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 Side Effects, and Drug Interactions - Tocainide HCl
Tonocard Side Effects, and Drug Interactions - Tocainide HCl
SIDE EFFECTS
TONOCARD commonly produces minor, transient, nervous system and gastrointestinal
adverse reactions, but is otherwise generally well tolerated. TONOCARD
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:
Body System /
Adverse REACTIONS |
Percent of Patients
Controlled Studies |
| Short-term (n=1,358) |
Long-term (n=262) |
| BODY AS A WHOLE |
| Tiredness/drowsiness/fatigue/lethargy/lassitude/sleepiness
|
1.6 |
0.8 |
| Hot/cold feelings |
0.5 |
1.5 |
| CARDIOVASCULAR |
| Hypotension |
3.4 |
2.7 |
| Bradycardia |
1.8 |
0.4 |
| Palpitations |
1.8 |
0.4 |
| Chest pain |
1.6 |
0.4 |
| Conduction disorders |
1.5 |
0.0 |
| Left ventricular failure |
1.4 |
0.0 |
| DIGESTIVE |
| Nausea |
15.2 |
14.5 |
| Vomiting |
8.3 |
4.6 |
| Anorexia |
1.2 |
1.9 |
| Diarrhea/ loose stools |
0.0 |
3.8 |
| NERVOUS SYSTEM/PSYCHIATRIC |
| Dizziness/vertigo |
8.0 |
15.3 |
| Paresthesia |
3.5 |
9.2 |
| Tremor |
2.9 |
8.4 |
| Confusion/disorientation/hallucinations |
2.1 |
2.7 |
| Headache |
2.1 |
4.6 |
| Nervousness |
1.5 |
0.4 |
| Altered mood/awareness |
1.5 |
3.4 |
| Incoordination/unsteadiness/walking disturbances |
1.2 |
0.0 |
| Anxiety |
1.1 |
1.5 |
| Ataxia |
0.2 |
3.0 |
| SKIN |
| Diaphoresis |
5.1 |
2.3 |
| Rash/skin lesion |
0.4 |
8.4 |
| SPECIAL SENSES |
| Blurred vision/visual disturbances |
1.3 |
1.5 |
| Tinnitus/hearing loss |
0.4 |
1.5 |
| Nystagmus |
0.0 |
1.1 |
An additional group of about 2,000 patients has been treated in a program
allowing for the use of TONOCARD under compassionate use circumstances.
These patients were seriously ill with the large majority on multiple
drug therapy, and comparatively high doses of TONOCARD 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:
Body System /
Adverse REACTIONS |
Percent of Patients Compassionate
Use (n=1,927) |
| CARDIOVASCULAR |
| Increased ventricular arrhythmias/PVCs |
10.9 |
| CHF/progression of CHF |
4.0 |
| Tachycardia |
3.2 |
| Hypotension |
1.8 |
| Conduction disorders |
1.3 |
| Bradycardia |
1.0 |
| DIGESTIVE |
| Nausea |
24.6 |
| Anorexia |
11.3 |
| Vomiting |
9.0 |
| Diarrhea/loose stools |
6.8 |
| MUSCULOSKELETAL |
| Arthritis/arthralgia |
4.7 |
| Myalgia |
1.7 |
| NERVOUS SYSTEM/PSYCHIATRIC |
| Dizziness/vertigo |
25.3 |
| Tremor |
21.6 |
| Nervousness |
11.5 |
| Confusion/disorientation/hallucinations |
11.2 |
| Altered mood/awareness |
11.0 |
| Ataxia |
10.8 |
| Paresthesia |
9.2 |
| SKIN |
| Rash/Skin lesion |
12.2 |
| Diaphoresis |
8.3 |
| Lupus |
1.6 |
| SPECIAL SENSES |
| Blurred vision/vision disturbances |
10.0 |
| Nystagmus |
1.1 |
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 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.
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 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.
DRUG INTERACTIONS
Tocainide and lidocaine are pharmacodynamically similar. The concomitant
use of these two agents may cause an increased incidence of adverse reactions,
including central nervous system adverse reactions such as seizure.
Specific interaction studies with cimetidine, digoxin, metoprolol and
warfarin have been conducted, no clinically significant interaction was
seen with cimetidine, digoxin or warfarin; but tocainide and metoprolol
had additive effects on wedge pressure and cardiac index. TONOCARD has
also been used in open studies with digitalis, beta-blocking agents, other
antiarrhythmic agents, anticoagulants, and diuretics, without evidence
of clinically significant interactions. Nevertheless, caution should be
exercised in the use of multiple drug therapy.
TONOCARD is equally effective in digitalized and non-digitalized patients.
In 17 patients with refractory ventricular arrhythmias on concomitant
therapy, serum digoxin levels (1.1 ±0.4 ng/mL) remained in the expected
normal range (0.5-2.5 ng/mL) during tocainide administration.
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