In a patient who missed a week of hydralazine 100 mg and is now admitted for severe hypertension, should the drug be restarted at the full dose immediately or initiated at a lower dose?

Restarting Hydralazine After One Week Interruption in Severe Hypertension

Start at a lower dose (10 mg IV initially) rather than resuming the full 100 mg oral dose immediately, as the patient has lost tolerance after a week-long interruption and requires careful dose titration to avoid unpredictable hypotensive responses.

Immediate Management Approach

For Acute Severe Hypertension (Hypertensive Emergency)

If this patient has evidence of target organ damage (hypertensive emergency), use IV hydralazine starting at 10 mg via slow IV infusion (maximum initial dose 20 mg), repeated every 4-6 hours as needed 1. However, recognize that:

• Hydralazine is not a first-line agent for most hypertensive emergencies due to unpredictable response and prolonged duration of action 2, 3
• More predictable IV agents with shorter half-lives (nicardipine, labetalol, or clevidipine) are preferred for better titratability 2, 3
• The blood pressure response to hydralazine is highly variable and can cause significant hypotension, particularly in hospitalized patients 4

For Severe Hypertension Without Target Organ Damage (Hypertensive Urgency)

If there is no evidence of acute target organ damage, this is a hypertensive urgency, not an emergency 1. In this scenario:

• Reinstitute oral antihypertensive therapy rather than using IV agents 1
• Do not restart at the full 100 mg dose immediately
• The patient requires dose re-titration after a week-long interruption

Oral Hydralazine Dose Titration Protocol

After a week without medication, restart at the initial dosing schedule per FDA labeling:

• Start with 10 mg four times daily for the first 2-4 days 5
• Increase to 25 mg four times daily for the balance of the first week 5
• For the second and subsequent weeks, increase to 50 mg four times daily 5
• Adjust to the patient's previous maintenance dose (100 mg) only after demonstrating tolerance 5

Rationale for Lower Starting Dose

• One week off hydralazine is sufficient to lose pharmacologic tolerance to its vasodilatory effects
• The FDA labeling explicitly requires gradual dose escalation starting from 10 mg four times daily, even in treatment-naive patients 5
• Hydralazine causes unpredictable BP responses, with changes highly variable and related to baseline BP 4
• Hypotension is a common adverse event when hydralazine is used inappropriately in hospitalized patients (occurred in 11 of 94 patients in one study) 4

Critical Monitoring Parameters

During dose re-escalation, monitor for:

• Reflex tachycardia (common adverse effect requiring beta-blocker co-administration) 2, 3
• Sodium and water retention (requires concurrent diuretic therapy) 2, 3
• Symptomatic hypotension within 10-30 minutes of administration, with effects lasting 2-4 hours 3
• Drug-induced lupus syndrome at higher doses (arthralgia, muscle aches, joint swelling, pericarditis, pleuritis, rash, or fever) 2

Optimal Long-Term Management Strategy

Hydralazine should be used in combination with a beta-blocker and diuretic to prevent reflex tachycardia and fluid retention 2, 3. The typical maintenance regimen is:

• Hydralazine 100-200 mg/day total, divided into 2-3 times daily dosing 3
• Research demonstrates no need to administer hydralazine more than twice daily for adequate 24-hour control 6
• Slow-release formulations allow once-daily dosing at 200 mg without increased side effects 7

Common Pitfalls to Avoid

• Do not use IV hydralazine for asymptomatic severe hypertension (36% of PRN administrations in one study were given for SBP <180 mmHg and DBP <110 mmHg, which is inappropriate) 8
• Do not assume the patient can immediately tolerate their previous maintenance dose after a week-long interruption
• Do not use hydralazine as monotherapy without addressing the underlying need for comprehensive antihypertensive regimen optimization 8
• Ensure the patient's home antihypertensive regimen is continued during hospitalization (40.8% of patients in one study were not continued on home medications) 8