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Drug overview for NITROGLYCERIN (nitroglycerin):
Generic name: NITROGLYCERIN
Drug class: Nitrates
Therapeutic class: Cardiovascular Therapy Agents
Nitroglycerin, an organic nitrate, is a vasodilating agent.
No enhanced Uses information available for this drug.
Generic name: NITROGLYCERIN
Drug class: Nitrates
Therapeutic class: Cardiovascular Therapy Agents
Nitroglycerin, an organic nitrate, is a vasodilating agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
NITROGLYCERIN 50 MG/10 ML VIAL
The following indications for NITROGLYCERIN (nitroglycerin) have been approved by the FDA:
Indications:
Induction of intraoperative hypotension
Left ventricular dysfunction following myocardial infarction
Perioperative hypertension
Unstable angina pectoris
Professional Synonyms:
Crescendo angina
Left ventricular dysfunction following acute MI
Left ventricular dysfunction following acute myocardial infarction
Left ventricular dysfunction following AMI
Left ventricular dysfunction following cardiac infarct
Left ventricular dysfunction following cardiac infarction
Left ventricular dysfunction following myocardial infarct
LV dysfunction following MI
Preinfarction syndrome
Unstable angina
Indications:
Induction of intraoperative hypotension
Left ventricular dysfunction following myocardial infarction
Perioperative hypertension
Unstable angina pectoris
Professional Synonyms:
Crescendo angina
Left ventricular dysfunction following acute MI
Left ventricular dysfunction following acute myocardial infarction
Left ventricular dysfunction following AMI
Left ventricular dysfunction following cardiac infarct
Left ventricular dysfunction following cardiac infarction
Left ventricular dysfunction following myocardial infarct
LV dysfunction following MI
Preinfarction syndrome
Unstable angina
The following dosing information is available for NITROGLYCERIN (nitroglycerin):
Dosage of nitroglycerin must be carefully adjusted according to the patient's requirements and response and the smallest effective dosage should be used. When nitroglycerin is administered IV, the type of IV administration set used, polyvinyl chloride (PVC) or non-PVC, must be considered in dosage estimations. It should be noted that dosages commonly used in early published studies were based on the use of PVC administration sets and are too high when non-PVC administration sets are used.
Continuous monitoring of blood pressure and heart rate, as well as other appropriate parameters (e.g., pulmonary capillary wedge pressure), must be performed in all patients. Adequate systemic blood pressure and coronary perfusion pressure must be maintained. Some patients with normal or low left ventricular filling pressures or pulmonary capillary wedge pressure may be extremely sensitive to the effects of IV nitroglycerin and may respond fully to dosages as low as 5 mcg/minute; these patients require particularly careful monitoring and dosage titration.
For the acute relief of angina pectoris, 1 or 2 sprays (0.4 or 0.8 mg, respectively) of nitroglycerin as a lingual solution or aerosol may be administered. If relief is not attained after the initial spray(s), additional single sprays may be given at 5-minute intervals as necessary; no more than 3 sprays should be given in a 15-minute period. If pain persists after a total of 3 doses within a 15-minute period, prompt medical attention is recommended.
Nitroglycerin lingual solution or aerosol also may be used prophylactically 5-10 minutes before situations likely to provoke angina attacks.
For the acute relief of angina pectoris, the manufacturer recommends 0.3-0.6 mg of nitroglycerin as sublingual tablets, placed under the tongue and allowed to dissolve at the first sign of an acute attack.
Most patients respond within 5 minutes of taking 1 or 2 doses. If relief is not attained after a single dose during an acute attack, additional doses may be given at 5-minute intervals. If chest pain persists after a total of 3 doses within a 15-minute period, or if the pain is different from the pain that is typically experienced, patients should be advised to seek prompt medical attention.
For prophylactic management in situations likely to provoke angina attacks, nitroglycerin sublingual tablets may be administered 5-10 minutes prior to engaging in such activities.
When a nitroglycerin transdermal system is used for the long-term prophylactic management of angina pectoris, the usual initial adult dosage is one transdermal dosage system, delivering the smallest available dose of nitroglycerin in its dosage series, applied every 24 hours. To minimize the occurrence of tolerance to the effects of nitroglycerin, a nitrate-free interval of 10-14 hours has been recommended; however, the minimum nitrate-free interval necessary for restoration of full first-dose effects of nitrate therapy has not been determined. Dosage may be adjusted by changing to the next larger dosage system in the series or by a combination of dosage systems in the series.
The transdermal systems shouldnot be used to treat acute attacks of angina.
When nitroglycerin is applied topically as an ointment, a suggested initial dosage is 0.5 inch (as squeezed from the tube) of the 2% ointment (i.e., approximately 7.5 mg) applied twice daily (once upon arising in the morning and repeated 6 hours later). When the dose to be applied is in multiples of whole inches, unit-dose preparations that provide the equivalent of 1 inch of the 2% ointment also may be used.
The initial dose may be doubled (i.e., increased to 1 inch or approximately 15 mg) and subsequently doubled again (i.e., increased to 2 inches or approximately 30 mg) if tolerated in patients failing to respond adequately. Doses used in clinical trials have ranged from 0.5-2 inches (approximately 7.5-30 mg).
Dosage should be titrated upward until angina is effectively controlled or adverse effects preclude further dosage increases.
The amount of nitroglycerin reaching the circulation varies directly with the size of the area of application and the amount of ointment applied. Coverage of an area approximately the size of the applicator (3.5 by 2.25 inches) should be sufficient to obtain the desired clinical effects, however, a larger area may be used. In clinical trials, the ointment generally has been spread over an area of 6 by 6 inches.
As with other nitroglycerin formulations, all regimens of nitroglycerin ointment should include a daily nitrate-free interval to avoid development of tolerance. It is not known whether nitroglycerin ointment is effective in preventing exertional angina for longer than 7 hours after application of a dose.
The onset of action of topical nitroglycerin ointment is not sufficiently rapid to treat acute attacks of angina; therefore, the ointment should not be used for this purpose.
The recommended initial adult IV dosage when non-PVC administration sets are used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and if later necessary, by increments of 20 mcg/minute. When PVC administration sets are used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.
Dosage is then titrated according to the response and tolerance of the patient.
For the treatment of continuing ischemic pain in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS), sublingual nitroglycerin 0.3-0.4 mg every 5 minutes for up to 3 doses is recommended.
Following use of sublingual nitroglycerin, the need for IV nitroglycerin should be assessed, if not contraindicated; experts state that IV nitroglycerin may be useful in patients with heart failure, hypertension, or persistent ischemia not relieved with sublingual nitroglycerin and administration of a beta-blocker.
The recommended initial adult IV dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.
Dosage should be titrated according to the patient's response. Blood pressure and heart rate should be continuously monitored during IV administration.
When IV nitroglycerin is used after acute MI, some experts recommend an initial continuous IV infusion rate of 10 mcg/minute, increasing the dosage as necessary according to hemodynamic and clinical response. Dosage will vary considerably among patients and should be adjusted based on individual requirements, blood pressure response, and adverse effects. The manufacturer states that the usual initial adult dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute; the rate may be increased by 5 mcg/minute every 3-5 minutes until blood pressure response is obtained or the infusion rate is 20 mcg/minute.
If no effect is obtained with 20 mcg/minute, dosage may be further increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute. Dosage should then be titrated according to the patient's response.
Blood pressure and heart rate should be continuously monitored during IV administration.
Continuous IV infusions of nitroglycerin have been given for 12 hours with no attenuation of effect.
When nitroglycerin is used to control perioperative hypertension or for the induction of intraoperative hypotension, the manufacturer recommends an initial adult IV dosage (using a nonadsorptive (e.g., non-PVC) administration set) of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or an infusion rate of 20 mcg/minute is reached. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; an initial infusion rate of 25 mcg/minute or greater has been used in studies employing PVC tubing.
Dosage should be titrated according to the patient's response and possible adverse effects. Blood pressure and heart rate should be continuously monitored during IV administration; in many cases, invasive monitoring of pulmonary capillary wedge pressure is indicated.
When nitroglycerin is used IV in hypertensive emergencies+, some experts recommend an initial adult dosage of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes up to a maximum of 20 mcg/minute. Adults with a hypertensive emergency with a compelling indication (e.g., eclampsia or severe preeclampsia or pheochromocytoma crisis) should have their systolic blood pressure reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes.
