Sublingual nitroglycerin is a fast-acting vasodilator used to relieve an angina attack (chest pain due to reduced oxygen supply to the heart). The tablet is placed under the tongue, where it is absorbed within minutes: the effect starts within 1 to 3 minutes and lasts about 25 minutes. It must not be used with erectile dysfunction medicines (sildenafil, tadalafil, vardenafil).
Never take tadalafil with nitrates (such as nitroglycerin). The combination can cause a sudden, dangerous drop in blood pressure, with a risk of fainting or heart attack.
Tadalafil potentiates the hypotensive effect of nitrates: both act on the nitric oxide/cGMP pathway, and their combined action causes marked arterial and venous vasodilation with a pronounced and potentially severe fall in blood pressure (symptomatic hypotension, syncope and, in extreme cases, ischaemic events). The contraindication is absolute with any nitrate form, including intermittent use for angina. Because tadalafil has a long half-life (about 17.5 h; effect up to 36 h), the safety window before giving a nitrate is longer than with sildenafil — no safe interval is documented, so the combination should simply be avoided. If chest pain occurs, the patient should seek immediate medical help and report tadalafil use.
PDE5 + nitrate: absolute contraindication. Both raise cGMP in vascular smooth muscle — additive vasodilation with potentially fatal profound hypotension. Do not co-administer; respect the 48–72 h window (long tadalafil half-life).
Both raise cGMP in vascular smooth muscle, causing additive vasodilation and profound hypotension.
Blood pressure and hypotension symptoms; haemodynamic status if chest pain occurs.
Syncope, severe dizziness, marked hypotension, chest pain — seek immediate care.
Absolute contraindication. Do not start tadalafil in patients taking nitrates; if a nitrate becomes necessary for angina, do so only after a prolonged interval and in a monitored setting.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16884667/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Never take vardenafil with nitrates (such as nitroglycerin). The combination can cause a sudden, dangerous drop in blood pressure, with a risk of fainting or heart attack.
Vardenafil potentiates the vasodilator action of nitrates through the same nitric oxide/cGMP pathway. The combination, with any nitrate form (including intermittent use for angina or NO donors), causes additive vasodilation with profound hypotension, syncope and a risk of ischaemic events. It is absolutely contraindicated. If a nitrate becomes clinically essential, wait at least 24 hours after the last vardenafil dose; patients with chest pain should seek immediate medical care.
PDE5 + nitrate: absolute contraindication. Additive GMPc-mediated vasodilation with potentially fatal profound hypotension; 24 h safety window after the last vardenafil dose.
Additive GMPc-mediated vasodilation (nitrate + PDE5), with a marked fall in blood pressure.
Blood pressure and hypotension symptoms.
Syncope, severe dizziness, marked hypotension, chest pain — seek immediate care.
Absolute contraindication; do not start vardenafil in patients on nitrates. If needed, at least 24 h after the last dose, in a monitored setting.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16884667/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Potentially fatal severe hypotension. Never combine PDE-5 inhibitors with nitrates.
Sildenafil inhibits PDE5 and markedly potentiates the vasodilating and hypotensive effect of nitrates (nitric oxide donors): the combination can cause severe hypotension, syncope, myocardial infarction and death. The approved sildenafil label formally contraindicates use with nitrates, in any form (sublingual, oral, topical, transdermal) and at any time. If the patient took sildenafil, at least 24 hours should elapse before giving a nitrate (48 hours for tadalafil, which has a longer half-life); in the event of angina after sildenafil, the emergency department should be contacted immediately.
Absolute contraindication: nitrates + PDE5 inhibitors cause severe, potentially fatal hypotension. Do not combine; after sildenafil, do not give nitrates within the following 24 hours.
Both raise cGMP — extreme vasodilation and marked blood pressure drop.
Immediate BP monitoring; seek emergency care on syncope or chest pain.
Syncope, severe dizziness, chest pain, tachycardia.
Absolute contraindication. If the patient took Sildenafil, wait at least 24 hours before any nitrate.
DailyMed/FDA (NIH/NLM) — approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b ; approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Alcohol potentiates the vasodilating effect of nitroglycerin, with a risk of severe hypotension and syncope.
Avoid alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Sublingual nitroglycerin has no relevant food interaction; alcohol is the main interaction to avoid.
Use as needed, with no relation to meals.
DailyMed/FDA (NIH/NLM) — approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Nitroglycerin-induced vasodilation can worsen outflow tract obstruction in hypertrophic obstructive cardiomyopathy.
Use with caution and monitor symptoms in this population.
DailyMed/FDA (NIH/NLM) — approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Nitroglycerin is a potent vasodilator and can worsen pre-existing hypotension.
Avoid in uncontrolled hypotension and monitor blood pressure during use.
DailyMed/FDA (NIH/NLM) — approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Data on nitroglycerin in pregnancy are limited; use only if the benefit outweighs the risk (e.g., hypertensive emergency).
Use only when strictly indicated.
Insufficient data on breast milk excretion; use with caution.
No specific contraception required.
DailyMed/FDA (NIH/NLM) — approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
The principal action is relaxation of vascular smooth muscle: dilation of large veins (peripheral pooling, reduced preload) and, dose-dependently, of arteries (reduced afterload), plus dilation of the large epicardial coronary arteries. It lowers systolic, diastolic and mean arterial pressure; heart rate rises slightly as a compensatory response. The vasodilatory effect begins 1-3 minutes after sublingual dosing, peaks at 5 minutes and lasts at least 25 minutes. Myocardial oxygen demand decreases and the supply/demand ratio improves.
Nitroglycerin generates nitric oxide (NO), which activates guanylate cyclase and raises cyclic GMP in smooth muscle and other tissues; this leads to dephosphorylation of myosin light chains (which regulate smooth muscle contraction) and vasodilation.
Rapid absorption after sublingual administration: mean peak plasma concentrations occur about 6-7 minutes after dosing. Absolute bioavailability is approximately 40%, but is variable due to factors such as sublingual hydration and mucosal metabolism.
A liver reductase is the main pathway of metabolism to glycerol di- and mononitrate metabolites and ultimately glycerol and organic nitrate; there is also extrahepatic metabolism in red blood cells and vascular walls. The 1,2- and 1,3-dinitroglycerin metabolites have half-lives of 36 and 32 minutes and about 2% and 10% of nitroglycerin activity; the mononitrates are inactive.
Very short elimination half-life — on average 2 to 3 minutes (range 1.5-7.5 minutes). Clearance (about 13.6 L/min) greatly exceeds hepatic blood flow; elimination is essentially by metabolism.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
