Tocainide HCl

The initial and most important signs and symptoms of. overdosage would be expected to be related to the central nervous system. Other adverse reactions, such as gastrointestinal disturbances, may follow. (See ADVERSE REACTIONS.)

Should convulsions or cardiopulmonary depression or arrest develop, the patency of the airway and adequacy of ventilation must be assured immediately. Should convulsions persist, despite ventilatory therapy with oxygen, small increments of anticonvulsive agents may be given intravenously. Examples of such agents include a benzodiazepine (e.g., diazepam), an ultrashort-acting barbiturate (e.g., thiopental or thiamylal), or a short-acting barbiturate (e.g., pentobarbital or secobarbital).

The oral LD50 of tocainide was calculated to be about 800 mg/kg in mice, 1000 mg/kg in rats, and 230 mg/kg in guinea pigs; deaths were usually preceded by convulsions.

Studies in normal individuals to date indicate that tocainide has a hemodialysis clearance approximately equivalent to its renal clearance.

TONOCARD (tocainide hcl) commonly produces minor, transient, nervous system and gastrointestinal adverse reactions, but is otherwise generally well tolerated. TONOCARD (tocainide hcl) has been evaluated in both short-term (n = 1,358) and long-term (n = 262) controlled studies as well as a compassionate use program. Dosages were lower in most of the controlled studies (1200 mg/day) and higher in the compassionate use program (1800 mg and more). In long-term (2-6 months) controlled studies, the most frequent adverse reactions were dizziness/vertigo (15.3 percent), nausea, (14.5 percent), paresthesia (9.2 percent), and tremor (8.4 percent). These reactions were generally mild, transient, dose-related and reversible with a reduction in dosage, by taking the drug with food, or by therapy discontinuation. Tremor, when present, may be useful as a clinical indicator that the maximum dose is being approached. Adverse reactions leading to therapy discontinuation occurred in 21 percent of patients in long-term controlled trials and were usually related to the nervous system or digestive system.

Adverse reactions occurring in greater than one percent of patients from the short-term and long-term controlled studies appear in the following table:

An additional group of about 2,000 patients has been treated in a program allowing for the use of TONOCARD (tocainide hcl) under compassionate use circumstances. These patients were seriously ill with the large majority on multiple drug therapy, and comparatively high doses of TONOCARD (tocainide hcl) were used. Fifty-four percent of the patients continued in the program for one year or longer, and 12 percent were treated for longer than three years, with the longest duration of therapy being nine years. Adverse reactions leading to therapy discontinuation occurred in 12 percent of patients (usually central nervous system effects or rash). A tabulation of adverse reactions occurring in one percent or more of patients follows:

Adverse reactions occurring in less than one percent of patients, in either the controlled studies on the compassionate use program or since the drug was marketed, are as follows:

Body as a Whole: Septicemia; septic shock; syncope; vasovagal episodes; edema; fever; chills; cinchonism; asthenia; malaise.

Cardiovascular: Ventricular fibrillation; extension of acute myocardial infarction; cardiogenic shock; pulmonary embolism; angina; AV block; hypertension; claudication; increased QRS duration; pleurisy/pericarditis; prolonged QT interval; right bundle branch block; cardiomegaly; sinus arrest; vasculitis; orthostatic hypotension; cold extremities.

Digestive: Hepatitis, jaundice (see PRECAUTlONS), abnormal liver function tests, pancreatitis, abdominal pain and discomfort; constipation; dysphagia; gastrointestinal symptoms (including dyspepsia); stomatitis; dry mouth; thirst.

Hematologic: Agranulocytosis; bone marrow depression; aplastic/hypoplastic anemia; hemolytic anemia; anemia; leukopenia; neutropenia; thrombocytopenia; eosinophilia.

Metabolic and Immune: Hypersensitivity Reaction (including some of the following symptoms or signs: rash, fever, joint pains, abnormal liver function tests, eosinophilia); increased ANA.

Musculoskeletal: Muscle cramps; muscle twitching/spasm; neck pain; pain radiating from neck pressure on shoulder.

Nervous System/Psychiatric: Coma; convulsions/seizures; myasthenia gravis; depression; psychosis; psychic disturbances; agitation; decreased mental acuity; dysarthria; impaired memory; increased stuttering/slurred speech; insomnia/sleeping disturbances; local anesthesia; dream abnormalities.

Respiratory: Respiratory arrest; pulmonary edema; pulmonary fibrosis; fibrosing alveolitis; pneumonia; interstitial pneumonitis; dyspnea; hiccups; yawning.

Skin: Stevens-Johnson syndrome; exfoliative dermatitis; erythema multiforme; urticaria; alopecia; pruritus; pallor/flushed face.

Special Senses: Diplopia; earache; taste perversion/smell perversion.

Urogenital: Urinary retention; polyuria/increased diuresis.

Agranulocytosis, bone marrow depression, leukopenia, neutropenia, aplastic/hypoplastic anemia, and thrombocytopenia have been reported (0.18 percent) in patients receiving TONOCARD (tocainide hcl) in controlled trials and the compassionate use program. Most of these events have been noted during the first 12 weeks of therapy. (See Boxed WARNINGS.)

Pulmonary fibrosis, interstitial pneumonitis, fibrosing alveolitis, pulmonary edema, and pneumonia, have been reported in patients receiving TONOCARD. (tocainide hcl) The incidence of pulmonary fibrosis (including interstitial pneumonitis and fibrosing alveolitis) was 0.11 percent in controlled trials and the compassionate use program. These events usually occurred in seriously ill patients. Symptoms of these pulmonary disorders and/or x-ray changes usually occurred following 3-18 weeks of therapy. Fatalities have been reported. (See Boxed WARNINGS.)

A number of disorders, in which a causal relationship with TONOCARD (tocainide hcl) has not been established, have been reported in seriously ill patients. These include: renal failure; renal dysfunction; myocardial infarction; cerebrovascular accidents and transient ischemic attacks. These disorders may be related to the patient†s underlying condition.

DRUG ABUSE AND DEPENDENCE

Drug withdrawal after chronic treatment has not shown any indication of psychological or physical dependence.

Read the entire FDA prescribing information for Tonocard (Tocainide HCl)