Isosorbide Dinitrate with Hydralazine: Dosing and Indications

Primary Indication

• The American Heart Association recommends the combination of isosorbide dinitrate and hydralazine for African American patients with symptomatic heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal guideline-directed medical therapy, to reduce mortality and morbidity 1, 2
• This combination represents a 43% relative risk reduction in mortality with a number needed to treat of only 7 patients to prevent one death over 36 months 3, 4

Secondary Indication

• The American College of Cardiology suggests that patients with symptomatic HFrEF who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency may benefit from this combination as an alternative 1, 5

Dosing Regimen

• The initial dose of the fixed-dose combination is 1 tablet (37.5 mg hydralazine/20 mg isosorbide dinitrate) three times daily, with a target dose of 2 tablets (75 mg hydralazine/40 mg isosorbide dinitrate) three times daily 1, 6
• The maximum daily dose is 225 mg hydralazine/120 mg isosorbide dinitrate total 1, 5

Critical Prescribing Considerations

• The American Heart Association advises against using isosorbide dinitrate with hydralazine and phosphodiesterase-5 inhibitors due to the risk of profound hypotension 7
• The American College of Cardiology recommends not substituting this combination for ACE inhibitors/ARBs in patients tolerating those medications well 1, 4

Monitoring Parameters

• Blood pressure and heart rate should be monitored, especially during dose titration, to watch for signs of hypotension 7