Ethmozine Side Effects

Please note - some side effects for Ethmozine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Ethmozine - for the Consumer

Ethmozine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Ethmozine:

Dizziness; headache; nausea; tiredness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; fast, irregular, or slow heartbeat; shortness of breath; swelling of the legs or ankles.

Ethmozine Side Effects - for the Professional

Ethmozine

The most serious adverse reaction reported for Ethmozine® is proarrhythmia. This occurred in 3.7% of 1072 patients with ventricular arrhythmias who received a wide range of doses under a variety of circumstances.

In addition to discontinuations because of proarrhythmias, in controlled clinical trials and in open studies, adverse reactions led to discontinuation of Ethmozine® in 7% of 1105 patients with ventricular and supraventricular arrhythmias, including 3.2% due to nausea, 1.6% due to ECG abnormalities (principally conduction defects, sinus pause, junctional rhythm, or AV block), 1% due to congestive heart failure and 0.3-0.4% due to dizziness, anxiety, drug fever, urinary retention, blurred vision, gastrointestinal upset, rash, and laboratory abnormalities.

The most frequently occurring adverse reactions in the 1072 patients (including all adverse experiences whether or not considered Ethmozine®-related by the investigator) were dizziness (15.1%), nausea (9.6%), headache (8.0%), fatigue (5.9%), palpitations (5.8%) and dyspnea (5.7%). