Isosorbide-5-mononitrate, the long-acting metabolite of isosorbide dinitrate, is a vasodilatory agent used for the prophylactic management of angina pectoris. Isosorbide mononitrate is not subject to first-pass metabolism and therefore has improved bioavailability and a significantly longer half-life than isosorbide dinitrate. Isosorbide mononitrate (Ismo(TM)) was approved by the FDA in December 1991. Monoket(R), a second immediate-release isosorbide mononitrate product, was granted FDA approval in June 1993. An extended-release formulation (Imdur(R)) was approved by the FDA in August 1993.
General Administration Information
NOTE: Isosorbide mononitrate should not be used to abort acute anginal attacks. The interdosing ('nitrate-free') interval sufficient to avoid tolerance to isosorbide mononitrate has not been completely defined. For immediate-release products (e.g., Ismo, Monoket), a twice daily dosage regimen with the two doses given 7 hours apart has been shown to avoid development of tolerance.
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-All dosage forms: Food may decrease the rate but not the extent of isosorbide dinitrate absorption. Administer with at least 4 ounces (120 mL) of fluid.
-Extended-release tablets: Swallow intact; do not crush or chew.
Allergic reactions (2% with immediate-release tablets) and hypersensitivity reactions have been reported with isosorbide mononitrate, but associated signs and symptoms are not specified in the manufacturer labeling.
A persistent, throbbing headache, which appears to be dose-related, can occur following isosorbide mononitrate administration. Although nitrate-induced headaches usually diminish quickly, and subside with continued treatment, acetaminophen or other analgesic agents may be given to alleviate the pain. Severe or prolonged headaches are rare but warrant prompt medical attention. In placebo controlled trials, headache was reported in 13-35% of patients receiving immediate release tablets and 38-57% of patients receiving extended release tablets.
In clinical trials with isosorbide mononitrate, dizziness was reported more frequently with the extended release tablets (8-11%) than with the immediate release tablets (4%). Fatigue was reported in 1-4% of patients with the immediate release tablets and in <= 5% with the extended release. Emotional lability was reported with the immediate release tablets (2% vs 0% placebo). Nervous system and psychological-related adverse reactions that were reported with both the extended release tablets (<= 5%) and the immediate release tablets (< 1%) include: anxiety, depression, impaired concentration, insomnia, nervousness, paresthesias, tremor, and vertigo. Confusion, libido decrease, impotence (erectile dysfunction), paroniria, hypoesthesia, malaise, migraine, neuritis, paresis, and ptosis were reported in <= 5% of patients receiving extended release tablets. Nightmares and restlessness were reported in < 1% of patients receiving immediate release tablets.
Cardiovascular and vascular adverse reactions have been reported with isosorbide mononitrate use. Cardiovascular disorder (unspecified, 2% with immediate-release tablets), chest pain (unspecified) (<= 2% immediate-release, <= 5% extended-release), and flushing (2% immediate-release, <= 5% extended-release) were reported in clinical trials. Reactions that were reported with both the extended release (<= 5%) and the immediate release (< 1%) tablets include: myocardial infarction, arrhythmia exacerbation, atrial arrhythmias, bradycardia, edema, hypertension, hypotension, palpitations, sinus tachycardia, and ventricular tachycardia. Heart failure, hot flashes, atrial fibrillation, bundle-branch block, extrasystole, aggravation of angina, heart murmur, abnormal heart sound, Q wave abnormality, intermittent claudication, leg ulcer, varicose vein, and syncope were reported in <= 5% of patients receiving extended release tablets. Apoplexy and pallor were reported in < 1% of patients receiving immediate release tablets. Orthostatic hypotension can occur following administration of nitrates and may be accompanied by paradoxical bradycardia and increased angina pectoris. Patients should be sitting or lying down during and immediately after nitrate therapy.
Gastrointestinal adverse reactions have been reported with isosorbide mononitrate. Nausea (3% with immediate-release tablets; <= 5% extended-release tablets), abdominal pain (2% immediate-release, <= 5% extended-release), and diarrhea (2% immediate-release, <= 5% extended-release) were reported in clinical trials. Dyspepsia, vomiting, and xerostomia were reported with both the extended release (<= 5%) and the immediate release (< 1%) tablets. Constipation, flatulence, gastric ulcer (including hemorrhagic gastric ulcer), gastritis, glossitis, hemorrhoids, loose stools, and melena were reported in <= 5% of patients receiving extended release tablets. Anorexia, thirst, weight loss, and dysgeusia (bitter taste) were reported in < 1% of patients receiving immediate release tablets.
