or beta-hCG measurement) that expulsion has been completed and that vaginal bleeding has stopped. In case of persistent bleeding (even light) beyond this follow-up, the disappearance of bleeding should be checked within a few days.
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 extrauterine pregnancy, and appropriate treatment should be considered. In the event of an ongoing pregnancy diagnosed after follow-up, termination by another method will be offered to the woman.
Since heavy bleeding requiring haemostatic curettage occurs in up to 5% of 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.

Infection.

As with other types of abortion, cases of serious bacterial infection, including very rare cases of fatal septic shock, have been reported following the use of mifepristone and misoprostol. No causal relationship between these events and the use of mifepristone and misoprostol has been established. Treating doctors evaluating a patient who is undergoing a medical abortion should be alert to the possibility of this rare event. In particular, a sustained fever of 38°C or higher, severe abdominal pain, or pelvic tenderness in the days after a medical abortion may be an indication of infection.
A high index of suspicion is needed to rule out sepsis (from e.g. Clostridium sordellii or other species e.g. Streptococcus) if a patient reports abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting or diarrhea) more than 24 hours after taking misoprostol. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. Most of these deaths occurred in women who used vaginally administered misoprostol however other forms of administration have been reported. No causal relationship between mifepristone and misoprostol use and an increased risk of infection or death has been established. Clostridium sordellii and other infections such as Streptococcus and other bacteria have also been reported very rarely following childbirth (vaginal delivery and caesarian section), and in other gynaecologic and nongynaecologic conditions. Reviews have estimated overall serious infection rates after medical abortion at less than 1%.

Effects on fertility.

During clinical trials, pregnancies occurred between embryo expulsion and the resumption of menses. To avoid the potential exposure of a subsequent pregnancy to GyMiso, it is recommended that conception be avoided during the next menstrual cycle. Reliable contraceptive precautions should therefore commence as early as possible after administration of GyMiso.
In fertility studies in rats in which treated females were mated with treated males, increased preimplantation losses were observed with misoprostol at oral doses greater than 1 mg/kg/day (11 times the recommended human dose, on a mg/m2 basis). Postimplantation loss was also increased at 10 mg/kg/day (114 times the recommended human dose, on a mg/m2 basis).

Use in pregnancy.

Use of misoprostol has been associated with birth defects. 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 foetal movements and of cranial nerves (hypomimia, abnormalities in suckling, deglutition, and eye movements). To date, a risk of malformation cannot be excluded.
Reproductive toxicity studies in animals showed embryotoxicity (increased resorptions) with oral doses of 1 mg/kg/day in rabbits, 10 mg/kg/day in rats, and 20 mg/kg in mice when treatment occurred during the period of organogenesis. An increased incidence of skeletal abnormalities was observed with an oral dose of 1 mg/kg/day in rabbits (possibly due to maternal toxicity) while an increased incidence of cleft palate was seen at a single oral dose of 30 mg/kg in mice (28 and 170 times the recommended human dose, on a mg/m2 body surface area basis, respectively).
Consequently, women should be informed that due to the risk of failure of the medical method of pregnancy termination and to the unknown risk to the fetus, follow-up is mandatory (see Special warnings and precautions for use). Should a failure of the medical method be diagnosed at follow-up (viable ongoing pregnancy), and should the patient still agree, pregnancy termination should be completed by another method.
Should the patient wish to continue with her pregnancy, she should be appropriately counseled as to the risk of birth defects. In that event of continuation of the pregnancy, careful ultrasonographic monitoring of the pregnancy should be carried out.

Use in lactation.

Misoprostol is rapidly metabolized in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. GyMiso should not be administered to breastfeeding mothers because the excretion of misoprostol acid could cause undesirable effects such as diarrhoea in breastfeeding infants.

Paediatric use.

Limited data are available for use of misoprostol in women under 18 years of age. There is no relevant use of misoprostol in the prepubertal paediatric population in the indication.

Use in the elderly.

There is no relevant use of misoprostol in the elderly population in the indication.

Genotoxicity.