The risks of overly aggressive therapy in any hypertensive crisis must always be considered. The initial goal of IV nitroglycerin therapy for a hypertensive emergency in adults without a compelling indication is to reduce systolic blood pressure by no more than 25% within the first hour, followed by further blood pressure reduction if stable to 160/110 or 160/100 mm Hg within the next 2-6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.
Continuous monitoring of blood pressure and heart rate, as well as other appropriate parameters (e.g., pulmonary capillary wedge pressure), must be performed in all patients. Adequate systemic blood pressure and coronary perfusion pressure must be maintained. Some patients with normal or low left ventricular filling pressures or pulmonary capillary wedge pressure may be extremely sensitive to the effects of IV nitroglycerin and may respond fully to dosages as low as 5 mcg/minute; these patients require particularly careful monitoring and dosage titration.
For the acute relief of angina pectoris, 1 or 2 sprays (0.4 or 0.8 mg, respectively) of nitroglycerin as a lingual solution or aerosol may be administered. If relief is not attained after the initial spray(s), additional single sprays may be given at 5-minute intervals as necessary; no more than 3 sprays should be given in a 15-minute period. If pain persists after a total of 3 doses within a 15-minute period, prompt medical attention is recommended.
Nitroglycerin lingual solution or aerosol also may be used prophylactically 5-10 minutes before situations likely to provoke angina attacks.
For the acute relief of angina pectoris, the manufacturer recommends 0.3-0.6 mg of nitroglycerin as sublingual tablets, placed under the tongue and allowed to dissolve at the first sign of an acute attack.
Most patients respond within 5 minutes of taking 1 or 2 doses. If relief is not attained after a single dose during an acute attack, additional doses may be given at 5-minute intervals. If chest pain persists after a total of 3 doses within a 15-minute period, or if the pain is different from the pain that is typically experienced, patients should be advised to seek prompt medical attention.
For prophylactic management in situations likely to provoke angina attacks, nitroglycerin sublingual tablets may be administered 5-10 minutes prior to engaging in such activities.
When a nitroglycerin transdermal system is used for the long-term prophylactic management of angina pectoris, the usual initial adult dosage is one transdermal dosage system, delivering the smallest available dose of nitroglycerin in its dosage series, applied every 24 hours. To minimize the occurrence of tolerance to the effects of nitroglycerin, a nitrate-free interval of 10-14 hours has been recommended; however, the minimum nitrate-free interval necessary for restoration of full first-dose effects of nitrate therapy has not been determined. Dosage may be adjusted by changing to the next larger dosage system in the series or by a combination of dosage systems in the series.
The transdermal systems shouldnot be used to treat acute attacks of angina.
When nitroglycerin is applied topically as an ointment, a suggested initial dosage is 0.5 inch (as squeezed from the tube) of the 2% ointment (i.e., approximately 7.5 mg) applied twice daily (once upon arising in the morning and repeated 6 hours later). When the dose to be applied is in multiples of whole inches, unit-dose preparations that provide the equivalent of 1 inch of the 2% ointment also may be used.
The initial dose may be doubled (i.e., increased to 1 inch or approximately 15 mg) and subsequently doubled again (i.e., increased to 2 inches or approximately 30 mg) if tolerated in patients failing to respond adequately. Doses used in clinical trials have ranged from 0.5-2 inches (approximately 7.5-30 mg).
Dosage should be titrated upward until angina is effectively controlled or adverse effects preclude further dosage increases.
The amount of nitroglycerin reaching the circulation varies directly with the size of the area of application and the amount of ointment applied. Coverage of an area approximately the size of the applicator (3.5 by 2.25 inches) should be sufficient to obtain the desired clinical effects, however, a larger area may be used. In clinical trials, the ointment generally has been spread over an area of 6 by 6 inches.
As with other nitroglycerin formulations, all regimens of nitroglycerin ointment should include a daily nitrate-free interval to avoid development of tolerance. It is not known whether nitroglycerin ointment is effective in preventing exertional angina for longer than 7 hours after application of a dose.
