Hematological Agent (Antiplatelet)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Neither the animal nor the limited human pregnancy data suggest that dipyridamole causes developmental toxicity.
FETAL RISK SUMMARY
Dipyridamole is a platelet inhibitor that is indicated as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement. The drug has a terminal elimination half-life of about 10 hours and is highly bound to plasma proteins (1).
Reproduction studies have been conducted in mice, rats, and rabbits at doses up to 1.3, 20, and 1.6 times the maximum recommended daily human dose based on BSA, respectively. No evidence of fetal harm was found in these studies (1).
No reports linking the use of dipyridamole with congenital defects have been located. The drug has been used in pregnancy (2–9). A single IV 30-mg dose of dipyridamole was shown to increase uterine perfusion in the 3rd trimester in 10 patients (10). In one pregnancy, a malformed infant was delivered, but the mother was also taking warfarin (2). The multiple defects in the infant were consistent with the fetal warfarin syndrome (see Coumarin Derivatives).
In a randomized, nonblinded study to prevent preeclampsia, 52 high-risk patients treated from the 13th week of gestation through delivery with daily doses of 300 mg of dipyridamole plus 150 mg of aspirin were compared with 50 high-risk controls (11). Four treated patients were excluded from analysis (spontaneous abortions before 16 weeks) vs. five controls (two lost to follow-up plus three spontaneous abortions). Hypertension occurred in 41 patients—19 treated and 22 controls. The outcome of pregnancy was significantly better in treated patients in three areas: preeclampsia (0 vs. 6), fetal and neonatal loss (0 vs. 5), and severe intrauterine growth restriction (0 vs. 4). No fetal malformations were observed in either group. Other reports and reviews have documented the benefits of this therapy, namely a reduction in the incidence of stillbirth, placental infarction, and intrauterine growth restriction (12–18).
BREASTFEEDING SUMMARY
Dipyridamole is excreted into breast milk (1). The effect of this exposure on a nursing infant is unknown.
References
1.Product information. Persantine. Boehringer Ingelheim Pharmaceuticals, 2004.
2.Tejani N. Anticoagulant therapy with cardiac valve prosthesis during pregnancy. Obstet Gynecol 1973;42:785–93.
3.Del Bosque MR. Dipiridamol and anticoagulants in the management of pregnant women with cardiac valvular prosthesis. Ginecol Obstet Mex 1973;33:191–8.
4.Littler WA, Bonnar J, Redman CWG, Beilin LJ, Lee GD. Reduced pulmonary arterial compliance in hypertensive patients. Lancet 1973;1:1274–8.
5.Biale Y, Lewenthal H, Gueron M, Beu-Aderath N. Caesarean section in patient with mitral-valve prosthesis. Lancet 1977;1:907.
6.Taguchi K. Pregnancy in patients with a prosthetic heart valve. Surg Gynecol Obstet 1977;145:206–8.
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8.Biale Y, Cantor A, Lewenthal H, Gueron M. The course of pregnancy in patients with artificial heart valves treated with dipyridamole. Int J Gynaecol Obstet 1980;18:128–32.
9.Salazar E, Zajarias A, Gutierrez N, Iturbe I. The problem of cardiac valve prostheses, anticoagulants, and pregnancy. Circulation 1984;70(Suppl 1): I169–77.
10.Lauchkner W, Schwarz R, Retzke U. Cardiovascular action of dipyridamole in advanced pregnancy. Zentralbl Gynaekol 1981;103:220–7.
11.Beaufils M, Uzan S, Donsimoni R, Colau JC. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet 1985;1:840–2.
12.Beaufils M, Uzan S, Donsimoni R, Colau JC. Prospective controlled study of early antiplatelet therapy in prevention of preeclampsia. Adv Nephrol 1986;15:87–94.
13.Wallenburg HCS, Rotmans N. Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole. Am J Obstet Gynecol 1987;157:1230–5.
14.Uzan S, Beaufils M, Bazin B, Danays T. Idiopathic recurrent fetal growth retardation and aspirin-dipyridamole therapy. Am J Obstet Gynecol 1989;160:763.
15.Wallenburg HCS, Rotmans N. Idiopathic recurrent fetal growth retardation and aspirin-dipyridamole therapy. Reply. Am J Obstet Gynecol 1989;160:763–4.
16.Wallenburg HCS, Rotmans N. Prophylactic low-dose aspirin and dipyridamole in pregnancy. Lancet 1988;1:939.
17.Capetta P, Airoldi ML, Tasca A, Bertulessi C, Rossi E, Polvani F. Prevention of pre-eclampsia and placental insufficiency. Lancet 1986;1:919.
18.Romero R, Lockwood C, Oyarzun E, Hobbins JC. Toxemia: new concepts in an old disease. Semin Perinatol 1988;12:302–23.