Misoprostol is a medication used to start labor, cause an abortion, prevent and treat stomach ulcers, and treat postpartum bleeding due to poor contraction of the uterus. For abortions, it is often used with mifepristone or methotrexate. By itself, effectiveness for this purpose is between 66% and 90%. It is taken either in the cheek, under the tongue, or placed in the vagina. A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties.
Mechanism of Action of Misoprostol
Misoprostol seems to inhibit gastric acid secretion by a direct action on the parietal cells through binding to the prostaglandin receptor. The activity of this receptor is mediated by G proteins which normally activate adenylate cyclase. The indirect inhibition of adenylate cyclase by Misoprostol may be dependent on guanosine-5’-triphosphate (GTP). The significant cytoprotective actions of misoprostol are related to several mechanisms. These include 1. Increased secretion of bicarbonate, 2. The considerable decrease in the volume and pepsin content of the gastric secretions, 3. It prevents harmful agents from disrupting the tight junctions between the epithelial cells which stops the subsequent back diffusion of H+ ions into the gastric mucosa, 4. The increased thickness of the mucus layer, 5. Enhanced mucosal blood flow as a result of direct vasodilatation, 6. Stabilization of tissue lysozymes/vascular endothelium, 7. Improvement of mucosal regeneration capacity, and 8. Replacement of prostaglandins that have been depleted as a result of various insults to the area. Misoprostol has also been shown to increase the amplitude and frequency of uterine contractions during pregnancy via selective binding to the EP-2/EP-3 prostanoid receptors.
Indications of Misoprostol
- Abortion
- Cervical ripening
- Gynecological conditions
- Duodenal ulcer
- Labor induction
- NSAID-induced ulcer prophylaxis
- Postpartum bleeding
- Stomach ulcer
- Gastric ulcer
- Incomplete abortion
- Missed abortion
- Postpartum hemorrhage
Indicated for the treatment of ulceration (duodenal, gastric and NSAID induced) and prophylaxis for NSAID induced ulceration. Misoprostol is also indicated for other uses that are not approved in Canada, including the medical termination of an intrauterine pregnancy used alone or in combination with methotrexate, as well as the induction of labor in a selected population of pregnant women with unfavorable cervices. This indication is avoided in women with prior uterine surgery or cesarean surgery due to an increased risk of possible uterine rupture. Misoprostol is also used for the prevention or treatment of serious postpartum hemorrhage.
Contra-Indications of Misoprostol
- Extreme Loss of body water
- Inflammatory bowel disease
- Tearing of the uterus while pregnant
- Operation of the uterus or the cervix
- Pregnancy
- Previous C Section
Dosage of Misoprostol
Strengths: 100 mcg; 200 mcg; 600mcg
Duodenal Ulcer
- 200 mcg orally 4 times a day after meals and at bedtime
- Maintenance dose: 100 to 200 mcg orally 4 times a day
Gastric Ulcer
- 200 mcg orally 4 times a day after meals and at bedtime
- Maintenance dose: 100 to 200 mcg orally 4 times a day
NSAID-Induced Ulcer Prophylaxis
- 200 mcg orally 4 times a day after meals and at bedtime
- Maintenance dose: 100 to 200 mcg orally 4 times a day
Labor Induction
American College of Obstetricians and Gynecologists (ACOG) Recommendations
- 25 mcg vaginally every 3 to 6 hours
- Some patients may require doses of 50 mcg every 6 hours
Postpartum Bleeding
ACOG Recommendations
- 800 to 1000 mcg rectally once
International Federation of Gynecology Obstetrics (FIGO) Recommendations
- 600 mcg orally OR 800 mcg sublingually once immediately after delivery
Abortion
ACOG Recommendations>First Trimester of Pregnancy
- Early Pregnancy Loss: 800 mcg intravaginally once; a second dose may be given if there is no response to the first dose no sooner than 3 hours after the first dose, and usually within 7 days
- Incomplete Abortion: 600 mcg orally once
- Missed Abortion: 800 mcg intravaginally OR 600 mcg sublingually once; the dose may be repeated every 3 hours for 2 additional doses
Side Effects of Misoprostol
The most common
- Constipation
- dizziness
- drowsiness
- dry mouth
- chest pain
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- fainting, fast or pounding heartbeats.