The onset of action of topical nitroglycerin ointment is not sufficiently rapid to treat acute attacks of angina; therefore, the ointment should not be used for this purpose.
The recommended initial adult IV dosage when non-PVC administration sets are used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and if later necessary, by increments of 20 mcg/minute. When PVC administration sets are used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.
Dosage is then titrated according to the response and tolerance of the patient.
For the treatment of continuing ischemic pain in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS), sublingual nitroglycerin 0.3-0.4 mg every 5 minutes for up to 3 doses is recommended.
Following use of sublingual nitroglycerin, the need for IV nitroglycerin should be assessed, if not contraindicated; experts state that IV nitroglycerin may be useful in patients with heart failure, hypertension, or persistent ischemia not relieved with sublingual nitroglycerin and administration of a beta-blocker.
The recommended initial adult IV dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or until the infusion rate is 20 mcg/minute. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute.
Dosage should be titrated according to the patient's response. Blood pressure and heart rate should be continuously monitored during IV administration.
When IV nitroglycerin is used after acute MI, some experts recommend an initial continuous IV infusion rate of 10 mcg/minute, increasing the dosage as necessary according to hemodynamic and clinical response. Dosage will vary considerably among patients and should be adjusted based on individual requirements, blood pressure response, and adverse effects. The manufacturer states that the usual initial adult dosage of nitroglycerin when a nonadsorptive (e.g., non-PVC) administration set is used is 5 mcg/minute; the rate may be increased by 5 mcg/minute every 3-5 minutes until blood pressure response is obtained or the infusion rate is 20 mcg/minute.
If no effect is obtained with 20 mcg/minute, dosage may be further increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; the usual initial adult dosage when these sets are used is 25 mcg/minute. Dosage should then be titrated according to the patient's response.
Blood pressure and heart rate should be continuously monitored during IV administration.
Continuous IV infusions of nitroglycerin have been given for 12 hours with no attenuation of effect.
When nitroglycerin is used to control perioperative hypertension or for the induction of intraoperative hypotension, the manufacturer recommends an initial adult IV dosage (using a nonadsorptive (e.g., non-PVC) administration set) of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes until a blood pressure response is obtained or an infusion rate of 20 mcg/minute is reached. If no effect is obtained with 20 mcg/minute, dosage may be increased by increments of 10 mcg/minute and, if necessary, by increments of 20 mcg/minute. When a PVC administration set is used, higher dosages generally are required; an initial infusion rate of 25 mcg/minute or greater has been used in studies employing PVC tubing.
Dosage should be titrated according to the patient's response and possible adverse effects. Blood pressure and heart rate should be continuously monitored during IV administration; in many cases, invasive monitoring of pulmonary capillary wedge pressure is indicated.
When nitroglycerin is used IV in hypertensive emergencies+, some experts recommend an initial adult dosage of 5 mcg/minute, with increases of 5 mcg/minute every 3-5 minutes up to a maximum of 20 mcg/minute. Adults with a hypertensive emergency with a compelling indication (e.g., eclampsia or severe preeclampsia or pheochromocytoma crisis) should have their systolic blood pressure reduced to less than 140 mm Hg during the first hour and, in patients with acute aortic dissection, to less than 120 mm Hg within the first 20 minutes.
The risks of overly aggressive therapy in any hypertensive crisis must always be considered. The initial goal of IV nitroglycerin therapy for a hypertensive emergency in adults without a compelling indication is to reduce systolic blood pressure by no more than 25% within the first hour, followed by further blood pressure reduction if stable to 160/110 or 160/100 mm Hg within the next 2-6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.
