"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
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Blood Dyscrasias: Agranulocytosis, bone marrow depression, leukopenia, neutropenia, aplastic/hypoplastic anemia, thrombocytopenia and sequelae such as septicemia and septic shock have been reported in patients receiving TONOCARD. (tocainide hcl) Most of these patients received TONOCARD (tocainide hcl) within the recommended dosage range. Fatalities have occurred (with approximately 25 percent mortality in reported agranulocytosis cases). Since most of these events have been noted during the first 12 weeks of therapy, it is recommended that complete blood counts, including white cell, differential and platelet counts be performed, optimally, at weekly intervals for the first three months of therapy; and frequently thereafter. Complete blood counts should be performed promptly if the patient develops any signs of infection (such as fever, chills, sore throat, or stomatitis), bruising, or bleeding. If any of these hematologic disorders is identified, TONOCARD (tocainide hcl) should be discontinued and appropriate treatment should be instituted if necessary. Blood counts usually return to normal within one month of discontinuation. Caution should be used in patients with pre-existing marrow failure or cytopenia of any type. (See ADVERSE REACTIONS.)
Pulmonary Fibrosis: Pulmonary fibrosis, interstitial pneumonitis, fibrosing alveolitis, pulmonary edema, and pneumonia have been reported in patients receiving TONOCARD. (tocainide hcl) Many of these events occurred in patients who were seriously ill. Fatalities have been reported. The experiences are usually characterized by bilateral infiltrates on x-ray and are frequently associated with dyspnea and cough. Fever may or may not be present. Patients should be instructed to promptly report the development of any pulmonary symptoms such as exertional dyspnea, cough or wheezing. Chest x-rays are advisable at that time. If these pulmonary disorders develop, TONOCARD should be discontinued. (See ADVERSE REACTIONS.)
|Mortality: In the National Heart, Lung and Blood Institute†s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3.0%). The average duration of treatment with encainide or flecainide in this study was ten months. |
The applicability of the CAST results to other populations (e. g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of TONOCARD (Tocainide HCl) and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life- threatening arrhythmias, the use of TONOCARD as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
In patients with known heart failure or minimal cardiac reserve, TONOCARD (tocainide hcl) should be used with caution because of the potential for aggravating the degree of heart failure.
Caution should be used in the institution or continuation of antiarrhythmic therapy in the presence of signs of increasing depression of cardiac conductivity.
Like all other oral antiarrhythmics, TONOCARD (tocainide hcl) has been reported to increase arrhythmias in some patients (see ADVERSE REACTIONS).
Information for Patients
See PATIENT INFORMATION section.
As with other antiarrhythmics, abnormal liver function tests, particularly in the early stages of therapy, have been reported. Periodic monitoring of liver function should be considered. Hepatitis and jaundice have been reported in some patients.
See DRUG INTERACTIONS section.
The carcinogenic potential of tocainide was studied in mice using oral doses up to 300 mg/kg/day (about 6 times the maximum recommended human dose) for up to 94 weeks in males and 102 weeks in females and in rats at doses up to 200 mg/kg/day for 24 months. Tocainide did not affect the type or incidence of neoplasia in the two studies.
Tocainide did not show any mutagenic potential when evaluated in vivo in the micronucleus test using mice at oral doses up to 187.5 mg/kg/day (about 7 times the usual human dose). Also, no mutagenic activity was seen in vitro in the Ames microbial mutagen test or in the mouse lymphoma forward mutation assay.
Reproduction and fertility studies in rats showed no adverse effects on male or female fertility at oral doses up to 200 mg/kg/day (about 8 times the usual human dose).
Pregnancy Category C. In a teratogenicity study in rabbits, tocainide was administered orally at doses of 25, 50, and 100 mg/kg/day (about 1 to 4 times the usual human dose). No evidence of a drug-related teratogenic effect was noted; however, these doses were maternotoxic and produced a dose-related increase in abortions and stillbirths. In a teratogenicity study in rats, an oral dose of 300 mg/kg/day (about 12 times the usual human dose) showed no evidence of treatment-related fetal malformations, but maternotoxicity and an increase in fetal resorptions were noted. An oral dose of 30 mg/kg/day (about twice the usual human dose) did not produce any adverse effects.
In reproduction studies in rats at maternotoxic oral doses of 200 and 300 mg/kg/day (about 8 and 12 times the usual human dose, respectively), dystocia, and delayed parturition occurred which was accompanied by an increase in stillbirths and decreased survival in offspring during the first week postpartum. Growth and viability of surviving offspring were not affected for the remainder of the lactation period.
It is not known whether tocainide is secreted in human milk. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from TONOCARD, (tocainide hcl) a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in children have not been established.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Additional Tonocard Information
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