Combipack of Mifepristone & Misoprostol Tablets Taj Pharma
Each pack contains 5 tablets:
A. 1 Mifepristone Tablet
Each uncoated tablet contains:
Mifepristone – 200 mg
B. 4 Misoprostol Tablets
Each uncoated tablet contains:
Misoprostol – 200 mcg
Mifepristone tablet for oral use.
Pack contains 1 tablet of mifepristone 200 mg to be given orally and 4 tablets of 200 mcg misoprostol to be given vaginally for the medical termination of pregnancy up to 63 days (9 weeks). This kit has been developed in accordance with guidelines issued by the Royal College of Obstetricians and Gynaecologists .
Mifepristone is a synthetic steroid with an anti-progestational action as a result of competition with progesterone at the progesterone receptors. This activity results in termination of pregnancy.
In women at doses of ≥1 mg/kg, mifepristone antagonises the endometrial and myometrial effects of progesterone. During pregnancy it sensitizes the myometrium to the contraction – inducing action of prostaglandin. During the first trimester, pre-treatment with mifepristone allows the dilatation and opening of the cervix uteri. While clinical data have demonstrated that mifepristone facilitates dilatation of the cervix, no data is available to indicate that this results in a lowering of the rate of early or late complications to the dilatation procedure.
In the event of an early termination of pregnancy, the combination of a prostaglandin analogue used in a sequential regimen after mifepristone leads to an increase in the success rate to about 95% of the cases and accelerates the expulsion of the conceptus.
In clinical trials, according to the prostaglandin used and the time of application, the results vary slightly. Combinations of mifepristone with prostaglandin analogues other than misoprostol and gemeprost have not been studied.
Mifepristone also exhibits anti-glucocorticoid and weak anti-androgenic activity. It binds to the glucocorticoid receptor. In animals at doses of 10 to 25 mg/kg it inhibits the action of dexamethasone. In man the anti-glucocorticoid action is manifested at a dose ≥ 4.5 mg/kg by a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. Glucocorticoid bioactivity may be depressed for several days following a single administration of 200 mg mifepristone for termination of pregnancy. The clinical implications of this are unclear; however vomiting and nausea may be increased in susceptible women.
Misoprostol is a synthetic prostaglandin E1 which is a potent inhibitor of gastric acid secretion in humans. It also causes the cervix to soften and the uterus to contract.
Prostaglandin E1 causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a change in calcium concentration, thereby initiating muscle contraction. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents.
Following oral administration of a single dose of 600 mg, mifepristone is rapidly absorbed, with a peak plasma concentration of 1.98 mg/L occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%.
Mifepristone is 98% bound to plasma proteins, albumin and alpha 1-acid glycoprotein. Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with respect to plasma concentration and clearance. Following a distribution phase, elimination of mifepristone is slow at first (50% eliminated between 12 and 72 hours) and then becomes more rapid with a terminal elimination half-life of 18 hours.
Metabolism of mifepristone is primarily via pathways involving N-demethylation and terminal hydroxylation of the 17-propynyl chain. In vitro studies have shown that CYP450 3A4 is primarily responsible for the metabolism. The three major metabolites identified in humans are: (1) RU 42 633, most widely found in plasma, is the N-monodemethylated metabolite; (2) RU 42 848, which results from the loss of two methyl groups from the 4-dimethylaminophenyl in position 11beta; and (3) RU 42 698, which results from terminal hydroxylation of the 17-propynyl chain.
By 11 days after a 600 mg dose of titrated compound, 83% of the drug has been accounted for by the faeces and 9% by the urine. Serum levels are undetectable by 11 days.
Misoprostol is extensively absorbed, and undergoes rapid de-esterification to its free acid (misoprostol acid), which is responsible for its clinical activity and, unlike the parent compound, is detectable in plasma. The alpha side chain undergoes beta oxidation and the beta side chain undergoes omega oxidation followed by reduction of the ketone to give prostaglandin F analogues.
