NITROLINGUAL PUMPSPRAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NITROLINGUAL PUMPSPRAY (NITROLINGUAL PUMPSPRAY).
Nitroglycerin is converted to nitric oxide (NO) in vascular smooth muscle, activating guanylate cyclase and increasing cyclic guanosine monophosphate (cGMP), leading to vasodilation of peripheral arteries and veins. This reduces preload and afterload, decreasing myocardial oxygen demand.
| Metabolism | Metabolized primarily in the liver by the enzyme glutathione nitrate reductase, and also by red blood cells and vascular smooth muscle. Metabolites include 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate, which have minimal vasodilatory activity. |
| Excretion | Renal excretion of inactive metabolites (nitrate ions) accounts for approximately 80% of elimination; biliary/fecal excretion is minimal (less than 5%). |
| Half-life | Terminal elimination half-life of nitroglycerin is 1–4 minutes; however, clinical hemodynamic effects last longer due to active metabolites and tissue distribution. |
| Protein binding | Approximately 60% bound, primarily to albumin. |
| Volume of Distribution | 3.3 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Sublingual spray: approximately 40% (due to first-pass metabolism in liver and gastrointestinal tissues after swallowing). |
| Onset of Action | Sublingual spray: 1–3 minutes for relief of acute angina. |
| Duration of Action | Sublingual spray: 30–60 minutes for hemodynamic effects (e.g., reduction in preload). Tolerance may develop with frequent use. |
1-2 sprays sublingually at onset of angina; may repeat every 5 minutes up to 3 doses in 15 minutes. Prophylaxis: 1 spray 5-10 minutes before activity.
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | Dose reduction may be needed in severe hepatic impairment (Child-Pugh C); start with lowest effective dose. |
| Pediatric use | Safety and efficacy not established; not recommended for use in pediatric patients. |
| Geriatric use | Initiate with lowest effective dose; increased sensitivity to hypotension due to age-related changes in baroreceptor reflexes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NITROLINGUAL PUMPSPRAY (NITROLINGUAL PUMPSPRAY).
| Breastfeeding | No human data on NTG excretion in breast milk. M/P ratio is unknown. Based on molecular weight (227.09 Da) and short half-life (1-3 min), transfer is likely minimal. Use with caution in breastfeeding only if clearly needed; monitor infant for hypotension or methemoglobinemia (rare). |
| Teratogenic Risk | Nitroglycerin (NTG) is classified as FDA Pregnancy Category C. Animal reproduction studies are inadequate. In first trimester, limited human data show no consistent association with major malformations. During second and third trimesters, use is reserved for acute hypertensive crises or pulmonary edema; potential risks include maternal hypotension leading to uteroplacental hypoperfusion and fetal hypoxia. Avoid near term due to risk of maternal hypotension and possible fetal distress. |
■ FDA Black Box Warning
Coadministration with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) is contraindicated due to the risk of severe hypotension, syncope, and myocardial ischemia.
| Serious Effects |
["Hypersensitivity to nitroglycerin or any component of the formulation","Concurrent use with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil)","Severe anemia","Increased intracranial pressure (e.g., head trauma, cerebral hemorrhage)","Constrictive pericarditis or cardiac tamponade"]
| Precautions | ["Hypotension: May cause severe hypotension in patients with hypovolemia or low systolic blood pressure.","Hepatic impairment: Use with caution in patients with severe hepatic disease.","Headache: Common and may be severe; tolerance may develop.","Sublingual administration: Do not inhale; spray onto or under the tongue.","Overuse: Excessive use may result in tolerance and reduced efficacy."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate continuously during administration. Assess for signs of hypotension (systolic BP <90 mmHg, dizziness). Fetal heart rate monitoring is recommended if used for preterm labor or in third trimester. Assess for methemoglobinemia (pulse oximetry, ABG with co-oximetry) with prolonged use or high doses. |
| Fertility Effects | No human data on fertility effects. In animal studies, no evidence of impaired fertility. Nitroglycerin's vasodilatory effects may theoretically affect uterine perfusion, but no adverse reproductive outcomes have been reported. No specific fertility concerns in clinical use. |