hydrALAZINE

General

Genetic Implications:

Pronunciation:
hye-dral-a-zeen

Trade Name(s)

• Apresoline 

Ther. Class.

antihypertensives

Pharm. Class.

vasodilators

Indications

Moderate to severe hypertension.

Unlabeled Use(s):

New York Heart Associated Class III or IV HF with reduced ejection fraction (in combination with isosorbide dinitrate).

Action

Direct-acting peripheral arteriolar vasodilator.

Therapeutic Effect(s):

Lowering of BP in hypertensive patients and decreased afterload in patients with HF.

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration; well absorbed from IM sites. IV administration results in complete bioavailability.

Distribution: Widely distributed.

Metabolism and Excretion: Mostly metabolized by the GI mucosa and liver by N-acetyltransferase   (rate of acetylation is genetically determined [slow acetylators have ↑ hydralazine levels and ↑ risk of toxicity; fast acetylators have ↓ hydralazine levels and ↓ response]).

Half-life: 2–8 hr.

TIME/ACTION PROFILE (antihypertensive effect)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Some products contain tartrazine and should be avoided in patients with known intolerance.

Use Cautiously in:

• Cardiovascular or cerebrovascular disease;
• Severe renal impairment (dose modification may be necessary);
• Severe hepatic impairment (dose modification may be necessary).

Adverse Reactions/Side Effects

CV: tachycardia, angina, arrhythmia, edema, orthostatic hypotension

Derm: rash

GI: diarrhea, nausea, vomiting

MS: arthralgias, arthritis

Neuro: dizziness, drowsiness, headache, peripheral neuropathy

Misc: drug-induced lupus syndrome

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• ↑ hypotension with acute ingestion of  alcohol, other  antihypertensives, or  nitrates.
•  MAO inhibitors  may exaggerate hypotension.
• May ↓ pressor response to  epinephrine.
•  NSAIDs  may ↓ antihypertensive response.
•  Beta blockers  ↓ tachycardia from hydralazine (therapy may be combined for this reason).
•  Metoprolol  and  propranolol  may ↑ levels and risk of toxicity.
• May ↑ levels and risk of toxicity of  metoprolol  and  propranolol.

Route/Dosage

PO (Adults): Hypertension:  10 mg 4 times daily initially. After 2–4 days, may ↑ to 25 mg 4 times daily for the rest of the 1st wk; may then ↑ to 50 mg 4 times daily (up to 300 mg/day). Once maintenance dose is established, twice-daily dosing may be used.   HF:  25–37.5 mg 4 times daily; may be ↑ up to 300 mg/day in 3–4 divided doses.

PO (Children  >1 mo): 0.75–1 mg/kg/day in 2–4 divided doses (max = 25 mg/dose) initially; may ↑ gradually to 5 mg/kg/day in infants and 7.5 mg/kg/day in children (max = 200 mg/day) in 2–4 divided doses.

IM IV (Adults): Hypertension:  5–40 mg repeated as needed.  Eclampsia:  5 mg every 15–20 min; if no response after a total of 20 mg, consider an alternative agent.

IM IV (Children  >1 mo): 0.1–0.2 mg/kg/dose every 4–6 hr (max = 20 mg/dose) as needed, up to 1.7–3.5 mg/kg/day in 4–6 divided doses.

Availability (generic available)

Tablets: 10 mg, 25 mg, 50 mg, 100 mg

Injection: 20 mg/mL

In Combination with: isosorbide dinitrate (BiDil). See combination drugs.

Assessment

• Monitor BP and HR frequently during initial dose adjustment and periodically during therapy (20 min after each dose). BP may start to fall within a few min after injection, with maximal effect in 10–80 min. Monitor the patient for ≥30–60 min prior to discharge from an ambulatory setting; monitoring time may vary based on the individual patient's response and any setting specific clinical guidelines. Observe for potential side effects, such as hypotension or reflex tachycardia.
•  About 50–65% of White, Black, South Indian, and Mexican people are slow acetylators at risk for ↑ levels and toxicity, while 80–90% of Inuit, Japanese, and Chinese people are rapid acetylators at risk for ↓ levels and treatment failure.

Lab Test Considerations:

Monitor CBC, electrolytes, and ANA titer prior to and periodically during prolonged therapy.

• May cause a positive direct Coombs test result.

Implementation

• Do not confuse hydralazine with hydroxyzine, hydromorphone, or hydrochlorothiazide.
  • IM or IV route should be used only when drug cannot be given orally.
  • May be administered concurrently with diuretics or beta blockers to permit lower doses and minimize side effects.
• PO Administer with meals consistently to enhance absorption.
  • Pharmacist may prepare oral solution from hydralazine injection for patients with difficulty swallowing.

Patient/Family Teaching

• Explain the purpose and side effects of hydralazine to patient. Emphasize the importance of continuing to take this medication, even if feeling well. Instruct patient to take medication at the same time each day; last dose of the day should be taken at bedtime. Take missed doses as soon as remembered; do not double doses. If >2 doses in a row are missed, consult health care professional. Must be discontinued gradually to avoid sudden ↑ in BP. Hydralazine controls but does not cure hypertension. Advise patient to read  Patient Information  before starting and periodically during therapy in case of changes.
• Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
• Encourage patient to comply with additional interventions for hypertension (weight ↓, low-sodium diet, smoking cessation, moderation of alcohol intake, regular exercise, stress management). Instruct patient and family on proper technique for BP monitoring. Advise them to check BP at least weekly and report significant changes.
• Patients should weigh themselves twice weekly and assess feet and ankles for fluid retention.
• May occasionally cause drowsiness. Advise patient to avoid driving or other activities requiring alertness until response to medication is known.
• Caution patient to avoid sudden changes in position to minimize orthostatic hypotension.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially cough, cold, or allergy remedies.
• Instruct patient to notify health care professional of medication prior to treatment or surgery.
• Advise patient to notify health care professional immediately if general tiredness; fever; muscle or joint aching; chest pain; skin rash; sore throat; or numbness, tingling, pain, or weakness of hands and feet occurs. Vitamin B₆  (pyridoxine) may be used to treat peripheral neuritis.
• Rep:  Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Decrease in BP without appearance of side effects.
• Decreased afterload in patients with HF.