Nitroglycerin is administered lingually, sublingually, topically, or by IV infusion.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| NITROGLYCERIN 50 MG/10 ML VIAL | Maintenance | Adults infuse 5 mcg/minute by continuous infusion route ; titrate to effect by 5 mcg/min every 3-5min up to 20 mcg/min then titrate by 10-20mcg/min |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| NITROGLYCERIN 50 MG/10 ML VIAL | Maintenance | Adults infuse 5 mcg/minute by continuous infusion route ; titrate to effect by 5 mcg/min every 3-5min up to 20 mcg/min then titrate by 10-20mcg/min |
The following drug interaction information is available for NITROGLYCERIN (nitroglycerin):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| CGMP Specific PDE Type-5 Inhibitors/Nitrates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nitrates activate guanyl cyclase, an enzyme that increases levels of cyclic guanosine monophosphate (cGMP). cGMP produces smooth muscle relaxation. Avanafil,(1) sildenafil,(2) tadalafil,(3,4) and vardenafil (5-7) inhibit phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP. Concurrent use of nitrates with avanafil,(1) sildenafil,(2) tadalafil,(3,4) or vardenafil(5-7) results in potentiation of the effect of nitrates. CLINICAL EFFECTS: The concurrent use of CGMP specific PDE type-5 inhibitors and nitrates potentiates the hypotensive effects of nitrates(1-7) which may result in dizziness, syncope, heart attack, or stroke.(4) The concurrent use of sildenafil and sodium nitroprusside may potentiate the antiaggregatory effect of sodium nitroprusside in addition to increased hypotensive effects.(2) PREDISPOSING FACTORS: Plasma levels of the PDE type-5 inhibitor may be higher in the following patients: those older than 65, with hepatic impairment, with severe renal impairment, or using concomitant CYP3A4 inhibitors. This may increase the severity of the interaction. PATIENT MANAGEMENT: The administration of avanafil to patients receiving organic nitrates, either regularly and/or intermittently, is contraindicated. In a patient who has taken avanafil, at least 12 hours should elapse after the last dose of avanafil before nitrate administration is considered and it should only be administered under close medical supervision with appropriate hemodynamic monitoring.(1) The administration of sildenafil to patients receiving organic nitrates, either regularly and/or intermittently, in any form is contraindicated.(2) The administration of tadalafil to patients receiving any form of organic nitrate, either regularly and/or intermittently, is contraindicated.(3,4) Patients should be instructed to seek immediate medical attention if they experience anginal chest pain following tadalafil. In such cases where nitrate administration is considered medically necessary, at least 48 hours should elapse after tadalafil administration before nitrate administration is considered. In such cases, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring.(4) The administration of vardenafil to patients receiving nitrates or nitric oxide donors is contraindicated.(5-7) In patients prescribed vardenafil in whom nitrate administration is deemed medically necessary in a life-threatening situation, the Canadian manufacturer of vardenafil states that at least 24 hours should have elapsed after the last dose of vardenafil before the nitrate administration is considered. Nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring.(7) The concomitant use of nicorandil(8) or subinguinal nitroglycerin(9) and PDE type-5 inhibitors is contraindicated. Treat hypotension resulting from concurrent use as a nitrate overdose, with elevation of the extremities and central volume expansion.(10) DISCUSSION: Nitrates activate guanylate cyclase, an enzyme that increases levels of cGMP. cGMP produces smooth muscle relaxation. Avanafil,(1) sildenafil,(2) tadalafil,(3,4) and vardenafil (5-7) inhibit PDE5, which is responsible for the breakdown of cGMP. Concurrent use of nitrates with avanafil,(1) sildenafil,(2) tadalafil,(3,4) or vardenafil(5-7) results in potentiation of the effect of nitrates. It is unknown when nitrates, if necessary, can be safely administered to patients who have taken CGMP specific PDE type-5 inhibitors. Following a single 100 mg oral dose of sildenafil, peak plasma levels are approximately 440 ng/mL and levels 24 hours post dose are approximately 2 ng/ml. Sildenafil plasma levels at 24 hours post dose are three to eight times higher in the following patients: those age greater than 65, those with hepatic impairment, those with severe renal impairment (creatinine clearance less than 30 ml/min), and those with concomitant use of potent CYP P-450-3A4 inhibitors (erythromycin). Although plasma levels of sildenafil are lower at 24 hours post dose, the manufacturer of sildenafil states that it is still unknown whether nitrates can safely be coadministered at that time.