Isosorbide Dinitrate + Hydralazine Hydrochloride

Isosorbide Dinitrate + Hydralazine Hydrochloride is a combination tablet used for the treatment of heart failure. Isosorbide dinitrate is a vasodilator affecting both arteries and veins; its dilator properties result from nitric oxide release and guanylyl cyclase activation, leading to vascular smooth muscle relaxation. Hydralazine hydrochloride is a selective dilator of arterial smooth muscle. Animal data suggests hydralazine may also mitigate tolerance to nitrates.

• Treatment of heart failure in self-identified black patients (as adjunct to standard therapy)

Adult Dose (Oral):

• Initial: 1 tablet three times daily
• Maximum (if tolerated): 2 tablets three times daily
• Titration can be rapid (3-5 days); some patients may experience side effects
• If intolerable side effects, decrease to one-half tablet three times daily

Child Dose: Safety and effectiveness not established

Cardiac: Palpitations

Gastrointestinal: Abdominal discomfort, constipation

Nervous: Dysgeusia, hypoaesthesia, migraine, syncope

Others: Tinnitus, vertigo, eyelid edema, vision blurred, facial pain, flushing, chest discomfort, peripheral edema, pain in extremity, myalgia, chromaturia, dyspnea, erectile dysfunction, erythema, hyperhidrosis, pruritus, face swelling

Precautions:

• Symptomatic hypotension, particularly with upright posture, may occur with even small doses; caution in volume or salt depleted patients
• Hydralazine may cause drug-induced SLE syndrome; symptoms usually regress upon discontinuation
• Hydralazine can cause tachycardia and hypotension potentially leading to myocardial ischemia and angina
• Hydralazine associated with peripheral neuritis (paresthesia, numbness, tingling); pyridoxine should be added
• Geriatric patients should start at low end of dosing range (reflecting decreased hepatic and renal function)

Contraindications:

• Hypersensitivity to isosorbide dinitrate, hydralazine hydrochloride or organic nitrates
• Patients taking PDE-5 inhibitors (avanafil, sildenafil, vardenafil, tadalafil)
• Patients taking soluble guanylate cyclase (sGC) stimulator riociguat

Drug Interactions:

• PDE-5 inhibitors potentiate hypotensive effects of nitrates (contraindicated)
• Soluble guanylate cyclase stimulator riociguat causes hypotension (contraindicated)

Use in Pregnancy: No data on use in pregnant women; available data on hydralazine during second and third trimesters have not shown association with adverse pregnancy outcomes.

Use in Lactation: Developmental and health benefits of breastfeeding should be considered along with mother's clinical need and potential adverse effects on breastfed child.

Renal Impairment: No studies; no dose adjustment required for hydralazine or isosorbide dinitrate; dialysis is not effective.

Hepatic Impairment: No studies; isosorbide dinitrate concentrations increase in cirrhosis; caution required.

Overdose: No documented cases; no specific antidote; cardiovascular system support is primary; dialysis is not effective.