A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tonocard Warnings, Precautions, Pregnancy, Nursing, Abuse - Tocainide HCl
Tonocard Warnings, Precautions, Pregnancy, Nursing, Abuse - Tocainide HCl
WARNINGS
WARNINGS
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. Most of these patients received
TONOCARD 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 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. 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. |
Acceleration of Ventricular Rate: Acceleration of ventricular
rate occurs infrequently when antiarrhythmics are administered to patients
with atrial flutter or fibrillation (see ADVERSE
REACTIONS).
PRECAUTIONS
General
In patients with known heart failure or minimal cardiac reserve, TONOCARD
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.
In patients with severe liver or kidney disease, the rate of drug elimination
may be significantly decreased (see DOSAGE
AND ADMINISTRATION).
Since antiarrhythmic drugs may be ineffective in patients with hypokalemia,
the possibility of a potassium deficit should be explored and, if present,
the deficit should be corrected.
Like all other oral antiarrhythmics, TONOCARD has been reported to increase
arrhythmias in some patients (see ADVERSE
REACTIONS).
Information for Patients
See PATIENT INFORMATION section.
Laboratory Tests
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.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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
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.
There are no adequate and well-controlled studies in pregnant women.
TONOCARD should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers
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, 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.
Pediatric Use
Safety and effectiveness in children have not been established.
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