New Use of old drug: Sildenafil Citrate ( Viagra) in treatment of preeclampsia.

photo courtesy: Avon Pharmacy

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality, and early-onset preeclampsia is responsible for long lasting consequences for the fetus.

A recent study published online July 07, 2016 in journal of obstetrics and gynecology concluded that treatment with sildenafil citrate prolonged pregnancy by an average of 4 days compared with placebo.

Sildenafil citrate, is a specific phosphodiesterase-5 inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP causing vasodilatation. Phosphodiesterase-5 is present in the human feto-placental circulation and sildenafil mediates vasodilatation and improve fetoplacental circulation by the same mechanism of action.[1]

This randomized, double blind placebo controlled trial recruited 100 patients with preeclampsia between 24 and 33 weeks of gestation, into two groups, one received 50 mg oral sildenafil citrate every 8 hours and other was put on placebo.

The patients also received additional antihypertensive treatment in the form of α-methyldopa (500 - 1500 mg/day) along with pindolol (10 - 30 mg/per day) as needed. Those patients who anticipated to go in labor received full corticosteroid coverage within 72 hours.

Patients in the treatment group on an average gained 4 days (14.4 days) as compared to the placebo group (10.4 days). This group also observed an improvement in blood flow in uterine and umbilical arteries (P< .001). and a significant reduction in Maternal Arterial Pressure within 24 hrs of randomization (P < .05).

Patients in placebo group required increased dose of the primary drug or addition of the new drug (P < .001).

Both groups were comparable in terms of perinatal morbidity, mortality, or adverse effects between groups. Each extra day gained between 24 and 32 weeks of gestations helps to improve the infant mortality statistics.

To confirm the benefits to the infant, "studies with a larger number of patients and an earlier start of medication are required," the authors opined.

The lead author Alberto Trapani Jr, MD, PhD, quoted that "Reduction in maternal [mean arterial pressure], without compromising uterine artery blood flow, provides reassurance that sildenafil may be useful as an antihypertensive drug in the context of placental vascular insufficiency."

Preliminary studies have demonstrated use of sildenafil citrate in early onset preeclampsia to improve fetal growth retardation, but more randomized trials and meta-analysis are needed before a recommendation for its use can be made in clinical practice.  [2] A randomized trial in 2009 demonstrated that although sildenafil does not prolong pregnancy but it was well tolerated without any maternal or fetal adverse effects in the escalating dose regimen 20-80 mg tid.[3]

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[1] Maharaj CH, O’Toole D, Lynch T, et al. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reproductive Biology and Endocrinology : RB&E. 2009;7:34. doi:10.1186/1477-7827-7-34.

[2] Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

P. von Dadelszen, S. Dwinnell, L. A. Magee, B. C. Carleton, A. Gruslin, B. Lee, K. I. Lim, R. M. Liston, S. P. Miller, D. Rurak, et al.

BJOG. 2011 April; 118(5): 624–628. doi: 10.1111/j.1471-0528.2010.02879.x

[3] http://www.ncbi.nlm.nih.gov/pubmed/19843000