Bulletin

Hydralazine Injection

12 January 2007

Products Affected - Description

All products are currently available.

Reason for the Shortage

American Regent would not provide a reason for the shortage. The FDA, American Regent, and Luitpold Pharmaceuticals had issued a voluntary recall of several lots of hydralazine injection (NDC 0517-0901-12, NDC 0517-0911-25) because the affected product may contain particulates. The initial recall notice, issued on July 24th, indicated that only one lot of Novaplus product was affected. However, the recall was expanded on August 11th to include additional lot numbers under both the Novaplus and the American Regent labels. American Regent distributes hydralazine manufactured by Luitpold Pharmaceuticals. The following lots are affected by this recall:
- Novaplus label: Lot #5411NO (exp 9/06); Lot #5457NO (exp 11/06); Lot #5561NO (exp 12/06); Lot #5669NO (exp 1/07); Lot #5710NO (exp 2/07); Lot #5784NO (exp 6/07); Lot #5797NO (exp 6/07): Lot #6411NO (exp 12/07)
- American Regent label: Lot #5411 (exp 9/06); Lot #5457 (exp 11/06); Lot #5552 (exp 12/06); Lot #5647 (exp 1/07); Lot #5669 (exp 1/07); Lot #5753 (exp 3/07); Lot #6411 (exp 12/07)
Abraxis Bioscience (formerly APP) could not meet the increased demand for product.

Estimated Resupply Dates

American Regent has all products readily available.¹

Abraxis Bioscience (formerly APP) has product readily available.⁴

Implications for Patient Care

Hydralazine is a peripheral vasodilator that reduces arterial blood pressure and peripheral vascular resistance while increasing heart rate, stroke volume, and cardiac output.^5,6Parenteral hydralazine is typically used for the treatment of severe essential hypertension, primarily when oral therapy cannot be given or when blood pressure must be lowered immediately (ie, hypertensive emergency, hypertensive urgency).^5,6,7 Common indications for hydralazine injection in selected situations are outlined in Table 1. Alternatives are addressed in the Management section.

Table 1. Common Indications for Parenteral Hydralazine Therapy in Selected Situations

Selected Situation	Comments
Hypertensive emergency7	Defined as blood pressure above 180/120 mm Hg with evidence of end-organ damage. Requires immediate blood pressure reduction and admission to an intensive care unit.
Hypertensive urgency7	Defined as blood pressure elevation without evidence of end-organ damage. May not require parenteral therapy.
Preeclampsia with acute severe hypertension when delivery is imminent.7	Therapy is required only for maternal safety. Parenteral agents are used for imminent delivery, otherwise oral agents are preferred.

Safety

The recalled hydralazine injection could potentially cause patient harm when injected, if particulates are present.^2,3

Alternative Agents & Management

Table 2 outlines alternative agents to hydralazine for the management of hypertensive emergencies. This list is not all-inclusive, other therapies may be recommended for specific disease states.⁷

Table 3 outlines oral, short-acting antihypertensive agents used to manage hypertensive urgencies. Parenteral hydralazine is not typically used to manage these patients.⁷

Hydralazine is the drug of choice for managing acute severe hypertension in preeclampsia (typically persistent diastolic pressures of 105 to 110 mm Hg or higher) when delivery is imminent. When supplies of hydralazine are available, reserve for this use. Table 4 lists therapeutic alternatives when hydralazine is not available.⁷

Table 2. Parenteral Agents for the Management of Hypertensive Emergency^7-9

Drug	Onset of Action	Duration of Action	Dosage Regimen	Comments
Fenoldopam	Less than 5 minutes	30 minutes	0.1-0.3 mcg/kg/minute by IV infusion	Use caution in patients with glaucoma
Hydralazine*	IV: 10-20 minutes IM: 20-30 minutes	IV: 1-4 hours IM: 4-6 hours	IV: 10-20 mg IM: 10-40 mg	Agent of choice in preeclampsia
Labetalol	5-10 minutes	3-6 hours	20-80 mg IV bolus every 10 minutes, or 0.5-2 mg/minute by IV infusion	Avoid use in patients with heart failure
Nicardipine	5-10 minutes	15-30 minutes, more than 4 hours in some patients	5-15 mg/hour IV	Avoid use in patients with heart failure; use with caution in patients with coronary ischemia.
Nitroprusside	Immediate	1- 10 minutes	0.25-10 mcg/kg/minute by IV infusion	Use caution in patients with elevated intracranial pressure or azotemia

*Product is in short supply.

