hydralazine/isosorbide dinitrate (hye-dral-a-zeen eye-so-sor-bide di-ni-trate) BiDil

 Indications

Management of heart failure in black patients.

Action

BiDil is a fixed-dose combination of isosorbide dinitrate,

a vasodilator with effects on both arteries and

veins, and hydralazine, a predominantly arterial vasodilator.

Therapeutic Effects: Improved survival, increased

time to hospitalization and decreased symptoms

of heart failure in black patients.

Pharmacokinetics

See pharmacokinetic sections in hydralazine and isosorbide

dinitrate monographs of Davis’s Drug Guide for

Nurses for more information.

Absorption: Hydralazine—10–26% absorbed in

HF patients, absorption can be saturated leading to

largeqin absorption with higher doses; isosorbide

dinitrate—variable absorbed (10–90%) reflecting

first-pass hepatic metabolism.

Distribution: Hydralazine—widely distributed,

crosses the placenta, minimal amounts in breast milk;

isosorbide dinitrate—accumulates in muscle and venous

wall.

Metabolism and Excretion: Hydralazine—

mostly metabolized by GI mucosa and liver; isosorbide

dinitrate—undergoes extensive first-pass metabolism

in the liver, mostly metabolized by the liver, some metabolites

are vasodilators.

Half-life: Hydralazine—4 hr; isosorbide dinitrate—

2 hr. 

TIME/ACTION PROFILE (effect on BP)

ROUTE ONSET PEAK DURATION

hydralazine 45 min 2 hr 2–4 hr

isosorbide 15–40 min unknown 4 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to either component;

Concurrent use of PDE-5 inhibitor (avanafil,

sildenafil, tadalafil, vardenafil) or riociguat.

Use Cautiously in: Severe renal/hepatic disease

(dose modification may be necessary); Head trauma or

cerebral hemorrhage; Geri: Start with lower doses; OB:

May compromise maternal/fetal circulation; Lactation:

Safety not established; Pedi: Safety not established.

Adverse Reactions/Side Effects

Hydralazine

CNS: dizziness, drowsiness, headache. CV: tachycardia,

angina, arrhythmias, edema, orthostatic hypotension.

GI: diarrhea, nausea, vomiting. Derm: rash. F

and E: sodium retention. MS: arthralgias, arthritis.

Neuro: peripheral neuritis. Misc: drug-induced lupus

syndrome.

Isosorbide Dinitrate

CNS: dizziness, headache, apprehension, weakness.

CV: hypotension, tachycardia, paradoxic bradycardia,

syncope. GI: abdominal pain, nausea, vomiting. Misc:

cross-tolerance, flushing, tolerance.

Interactions

Drug-Drug: Concurrent use of avanafil, sildenafil,

tadalafil, or vardenafil may result in severe hypotension;

concurrent use contraindicated. Concurrent use

of riociguat may result in severe hypotension; concurrent

use contraindicated.qrisk of hypotension with

other antihypertensives, acute ingestion of alcohol,

and phenothiazines. MAO inhibitors may exaggerate

hypotension. Maypthe pressor response to epinephrine.

Beta blockersptachycardia from hydralazine

(therapy may be combined for this reason).

Metoprolol and propranolol mayqhydralazine levels.

Hydralazineqlevels of metoprolol and propranolol.

Route/Dosage

PO (Adults): 1 tablet 3 times daily, may beqto 2 tablets

3 times daily.

Availability

Tablets: hydralazine 37.5 mg/isosorbide dinitrate 20 mg.