Misoprostol has been evaluated in tests for mutagenicity in bacterial, yeast and mammalian cells, and for clastogenicity in vitro (Chinese hamster ovary cells) and in vivo (mouse bone marrow micronucleus test). No evidence of genotoxicity was observed.

Carcinogenicity.

The potential carcinogenicity of misoprostol has been evaluated in both mice and rats. There was no evidence of an effect of misoprostol on tumour occurrence or incidence in rats receiving oral doses up to 2.4 mg/kg/day for 24 months. Similarly, there was no effect of misoprostol on tumour occurrence or incidence in mice receiving oral doses up to 16 mg/kg/day for 21 months. These doses are at least 27 times the recommended human dose, on a mg/m2 body surface area basis.

Effect on laboratory tests.

There are no known effects of misoprostol on laboratory tests.

Interactions

The serum protein binding of misoprostol acid was not affected by indomethacin, ranitidine, digoxin, phenylbutazone, warfarin, diazepam, methyldopa, propranolol, triamterene, cimetidine, paracetamol, ibuprofen, chlorpropamide and hydrochlorothiazide. With salicylic acid (300 microgram/mL), the protein binding of misoprostol was lowered from 84 to 52% which is not considered clinically significant since the binding of misoprostol acid is not extensive and its elimination half-life is very short.
In laboratory studies, misoprostol has no significant effect on the cytochrome P450 linked hepatic mixed function oxidase system, and therefore should not affect the metabolism of theophylline, warfarin, benzodiazepines or other drugs normally metabolized by this system. No drug interactions have been attributed to misoprostol in extensive clinical trials. As such, other drugs would be unlikely to interfere with misoprostol's metabolism in either normal or hepatically impaired patients.

Adverse Effects

The most frequent undesirable effects which are observed during treatment with misoprostol are the following.

Gastrointestinal disorders.

Nausea (transient and mild), vomiting, diarrhea, abdominal pain.

Reproductive system disorders.

Very frequent uterine contractions observed in the hours following misoprostol intake; vaginal bleeding, sometimes heavy and prolonged when used with mifepristone for medical termination of pregnancy (see Special warnings and precautions for use).

General disorders.

Headache, dizziness, and chills and fever.
Because castor oil is an excipient, digestive symptoms (nausea, vomiting, abdominal pain) can be observed.
The adverse events reported with mifepristone and a prostaglandin analogue, classified according to frequency and system organ class, are summarized as shown in Table 1.
Adverse events reported with mifepristone, classified as uncommon (≥ 1/1000 to < 1/100) are summarized as shown below.

Reproductive system and breast disorders.

Haemorrhagic shock, salpinitis.

Infections and infestations.

Infection.

Vascular disorders.

Hot flush.

Skin and subcutaneous tissue disorder.

Skin rash/ pruritus.
Adverse events reported with mifepristone, classified as rare (≥ 1/10,000 to < 1/1000) and very rare (< 1/10,000*) are summarized as shown below.

Gastrointestinal disorders.

Gastric bleeding.

Nervous system disorders.

Epilepsy, neurogenic tinnitus.

Reproductive system and breast disorders.

Bilateral adnexal mass, intrauterine adhesion, ovarian cyst rupture, breast abscess, hematosalpynx, uterine rupture.

General disorders and administration site conditions.

Anaphylaxis, periorbital edema.

Infections and infestations.

Toxic shock syndrome.

Vascular disorders.

Superficial thrombophlebitis, hypotension.

Cardiac disorders.

Myocardial infarction, induced Adam-Stokes syndrome.

Respiratory, thoracic and mediastinal disorders.

Bronchospasm, induced bronchial asthma.

Skin and subcutaneous tissue disorders.

Urticarial reaction, toxic epidermal necrolysis.

Pregnancy, puerperium and perinatal conditions.

Hydatiform mole, ectopic pregnancy, amniotic band syndrome, gestational trophoblastic tumor, uteroplacental apoplexy.

Hepatobiliary disorders.

Abnormal liver function tests, hepatic failure, hepatorenal failure.