In normal volunteers, misoprostol is rapidly absorbed after oral administration with a Tmax of misoprostol acid of 12 – 3 minutes and a terminal half-life of 20 – 40 minutes.
There is high variability of plasma levels of misoprostol acid between and within studies but mean values after single doses show a linear relationship with dose over the range of 200-400 mcg. No accumulation of misoprostol acid was noted in multiple dose studies; plasma steady state was achieved within 2 days.
Maximum plasma concentrations of misoprostol acid are diminished when the dose is taken with food and total availability of misoprostol acid is reduced by use of concomitant antacid. Clinical trials were conducted with concomitant antacid, however, this effect does not appear to be clinically important. After oral administration of radiolabeled misoprostol, about 80% of detected radioactivity appears in urine.
In contrast, after vaginal administration, the plasma concentration gradually increased, reaching maximum levels after 70 – 80 minutes and slowly declined with detectable levels present after 6 hours. Vaginal misoprostol was present in the circulation longer than oral misoprostol and hence its duration of stimulation of the uterus exceeds that of oral misoprostol. When misoprostol is administered vaginally, the plasma concentrations of misoprostol acid peak in 1 – 2 hours and then decline slowly. Vaginal application of misoprostol results in slower increases and lower peak plasma concentrations of misoprostol acid than does oral administration, but overall exposure to the drug is increased.
Pack is indicated for the medical termination of intrauterine pregnancy of up to 63 days gestation based on the first day of the last menstrual period.
Dosage and Administration
Pack is indicated for the medical termination of intrauterine pregnancy of up to 63 days of gestation. For purposes of this treatment, pregnancy is dated from the first day of the last menstrual period in a presumed 28-day cycle with ovulation occurring at mid-cycle.
The duration of pregnancy may be determined from menstrual history and by clinical examination. Ultrasonographic scan should be used if the duration of pregnancy is uncertain, or if ectopic pregnancy is suspected.
Any intrauterine device (IUD) should be removed before treatment with mifepristone and misoprostol begins. Pregnancy termination by surgery is recommended in cases when Pack fails to cause termination of intrauterine pregnancy.
Mifepristone may be administered by or under the supervision of a Gynaecologist, able to assess the gestational age of an embryo and to diagnose ectopic pregnancies. The Gynaecologist must also be able to provide surgical intervention in cases of incomplete abortion or severe bleeding, or have made plans to provide such care through others, and be able to assure the patient access to medical facilities equipped to provide blood transfusions and resuscitation, if necessary.
The dosage is mifepristone 200 mg orally followed 1 – 3 days later by misoprostol 800 mcg (4 tablets of 200 mcg) vaginally. The misoprostol may be administered by a health care provider or self-administered by the woman. For women at 49 – 63 days of gestation, if abortion has not occurred 4 hours after administration of misoprostol, a second dose of misoprostol 400 mcg (2 tablets of 200 mcg) may be administered vaginally or orally (depending upon preference and amount of bleeding).
The patient should return for a follow-up visit approximately 14 days after the administration of mifepristone. This visit is very important to confirm by clinical examination or ultrasonographic scan that a complete termination of pregnancy has occurred.
Patients who have an ongoing pregnancy at this visit have a risk of foetal malformation resulting from the treatment. Surgical termination is recommended to manage medical abortion treatment failures.
Administration of mifepristone and misoprostol for the termination of pregnancy (the “treatment procedure”) is contraindicated in patients with any one of the following conditions:
- History of allergy or known hypersensitivity to mifepristone, misoprostol or other prostaglandin
- Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass (the treatment procedure will not be effective to terminate an ectopic pregnancy)
- IUD in place
- Chronic adrenal failure
- Haemorrhagic disorders or concurrent anticoagulant therapy
- Inherited porphyria
- Concurrent long-term corticosteroid therapy
- Severe asthma uncontrolled by therapy
Because it is important to have access to appropriate medical care if an emergency develops, the treatment procedure is contraindicated if a patient does not have adequate access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood transfusions, and emergency resuscitation during the period from the first visit until discharged by the administering health care provider.
