688 Kuenen, Slee, Seldenrijk, Wagenaar

1 Norris HJ, Parmley T. Mesenchymal tumors of the uterus. 5 Mazzola A, Gregorini R, Procaccini B, et al. Intracaval and V. Intravenous leiomyomatosis. A clinical and pathological intracardiac leiomyomatosis of uterine origin. Ann Vasc Surg

study of 14 cases. Cancer 1975; 36: 2164-78. 1986; 1: 134-8. Postgrad Med J: first published as 10.1136/pgmj.72.853.688 on 1 November 1996. Downloaded from 2 Cooper MM, Guillem J, Dalton J, et al. Recurrent 6 Clement PB. Intravenous leiomyomatosis of the uterus. intravenous leiomyomatosis with cardiac extension. Ann PatholAnnu 1988; 23: 153-83. Thorac Surg 1992; 53: 139-41. 7 Clement PB, Young RH, Scully RE. Intravenous leiomyo- 3 Mulvany NJ, Slavin JL, Ostor AG, Fortune DW. Intrave- matosis of the uterus. A clinicopathological analysis of 16 nous leiomyomatosis ofthe uterus: a clinicopathologic study cases with unusual histologic features. Am J Surg Pathol of 22 cases. IntJ Gynecol Pathol 1994; 13: 1-9. 1988; 12: 932-45. 4 Timmis AD, Smallpiece C, Davies AC, Macarthur AM, 8 Bahary CM, Gorodeski IG, Nilly M, et al. Intravascular Gishen P, Jackson G. Intracardiac spread of intravenous leiomyomatosis. Obstet Gynecol 1983; 59: 73s. leiomyomatosis with successful surgical excision. N Engl J Med 1980; 303: 1043 - 4.

Treatment of hyperemesis gravidarum with the 5-HT3 antagonist ondansetron (Zofran)

DG Tincello, MJ Johnstone

Summary dehydrated and tachycardiac on admission Ondansetron is a 5-hydroxytryptamine and urinalysis revealed moderate ketonuria receptor antagonist which is known to be (2+ on ward dipstick testing). She had lost a highly effective anti-emetic drug for 10 kg in weight (20% of the pre-pregnancy chemotherapy-associated nausea and vo- weight). Intravenous fluid replacement was miting and for postoperative nausea. We recommenced. The patient and her parmer report here a case where ondansetron was were unwilling to consider termination of used in severe hyperemesis gravidarum to pregnancy or parenteral nutrition. After 14 avoid parenteral nutrition. The drug was days with no relief from vomiting, ondansetron used intermittently in every trimester with (Zofran) 8 mg intravenously twice daily was no apparent adverse effects on mother or commenced resulting in dramatic cessation of infant. vomiting after a single dose although the nausea persisted. She was able to tolerate a Keywords: hyperemesis gravidarum, ondansetron, 5- light diet and oral therapy two days later and

hydroxytryptamine receptor was well enough to be discharged 14 days after http://pmj.bmj.com/ admission, taking ondansetron 4 mg tid orally. At formal antenatal booking two weeks later A 29-year-old woman presented at eight weeks she was still nauseated. The vomiting was gestation in her first pregnancy with nausea controlled on an oral dose of ondansetron and vomiting and a weight loss of 3.5 kg. On admission she was clinically dehydrated and

tachycardic, although there was no ketonuria. on September 29, 2021 by guest. Protected copyright. Intravenous fluid replacement was com- Ondansetron (Zofran) menced together with intramuscular pro- Uses methazine (Phenergan) for nausea. An * management of nausea and vomiting induced ultrasound scan confirmed a singleton preg- by cytotoxic chemotherapy and radiotherapy nancy of the same gestation. Two days after * prevention and treatment of postoperative admission the vomiting was unrelieved and so nausea and vomiting intramuscular prochlorperazine (Stemetil) was to the therapy was Mode of action added regime. (Rectal * highly selective 5-HT3-receptor antagonist Department of refused by the patient.) This combination did * precise mode of action not known, but 5-HT3 Obstetrics and not relieve her symptoms and she remained on receptors are present in vagal afferents from the Gynaecology, intravenous fluids, unable to tolerate any oral small intestine and in the floor of the fourth Fazakerley Hospital, intake. Potassium chloride supplementation ventricle Aintree Hospitals NHS was required to correct hypokalaemia of * mode of action probably by antagonism of the Trust, Liverpool 2.9 mmol/l. On the 14th day of admission receptors in both central and peripheral sites L9 4AL, UK DG Tincello intramuscular metoclopramide (Maxalon) was Side-effects MJ Johnstone added with gradual relief ofher symptoms over * constipation, headaches, flushing/sensation of the following seven days. She was then warmth of the head and epigastrium Correspondence to discharged on oral metoclopramide. * transient disturbances of liver Dr DG Tincello, Liverpool At 12 weeks gestation the patient was aminotransferases Women's Hospital, Crown * visual Street, Liverpool L8 7SS, readmitted with worsening recurrent nausea rarely, hypersensitivity reactions, UK and vomiting which failed to respond to any of disturbances, chest pain, cardiac arrhythmias Accepted 12 January 1996 the drugs previously used. She was again Treatment of hyperemesis gravidarum 689