Blood and lymphatic system disorders.

Thrombotic thrombocytopenic purpura, thrombocytopenia, induced systemic lupus erythematosus.

Renal and urinary disorders.

Renal failure.

Neoplasms (benign, malignant and unspecified).

Elevated alpha-fetoprotein, elevated carcinoembryonic antigen.

Musculoskeletal and connective tissue disorders.

Limb spasm.

Eye disorders.

Ophthalmoplegia.

Psychiatric disorders.

Mania.
*Including occasional case reports.
Bleeding is an almost constant part of the procedure, whatever the prostaglandin analogue used, and at any pregnancy term, although it is usually more abundant when pregnancy age increases. It can occur after mifepristone alone. When heavy, it usually reflects incomplete abortion and is observed in approximately 3 to 12% of cases, depending on the pregnancy age and the prostaglandin analogue used, and needs specific treatment. It can necessitate a blood transfusion in 0.5 to 1 percent of cases. It can be prolonged for several days after prostaglandin analogue administration and sometimes leads to a decrease in hemoglobin levels. This potentially severe complication justifies that after intake (i) follow-up takes place approximately 14 to 21 days after mifepristone and GyMiso administration to ensure that expulsion is complete with no persisting bleeding and (ii) until follow-up has taken place, the woman remains close to a facility where she can be treated at any moment in case of severe or prolonged bleeding.
Infectious complications, including Clostridium sordellii toxic shock appear extremely rare but can lead to fatal outcome. A high index of suspicion is needed to rule out sepsis (from e.g. Clostridium sordellii or other species e.g. Streptococcus) if a patient reports abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting or diarrhoea) more than 24 hours after taking misoprostol. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, haemoconcentration, and general malaise. Most of these deaths occurred in women who used vaginally administered misoprostol. No causal relationship between mifepristone and misoprostol use and an increased risk of infection or death has been established.
The issue of the outcome of persisting pregnancy in the case of failure of the medical method remains incompletely solved; a risk of malformation attributable to mifepristone or to prostaglandin analogues such as misoprostol cannot be excluded, and women should be adequately counseled in such a situation. Another fact to take into consideration is the possibility of a pregnancy persisting in the form of an ectopic pregnancy, since evidence suggests that the method does not appear able to terminate an ectopic pregnancy.

Dosage and Administration

Medical termination of early pregnancy of up to 49 days of gestation, in combination with Mifepristone Linepharma 200 mg tablet.
GyMiso must be administered 36 to 48 hours after the oral intake of mifepristone.
GyMiso dosage is 800 micrograms, i.e. 4 tablets in a single intake, orally, or if preferred taken as two doses of 400 micrograms, i.e. two tablets taken orally followed two hours later by another two tablets. GyMiso tablets may be taken buccally i.e. kept between the cheek and the gum for 30 minutes before any fragments being swallowed with water.
A repeat dose of misoprostol may be offered after 1-7 days if abortion has not occurred.
No dosage adjustment of misoprostol is necessary with renal or hepatic insufficiency when administered at the recommended doses.
There are no data available on the effect of food intake on the absorption of misoprostol. Misoprostol should be taken 2 hours before or 2 hours after a meal.
Refer also to Contraindicatons, Precautions and Special warnings and precautions for use.

Overdosage

The toxic dose of misoprostol in humans has not been determined. Cumulative total daily doses of 1600 micrograms have been tolerated, with only symptoms of gastrointestinal discomfort reported.
Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhea, fever, palpitations, hypotension or bradycardia. Hypertension and tachycardia have also been reported following overdoses. Overdose in pregnancy has resulted in uterine contractions with fetal death.
There is no specific antidote. Treatment should be symptomatic and supportive. Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal may reduce absorption of misoprostol if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Presentation

Tablets (white, round, flat, marked ML on one side, 200 on reverse), 200 microgram: 4's (dual faced aluminium blisters in a box).

Storage

Keep out of the reach of children.
Do not use after the expiry date printed on the outer packaging.
Store below 25°C in the original packaging.

Poison Schedule

S4.