Table 3. Recommended Agents for the Management of Hypertensive Urgency^7-9

Drug	Onset of Action	Duration of Action	Dosage Regimen	Comments
Captopril oral tablets	60-90 minutes (peak effect)	Dose related	12.5-25 mg orally or sublingually, may repeat as needed	Avoid use in pregnancy.
Clonidine oral tablets	30-60 minutes	6-10 hours	0.1-0.2 mg orally or sublingually, followed by 0.1 mg every hour if needed, up to a maximum of 0.6 mg	Use caution in patients with coronary insufficiency, arrhythmias, recent MI or stroke, or chronic renal insufficiency.
Labetalol oral tablets	20-120 minutes	8-24 hours	200-300 mg orally, may repeat every 2 to 3 hours as needed	Monitor effects closely due to prolonged duration of action

Table 4. Therapeutic Alternatives for the Management of Severe Hypertension in Preeclampsia^7-9

Drug	Onset of Action	Duration of Action	Dosage Regimen	Comments
Hydralazine injection*	IV: 10-20 minutes	IV: 1-4 hours	IV: 5 mg IV bolus, followed by 10 mg every 20-30 minutes, up to a maximum of 25 mg. May repeat in several hours if needed	Preferred agent for this use. Reserve supplies if possible.
Labetalol injection	5-10 minutes	3-6 hours	20 mg IV bolus, followed by 40 mg IV in 10 minutes, then 80 mg IV every 10 minutes for two additional doses, up to a maximum of 220 mg	Second-line agent for this use.
Nifedipine immediate-release oral capsules	About 20 minutes	Not available, typically dosed 3 times daily	10 mg orally, repeated every 20 minutes, up to a maximum of 30 mg	Use is controversial. Precipitous drop in blood pressure may occur when used in combination with magnesium sulfate.
Nitroprusside	Immediate	1-10 minutes	0.25 mcg/kg/minute by IV infusion, may titrate up to maximum of 5 mcg/kg/minute	Reserve for use when other agents are ineffective. Fetal cyanide poisoning may occur if used for more than 4 hours.

*Product is in short supply.

Related Shortages

References

American Regent Customer Service (personal communications). August 18, September 7, September 28, October 3, October 30, November 29, and December 4, 2006; and January 3 and 12, 2007.
Luitpold Pharmaceuticals. Notification of voluntary recall (written communication). Available online at http://www.fda.gov/medwatch/safety/2006/Hydralazine_recall.pdf July 24, 2006.
Luitpold Pharmaceuticals. Notification of voluntary recall (written communication). August 11, 2006.
Abraxis Bioscience (formerly APP) Customer Service (personal communication). August 18, September 7, September 28, October 3, October 30, November 29, and December 4, 2006; and January 3 and 12, 2007.
Hydralazine hydrochloride injection package insert. Shirley, NY: American Regent, 2003.
Hydralazine hydrochloride injection package insert. Schaumburg, IL: APP, 2004.
National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. NIH Publication 04-5230. Available online at http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf(accessed on August 30, 2006). Bethesda, MD: National Institutes of Health, National Heart, Lung, and Blood Institute; 2004.

Updated

Updated January 12, 2007 by M. Christina Beckwith, Pharm.D., Drug Information Specialist. Created August 30, 2006, by M. Christina Beckwith, Pharm.D., and Erin R. Fox, Pharm.D., Drug Information Specialists. Copyright 2007, Drug Information Service, University of Utah, Salt Lake City, UT.

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