Methemoglobinemia is a rare adverse reaction with nitrate products. Symptoms of methemoglobinemia include cyanosis (blue discoloration of the lips and mucous membranes), nausea, vomiting, coma, and shock. These symptoms are usually associated with high doses/overdoses of isosorbide dinitrate, but can be seen at normal therapeutic doses. If methemoglobinemia is diagnosed, the treatment of choice is methylene blue (1-2 mg/kg by slow intravenous injection).
Tolerance to isosorbide mononitrate or attenuation of the drug's vasodilatory effects can develop when large or sustained dosages are given. This effect is probably related to both the size of the dose and the frequency of the dosing interval. If tolerance occurs, it is recommended that isosorbide mononitrate be administered in two doses, 7 hours apart, followed by a 17-hour, drug-free interval. This interval is crucial because it allows plasma concentrations of isosorbide mononitrate to decrease, preventing drug tolerance and avoiding the development of attenuation of the drug's antianginal effects.
Ophthalmic and otologic adverse events have been reported in clinical trials with isosorbide mononitrate. Patients receiving the extended-release tablets have reported (<= 5% incidence) earache, tinnitus, tympanic membrane perforation, conjunctivitis, photophobia, and visual impairment. Patients receiving the immediate-release tablets have reported (< 1% incidence) amblyopia and susurrus aurium (murmur in the ear).
Musculoskeletal adverse events have been reported in clinical trials with isosorbide mononitrate. Arthralgia, asthenia, frozen shoulder, muscle weakness, musculoskeletal pain, myalgia, myositis, tendon disorder, and torticollis were reported in patients receiving the extended-release tablets (<= 5% incidence). Muscle cramps, back pain, and neck pain were reported in patients receiving the immediate-release tablets have reported (< 1% incidence).
Hematologic, metabolic, and other laboratory abnormalities have been reported in clinical trials with isosorbide mononitrate extended-release tablets (<= 5% incidence rate), including elevated hepatic enzymes (SGOT and SGPT), hyperuricemia, hypokalemia, purpura, thrombocytopenia, and hypochromic anemia.
Renal, urogenital, and reproductive system adverse effects have been reported during clinical trials with isosorbide mononitrate. Patients receiving the extended-release tablets have reported (<= 5% incidence) polyuria, renal calculus, atrophic vaginitis, and breast pain. Patients receiving the immediate-release tablets have reported (< 1% incidence) prostatic disorder.
Dermatologic adverse events have been reported in clinical trials with isosorbide mononitrate, including hyperhidrosis (< 1% immediate-release tablets; <= 5% extended-release tablets), pruritus (2%; <= 5%), and rash (unspecified) (<= 2%; <= 5%). Also reported were acne vulgaris, hair texture abnormality, and skin nodules in <= 5% of patients receiving extended-release tablets.
Respiratory adverse reactions have been reported with isosorbide mononitrate. Increased cough (<= 2% with immediate-release tablets; <= 5% extended-release tablets), dyspnea (< 1%; <= 5%), and sinusitis (< 1%; <= 5%) were reported in clinical trials. Bronchitis, bronchospasm, increased sputum, nasal congestion, pharyngitis, pulmonary infiltration, rales, and rhinitis were reported in <= 5% of patients receiving extended release tablets. Asthma was reported in < 1% of patients receiving immediate release tablets.
Infection has been reported in patients receiving isosorbide mononitrate during clinical trials, including respiratory infection (1-4% with immediate-release tablets), pneumonia (<= 5% with extended-release tablets), urinary tract infection (<= 5%, extended-release), candidiasis (<= 5%, extended-release), flu-like symptoms (<= 5%, extended-release), and unspecified bacterial and viral infections (<= 5%, extended-release).
Use isosorbide mononitrate cautiously in patients with recent myocardial infarction because drug-induced hypotension and/or tachycardia can worsen or expand ischemic damage, and the effects of long-acting nitrates are difficult to terminate quickly. Patients with low filling (diastolic) pressure are particularly predisposed to this effect.
