What are the contraindications for starting Bidil (hydralazine and isosorbide dinitrate) in patients with certain medical conditions, such as impaired renal function, severe hepatic impairment, or a history of hypersensitivity to hydralazine or isosorbide dinitrate?

Contraindications for Starting BiDil

BiDil (hydralazine/isosorbide dinitrate combination) is absolutely contraindicated in patients with hypersensitivity to either component, coronary artery disease, mitral valvular rheumatic heart disease, and in those taking phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) or riociguat due to risk of severe hypotension. 1, 2

Absolute Contraindications

Hydralazine Component

• Hypersensitivity to hydralazine 1
• Coronary artery disease - hydralazine causes myocardial stimulation that can precipitate anginal attacks, ECG changes of myocardial ischemia, and has been implicated in myocardial infarction 1
• Mitral valvular rheumatic heart disease - the hyperdynamic circulation caused by hydralazine may increase pulmonary artery pressure in these patients 1

Isosorbide Dinitrate Component

• Hypersensitivity to isosorbide dinitrate or any ingredient 2
• Concurrent use of phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) - can cause severe hypotension, syncope, or myocardial ischemia 2
• Concurrent use of riociguat (soluble guanylate cyclase stimulator) - causes hypotension 2

Relative Contraindications and High-Risk Situations

Renal Impairment

• Advanced renal damage requires extreme caution 1
• While hydralazine can increase renal blood flow in hypertensive patients with normal kidneys, it should be used cautiously in advanced renal disease 1
• In dialysis-dependent ESRD, BiDil appears tolerable but requires careful monitoring, with dose escalation over 3 weeks recommended 3

Hepatic Impairment

• Severe hepatic impairment is a relative contraindication 1
• Hydralazine can cause cholestatic hepatitis, mixed hepatocellular injury, acute hepatitis, and centrilobular necrosis 4
• Hepatotoxicity may occur after both short-term (2-10 days) and long-term therapy 4

Cerebrovascular Disease

• Cerebral vascular accidents - use with caution due to risk of postural hypotension 1

Suspected Coronary Disease

• Even suspected coronary artery disease warrants extreme caution, as hydralazine's myocardial stimulation can provoke ischemia 1

Critical Monitoring and Safety Considerations

Postural Hypotension Risk

• BiDil combination causes significant postural hypotension and tachycardia 5
• In one study, mean arterial pressure fell from 84±10 to 66±11 mm Hg when patients moved from supine to upright position 5
• Heart rate increased from 87±17 to 99±17 beats/min in the upright position during therapy 5
• Perform both supine AND upright hemodynamic assessments during initiation 5

Drug-Induced Vasculitis

• Hydralazine can cause ANCA-associated vasculitis and drug-induced lupus 6
• Monitor for arthralgia, fever, chest pain, continued malaise, or unexplained symptoms 1
• Obtain complete blood counts and antinuclear antibody titers before therapy and periodically during treatment 1
• Positive ANA requires careful risk-benefit assessment 1

Hematologic Toxicity

• Blood dyscrasias including reduction in hemoglobin, leukopenia, agranulocytosis, and purpura have been reported 1
• If abnormalities develop, discontinue therapy immediately 1

Peripheral Neuropathy

• Peripheral neuritis (paresthesia, numbness, tingling) suggests antipyridoxine effect 1
• Consider adding pyridoxine if symptoms develop 1

Important Drug Interactions

• MAO inhibitors should be used with caution 1
• Diazoxide and other potent parenteral antihypertensives can cause profound hypotensive episodes when combined with hydralazine 1
• Patients require continuous observation for several hours when combining these agents 1

Clinical Context for Use

While BiDil has these contraindications, it remains a Class I recommendation for African-American patients with moderate-severe heart failure symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics 7. It is also reasonable as add-on therapy for patients with reduced LVEF who have persistent symptoms despite ACE inhibitor and beta blocker therapy 7.