Nitrates

Drug interaction

Nitrates

Interacting drug Pharmacodynamic interactionPharmacokinetic interaction Clinical implicaciones
Acetylcysteine Potentiates GTN-induced coronary vasodilation and may reverse nitrate tolerance No special precautions
Alcohol Additive hypotensive effects Higher risk of postural hypotension, dizziness and syncope. The dose of nitrates should be up-titrated gradually.
Alteplase (t-PA)I.V. GTN decreases the thrombolytic effect of alteplase in patients with acute MIGTN decreases the bioavalilability of t-PACaution should be observed in patients receiving GTN during alteplase therapy.
Anticholinergic drugs:
- Disopyramide
- Tricyclic antidepressants (amitriptyline, desipramine, doxepin, others)
They cause dry mouth and diminished salivary secretions and reduce the effects of sublingual GTN.Reduce the absorption of GTN tabletsIncrease salivation with chewing gum or artificial saliva products. Use transdermal formulations of GTN
Antihypertensives: ACE inhibitors/ARBs β-blockersAdditive hypotensive effectsHigher risk of postural hypotension, dizziness and syncope. The dose of nitrates should be up-titrated gradually.
Calcium antagonists
Diuretics
ApomorphineAdditive hypotensive effectsHigher risk of postural hypotension, dizziness and syncope. The dose of nitrates should be up-titrated gradually.
AspirinAspirin reduces the headaches produced by nitrates. The vasodilatory and hemodynamic effects of GTN may be enhanced by aspirinReduces the hepatic metabolism and increases GTN plasma levelsThe dose of GTN should be reduced. Monitor the vasodilator response to GTN. A confusing interaction with other NSAIDs
β-blockersDecrease myocardial O2 demands, increase subendocardial coronary blood flow and suppress the tachycardia induced by nitratesThe combination increase the antianginal effects of each agent
Calcium antagonistsDecrease myocardial O2 demands and increase coronary blood flowThe combination increase the antianginal effects of each agent
Ergot alkaloids (ergonovin, ergotamine, dihydroergotamine)They produce coronary vasospasm and can precipitate angina pectorisGTN markedly decreases the first-pass metabolism of dihydroergotamine and increases its oral bioavailabilityAvoid the combination of GTN with ergotamine and related drugs
HeparinI.V. GTN can reduce the anticoagulant effect of heparinThe heparin dosage must be adjusted and the activated partial thromboplastin time (APTT) should be monitored when GTN is added or discontinued. After discontinuation of GTN, it can be necessary to reduce the heparin dose
Morphine-like analgesics.GTN may slow their metabolismMonitor the clinical response
Neuroleptics (phenothiazines)Additive hypotensive effects Higher risk of postural hypotension, dizziness and syncope. The dose of nitrates should be up-titrated gradually.
Phosphodiesterase type 5 inhibitors:
- Sildenafil
- Taladafil
- Vardenafil
They potentiate the hypotensive effects of organic nitrates. Increased risk of life-threatening hypotension and myocardial ischemiaThe combination is contraindicated. They should not be given concurrently (within 24 hours for sildenafil and vardenafil, 48 hours for taladafil) with nitrates. In emergency situations α-adrenergic agonists (norepinephrine) may be needed. In patients with prostatism taking tamsulosin nitrates can be prescribed
Tricyclic antidepressants Additive hypotensive effectsHigher risk of postural hypotension, dizziness and syncope. The dose of nitrates should be up-titrated gradually.

Cautions

  • GTN activity decay when tablets are exposed to air and opened containers should be discarded within 3 months; keep GTN in airtight containers
  • Patients should be carefully instructed about how to use short-acting sublingal GTN for acute relief of symptom
  • In patients previously treated with organic nitrates, a higher dose of GTN may be necessary to achieve the desired hemodynamic effect.
  • Symptoms and hemodynamics should be monitored frequently during the administration of IV nitrates
  • Hypotension associated with GTN overdose is due to venodilatation and hypovolemia; thus, therapy should be directed to increase central fluid volume.

Abbreviations

ACEI: angiotensin-converting enzyme inhibitors
ARBs: angiotensin receptor blockers
GTN: nitroglycerin
I.V.: intravenous
MI: myocardial infarction
NSAIDs: nonsteroidal anti-inflammatory drugs

 

Disclaimer: The information contained in these tables is intended for use by medical professionals and is for informational purposes only. The tables do not cover all possible drug interactions. As a medical professional you retain full responsibility and should use your own clinical judgement and expertise. Although we attempt to provide accurate and up-to-date information, no guarantee is made to that effect.