HydrALAZINE HCl

Brand names Apresoline, generic

Medication error Look-alike, sound-alike drug names. Tall man lettering is recommended to decrease confu- potential sion between hydrALAZINE hydroxyzine and hydroMORPHONE.(2) Caution should be used in converting between oral and IV dosing as dosing errors may occur.

Contraindications Contraindications: Patients with hypersensitivity to hydralazine or dihydralazine.(3) Also and warnings contraindicated in (1) severe tachycardia and heart failure with a high cardiac output (e.g., thyrotoxicosis); (2) myocardial insufficiency due to mechanical obstruction (e.g., aortic or mitral stenosis or constrictive pericarditis); (3) isolated right-ventricular heart failure due to pulmonary hypertension; (4) dissecting aortic aneurysm; and (5) idiopathic systemic lupus erythematosus (SLE) and related diseases.(3) Warnings: Prolonged treatment (>6 months) may provoke a SLE-like syndrome. More commonly occurs in slow acetylators, females, and those with renal dysfunction.(3) If SLE or similar symptoms develop, hydralazine should be discontinued unless benefit of continued therapy outweighs potential risk. Can cause angina attacks and ECG changes of myocardial ischemia, so use cautiously in patients with coronary artery disease.(3) Use with caution in patients with several renal disease or cerebrovascular accident.(3)

Infusion-related May cause reflex tachycardia, headaches, flushing, and fluid retention, which may be cautions managed with adjuvant beta-blocker and/or diuretic.(26,28) Combination with beta-blocker may also reduce hydralazine dose requirements.(3) Monitor blood pressure and heart rate during and after infusion.(3) When combined with other potent IV antihypertensive agents, such as diazoxide, hypo- tensive episodes can be prolonged; monitor patients for several hours after a precipitous decrease in blood pressure.(3)

Dosage Care should be taken in converting between oral and IV dosing (2:1 conversion ratio).(3) Average maximum decrease in blood pressure should occur within 10–80 minutes.(2) Heart failure: As an arteriolar vasodilator, hydralazine reduces afterload. 0.1–0.5 mg/kg (up to 20 mg over 1–2 minutes,(4,6,10-12,16) If response is inadequate after 30 minutes, a second 0.5 mg/kg (up to 20 mg) dose can be given.(6) This may be followed by 0.1–0.5 mg/kg q 6 hr.(11) Maximum dose is 2 mg/kg q 6 hr.(11) Hypertensive emergency: 0.1–0.6 mg/kg (up to 20 mg) given q 4–6 hr(18,26,28) One group recommended that the blood pressures should drop by one third of the desired decrease in blood pressure within 6 hours, a further one-third decrease within the next 24–36 hours, with the final one-third decrease over the next 48–72 hours.(4) If the patient is stable, a blood pressure decrease of <25% within minutes to 1 hour followed by further decreases over the next 2–6 hours has been suggested.

Dosage adjustment Adjust dosage in patients with renal dysfunction.(20) If CrCl is 10–50 mL/min, administer in organ dysfunction a normal dose q 8 hr.(20) If CrCl is <10 mL/min, administer a normal dose q 12–24 hr in slow acetylators and q 8–16 hr in fast acetylators.(20) Although hydralazine undergoes extensive metabolism, the manufacturer does not recommend dosage adjustment in those with hepatic failure.(3)

Maximum dosage 2 mg/kg q 3–6 hr(11,12,15) up to 9 mg/kg/day,(21) or a dose of 20(22)–25(8,13) mg

Additives Contains 103.6 mg propylene glycol, 0.65 mg methylparaben, and 0.35 mg polyparaben per mL.(23) (See Appendix C for more specific information about potential adverse effects of propylene glycol and parabens.)  462 HydrALAZINE HCl

Suitable diluents Does not require dilution. Should not be added to infusion solutions.(23)

Maximum 20 mg/mL(23) concentration

Preparation and Parenteral products should be visually inspected for particulate matter and discoloration delivery before use. Refer to appropriate references for more information on compatibility with other drugs and solutions; compatibility following Y-site delivery, and suggested storage and extended stability.(23) Preparation: Hydralazine should not be diluted in dextrose or other sugar-containing solutions because of the formation of hydrazones, which are associated with toxicity (e.g., headache, nausea, vomiting).(23) Stability: Store at controlled room temperature and protect from freezing. Refrigeration of intact containers may result in precipitation or crystallization.(23) Use immediately after vial is opened. Color changes that occur within 8–12 hours after admixture with most IV solutions do not indicate loss of potency.(23) Delivery system issues: Hydralazine in NS in PVC bags has been shown to exhibit a 10% loss in 1 week at room temperature, but it did not exhibit any loss due to sorption through an infusion set over a 7-hour simulation period.(23) May discolor upon contact with metal; discolored solutions should be discarded.(3) Photosensitivity: Exposure to light may increase the rate of decomposition during long- term storage (more rapid decomposition in PVC containers compared to glass bottles).

IV push Over 1–2 minutes,(6,23,26,28) with a maximum rate of 5 mg/min

Intermittent Not used infusion

Continuous infusion Not generally recommended due to solution stability.(23) One reference suggest 1.5 mcg/ kg/min.(11)

Other routes of 0.2–0.6 mg/kg/dose may be given IM.(25,26,28) administration

Comments Significant adverse effects: Should peripheral neuritis (paresthesias, numbness, tin- gling) occur the can be treated with pyridoxine.(3) Blood dyscrasias may occur.(3) Monitoring: Blood pressure should be monitored frequently. CBCs and antinuclear antibodies (ANAs) should be measured before and periodically during therapy. Benefit over risk should be determined when beginning or continuing therapy in a patient with a positive ANA titer.(3) Because acetylation is a major route of elimination for hydralazine, its metabolism will vary depending on whether the patient is a fast and slow acetylator. Most patients who develop symptoms of SLE are slow acetylators. If symptoms occur, appropriate labora- tory studies should be performed. If a test is positive hydralazine should be discontinued unless potential benefit outweigh the risk. Drug interactions: Consult appropriate resources for recommendations before combining any drug with hydralazine. May paradoxically reduce pressor response to epinephrine.(3) Use monoamine oxidase inhibitors with caution due to potentiation of hypotensive effects.(3) Many other drugs may potentiate the hypotensive effects of hydralazine.  463