Miso

Each tablet contains Misoprostol 200 mcg. Miso also contains the following excipients: Microcrystalline cellulose, sodium starch glycolate (type A), hydogenated castor oil and hypromellose.

Miso (Miso) is indicated for reducing the risk of NSAID (nonsteroidal anti-inflammatory drugs, including aspirin)–induced gastric ulcers in patients at high risk of complications from gastric ulcer, e.g., the elderly and patients with concomitant debilitating disease, as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcer. Miso has not been shown to reduce the risk of duodenal ulcers in patients taking NSAIDs. Miso should be taken for the duration of NSAID therapy. Miso has been shown to reduce the risk of gastric ulcers in controlled studies of 3 months' duration. It had no effect, compared to placebo, on gastrointestinal pain or discomfort associated with NSAID use.

Miso is taken to prevent stomach ulcers in patients taking anti-inflammatory drugs, including aspirin. Miso may also be used for other conditions as determined by your doctor.

Miso helps the stomach protect itself against acid damage. It also decreases the amount of acid produced by the stomach.

Miso is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Miso may be used in certain patients with the following medical conditions:

• Abortion, first trimester
• Abortion, second trimester
• Cervical ripening
• Induction of labor
• Postpartum hemorrhage

Usual Adult Dose for Duodenal Ulcer

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for Gastric Ulcer

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for NSAID-Induced Ulcer Prophylaxis

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for Labor Induction

25 mcg vaginally every 4 to 6 hours.

Usual Adult Dose for Postpartum Bleeding

Prophylaxis: 400 to 600 mcg orally or rectally after delivery of the baby, but before delivery of the placenta.

Usual Adult Dose for Cervical Ripening

Before surgical abortion: 400 mcg vaginally, 3 to 4 hours before suction curettage.

Usual Adult Dose for Abortion

First Trimester of Pregnancy: 400 mcg orally once as a single dose 48 hours after mifepristone administration. Alternatively, 800 mcg vaginally 48 hours after mifepristone administration. When used with methotrexate, 5 to 7 days later give 800 mcg vaginally (Miso dose may be repeated 24 hours later if needed).

In Failed Pregnancy or Fetal Death: 800 mcg vaginally once or twice (doses given 24 hours apart).

Second Trimester of Pregnancy: 600 mcg vaginally, 36 to 48 hours after mifepristone administration, followed by 400 mcg orally or vaginally every 3 hours to a maximum of 5 doses in the first 24 hours.

Third Trimester of Pregnancy - Fetal Death: 100 mcg vaginally every 12 hours.

Usual Adult Dose for Gynecologic Surgery

Study (n=204) - Operative hysteroscopy: 400 mcg orally 12 to 24 hours before surgery.

Usual Pediatric Dose for NSAID-Induced Ulcer Prophylaxis

Study (n=25)

>7 years: 9.8 mcg/kg/day, given in two equally divided doses daily, to a maximum of 800 mcg/day.

Renal Dose Adjustments

No dose adjustment is routinely needed, but dosage can be reduced if the 200 mcg dose is not tolerated.

Liver Dose Adjustments

Data not available

Dose Adjustments

The dose may be reduced to 100 mcg orally 4 times a day or 200 mcg orally 2 times a day if the patient is unable to tolerate the recommended regimen or if the patient is maintained on chronic hemodialysis.

50 mcg every 6 hours may be appropriate for cervical ripening or labor induction in the third trimester in some situations, although higher doses appear to be associated with uterine tachysystole and possibly with uterine hyperstimulation and meconium staining of amniotic fluid.

Miso should not be administered more frequently than every 3 to 6 hours.

Precautions

Consult WARNINGS section for dosing related precautions.

Dialysis

In patients maintained on prolonged hemodialysis, start patient at the lower dose.

It is not known if Miso is dialyzable. However, because Miso is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage.

Other Comments

Miso is not considered a first-line agent for the treatment of duodenal ulcers, or gastric ulcers. There is no evidence that Miso is more efficacious than H2-antagonists in these settings.

Miso can cause miscarriage, often associated with potentially dangerous bleeding. This may result in hospitalization, surgery, infertility or death. Do not take Miso if pregnant and do not become pregnant while on this medication. If pregnancy occurs during Miso therapy, discontinue the drug and contact physician immediately.

ADDITIONAL CONSIDERATIONS: Patients should not give medication to anyone else. Patient should read the leaflet included with medication each time the prescription is renewed.

See also:
What is the most important information I should know about Miso?

Hypersensitivity to Miso or to any components of Miso or to other prostaglandins.