More common
- Seizures
- Syndrome of inappropriate secretion of antidiuretic hormone
- Fast or irregular heartbeat
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- confusion
- diarrhea or loose stools
- heartburn
- sleepiness or unusual drowsiness
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- Abnormal dreams
- change in sense of taste
- congestion
- discouragement, feeling sad, or empty
- Suicide attempts
- Acting on dangerous impulses
- Aggressive or violent behavior
- Thoughts about suicide or dying
- New or worse depression
- New or worse anxiety or panic attacks
- Agitation, restlessness, anger, or irritability
- Trouble sleeping
- An increase in activity or talking more than normal
Drug Interactions of Misoprostol
Misoprostol may interact with following drugs, supplements & may decrease the efficacy of drugs
- crofelemer
- eluxadoline
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Aceclofenac The therapeutic efficacy of Misoprostol can be decreased when used in combination with Aceclofenac. Approved, Investigational Acemetacin The therapeutic efficacy of Misoprostol can be decreased when used in combination with Acemetacin. Approved, Experimental, Investigational Acetylsalicylic acid The therapeutic efficacy of Misoprostol can be decreased when used in combination with an Acetylsalicylic acid. Approved, Vet Approved Adapalene The therapeutic efficacy of Misoprostol can be decreased when used in combination with Adapalene. Approved Alclofenac The therapeutic efficacy of Misoprostol can be decreased when used in combination with Alclofenac. Approved, Withdrawn Almasilate The risk or severity of adverse effects can be increased when Almasilate is combined with Misoprostol. Approved, Experimental Alminoprofen The therapeutic efficacy of Misoprostol can be decreased when used in combination with Alminoprofen. Experimental Aloglutamol The risk or severity of adverse effects can be increased when Aloglutamol is combined with Misoprostol. Experimental Aluminium The risk or severity of adverse effects can be increased when Aluminium is combined with Misoprostol. -
Calcium Carbonate The risk or severity of adverse effects can be increased when Calcium Carbonate is combined with Misoprostol. Approved, Investigational Calcium silicate The risk or severity of adverse effects can be increased when Calcium silicate is combined with Misoprostol. Experimental Carbaspirin calcium The therapeutic efficacy of Misoprostol can be decreased when used in combination with Carbaspirin calcium. -
Chloroquine The therapeutic efficacy of Misoprostol can be decreased when used in combination with Chloroquine. Approved, Investigational, Vet Approved Choline magnesium trisalicylate The therapeutic efficacy of Misoprostol can be decreased when used in combination with Choline magnesium trisalicylate. Approved Clonixin The therapeutic efficacy of Misoprostol can be decreased when used in combination with Clonixin. Approved Curcumin The therapeutic efficacy of Misoprostol can be decreased when used in combination with Curcumin. Approved, Investigational Diclofenac The therapeutic efficacy of Misoprostol can be decreased when used in combination with Diclofenac. -
Etanercept The therapeutic efficacy of Misoprostol can be decreased when used in combination with Etanercept. Approved, Investigational Ethenzamide The therapeutic efficacy of Misoprostol can be decreased when used in combination with Ethenzamide. Experimental Etodolac The therapeutic efficacy of Misoprostol can be decreased when used in combination with Etodolac. Approved, Investigational, Vet Approved Etofenamate The therapeutic efficacy of Misoprostol can be decreased when used in combination with Etofenamate. Approved, Investigational Etoricoxib The therapeutic efficacy of Misoprostol can be decreased when used in combination with Etoricoxib.
Pregnancy & Lactation
- FDA PregnancyCategory X
Pregnancy
- Women who may become pregnant should use adequate birth control (e.g., birth control pills, condoms, or intrauterine devices) while taking misoprostol. Since misoprostol increases the risk of miscarriage, a woman who may be pregnant should not start taking misoprostol until she is sure that she is not pregnant. If you suspect you are pregnant, stop the medication and contact your doctor.
Lactation
- Breast-feeding mothers should not take misoprostol, as it may cause significant diarrhea for breast-feeding infants. The safety and effectiveness of this medication have not been established for children and adolescents under 18 years of age.
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