Isosorbide dinitrate or mononitrate is used for the acute relief of angina pectoris, for prophylactic management in situations likely to provoke angina attacks, and for long-term prophylactic management of angina pectoris.
Conventional measures in the management of angina pectoris are aimed at reducing the frequency, duration, and severity of attacks, and include coronary risk reduction (e.g., discontinuance of smoking, weight control, antilipemic strategies), rest, avoidance of precipitating circumstances (e.g., eating heavy meals, getting emotionally upset, performing strenuous exercise, exposure to cold air) and, if possible, treatment of the underlying cause.
β-Adrenergic blocking agents generally are considered among the initial antianginal drugs of choice in the long-term prophylactic management of chronic stable angina with or without prior MI to reduce symptoms and to prevent MI and/or death.
Isosorbide dinitrate or mononitrate can be used alone or in combination as either second-line or third-line therapy in patients previously treated with a β-adrenergic blocking agent.
Prolonged use of oral nitrates has been associated with the development of tolerance to the hemodynamic and antianginal effects and possibly with cross-tolerance to sublingual nitrates. (See Tolerance and Dependence under Cautions.)
Generally considered for monotherapy in the prophylactic management of angina pectoris only when β-adrenergic blocking agents or calcium-channel blocking agents are contraindicated, associated with unacceptable adverse effects, or are ineffective.
If a β-adrenergic blocking agent is not effective in controlling chronic stable angina, long-acting nitrates may be added to β-blocker therapy.
CHF: Fixed-combination Therapy with Hydralazine in Self-identified Black Patients
In fixed combination with hydralazine as adjunct to standard therapy for the treatment of CHF in self-identified black patients to improve survival, decrease rate of hospitalization for worsened heart failure, and improve patient-reported functional status.
CHF: Other Therapies in the General Population
Isosorbide dinitrate (in combination with cardiac glycosides and diuretics or with hydralazine) effective for the treatment of CHF† or other low cardiac output states†.
Concomitant therapy with isosorbide dinitrate and hydralazine may decrease mortality in patients with CHF; usually reserved for patients who fail to respond to or are intolerant of first-line therapy (e.g., ACE inhibitors) or in combination with such therapy.
Do not use isosorbide dinitrate as monotherapy for CHF.
Diffuse Esophageal Spasm
Isosorbide dinitrate has been used effectively for diffuse esophageal spasm† without gastroesophageal reflux to relieve pain, dysphagia, and spasm.
Dosage and Administration
Administration
Isosorbide Dinitrate
Administer sublingually, intrabuccally, or orally.
Sublingual or intrabuccal nitrates may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia).
Do not chew extended-release preparations.
The patient should be sitting immediately after sublingual or intrabuccal administration.
Isosorbide Mononitrate
Administer orally.
Extended-release tablets can be administered as whole or halved tablets, but swallow intact and do not chew or crush.
Administer extended-release tablets with adequate amounts of fluid (e.g., 120 mL) on arising in the morning.
Dosage
Adjust dosage of isosorbide dinitrate and isosorbide mononitrate carefully according to the patient’s requirements and response; use the smallest effective dosage.
Although many clinicians do not gradually reduce the dosage when discontinuance of oral nitrates is planned, it appears prudent that dosage be gradually reduced (e.g., over a period of about 1–2 weeks) to avoid withdrawal manifestations. Supplementary sublingual nitroglycerin doses should be given if necessary during dosage reduction.
Adults
Angina
Acute Symptomatic Relief and Prophylactic Management
Do not use extended-release isosorbide dinitrate preparations or any isosorbide mononitrate preparation to abort an acute anginal episode or for acute relief of angina or in the prophylactic management in situations likely to provoke angina attacks; onset is not sufficiently rapid.
Sublingual
Patients who fail to respond to nitroglycerin lingual or sublingual: 2.5–5 mg of isosorbide dinitrate.
If relief is not attained after a single dose during an acute attack, may give additional doses at 5- to 10-minute intervals; give no more than 3 doses in a 15- to 30-minute period.
Prophylactic management in situations likely to provoke angina attacks in patients who fail to respond to sublingual nitroglycerin: place 2.5–5 mg of isosorbide dinitrate under the tongue about 15 minutes prior to engaging in such activities.
