Misoprostol is a synthetic prostaglandin E1. Misoprostol causes the cervix to soften and the uterus to contract.
Mifepristone is a progesterone antagonist. The anti-progesterone activity of Mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Mifepristone also exhibits anti-glucocorticoid and weak anti-androgenic activity.
Misoprostol belongs to a group of hormones called prostaglandin which cause uterine contractions. Prostaglandin E1 causes myometrial contractions by interacting with specific receptors on myometrial cells. Misoprostol causes the cervix to soften and the uterus to contract, resulting in the explusion of the uterine contents.
Absorption: Mifepristone is rapidly absorbed after oral administration. The absolute bioavailability of a 20 mg oral dose is 69%.
Distribution: 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.
Metabolism: Metabolism of Mifepristone is primarily via pathways involving N-demethylation and terminal hydroxylation of the 17-propynyl chain.
Excretion : Mifepristone 83% excreted in feces and 9% by urine.
Misoprostol is extensively absorbed, and undergoes rapid de-esterification to its free 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 analogs. The compound is a lipophilic methyl ester pro-drug and is readily metabolized to the free acid, which is the biologically active form.
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. Vaginal application of Misoprostol results in slower increase and lower peak plasma concentrations of Misoprostol acid than doses of oral administration. Vaginal use increases drug exposure than oral use.
Mifepristone and Misoprostol:
• Although specific drug or food Interactions with Mifepristone have not been studied, on the basis of this drug's metabolism by CYP 3a4, 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.
• Misoprostol has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis. Misoprostol has no clinically significant effect on the kinetics of diclofenac or ibuprofen. The most common side effects of Misoprostol are diarrhoea and abdominal pain. These side effects may be increased if Misoprostol is taken concurrently with antacids.
Dosage & Administration:
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 clinician or self-administered by the woman.
• 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.
Warnings and Precautions:
This combination has been prescribed for the patient's specific condition. It may be dangerous to any other non pregnant lady.
Mifepristone and Misoprostol:
• There are no data on use 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 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.
• Gastro-intestinal side effects like diarrhoea, abdominal pain, nausea, flatulence
• Dyspepsia, headache, vomiting and constipation
• Pain due to uterine contractions
• Pelvic pain
• Severe genital bleeding
Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhoea fever palpitations, hypotension or bradycardia.
Store in a cool, dark & dry place.
Keep out of reach of children