A fixed-dose combination of a nitrate vasodilator (Isosorbide Dinitrate) and a direct-acting arteriolar vasodilator (Hydralazine). This combination is primarily used in the management of chronic heart failure (HF), specifically for patients of African descent or those intolerant to ACE inhibitors/ARBs, as per landmark trials. It reduces preload and afterload, improving cardiac output and symptoms.
Adult: Heart Failure: Typically, one tablet (Isosorbide Dinitrate 20mg + Hydralazine 37.5mg) three times daily. Initiation often starts with half a tablet TID and titrated upward over weeks to the target dose to improve tolerability. Maximum studied dose in trials: Isosorbide Dinitrate 40mg + Hydralazine 75mg TID.
Note: Take orally with or without food. To prevent nitrate tolerance, the dosing schedule should provide a daily nitrate-free interval of 10-12 hours (e.g., doses at 8 AM, 2 PM, and 6 PM, avoiding bedtime dose). Do not crush or chew. Swallow whole with a glass of water.
The combination works synergistically to reduce cardiac workload and improve hemodynamics in heart failure. Isosorbide Dinitrate primarily acts as a venodilator, reducing preload by pooling blood in the venous capacitance vessels. Hydralazine acts as a direct arteriolar vasodilator, reducing afterload by decreasing systemic vascular resistance. Together, they lower ventricular filling pressures and increase cardiac output without a significant reflex tachycardia (partly due to nitrate-mediated counteraction).
Pregnancy: Category C (US FDA). Hydralazine has been used for hypertensive disorders of pregnancy (like pre-eclampsia), but the fixed-dose combination is not recommended. Isosorbide dinitrate use is limited. Use only if potential benefit justifies potential fetal risk. Consult specialist.
Driving: May cause dizziness, lightheadedness, or syncope, especially during initiation. Patients should not drive or operate machinery until they know how the medication affects them.
| Phosphodiesterase-5 Inhibitors (Sildenafil, Tadalafil, Vardenafil) | Profound, life-threatening hypotension due to synergistic vasodilation | Contraindicated |
| Other Antihypertensives (Beta-blockers, ACEi, ARBs, Diuretics, Calcium channel blockers) | Additive hypotensive effect; risk of severe hypotension | Major |
| Alcohol | Enhanced vasodilation and hypotensive effect | Major |
| Diazepam, Midazolam | Hydralazine may increase plasma levels of these drugs | Moderate |
| MAO Inhibitors (e.g., Phenelzine) | May potentiate hypotensive effect | Moderate |
| Sympathomimetics (e.g., Epinephrine) | May decrease antihypertensive effect of hydralazine | Moderate |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | May attenuate the hypotensive effect | Moderate |
| Dihydroergotamine | Nitrates may reduce its vasoconstrictive effect | Moderate |
Same composition (Isosorbide Dinitrate (20mg) + Hydralazine (37.5mg)), different brands: