Is Nitrocontin (nitroglycerin) safe to use during pregnancy?

Nitroglycerin (Nitrocontin) Safety in Pregnancy

Nitroglycerin is safe to use during pregnancy for specific acute obstetric indications, particularly severe hypertension with pulmonary edema and uterine relaxation emergencies, though it should not be used for routine labor management or retained placenta. 1, 2

FDA Pregnancy Classification and Safety Data

• Nitroglycerin is classified as Pregnancy Category B, indicating that animal reproduction studies showed no toxic effects on dams or fetuses at doses up to 80 mg/kg/day in rats and 240 mg/kg/day in rabbits, though adequate human studies are lacking 2
• The FDA label states nitroglycerin should be given to pregnant women "only if clearly needed," reflecting the limited but reassuring human data 2
• Animal teratology studies with topically applied nitroglycerin ointment revealed no teratogenic effects 2

Approved Clinical Indications During Pregnancy

Severe Hypertension with Pulmonary Edema

• Intravenous nitroglycerin is specifically recommended for severe pregnancy-induced hypertension complicated by pulmonary edema 1
• This represents a first-line indication where maternal benefits clearly outweigh potential risks 1

Uterine Relaxation for Obstetric Emergencies

• Nitroglycerin may be used as an alternative to terbutaline or general anesthesia with halogenated agents for uterine relaxation during removal of retained placental tissue 1
• The American Society of Anesthesiologists recommends incremental IV doses of 50-100 mcg boluses or sublingual administration to achieve uterine relaxation while minimizing hypotension 3
• Nitroglycerin is effective for uterine relaxation during obstetric emergencies like uterine inversion 3

Alternative to ACE Inhibitors in Peripartum Cardiomyopathy

• For pregnant women with peripartum cardiomyopathy, hydralazine with or without IV nitroglycerin or long-acting nitrates can be used as an alternative to ACE inhibitors/ARBs, which are contraindicated 1

Situations Where Nitroglycerin Should NOT Be Used

Routine Labor Management

• Sublingual nitroglycerin (even at 3 doses of 800 mcg each) does not reduce uterine activity or tone during active labor and should not be used for this purpose 4
• Research demonstrates no effect on intrauterine pressure, cervical dilation, or basal uterine tone despite lowering maternal blood pressure 4

Retained Placenta

• A large UK randomized controlled trial (N=1,107) found nitroglycerin neither clinically effective nor cost-effective for retained placenta 5
• There was no difference in need for manual removal of placenta (93.3% nitroglycerin vs 92.0% placebo, p=0.393) 5
• The trial concluded nitroglycerin should not be used for this indication due to lack of efficacy and increased side effects 5

Hemodynamic Effects and Monitoring Requirements

Maternal Effects

• Nitroglycerin causes significant decreases in maternal mean arterial pressure (from 122±8 to 117±7 mm Hg in preeclampsia studies) 6
• Hypotension occurs in approximately 25% of patients receiving IV nitroglycerin for uterine relaxation, with mean nadir of 93 mm Hg 7
• Systolic blood pressure should not drop below 90 mmHg, and hypotension is rapidly reversed with small doses of ephedrine (4.5-6 mg) 3, 7
• Maternal heart rate increases significantly with nitroglycerin administration 8

Fetal-Placental Effects

• Transdermal nitroglycerin (10 mg/24 hours) reduces uterine artery pulsatility and resistance indices by 17-18% in preeclamptic pregnancies, suggesting improved uteroplacental blood flow 6
• Nitroglycerin does not adversely affect umbilical or fetal middle cerebral artery blood flow 6
• Animal studies show no adverse effects on fetal carotid blood flow, cerebral substrate metabolism, or fetal heart rate 8
• Fetal heart rate remains unaffected by maternal nitroglycerin administration in human studies 4

Dosing Protocols for Approved Indications

Severe Hypertension with Pulmonary Edema

• Use intravenous nitroglycerin with continuous hemodynamic monitoring 1
• Specific dosing should follow standard acute hypertensive emergency protocols 1

Uterine Relaxation Emergencies

• Initial dose: 50-100 mcg IV bolus or sublingual nitroglycerin 3
• Administer incrementally to minimize hypotension while achieving adequate uterine relaxation 3
• Sublingual route can be considered when IV access is not immediately available 3
• Hemodynamic status must be assessed before administration, particularly in patients with significant blood loss 3

Peripartum Cardiomyopathy

• Use in combination with hydralazine as alternative to ACE inhibitors during pregnancy 1
• Can use IV nitroglycerin or long-acting nitrates depending on clinical scenario 1

Critical Contraindications and Drug Interactions

• Absolute contraindication: Recent phosphodiesterase-5 inhibitor use (sildenafil within 24 hours, tadalafil within 48 hours) due to risk of profound hypotension 3, 2
• Nitroglycerin reduces the anticoagulant effect of heparin; monitor aPTT in patients receiving concurrent heparin 2
• Avoid concurrent use with ergotamine, which can precipitate angina 2
• Tricyclic antidepressants and anticholinergics may impair sublingual dissolution 2

Common Side Effects

• Palpitations occur more frequently with nitroglycerin (9.8% vs 4.0% placebo, OR 2.60, p=0.003) 5
• Headache may occur but is less concerning in emergency settings 3
• Maternal hypotension is the most clinically significant side effect requiring monitoring 3, 7

Lactation Considerations

• It is unknown whether nitroglycerin is excreted in human breast milk 2
• The FDA recommends caution when administering nitroglycerin to nursing women 2
• Given the short half-life and acute use scenarios, breastfeeding concerns are minimal for emergency indications 2

Key Clinical Pitfalls to Avoid

• Do not use nitroglycerin for routine labor management or to reduce uterine contractility during active labor—it is ineffective for this purpose 4
• Do not use nitroglycerin for medical management of retained placenta—high-quality RCT evidence shows no benefit 5
• Always assess hemodynamic status before administration, especially in patients with hemorrhage or hypovolemia 3
• Have ephedrine readily available to treat hypotension 7
• Monitor blood pressure continuously during administration 3
• Screen for recent PDE-5 inhibitor use before administration 3, 2