Can Imdur (isosorbide mononitrate) and hydralazine be given together?

Hydralazine and Isosorbide Dinitrate (Imdur) Combination Therapy in Heart Failure

Yes, hydralazine and isosorbide dinitrate (Imdur) can be safely and effectively given together, and this combination is specifically recommended for certain heart failure patients to reduce morbidity and mortality. 1

Indications for Combination Therapy

• The combination of hydralazine and isosorbide dinitrate is recommended as Class I (Level of Evidence A) therapy for self-identified African American patients with NYHA class III-IV heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy with ACE inhibitors, beta blockers, and aldosterone antagonists 1

• This combination is also recommended as Class IIa (Level of Evidence B) for patients with current or prior symptomatic HFrEF who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency 1

• The combination provides both arterial vasodilation (primarily from hydralazine) and venous vasodilation (primarily from isosorbide dinitrate), offering comprehensive hemodynamic benefits 1

Clinical Benefits

• In clinical trials, the combination therapy has demonstrated a 43% reduction in mortality risk and a 33% reduction in heart failure hospitalizations 1

• The number needed to treat (NNT) for mortality reduction is only 7 when standardized to 36 months, making this one of the most effective therapies for heart failure 1

• The combination improves quality of life scores in addition to reducing mortality and hospitalizations 2

• Even in patients with low systolic blood pressure (below 126 mmHg), the combination remains effective without further reducing blood pressure in those who already have low BP 3

Dosing and Administration

• When using the fixed-dose combination, start with 1 tablet containing 37.5 mg hydralazine and 20 mg isosorbide dinitrate three times daily 1

• Dose can be increased to 2 tablets three times daily for a total daily dose of 225 mg hydralazine and 120 mg isosorbide dinitrate 1

• When the drugs are used separately, both should be administered at least three times daily 1

• Initial low doses may be progressively increased to achieve the target dose 1

• A nitrate-free interval of at least 10 hours may help minimize nitrate tolerance 1, 4

Potential Adverse Effects and Monitoring

• Common adverse effects include headache (49.5% vs 21.1% with placebo), dizziness (30.1% vs 13.7%), and gastrointestinal complaints 2

• Nausea and vomiting (9.7% vs 6.1%), hypotension (7.9% vs 4.4%), and tachycardia (4.1% vs 2.7%) may also occur 2

• Patient adherence can be challenging due to the multiple daily dosing and side effect profile 1

• Consider slower titration to enhance tolerance if side effects are problematic 1

Special Populations

• The combination has been studied in dialysis-dependent patients and appears to be well-tolerated, with no serious hypotension events reported in a small trial 5

• For non-African American patients with HFrEF, the benefit remains to be fully investigated, but the combination may be considered for those who cannot tolerate ACE inhibitors or ARBs 1, 6

• The combination should not be used as first-line therapy in patients who have not tried standard neurohumoral antagonist therapy (ACE inhibitors, ARBs) 1

Important Considerations

• Hydralazine may help prevent the development of nitrate tolerance when used in combination with isosorbide dinitrate 1, 2

• The combination has antioxidant properties and may improve nitric oxide bioavailability, which may explain its particular efficacy in African American patients 1, 7

• Despite its proven benefits, this combination therapy remains underutilized in clinical practice 7