Use isosorbide mononitrate cautiously in patients with hypotension because the drug can worsen hypotension, cause a paradoxical bradycardia, and/or exacerbate angina. Preexisting orthostatic hypotension, hypovolemia, or dehydration can worsen this effect. Nitrate-induced hypotension has resulted in syncope or fatalities. Nitrate therapy can also worsen angina due to hypertrophic cardiomyopathy.
Isosorbide mononitrate should not be used in patients with increased intracranial pressure (e.g., recent head trauma or intracranial bleeding) because it's vasodilatory effects on the meningeal blood vessels can exacerbate these conditions.
Isosorbide mononitrate is should be avoided in patients with closed-angle glaucoma due to the risk of drug-induced increased intraocular pressure.
Isosorbide mononitrate is contraindicated in patients with severe anemia because it oxidation of hemoglobin to methemoglobin, which could exacerbate this condition.
Isosorbide mononitrate is absolutely contraindicated in patients who have known nitrate hypersensitivity.
When isosorbide dinitrate is to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina.
Isosorbide mononitrate is generally classified as pregnancy risk category C. Although no adequate human studies have examined the effects of this drug on the fetus, and animal reproduction studies have shown adverse fetal effects for the initial isosorbide mononitrate product (Ismo). Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother. The FDA ratings for the specific isosorbide mononitrate products vary, with Ismo classified as pregnancy category C. In contrast, Monoket and Imdur are specifically classified by the FDA as pregnancy risk category B drugs, as the animal studies did not show adverse fetal effects; however, no adequate and well-controlled studies in pregnant women are available. Because animal studies are not always predictive of human response, Imdur and Monoket should only be used during pregnancy when clearly needed.
It is not known whether isosorbide mononitrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isosorbide mononitate is administered to a woman who is breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The safety and effectiveness of isosorbide mononitrate in neonates, infants, children, and adolescents have not been established.
Use isosorbide mononitrate cautiously in patients with hepatic disease because metabolism of the drug can be impaired, resulting in an increased risk of methemoglobinemia.
Clinical experience has not identified differences in responses to isosorbide mononitrate in geriatric vs. younger adult patients. Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide mononitrate in any group. When dosing isosorbide mononitrate in the older adult, it may be prudent to start the dose at the low end of the dosing range and monitor the patients closely for hypotensive effects. Subsequent dosage adjustments should be made based on clinical response.
For the treatment of angina pectoris due to coronary artery disease:
Oral dosage (immediate-release):
Adults: 20 mg PO twice daily, initially, with doses given 7 hours apart. May consider 5 mg PO twice daily, initially, in persons with small stature; increase dose to at least 10 mg PO twice daily by day 2 to 3. Doses more than 20 mg twice daily have not been adequately studied.
Oral dosage (extended-release):
Adults: 30 or 60 mg PO once daily, initially. May increase dose to 120 mg PO once daily after several days. Max: 240 mg/day, rarely needed.
For the treatment of portal hypertension* and/or variceal bleeding prophylaxis* in patients with esophageal varices*:
-for the prevention of first variceal bleed (primary variceal bleeding prophylaxis):
Oral dosage:
Adults: Nitrates either alone or in combination with beta-blockers should NOT be used in the primary prophylaxis of variceal hemorrhage.
-for the prevention of reurrence of variceal bleed (secondary variceal bleeding prophylaxis):
Oral dosage:
Adults: 10 mg PO once daily at night initially, and titrated to the maximal tolerated dose (Max: 20 mg PO twice daily) after a nonselective beta-blocker is titrated to a resting heart rate reduction of 25% from baseline or to 55 bpm. Nonselective beta-blockers adjusted to the maximal tolerated dose plus a nitrate and endoscopic variceal ligation are recommended for patients without shunt surgery/TIPS and no evidence of hemorrhage for 24 hours or more. In 1 study, a regimen of only propranolol (initial dose, 20 mg PO 3 times daily, then titrated) led to re-bleeding in 28 of 49 patients as compared with 18 of 46 patients who received propranolol plus isosorbide mononitrate, if tolerated. In another study, significantly fewer patients who got nadolol, isosorbide mononitrate, and endoscopic band ligation had variceal re-bleeding (14 of 80 patients) as compared with those who received pharmacologic therapy alone (25 of 78 patients). Nadolol was titrated to a maximum tolerated dose or up to 240 mg/day PO before isosorbide mononitrate initiation of 10 mg PO once daily at night and titration to the maximal tolerated dose or 20 mg PO twice daily.