4 mg tid. Throughout the rest ofher pregnancy Summary points

she remained nauseated but any vomiting was Postgrad Med J: first published as 10.1136/pgmj.72.853.688 on 1 November 1996. Downloaded from controlled with oral ondansetron. The patient * hyperemesis gravidarum can be a life- self-medicated on an intermittent basis once or threatening condition twice daily. Whenever treatment was stopped * standard anti-emetic drugs are often of limited the patient experienced a recurrence of vomit- efficacy * ondansetron appears to be an effective ing. She was able to eat enough to maintain her treatment in hyperemesis gravidarum body weight and finally discontinued therapy at * further information from larger studies will be 33 weeks gestation. She still had occasional needed before widespread use of ondansetron episodes of vomiting and the nausea persisted in pregnancy can be recommended throughout her pregnancy. She went into labour spontaneously at 39 weeks gestation and was delivered of a healthy male infant weighing 2.7 kg with no detectable abnorm- Ondansetron is a 5-hydroxytryptamine (5-HT) ality. At her postnatal check, she was in good antagonist with action specific for the 5-HT health with resolution of her vomiting and the receptors within the peripheral and central baby remained well. nervous system (5-HT, receptors).3 The main action of the drug is within the central nervous Discussion system3 although it does also increase gastric emptying.4 The drug is highly effective at This case reports the use of ondansetron from reducing the emetic side-effects of chemother- 14 weeks to 33 weeks gestation in a primi- apy5 or radiotherapy6 and is also effective at gravida to control severe hyperemesis which reducing postoperative nausea and vomiting.7 was refractory to conventional treatments. The Extensive premarketing tests showed that patient had lost 20% of her pre-pregnancy ondansetron had a wide therapeutic index, no weight and was unable to tolerate any oral interaction with commonly prescribed drugs fluid. The potential theoretical risks of this and minimal side-effects.4 drug treatment were clearly understood by the The paucity of data on the use of ondanse- patient and her partner. The anti-emetic effect tron in pregnancy make it difficult to be certain of ondansetron was dramatic in its rapidity of of the safety of the drug in pregnancy. This action and its efficacy in preventing further report describes the longest published duration vomiting. of use of ondansetron from the second The literature contains only two brief trimester through to the third without any references to the use of ondansetron in adverse clinical effects. The possibility of a late pregnancy. In the first, the drug was used for adverse effect upon foetal and infant develop- two weeks in the first trimester in a patient with ment cannot be ruled out at this time, and it is severe hyperemesis leading to weight loss and not possible to make any comment as to the dehydration.' The patient's condition did not safety of the drug if used early in the first recur following cessation of drug, and a healthy trimester during organogenesis. However, the infant was born at term. The second report general safety of the drug and the evidence involved the use of ondansetron to control from the cases now reported indicate that http://pmj.bmj.com/ nausea in a patient with renal disease in ondansetron may have a role in the manage- pregnancy.2 The drug was used for three weeks ment of the patient with severe, refractory during the third trimester and no adverse effect hyperemesis which persists beyond the first was seen in the infant. trimester.

1 Guikontes E, Spantideas A, Diakakis J. Ondansetron and 5 Marty M. Ondansetron in the of acute prophylaxis cisplatin on September 29, 2021 by guest. Protected copyright. hyperemesis gravidarum. Lancet 1992; 340: 1223. induced nausea and vomiting. EurJ7 Cancer Clin Oncol 1989; 2 World MJ. Ondansetron and hyperemesis gravidarum. 25 (suppl 1): S41 - S45. Lancet 1993; 341: 185. 6 Priestman TJ. Clinical studies with ondansetron in the 3 Tyers MB, Bunce KT, Humphrey PP. Pharmacological and control ofradiation induced emesis. EurJ7 Cancer Clin Oncol anti-emetic properties of ondansetron. Eur J Cancer Clin 1989; 25 (suppl 1): S29-S33. Oncol 1989; 25(suppl 1): S15-S19. 7 Alon E, Himmelseher S. Ondansetron in the treatment of 4 Blackwell CP, Harding SM. The clinical pharmacology of post-operative vomiting: a randomized, double-blind com- ondansetron. EurJ'CancerClin Oncol 1989 (suppl 1): S21- parison with droperidol and metoclopramide. Anaesth AnaIg S24. 1992; 75: 561-5.