(2) In vitro studies with human platelets have shown that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside.(2) In a study of 150 subjects who received tadalafil (20 mg) daily for 7 days, sublingual nitroglycerin was administered at 2, 4, 8, 24, 48, 72, and 96 hours after tadalafil. A significant interaction between tadalafil and nitroglycerin was observed up to and including 24 hours post-tadalafil. At 48 hours, the interaction was not observed by most hemodynamic measures. After 48 hours, the interaction was not detectable.(4) In a population-based cohort study of 61,487 men who received nitrates, 5,710 (9%) concurrently received PDE Type-5 inhibitors (PDE5i). Crude hazard ratios found a significant and inverse association between combination use of nitrates and PDE5i and all cause, cardiovascular, and non-cardiovascular mortality. All-cause mortality incidence rates were 2.69 cases per 100 person-years for the nitrate and PDE5i group vs 3.83 cases per 100 person-years in the nitrate-only group. Concurrent use of nitrates and PDE5i found a multivariate adjusted HR for all-cause mortality of 1.39 (95% CI: 1.28-1.51). Concurrent use of nitrates and PDE5i found an adjusted HR for cardiovascular death, non-cardiovascular death, myocardial infarction, heart failure, revascularization, and major adverse cardiovascular event (MACE) in patients treated with both nitrates and PDE5i was 1.34 (95% CI: 1.11-1.62), 1.40 (95% CI: 1.27-1.54), 1.72 (95% CI: 1.55-1.90), 1.67 (95% CI: 1.48-1.90), 1.95 (95% CI: 1.78-2.13), and 1.70 (95% CI: 1.58-1.83), respectively, compared with patients with nitrates only.(11) |
ADCIRCA, ALYQ, AVANAFIL, CIALIS, ENTADFI, OPSYNVI, REVATIO, SILDENAFIL CITRATE, STENDRA, TADALAFIL, TADLIQ, VARDENAFIL HCL, VIAGRA |
| Riociguat/Nitrates & Nitric Oxide Donors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nitrates activate guanyl cyclase, an enzyme that increases levels of cyclic guanosine monophosphate (cGMP), which produces smooth muscle relaxation. Riociguat stimulates the nitric oxide-soluble guanylate cyclase-cGMP pathway and also increases cGMP. Concurrent use of nitrates with riociguat results in potentiation of the effect of both agents.(1) CLINICAL EFFECTS: The concurrent use riociguat and nitrates potentiates the hypotensive effects of both agents, which may result in dizziness, syncope, heart attack, or stroke.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The administration of riociguat to patients receiving nitrates, or nitric oxide donors, in any form is contraindicated.(1) DISCUSSION: Riociguat (2.5 mg) potentiated the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) when taken 4 hour and 8 hours after riociguat. Syncope was reported in some patients.(1) |
ADEMPAS |
There are 2 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Ergot Alkaloids/Nitrates SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Decreased first-pass metabolism of ergot alkaloids. Ergot alkaloids may precipitate angina pectoris. CLINICAL EFFECTS: Increased standing systolic blood pressure and angina attacks may occur. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid administration of ergot alkaloids to patients receiving nitroglycerin for angina. When it is necessary to give this combination, monitor the patient for increased effects of the ergot alkaloid. Reduce the dose of ergot alkaloid as necessary. DISCUSSION: Dihydroergotamine has been reported to precipitate angina pectoris. Nitroglycerin administration to patients receiving dihydroergotamine increased the plasma dihydroergotamine level and area under the plasma concentration-time curve. An increase in the mean standing systolic blood pressure was measured. |
DIHYDROERGOTAMINE MESYLATE, ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT, MIGRANAL, TRUDHESA |
| Alteplase/Nitroglycerin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Nitroglycerin may increase hepatic blood flow, enhancing the hepatic metabolism of alteplase (t-PA). CLINICAL EFFECTS: The thrombolytic effect of alteplase may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid coadministration of alteplase and nitroglycerin. If both drugs must be given concomitantly use caution when administering these agents. Be aware that the therapeutic effects of alteplase may be impaired. DISCUSSION: In a study, nitroglycerin administration decreased plasma levels of alteplase reducing the thrombolytic effects. In a non-randomized study involving patients with suspected infarction, stable coronary artery reperfusion occurred in 91% of the patients receiving alteplase plus saline solution compared to 44% receiving alteplase plus intravenous nitroglycerin. Patients receiving alteplase and nitroglycerin concomitantly had lower mean plasma t-PA antigen concentrations than patients receiving alteplase alone. The differences persisted for more than 6 hours after completing the alteplase infusion.(1) In an earlier subset of the above study, patients with acute myocardial infarctions who received alteplase alone demonstrated an earlier peak serum creatine kinase and showed signs of reperfusion more frequently and sooner than did patients receiving alteplase plus nitroglycerin. In addition, patients receiving alteplase and nitroglycerin had a greater incidence of in-hospital adverse events and a higher incidence of reocclusion.(2) |