Use in pregnancy: Miso is contraindicated in pregnant women or in whom pregnancy has not been excluded, or who are planning a pregnancy as Miso increases uterine tone and contractions in pregnancy which may cause partial or complete expulsion of the products of conception. Use in pregnancy has been associated with birth defects.

Miso is contraindicated in women who are pregnant because it induces uterine contractions and is associated with abortion, premature birth, foetal death and birth defects. First trimester exposure to Miso is associated with a significantly increased risk of 2 birth defects: Mobius sequence (ie, palsies of cranial nerves VI and VII), and terminal transverse limb defects. Other defects including arthrogryposis have been observed.

The risk of uterine rupture increases with advancing gestational age and with prior uterine surgery, including Caesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture.

Women of childbearing potential should not be started on Miso until pregnancy is excluded and should be fully counseled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use of the product should be discontinued.

In such patients, it is advised that Miso should only be used if the patient takes effective contraceptive measures or has been advised of the risks of taking Miso if pregnant.

Use in lactation: Miso is rapidly metabolised in the mother to Miso acid, which is biologically active and is excreted in breast milk. Miso should not be administered to nursing mothers because the excretion of Miso acid could cause adverse reactions eg, diarrhoea in nursing infants.

Use Miso as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Miso. Talk to your pharmacist if you have questions about this information.
• Take Miso by mouth with food unless your doctor tells you otherwise.
• The last dose of the day should be taken at bedtime. Taking Miso after meals and at bedtime may decrease the risk of diarrhea.
• Do not take an antacid that has magnesium in it within 1 hour before or 2 hours after you take Miso.
• If you miss a dose of Miso, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Miso.

Use: Labeled Indications

NSAID-induced gastric ulcers, prevention: To reduce the risk of NSAID-induced gastric ulcers in patients at high risk of complications

Termination of intrauterine pregnancy: Medical termination of intrauterine pregnancy through 70 days' gestation in combination with mifepristone (Mifeprex prescribing information March 2016)

Off Label Uses

Cervical ripening and labor induction

Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin: Induction of Labor, Miso tablets administered intravaginally for cervical ripening and labor induction is effective and recommended in the management of this condition.

See also:
What other drugs will affect Miso?

Antacids: May enhance the adverse/toxic effect of Miso. More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of Miso and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Potassium Bicarbonate; Sodium Bicarbonate. Avoid combination

Carbetocin: Miso may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Avoid combination

Oxytocin: Miso may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of Miso recommends avoiding concomitant use with oxytocin. Miso may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Consider therapy modification

Phenylbutazone: May enhance the neurotoxic effect of Miso. Specifically, the combination may result in headache, dizziness, and transient diplopia. Monitor therapy

See also:
What are the possible side effects of Miso?

The following have been reported as adverse events in subjects receiving Miso:

Gastrointestinal

In subjects receiving Miso 400 or 800 mcg daily in clinical trials, the most frequent gastrointestinal adverse events were diarrhea and abdominal pain. The incidence of diarrhea at 800 mcg in controlled trials in patients on NSAIDs ranged from 14–40% and in all studies (over 5,000 patients) averaged 13%. Abdominal pain occurred in 13–20% of patients in NSAID trials and about 7% in all studies, but there was no consistent difference from placebo.

Diarrhea was dose related and usually developed early in the course of therapy (after 13 days), usually was self-limiting (often resolving after 8 days), but sometimes required discontinuation of Miso (2% of the patients). Rare instances of profound diarrhea leading to severe dehydration have been reported. Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if Miso is prescribed. The incidence of diarrhea can be minimized by administering after meals and at bedtime, and by avoiding coadministration of Miso with magnesium-containing antacids.

Gynecological

Women who received Miso during clinical trials reported the following gynecological disorders: spotting (0.7%), cramps (0.6%), hypermenorrhea (0.5%), menstrual disorder (0.3%) and dysmenorrhea (0.1%). Postmenopausal vaginal bleeding may be related to Miso administration. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology.

Elderly

There were no significant differences in the safety profile of Miso in approximately 500 ulcer patients who were 65 years of age or older compared with younger patients.

Additional adverse events which were reported are categorized as follows:

Incidence greater than 1%

In clinical trials, the following adverse reactions were reported by more than 1% of the subjects receiving Miso 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 Miso and placebo.

Causal relationship unknown

The following adverse events were infrequently reported. Causal relationships between Miso and these events have not been established but cannot be excluded:

Body as a whole: aches/pains, asthenia, fatigue, fever, chills, 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, dyspnea, pneumonia, epistaxis.

Cardiovascular: chest pain, edema, 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, hematuria, 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: anemia, abnormal differential, thrombocytopenia, purpura, ESR increased.