Mifepristone also should not be used by any patient who may be unable to understand the effects of the treatment procedure or to comply with its regimen.
Warnings and Precautions
In the absence of specific studies, mifepristone is not recommended in patients with:
- Renal failure
- Hepatic failure
The administration of mifepristone must be under the supervision of a qualified Gynaecologist.
The use of mifepristone is assumed to require the same preventive measures as those taken prior to and during surgical abortion to prevent rhesus immunization.
There are no data on the safety and efficacy of mifepristone in women with chronic medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal disease; insulin-dependent diabetes mellitus; severe anaemia or heavy smoking. Women who are more than 35 years of age and who also smoke 10 or more cigarettes per day should be treated with caution because such patients were generally excluded from clinical trials of mifepristone.
Although there is no clinical evidence, the effectiveness of mifepristone may be lower if misoprostol is administered more than 2 days after mifepristone administration.
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.
Information for Patients
Patients should be fully advised of the treatment procedure and its effects. Each patient must understand:
- the necessity to combine treatment with prostaglandin to be administered at a second visit
- the necessity of completing the treatment schedule, including a follow-up visit approximately 14 days after taking mifepristone
- that vaginal bleeding and uterine cramping probably will occur
- that prolonged heavy vaginal bleeding is not proof of a complete abortion
- that if the treatment fails, there is a risk of foetal malformation
- that medical abortion treatment failures are managed by surgical termination
- the steps to take in an emergency situation, including precise instructions and a telephone number that she can call if she has any problems or concerns
Another pregnancy can occur following termination of pregnancy and before resumption of normal menses. Contraception can be initiated as soon as the termination of the pregnancy has been confirmed, or before the woman resumes sexual intercourse.
Clinical examination is necessary to confirm the complete termination of pregnancy after the treatment procedure. Changes in quantitative human chorionic gonadotropin (hCG) levels will not be decisive until at least 10 days after the administration of mifepristone. A continuing pregnancy can be confirmed by ultrasonographic scan.
The existence of debris in the uterus following the treatment procedure will not necessarily require surgery for its removal.
Decreases in haemoglobin concentration, haematocrit and red blood cell count occur in some women who bleed heavily. Haemoglobin decreases of more than 2 g/dL occurred in 5.5% of subjects during the French clinical trials of mifepristone and misoprostol.
Clinically significant changes in serum enzyme (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyltransferase ) activities were rarely reported.
Patients must be monitored and undergo appropriate medical evaluation and intervention should any of the serious adverse events mentioned below occur following a spontaneous, surgical or medical abortion, including following mifepristone use:
Vaginal bleeding occurs in almost all patients during a medical abortion. Prolonged heavy bleeding (soaking through two thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete abortion or other complications or an unnoticed extra-uterine pregnancy, and prompt medical or surgical intervention may be considered. Patients should be counseled to seek immediate medical attention if they experience prolonged heavy vaginal bleeding following a medical abortion.
According to data from the US and French trials, women should expect to experience vaginal bleeding or spotting for an average of 9 – 16 days, while up to 8% of all subjects may experience some type of bleeding for 30 days or more. In general, the duration of bleeding and spotting increased as the duration of the pregnancy increased.
The patient should be informed not to travel far away from the prescribing centre as long as complete expulsion has not been recorded. She should be given precise instructions as to whom she should contact and where to go in the event of any problems, particularly in the case of very heavy vaginal bleeding.
In the event of an ongoing pregnancy diagnosed after the follow-up visit, termination by another method should be proposed to the woman.
Since heavy bleeding requiring haemostatic curettage occurs in 0 – 1.4% 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 specialized consultants according to the type of haemostatic disorder and the level of anaemia.
Excessive vaginal bleeding usually requires treatment by uterotonics, vasoconstrictor drugs, curettage, administration of saline infusions, and/or blood transfusions.
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, 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.
