Misoprostol increased

Misoprostol increases the incidence of abdominal pain and diarrhoea when used with diclofenac or indometacin. Isolated cases of neurological adverse effects have been seen with naproxen or phenylbutazone given with misoprostol. However, no important pharmacokinetic interactions seem to occur between aspirin, diclofenac, ibuprofen or indometacin and misoprostol. NSAIDs are reported not to affect the abortive effects of intravaginal misoprostol. 

Geriatric Considerations - Summary Use of NSAIDs in older adults increases the risk of GI complications including gastric ulceration, bleeding, and perforation. These complications are not necessarily preceded by less severe GI symptoms. Concomitant use of a proton pump inhibitor or misoprostol reduces the risk for gastric ulceration and bleeding, but may not prevent long-term GI toxicity. No clinical data exist to support reduced GI toxicity with the use of diclofenac. 

Antiprogestins (eg, mifepristone) have been combined with an oral oxytocic synthetic analog of PGE1 (misoprostol) to produce early abortion. This regimen is available in the USA and Europe (see Chapter 39). The ease of use and the effectiveness of the combination have aroused considerable opposition in some quarters. The major toxicities are cramping pain and diarrhea. The oral and vaginal routes of administration are equally effective, but the vaginal route has been associated with an increased incidence of sepsis, so the oral route is now recommended. 

A systematic review of the use of misoprostol for induction of labor has been published (16). The meta-analysis included all randomized clinical trials registered in the Cochrane Pregnancy and Childbirth Group. Vaginal misoprostol was associated with increased uterine hyperstimulation, both without fetal heart changes (RR = 1.67 Cl = 1.30, 2.14) and with associated fetal heart rate changes (RR = 1.45 Cl = 1.04, 2.04). There was also an increase in meconium-stained amniotic fluid (RR = 1.38 Cl = 1.06,1.79). 

In another case-control study in Brazil, congenital anomalies were compared in 34 misoprostol-exposed children and 4639 unexposed controls (35). Misoprostol exposure significantly increased the risk of arthrogryposis (OR = 8.5 95% Cl = 2, 37), hydrocephalus... 

Mothers who used misoprostol during pregnancy as an abortifacient had an increased risk of having a baby with congenital anomalies (OR = 2.4 95% Cl = 1.0, 6.2), as reported in a case-control study in Fortaleza, Brazil (36). Multiple malformations have been described associated with the use of misoprostol (37). 

Oxytocin is frequently given to induce and maintain labor after the cervix has ripened naturally or with the aid of misoprostol. For induction of labor, oxytocin should be administered intravenously via an infusion pump with appropriate fetal and maternal monitoring. An initial infusion rate of 1 mU/min is increased every 15-30 minutes until a physiologic contraction pattern is established. The maximum infusion rate is 20 mU/min. For postpartum uterine bleeding, 10-40 units is added to 1 L of 5% dextrose, and the infusion rate is titrated to control uterine atony. Alternatively, 10 units can be given intramuscularly after delivery of the placenta. To induce milk let-down, one puff is sprayed into each nostril in the sitting position 2-3 minutes before nursing. 

Davies et al (1994) induced small intestinal permeability by anti-inflammatory drugs in rats. After oral administration of 51Cr-EDTA urinary excretion was increased by non-steroidal anti-inflammatory drugs. Misoprostol and sulfasalazin significantly reduced the effect of in-dome thacin. 

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