DIAZOXIDE

Fetal Risk Summary

Diazoxide readily crosses the placenta and reaches fetal plasma concentrations similar to maternal levels (1). The drug has been used for the treatment of severe hypertension associated with pregnancy (1,2,3,4,5,6,7,8,9,10,11 and 12). Daily doses of 30, 21, and 10 mg/kg in rats, rabbits, and dogs, respectively, were associated with reduced fetal and pup survival, and reduced fetal growth (13).

Some investigators have cautioned against the use of diazoxide in pregnancy (14,15). In one study, the decrease in maternal blood pressure was sufficient to produce a state of clinical shock and endanger placental perfusion (14). Transient fetal bradycardia has been reported in other studies following a rapid, marked decrease in maternal blood pressure (7,16). Fatal maternal hypotension has been reported in one patient after diazoxide therapy (17). Some investigators have recommended the infusion technique for administering diazoxide rather than rapid boluses to prevent maternal and fetal complications (18). However, small bolus doses at frequent intervals (30 mg every 1–2 minutes) have been used successfully to treat maternal hypertension without producing fetal toxicity (19).

Diazoxide is a potent relaxant of uterine smooth muscle and may inhibit uterine contractions if given during labor (2,3,5,6 and 7,20,21 and 22). The degree and duration of uterine inhibition are dose dependent (21). Augmentation of labor with oxytocin may be required in patients receiving diazoxide.

Hyperglycemia in the newborn (glucose 500–700 mg/dL) secondary to IV diazoxide therapy in a mother just prior to delivery has been observed to persist for up to 3 days (23). In some series, all of the mothers and newborns had hyperglycemia without ketoacidosis (14). The glucose levels returned to near normal within 24 hours.

The use of oral diazoxide for the last 19–69 days of pregnancy has been associated with alopecia, hypertrichosis lanuginosa, and decreased ossification of the wrist (1). However, long-term oral therapy has not caused similar problems in other newborns exposed in utero (4).

Because other antihypertensive drugs are available for severe maternal hypertension and the long-term effects on the infant have not been evaluated, diazoxide should be used with caution, if at all, during pregnancy. If diazoxide is needed after other therapies have failed, small doses are recommended.

Breast Feeding Summary

No reports describing the use of diazoxide during lactation have been located. The molecular weight (about 231) is low enough, however, that passage into milk should be expected.

References

1. Milner RDG, Chouksey SK. Effects of fetal exposure to diazoxide in man. Arch Dis Child 1972;47:537–43.
2. Finnerty FA Jr, Kakaviatos N, Tuckman J, Magill J. Clinical evaluation of diazoxide: a new treatment for acute hypertension. Circulation 1963;28:203–8.
3. Finnerty FA Jr. Advantages and disadvantages of furosemide in the edematous states of pregnancy. Am J Obstet Gynecol 1969;105:1022–7.
4. Pohl JEF, Thurston H, Davis D, Morgan MY. Successful use of oral diazoxide in the treatment of severe toxaemia of pregnancy. Br Med J 1972;2:568–70.
5. Pennington JC, Picker RH. Diazoxide and the treatment of the acute hypertensive emergency in obstetrics. Med J Aust 1972;2:1051–4.
6. Koch-Weser J. Diazoxide. N Engl J Med 1976;294:1271–4.
7. Morris JA, Arce JJ, Hamilton CJ, Davidson EC, Maidman JE, Clark JH, Bloom RS. The management of severe preeclampsia and eclampsia with intravenous diazoxide. Obstet Gynecol 1977;49:675–80.
8. Keith TA III. Hypertension crisis: recognition and management. JAMA 1977;237:1570–7.
9. MacLean AB, Doig JR, Aickin DR. Hypovolaemia, pre-eclampsia and diuretics. Br J Obstet Gynaecol 1978;85:597–601.
10. Barr PA, Gallery ED. Effect of diazoxide on the antepartum cardiotocograph in severe pregnancy-associated hypertension. Aust NZ J Obstet Gynaecol 1981;21:11–5.
11. MacLean AB, Doig JR, Chatfield WR, Aickin DR. Small-dose diazoxide administration in pregnancy. Aust NZ J Obstet Gynaecol 1981;21:7–10.
12. During VR. Clinical experience obtained from use of diazoxide (Hypertonalum) for treatment of acute intrapartum hypertensive crisis. Zentralbl Gynakol 1982;104:89–93.
13. Product information. Hyperstat. Schering, 2000.
14. Neuman J, Weiss B, Rabello Y, Cabal L, Freeman RK. Diazoxide for the acute control of severe hypertension complicating pregnancy: a pilot study. Obstet Gynecol 1979;53(Suppl):50S–5S.
15. Perkins RP. Treatment of toxemia of pregnancy. JAMA 1977;238:2143–4.
16. Michael CA. Intravenous diazoxide in the treatment of severe preeclamptic toxaemia and eclampsia. Aust NZ J Obstet Gynaecol 1973;13:143–6.
17. Henrich WL, Cronin R, Miller PD, Anderson RJ. Hypotensive sequelae of diazoxide and hydralazine therapy. JAMA 1977;237:264–5.
18. Thien T, Koene RAP, Schijf C, Pieters GFFM, Eskes TKAB, Wijdeveld PGAB. Infusion of diazoxide in severe hypertension during pregnancy. Eur J Obstet Gynaecol Reprod Biol 1980;10:367–74.
19. Dudley DKL. Minibolus diazoxide in the management of severe hypertension in pregnancy. Am J Obstet Gynecol 1985;151:196–200.
20. Barden TP, Keenan WJ. Effects of diazoxide in human labor and the fetus-neonate (abstract). Obstet Gynecol 1971;37:631–2.
21. Landesman R, Adeodato de Souza FJ, Countinho EM, Wilson KH, Bomfim de Sousa FM. The inhibitory effect of diazoxide in normal term labor. Am J Obstet Gynecol 1969;103:430–3.
22. Paulissian R. Diazoxide. Int Anesthesiol Clin 1978;16:201–36.
23. Milsap RL, Auld PAM. Neonatal hyperglycemia following maternal diazoxide administration. JAMA 1980;243:144–5.