Infection and Sepsis
No causal relationship between these events and the use of mifepristone and misoprostol has been established. The Gynaecologist 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 100.4°F 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 (e.g. Clostridium sordellii) 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 leucocytosis with a marked left shift, tachycardia, haemoconcentration, and general malaise. These deaths occurred in women who used vaginally administered misoprostol, but no causal relationship between vaginal misoprostol use and an increased risk of infection or death has been established. Clostridium sordellii infections have also been reported very rarely following childbirth (vaginal delivery and caesarean section), and in other gynaecologic and non-gynaecologic conditions.
Confirmation of Pregnancy Termination
Patients should be scheduled for and return for a follow-up visit at approximately 14 days after administration of mifepristone to confirm that the pregnancy is completely terminated and to assess the degree of bleeding. Termination can be confirmed by clinical examination or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion. Medical abortion failures should be managed with surgical termination. Advise the patient whether you will provide such care or will refer her to another provider as part of counseling prior to prescribing mifepristone.
Mifepristone is contraindicated in patients with a confirmed or suspected ectopic pregnancy since mifepristone is not effective for terminating these pregnancies. Gynaecologists should remain alert to the possibility that a patient who is undergoing a medical abortion could have an undiagnosed ectopic pregnancy since some of the expected symptoms of a medical abortion may be similar to those of a ruptured ectopic pregnancy. The presence of an ectopic pregnancy may have been missed even if the patient underwent ultrasonography prior to being prescribed mifepristone.
The patient should not give misoprostol to anyone else.
- Misoprostol has been prescribed for the patient’s specific condition, it may not be the correct treatment for another person, and may be dangerous to the other person if she is or were to become pregnant.
- Some authors suggest moistening misoprostol with 3 – 4 drops of saline / distilled water when used for vaginal administration.
- During the period immediately following the administration of misoprostol, the patient may need medication for cramps or gastrointestinal symptoms. The patient should be given instructions on what to do if significant discomfort, excessive bleeding or other adverse reactions occur and should be given a phone number to call if she has questions following the administration of misoprostol.
Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug’s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John’s Wort, and certain anticonvulsants (phenytoin, phenobarbital, 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 drugs 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 drugs that are CYP3A4 substrates and have narrow therapeutic range, including some agents used during general anaesthesia.
Misoprostol has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis. Misoprostol does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin.
Misoprostol is predominantly metabolized via fatty acid oxidizing systems and has shown no adverse effect on the hepatic microsomal mixed function oxidase (P450) enzyme system. In specific studies, no clinically significant pharmacokinetic interaction has been demonstrated with antipyrine or diazepam. A modest increase in propranolol concentrations (mean approximately 20% in AUC, 30% in Cmax) has been observed with multiple dosing of misoprostol. In extensive clinical studies no drug interactions have been attributed to misoprostol. Drug interaction studies with misoprostol and several NSAIDs showed no clinically significant effect on the kinetics of ibuprofen, diclofenac, piroxicam, aspirin, naproxen or indomethacin. Concomitant administration of NSAIDs and misoprostol in rare cases can cause a transaminase increase and peripheral oedema.
Magnesium-containing antacids should be avoided during treatment with misoprostol as this may worsen the misoprostol-induced diarrhoea.
Mifepristone is not recommended in patients with renal impairment.
Pharmacokinetic studies in patients with varying degrees of renal impairment showed an approximate doubling of T1/2, Cmax, and AUC compared to normal, but no clear correlation between the degree of impairment and AUC. In subjects over 64 years of age, the AUC for misoprostol acid is increased. No routine dosage adjustment is recommended in older patients or patients with renal impairment, but dosage may need to be reduced if the usual dose is not tolerated.
Mifepristone is not recommended in patients with hepatic impairment.
Misoprostol is metabolized by fatty acid oxidizing systems present in organs throughout the body. Its metabolism and plasma levels are therefore unlikely to be affected markedly in patients with hepatic impairment.
Pack is indicated for use in the termination of pregnancy (through 63 days pregnancy) and has no other approved indication for use during pregnancy. In humans, the few reported cases of malformations do not allow a causality assessment for mifepristone alone or associated to prostaglandin. Therefore, data is too limited to determine whether the molecule is a human teratogen. 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 foetus, the post-treatment visit is mandatory; and
- Should a failure of the method be diagnosed at the post-treatment visit (viable ongoing pregnancy), and should the patient still agree, pregnancy termination should be completed by another method.
