Isoxsuprine

 Risk Factor: C
 Class: CARDIOVASCULAR DRUGS / Vasodilators

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

No reports linking the use of isoxsuprine with congenital defects have been located. Isoxsuprine, a b-sympathomimetic, is indicated for vasodilation, but it has been used to prevent premature labor (1,2,3,4,5 and 6). Uterine inhibitory effects usually require high IV doses, which increase the risk for serious adverse effects (7,8). Maternal heart rate increases and blood pressure decreases are usually mild at lower doses (2,4,6). A decrease in the incidence of neonatal respiratory distress syndrome has been observed (9). However, in one study, neonatal respiratory depression was increased if cord serum levels exceeded 10 ng/mL (10). The depression was always associated with hypotension, so the mechanism of the defect may have been related to pulmonary hypoperfusion.

Neonatal toxicity is generally rare if cord levels of isoxsuprine are less than 2 ng/mL (corresponding to a drug-free interval of more than 5 hours), but levels greater than 10 ng/mL (drug-free interval of 2 hours of less) were associated with severe neonatal problems (10). These problems include hypocalcemia, hypoglycemia, ileus, hypotension, and death (10,11 and 12). Hypotension and neonatal death occurred primarily in infants of 2631 weeks' gestation, especially if cord levels exceeded 10 ng/mL, and in infants whose mothers developed hypotension or tachycardia during isoxsuprine infusion (10,11). Neonatal ileus, up to 33% in some series, was not related to cord isoxsuprine concentrations, but hypotension and hypocalcemia were directly related, reaching 89% and 100%, respectively, when cord levels exceeded 10 ng/mL (10,12). Fetal tachycardia is a common side effect. As compared with controls, no increase in late or variable decelerations was seen (10). In contrast to the above, infusion of isoxsuprine 30 minutes before cesarean section under general anesthesia was not observed to produce adverse effects in the mother, fetus, or newborn (13). Cord concentrations were not measured.

Long-term evaluation of infants exposed to b-mimetics in utero has been reported but not specifically for isoxsuprine (14). No harmful effects in the infants resulting from this exposure were observed.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 54 of which were exposed to isoxsuprine during the 1st trimester (15, pp. 346347). For use anytime during pregnancy, 858 exposures were recorded (15, p. 439). In neither case was evidence found for an association with malformations.

Breast Feeding Summary

No data are available.

References

1. Bishop EH, Woutersz TB. Isoxsuprine, a myometrial relaxant. A preliminary report. Obstet Gynecol 1961;17:4426.
2. Hendricks CH, Cibils LA, Pose SV, Eskes TKAB. The pharmacological control of excessive uterine activity with isoxsuprine. Am J Obstet Gynecol 1961;82:106478.
3. Bishop EH, Woutersz TB. Arrest of premature labor. JAMA 1961;178:8124.
4. Stander RW, Barden TP, Thompson JF, Pugh WR, Werts CE. Fetal cardiac effects of maternal isoxsuprine infusion. Am J Obstet Gynecol 1964;89:792800.
5. Hendricks CH. The use of isoxsuprine for the arrest of premature labor. Clin Obstet Gynecol 1964;7:68794.
6. Allen HH, Short H, Fraleigh DM. The use of isoxsuprine in the management of premature labor. Appl Ther 1965;7:5447.
7. Anonymous. Drugs acting on the uterus. Br Med J 1964;1:12346.
8. Briscoe CC. Failure of oral isoxsuprine to prevent prematurity. Am J Obstet Gynecol 1966;95:8856.
9. Kero P, Hirvonen T, Valimaki I. Perinatal isoxsuprine and respiratory distress syndrome. Lancet 1973;2:198.
10. Brazy JE, Little V, Grimm J, Pupkin M. Risk:benefit considerations for the use of isoxsuprine in the treatment of premature labor. Obstet Gynecol 1981;58:297303.
11. Brazy JE, Pupkin MJ. Effects of maternal isoxsuprine administration on preterm infants. J Pediatr 1979;94:4448.
12. Brazy JE, Little V, Grimm J. Isoxsuprine in the perinatal period. II. Relationships between neonatal symptoms, drug exposure, and drug concentration at the time of birth. J Pediatr 1981;98:14651.
13. Jouppila R, Kauppila A, Tuimala R, Pakarinen A, Moilanen K. Maternal, fetal and neonatal effects of beta-adrenergic stimulation in connection with cesarean section. Acta Obstet Gynecol Scand 1980;59:48993.
14. Freysz H, Willard D, Lehr A, Messer J. Boog G. A long term evaluation of infants who received a beta-mimetic drug while in utero. J Perinat Med 1977;5:949.
15. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
    
    

Questions and Answers

Need information on a horse with arthritis getting isoxsuprine?, I am looking at getting a 9 y/o, 17.1 hh gelding that was used as a jumper and also dressage. He has arthritis, which I am guessing was a result from being used as a jumper. He gets a supplement for the arthritis and is also on isoxsuprine and bute daily. Just wondering why the isoxsuprine?

Isoxsuprine is a vasodialator. The most common reason it is prescribed for horses is as an adjunct to special shoeing as a treatment for navicular disease. If I were you, I wouldn't touch this horse with a ten-foot pole until/unless a vet exam gives him a clean bill of health with regards to navicular.

FWIW, and this is just my opinion, a horse that is just nine years old and having to be medicated for arthritis would be a horse I would consider buying only if I was prepared to retire him and care for him for the rest of his life within five years or less. If that horse had navicular disease on top of arthritis of other joints, I think you would have to look on this horse as basically unsaleable. So if you buy him, you will be responsible for his well-being for a very long time, and caring for navicular horses to keep them relatively pain-free is neither inexpensive nor easy.

Just a guess: is the horse a dynamite jumper offered at a bargain-basement price?
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I read the additional information you provided. I've known several horses that had navicular disease, and treating them is expensive, difficult, worrisome, and only can postpone the deterioriation. Having the horse "nerved" can keep the pain at bay, but once the procedure is performed IMO it is unethical to sell the horse because of the danger to the rider in riding such a horse. A trainer I knew used to buy navicular hunters for next to nothing, have the horse nerved and sell the horse to novice clients who didn't know what they were getting into. The horses this trainer bought were typically show horses with superb records which had recently gotten a diagnosis of navicular. The trainer's pitch to the clients was that they would get championship performance at a fraction of the price it would normally cost to buy such a talented horse, and once the horse became too unsound to ride, they could donate it to a program that used horses for disabled kids or a similar program of light use. The problem with this scenario is that the programs she would donate the horses to couldn't afford to keep them indefinitely with the expenses associated with shoeing and vet care, and the horse would usually have to be euthanized fairly soon. I believe that a person who is willing to care for a navicular horse needs to have a long and serious conversation with a vet who has examined the horse and decide if they are willing to spend the money involved in keeping the horse pain-free. I am in favor of providing a loving home for every horse possible, but I am also in favor of completely informed decisions. Caring for a navicular horse is not for everyone, and the outlook for some horses is worse than for others. Every case has to be careful considered on its own.

Good luck.