ACTIVASE, CATHFLO ACTIVASE |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Apomorphine/Selected Antihypertensives and Vasodilators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1) CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1) PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1) PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1) DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1) |
APOKYN, APOMORPHINE HCL, ONAPGO |
The following contraindication information is available for NITROGLYCERIN (nitroglycerin):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 4 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Constrictive pericarditis |
| Intracranial hypertension |
| Pericardial tamponade |
| Restrictive cardiomyopathy |
There are 5 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Hypotension |
| Intracerebral hemorrhage |
| Methemoglobinemia |
| Severe anemia |
| Severe hypoxemia |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Hypertrophic cardiomyopathy |
The following adverse reaction information is available for NITROGLYCERIN (nitroglycerin):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 10 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Syncope |
None. |
| Rare/Very Rare |
|---|
|
Allergic dermatitis Anaphylaxis Blurred vision Exfoliative dermatitis Hypoxia Methemoglobinemia Severe headache disorder Stevens-johnson syndrome Xerostomia |
There are 20 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Dizziness Flushing Headache disorder Hypotension Nervousness Orthostatic hypotension Paresthesia |
Nausea Palpitations Tachycardia Vomiting |
| Rare/Very Rare |
|---|
|
Accidental fall Drowsy Dyspnea Fatigue General weakness Hyperhidrosis Pallor Skin rash Vertigo |
The following precautions are available for NITROGLYCERIN (nitroglycerin):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
No enhanced Pregnancy information available for this drug.
No enhanced Lactation information available for this drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for NITROGLYCERIN (nitroglycerin):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for NITROGLYCERIN (nitroglycerin)'s list of indications:
| Induction of intraoperative hypotension | |
| I95.89 | Other hypotension |
| Left ventricular dysfunction following MI | |
| I23.8 | Other current complications following acute myocardial infarction |
| I50.1 | Left ventricular failure, unspecified |
| Perioperative hypertension | |
| I97.3 | Postprocedural hypertension |
| Unstable angina pectoris | |
| I20.0 | Unstable angina |
| I20.2 | Refractory angina pectoris |
| I25.110 | Atherosclerotic heart disease of native coronary artery with unstable angina pectoris |
| I25.112 | Atherosclerotic heart disease of native coronary artery with refractory angina pectoris |
| I25.700 | Atherosclerosis of coronary artery bypass graft(s), unspecified, with unstable angina pectoris |
| I25.702 | Atherosclerosis of coronary artery bypass graft(s), unspecified, with refractory angina pectoris |
| I25.710 | Atherosclerosis of autologous vein coronary artery bypass graft(s) with unstable angina pectoris |
| I25.712 | Atherosclerosis of autologous vein coronary artery bypass graft(s) with refractory angina pectoris |
| I25.720 | Atherosclerosis of autologous artery coronary artery bypass graft(s) with unstable angina pectoris |
| I25.722 | Atherosclerosis of autologous artery coronary artery bypass graft(s) with refractory angina pectoris |
| I25.730 | Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with unstable angina pectoris |
| I25.732 | Atherosclerosis of nonautologous biological coronary artery bypass graft(s) with refractory angina pectoris |
| I25.750 | Atherosclerosis of native coronary artery of transplanted heart with unstable angina |
| I25.752 | Atherosclerosis of native coronary artery of transplanted heart with refractory angina pectoris |
| I25.760 | Atherosclerosis of bypass graft of coronary artery of transplanted heart with unstable angina |
| I25.762 | Atherosclerosis of bypass graft of coronary artery of transplanted heart with refractory angina pectoris |
| I25.790 | Atherosclerosis of other coronary artery bypass graft(s) with unstable angina pectoris |
| I25.792 | Atherosclerosis of other coronary artery bypass graft(s) with refractory angina pectoris |
Formulary Reference Tool