Intrabuccal
Patients who fail to respond to nitroglycerin lingual or sublingual: 2.5–5 mg of isosorbide dinitrate.
If relief is not attained after a single dose during an acute attack, may give additional doses at 5- to 10-minute intervals; no more than 3 doses should be given in a 15- to 30-minute period.
Prophylactic management in situations likely to provoke angina attacks in patients who fail to respond to sublingual nitroglycerin: 2.5–5 mg of isosorbide dinitrate should be placed under the tongue approximately 15 minutes prior to engaging in such activities.
Long-term Prophylactic Management
Oral (Isosorbide Dinitrate Conventional Tablets)
Initially, isosorbide dinitrate conventional tablets (e.g., Isordil® Titradose®) 5–20 mg administered 2–3 times daily, followed by maintenance dosage of 10–40 mg administered 2–3 times daily (some patients may require higher dosages).
Suggested schedules: Usually, at 7 a.m., 12 p.m., and 5 p.m. in chronic stable angina or at 7 a.m. and 12 p.m. in less severely symptomatic angina in order to allow for a nitrate-free interval of 10–14 hours.
May need to adjust schedule for those arising earlier than 7 a.m. since early morning angina is common.
Less frequent administration of isosorbide dinitrate may reduce the development of tolerance to the drug’s antianginal effects.
Initially, (e.g., Imdur®): 30 mg (as a single 30-mg tablet or as ½ of a 60-mg tablet) or 60 mg (as a single 60-mg tablet) once daily.
May increase dosage to 120 mg (as a single 120-mg tablet or as two 60-mg tablets) once daily after several days; 240-mg dosages rarely needed.
CHF
Fixed-combination Therapy with Hydralazine in Self-identified Black Patients
Oral (Isosorbide Dinitrate in Fixed Combination with Hydralazine Hydrochloride Tablets)
Initially, isosorbide dinitrate 20 mg and hydralazine hydrochloride 37.5 mg (1 tablet of BiDil®) 3 times daily. May titrate dosage to a maximum tolerated dosage not to exceed 2 tablets (a total of 40 mg of isosorbide dinitrate and 75 mg of hydralazine hydrochloride) 3 times daily. Rapid titration (over 3–5 days) may be possible; however, slower titration may be needed due to adverse effects. May decrease dosage to as little as ½ of the fixed-combination tablet 3 times daily in patients who experience intolerable effects, but attempt to titrate dosage up once adverse effects subside.
Other Therapies in the General Population
Oral (Isosorbide Dinitrate Conventional Tablets)
Initially, 80 mg of isosorbide dinitrate (administered as ½ of a 40 mg conventional tablet 4 times daily) daily in combination with oral dosages of 150 mg of hydralazine hydrochloride (as a single 37.5 mg tablet 4 times daily) daily for 2 weeks.†
If initial dosages are tolerated, increase daily dosages to 160 mg of isosorbide dinitrate and 300 mg of hydralazine hydrochloride.†
Diffuse Esophageal Spasm
Oral (Isosorbide Dinitrate Conventional Tablets)
10–30 mg 4 times daily.
Prescribing Limits
Adults
Angina
Acute Symptomatic Relief and Prophylactic Management
Sublingual
No more than 3 doses in a 15- to 30-minute period.
Intrabuccal
No more than 3 doses in a 15- to 30-minute period.
Fixed-combination Therapy with Hydralazine Hydrochloride in Self-identified Black Patients
Oral (Isosorbide Dinitrate in Fixed Combination with Hydralazine Hydrochloride Tablets)
Maximum 40 mg of isosorbide dinitrate and 75 mg of hydralazine hydrochloride (2 tablets of BiDil®) 3 times daily.
Special Populations
Hepatic Impairment
No specific dosage recommendations for hepatic impairment.
Renal Impairment
No specific dosage recommendations for renal impairment.
Geriatric Patients
One manufacturer of isosorbide mononitrate states that dosage should be selected with caution, usually initiating therapy at the low end of the range, although age, renal, hepatic, and cardiovascular dysfunction do not appear to have a significant effect on drug clearance.
The manufacturer of the fixed combination of isosorbide dinitrate and hydralazine hydrochloride states that dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Media Gallery
Drug Info Tools
