Isozine

Isozine tablet is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient-reported functional status.
Limitations of use
: There is little experience in patients with NYHA class IV heart failure.

Dosage & Administration

Route of administration
: Isozine should be taken in oral route.
This tablet should be initiated at a dose of one tablet, three times a day. Dosing should be titrated to a maximum of two tablets three times daily, if tolerated. Although titration of this tablet can be rapid (3-5 days), some patients may experience side effects and may take longer to reach their maximum tolerated dose. The dosage may be decreased to as one-half of this tablet three times a day, if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside.
Use in children and adolescents
: The safety and effectiveness of this combination in children have not been established.

The following adverse reactions have been identified during post-approval use of this tablet-
Cardiac Disorders: Palpitations
Ear and labyrinth disorders: Tinnitus, vertigo
Eye Disorders: Eyelid edema, vision blurred
Gastrointestinal Disorders: Abdominal discomfort, constipation
General Disorders and Administration Site Conditions: Facial pain, flushing, chest discomfort, chest pain, peripheral edema
Musculoskeletal and Connective Tissue Disorders: Pain in extremity, myalgia
Nervous Disorders: Dysgeusia, hypoaesthesia, migraine, syncope
Renal and Urinary Disorders: Chromaturia, pulmonary renal syndrome
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea
Reproductive System and Breast Disorders: Erectile dysfunction
Skin and Subcutaneous Tissue Disorders: Erythema, hyperhidrosis, pruritus, face swelling

Symptomatic hypotension, particularly with upright posture, may occur with even small doses of Isozine. Hypotension is most likely to occur in patients who have been volume or salt depleted; it should be corrected prior to initiation of Isozine. Hydralazine hydrochloride has been reported to cause a drug-induced systemic lupus erythematosus (SLE) syndrome. Symptoms and signs usually regress when hydralazine hydrochloride is discontinued. Hydralazine hydrochloride can cause tachycardia and hypotension potentially leading to myocardial ischemia and angina, particularly in patients with hypertrophic cardiomyopathy. Hydralazine hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness and tingling, which may be related to an antipyridoxine effect. Pyridoxine should be added to Isozine therapy if such symptoms develop.

The mechanism of action underlying the beneficial effects in the treatment of heart failure has not been established. Isosorbide dinitrate is a vasodilator affecting both arteries and veins. Its dilator properties result from the release of nitric oxide and the subsequent activation of guanylyl cyclase, and ultimate relaxation of vascular smooth muscle. Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of chronically-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours is response to nitrates restored. Hydralazine hydrochloride is a selective dilator of arterial smooth muscle. Animal data suggests that hydralazine may also mitigate tolerance to nitrates.