Maximum Dosage Limits:
-Adults
40 mg/day PO for immediate-release tablets (e.g., Ismo, Monoket); 240 mg/day PO for extended-release tablets (e.g., Imdur).
-Elderly
40 mg/day PO for immediate-release tablets (e.g., Ismo, Monoket); 240 mg/day PO for extended-release tablets (e.g., Imdur).
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
Intermittent hemodialysis
Isosorbide mononitrate is significantly removed from the blood during hemodialysis (AUC is decreased by 30%); however, supplemental dosage is generally not needed following dialysis.
*non-FDA-approved indication
Acebutolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Alfuzosin: (Moderate) The manufacturer of alfuzosin warns that concurrent use with nitrates has the potential to cause hypotension, orthostatic hypotension, or syncope. Caution is advisable when coadministering alfuzosin and a nitrate to patients with symptomatic hypotension or those who have had a previous hypotensive response to either agent.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Alpha-blockers: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Amiloride: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Amlodipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Atorvastatin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Benazepril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Celecoxib: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Olmesartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Valsartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Amphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Amphetamine; Dextroamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Angiotensin II receptor antagonists: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Apomorphine: (Major) Coadministration of apomorphine and nitrates can cause large decreases in blood pressure. The effect is especially of concern with use of sublingual nitroglycerin products. Instruct patients to lie down before taking a sublingual nitroglycerin dose and to remain supine for at least 45 minutes after to reduce orthostatic risk. In one evaluation, the largest mean decreases in standing systolic and diastolic blood pressure during use of apomorphine and sublingual nitroglycerin were 14.3 mmHg and 13.5 mmHg, respectively. The largest recorded decreases in standing systolic and diastolic blood pressures were 65 mmHg and 43 mmHg during use of apomorphine and sublingual nitroglycerin together.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Atenolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Avanafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Azilsartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Azilsartan; Chlorthalidone: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Benazepril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Benzalkonium Chloride; Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine; Butamben; Tetracaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Beta-adrenergic blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Betaxolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Bisoprolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Brimonidine; Timolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Bumetanide: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Cabergoline: (Moderate) Cabergoline should be used cautiously with drugs that can lower blood pressure, including systemic nitrates. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium-channel blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Candesartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Captopril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Carbonic anhydrase inhibitors: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Carteolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Carvedilol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chloroprocaine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Clevidipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Clonidine: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Codeine; Phenylephrine; Promethazine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dapsone: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexmethylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextroamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Diazoxide: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Diethylpropion: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dihydroergotamine: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Diltiazem: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dobutamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dopamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dorzolamide; Timolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Doxapram: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Doxazosin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Enalapril, Enalaprilat: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Ephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Ephedrine; Guaifenesin: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Epinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Eplerenone: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Epoprostenol: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Eprosartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Ergotamine: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergotamine; Caffeine: (Major) Avoid concomitant use of oral nitrates and ergotamine. If concomitant use is necessary, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Esmolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Ethacrynic Acid: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Felodipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Fenoldopam: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Finasteride; Tadalafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Fosinopril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Furosemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Guanfacine: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Hydralazine: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Iloprost: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Irbesartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Isoproterenol: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Isradipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Labetalol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Levamlodipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Levobunolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lisdexamfetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Lisinopril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Losartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Macitentan; Tadalafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Mannitol: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Mecamylamine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Methamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Methazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Methyldopa: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Methylergonovine: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Methylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Metolazone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Metoprolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Midodrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Minoxidil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Moexipril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nadolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Nebivolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Nebivolol; Valsartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Nicardipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
NIFEdipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nimodipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nisoldipine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroprusside: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Norepinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Olmesartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension and enhance the orthostatic effects of nitrates. Orthostatic vital signs should be monitored in patients receiving paliperidone and nitrates who are susceptible to hypotension.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Perindopril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Perindopril; Amlodipine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Phendimetrazine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phenoxybenzamine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Phentermine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phentermine; Topiramate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phentolamine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phosphodiesterase inhibitors: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Pindolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Prazosin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Promethazine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Propranolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Quinapril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Racepinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Ramipril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Riociguat: (Contraindicated) Coadministration of riociguat and nitrates or nitric oxide donors (e.g., amyl nitrite) is contraindicated due to the risk of hypotension. The blood pressure lowering effect of sublingual nitroglycerin was potentiated when administered 4 and 8 hours after riociguat. Syncope was reported in some patients.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rosiglitazone: (Major) The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
Sacubitril; Valsartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Sildenafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent nitrates. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Spironolactone: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Sympathomimetics: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Tadalafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Telmisartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Telmisartan; Amlodipine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Terazosin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents or rapid-onset vasodilators, such as nitrates.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Timolol: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Torsemide: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Trandolapril: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Trandolapril; Verapamil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Treprostinil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Triamterene: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Valsartan: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Vardenafil: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Verapamil: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Similar to other nitrites and organic nitrates, isosorbide mononitrate is converted to nitric oxide (NO), a reactive free radical. Nitric oxide is also formed endogenously and is believed to be endothelial-derived growth factor. Among other properties, NO is believed to produce vasodilation. Nitric oxide, the active intermediate compound common to all agents of this class, activates the enzyme guanylate cyclase, thereby stimulating the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP). This second messenger then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber and the subsequent release, or extrusion, of calcium ions. The contractile state of smooth muscle is normally maintained by a phosphorylated myosin light chain (stimulated by an increase in calcium ions). Thus, the nitrite- or nitrate-induced dephosphorylation of the myosin light chain signals the cell to release calcium, thereby relaxing the smooth muscle cells and producing vasodilation.
It is believed that nitrates reduce myocardial oxygen demand by causing direct relaxation of vascular smooth muscle. This results in dilation of peripheral venous vessels, causing pooling of venous blood and decreased venous return to the heart, which decreases preload. Peripheral arteries are also dilated, although this effect occurs at dosages larger than those required to dilate veins. Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Thus, nitrates reduce both venous filling pressures and arterial impedance, resulting in a reduction of left ventricular systolic wall tension. Nitrate-induced reduction of wall tension from reduced ventricular volume and pressure leads to a lowering of myocardial oxygen demand.
Nitrates can increase total coronary blood flow in patients with normal coronary arteries. However, in patients with ischemic heart disease, the drug may not increase total coronary blood flow but may simply redistribute blood to ischemic areas. This effect is believed to be due to the drug's preferential dilation of the larger conductive vessels of the coronary circulation, which, in the presence of coronary atherosclerosis, redirects the distribution of the coronary blood supply to ischemic areas.
Nitrates cause a transient reflex compensatory increase in heart rate and myocardial contractility, which normally would increase myocardial oxygen consumption, yet the nitrate-induced decrease in ventricular wall tension results in a net decrease in myocardial oxygen demand and amelioration of the pain of angina pectoris. In addition, isosorbide relaxes all other types of smooth muscle including bronchial, biliary, GI, ureteral, and uterine. Nitrites and nitrates are functional antagonists of acetylcholine, norepinephrine, and histamine.
In individuals who have little compensatory tachycardia response, syncope can result from the decrease in blood pressure that occurs following higher doses of nitrates and nitrites. Although this is not likely to occur with doses of nitrates that do not cause blood pressure reduction, patients should be sitting or lying down during and immediately after administration of isosorbide dinitrate.
Isosorbide-5-mononitrate is administered orally. Less than 4% of an oral dose is plasma protein-bound, with isosorbide being only minimally distributed throughout the body. The drug is metabolized via glucuronidation to the mononitrate glucuronide and other inactive metabolites. At least 99% of the drug is metabolized prior to elimination in the urine. The plasma half-life of the drug is approximately 5 hours and is not affected by age or renal or hepatic impairment.
-Route-Specific Pharmacokinetics
Oral Route
Isosorbide-5-mononitrate is rapidly and completely absorbed from the GI tract and is not metabolized in the liver. Thus, the absolute bioavailability following oral administration is nearly 100%, and maximal serum concentrations are achieved in 30-60 minutes. Peak antianginal effects are evident in 1-4 hours.