GUANFACINE

Fetal Risk Summary

Guanfacine is a centrally acting antihypertensive agent. The drug did not produce reproductive dysfunction or adverse fetal effects in rats and rabbits given doses 70 and 20 times the maximum recommended human dose (MRHD) (1). At doses 200 and 100 times the MRHD, respectively, increased fetal mortality and maternal toxicity were observed. Although guanfacine crosses the placenta in animals (1,2), this has not been studied in humans.

The manufacturer is aware of two unreported cases of exposure during pregnancy that resulted in the birth of healthy infants (personal communication, A.H. Robins Company, 1987). A third patient, who was participating in a clinical trial of the drug for the treatment of hypertension, became pregnant during treatment (3). Guanfacine therapy was discontinued at approximately 8 weeks of gestation. She subsequently delivered a healthy male infant.

Guanfacine is not approved for the treatment of preeclampsia, but one study has been located that describes the use of the agent for this purpose. A 1980 German report summarized the use of guanfacine for the treatment of hypertension secondary to preeclampsia in 30 women (4). The gestational ages of the women at the time of treatment were not specified. Therapy was administered for 16–68 days with doses ranging from 1–4 mg/day (mean dose approximately 2 mg/day). Mean systolic blood pressures (supine/standing) before treatment were about 160/164 mm Hg compared with 136/139 mm Hg just before parturition. Mean diastolic pressures (supine/standing) before treatment and just before delivery were 105/106 and 88/92 mm Hg, respectively. No significant changes in fetal heart rate were observed during the trial. Six infants were growth retarded, but this was probably secondary to the maternal hypertension. No drug-induced adverse effects were observed in any of the infants, and all were developing normally on follow-up (duration of follow-up not specified).

Breast Feeding Summary

Guanfacine is excreted into the milk of animals, but human studies have not been located. In rats, milk concentrations of guanfacine were 75% of the level in the plasma (1). The molecular weight (about 283 for the hydrochloride salt) is low enough that excretion into human milk should be expected. The potential effects on a nursing infant from this exposure are unknown. Guanfacine reduces serum prolactin concentrations in some patients and, theoretically, could cause inhibition of milk secretion.

References

1. Product information. Tenex. A.H. Robins Company, 2000.
2. Sorkin EM, Heel RC. Guanfacine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. Drugs 1986;31:301–36.
3. Karesoja M, Takkunen H. Guanfacine, a new centrally acting antihypertensive agent in long-term therapy. Curr Ther Res 1981;29:60–5.
4. Philipp E. Guanfacine in the treatment of hypertension due to pre-eclamptic toxaemia in thirty women. Br J Clin Pharmacol 1980;10(Suppl 1):137S–40S.