Cases of ongoing pregnancies not terminated by surgical abortion at the end of treatment with mifepristone alone have reported of sirenomelia and cleft palate.
Several reports in the literature indicate that prostaglandins, including misoprostol, may have teratogenic effects in human beings. Skull defects, cranial nerve palsies, delayed growth and psychomotor development, facial malformation and limb defects have all been reported after exposure during the first trimester.
The indication for use of Pack is for the termination of pregnancy through 63 days’ duration of pregnancy (as dated from the first day of the last menstrual period). These drugs together disrupt pregnancy by causing decidual necrosis, myometrial contractions and cervical softening, leading to the expulsion of the products of conception.
Mifepristone is a lipophilic compound and may theoretically be excreted in the mother’s breast milk. Many hormones with a similar chemical structure, however, are excreted in breast milk. However, no data is available. Since the effects of mifepristone on infants are unknown, breastfeeding women should consult with their Gynaecologist to decide if they should discard their breast milk for a few days following administration of the medications.
Misoprostol is rapidly metabolized in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. There are no published reports of adverse effects of misoprostol in breastfeeding infants of mothers taking misoprostol. Misoprostol should not be administered to nursing mothers because the excretion of misoprostol acid could cause undesirable effects such as diarrhoea in nursing infants.
Safety and effectiveness of mifepristone and misoprostol in paediatric patients have not been established.
The treatment procedure is designed to induce the vaginal bleeding and uterine cramping necessary to produce an abortion. Nearly all of the women who receive mifepristone and misoprostol will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day 3 of the treatment procedure. Women typically experience abdominal pain, including uterine cramping. Other commonly reported side effects were nausea, vomiting and diarrhoea. Pelvic pain, fainting, headache, dizziness and asthenia occurred rarely. Some adverse reactions reported during the 4 hours following administration of misoprostol were judged by women as being more severe than others: the percentage of women who considered any particular adverse event as severe ranged from 2 – 35%. After the third day of the treatment procedure, the number of reports of adverse reactions declined progressively, so by day 14, reports were rare except for reports of bleeding and spotting.
Serious bacterial infection, bleeding, ectopic pregnancies that have ruptured, and death, including another death from sepsis were reported.
Nervous System Disorders
Rare: Headache, insomnia, anxiety, syncope.
Very common: Nausea, vomiting, diarrhoea (these gastrointestinal effects related to prostaglandin use are frequently reported), dyspepsia.
Common: Cramping, light or moderate.
Skin and Subcutaneous Tissue Disorders
Uncommon: Hypersensitivity, skin rashes (0.2%).
Rare: Single cases of urticaria, erythroderma, erythema nodosum, toxic epidermal necrolysis have also been reported.
Infections and Infestations
Common: Infection following abortion. Suspected or confirmed infections (endometritis, pelvic inflammatory disease, salpingitis) have been reported in less than 5% of women.
Rare: Viral infection, vaginitis, sinusitis.
Very rare: Cases of fatal toxic shock caused by Clostridium sordellii endometritis, presenting without fever or other obvious symptoms of infection, have been reported after medical abortion with the use of 200 mg mifepristone followed by non-authorized vaginal administration of misoprostol tablets for oral use. The health care providers should be aware of this potentially fatal complication.
Uncommon: Hypotension (0.25%)
General Disorders and Administration Site Conditions
Rare: Malaise, fatigue, vagal symptoms (hot flushes, dizziness, chills), rigors, fever, back pain, asthenia, leg pain, anaemia, fainting.
Reproductive System and Breast Disorders
Very common: Uterine contractions or cramping (10 – 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. Leucorrhoea and pelvic pain have also been reported.
The following adverse reactions have also been reported during post-approval use of mifepristone and misoprostol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. No causal relationship between these events and mifepristone and misoprostol has been established: allergic reaction (including rash, hives, itching), hypotension (including orthostatic), lightheadedness, loss of consciousness, post-abortal infection (including endomyometritis, parametritis), ruptured ectopic pregnancy, shortness of breath, and tachycardia (including racing pulse, heart palpitations, heart pounding).
- Gastrointestinal side effects like diarrhoea (usually dose related and self-limiting), abdominal pain, nausea, flatulence, dyspepsia, headache, vomiting and constipation
Obstetrics and Gynaecological Use
- Patient may experience pain due to uterine contractions
- Severe genital bleeding
- Pelvic pain
- Uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy)
Women who received misoprostol during clinical trials reported the following gynaecological disorders: Spotting (0.7%), cramps (0.6%), hypermenorrhoea (0.5%), menstrual disorder (0.3%) and dysmenorrhoea (0.1%). Postmenopausal vaginal bleeding may be related to misoprostol administration. If it occurs, diagnostic workup should be undertaken to rule out gynaecological pathology.
Incidence > 1%
In clinical trials, the following adverse reactions were reported by more than
1% of the subjects receiving misoprostol and may be causally related to the drug: Nausea (3.2%), flatulence (2.9%), headache (2.4%), dyspepsia (2.0%), vomiting (1.3%), and constipation (1.1%). However, there were no significant differences between the incidences of these events for misoprostol and placebo.
Causal Relationship Unknown
The following adverse events were infrequently reported. Causal relationships between misoprostol and these events have not been established but cannot be excluded:
Body as a Whole: Aches/pains, asthenia, fatigue, fever, rigors, weight changes.
Skin: Rash, dermatitis, alopecia, pallor, breast pain.
Special Senses: Abnormal taste, abnormal vision, conjunctivitis, deafness, tinnitus, earache.
Respiratory: Upper respiratory tract infection, bronchitis, bronchospasm, dyspnoea, pneumonia, epistaxis.
Cardiovascular: Chest pain, oedema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased cardiac enzymes, syncope, myocardial infarction (some fatal), thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, and CVA).
Gastrointestinal: GI bleeding, GI inflammation/infection, rectal disorder, abnormal hepatobiliary function, gingivitis, reflux, dysphagia, amylase increase.
Hypersensitivity: Anaphylactic reaction.
Metabolic: Glycosuria, gout, increased nitrogen, increased alkaline phosphatase.
Genitourinary: Polyuria, dysuria, haematuria, urinary tract infection.
Nervous system/Psychiatric: Anxiety, change in appetite, depression, drowsiness, dizziness, thirst, impotence, loss of libido, sweating increase, neuropathy, neurosis, confusion.
Musculoskeletal: Arthralgia, myalgia, muscle cramps, stiffness, back pain.
Blood/Coagulation: Anaemia, abnormal differential, thrombocytopaenia, purpura, ESR increased.
Reproductive System and Breast Disorders: Vaginal haemorrhage (including postmenopausal bleeding), intermenstrual bleeding, menstrual disorder, uterine cramping, menorrhagia, dysmenorrhoea, uterine haemorrhage.
Congenital, Familial and Genetic Disorders: Birth defects.
No serious adverse reactions were reported in tolerance studies in healthy non-pregnant female and healthy male subjects where mifepristone was administered in single doses greater than threefold of that recommended for termination of pregnancy. In the event of accidental massive ingestion, signs of adrenal failure might occur. Signs of acute intoxication may require specialist treatment including the administration of dexamethasone.
The toxic dose of misoprostol in humans has not been determined. Cumulative total daily doses of 1600 mcg have been tolerated, with only symptoms of gastrointestinal discomfort being reported. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhoea, fever, palpitations, hypotension or bradycardia. Symptoms should be treated with supportive therapy. It is not known if misoprostol acid is dialyzable. However, because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage. In cases of overdose, standard supportive measures should be adopted as required.
Storage and Handling Instructions
Store below 25oC.
Pack contains 1 tablet of mifepristone and 4 tablets of misoprostol.
Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST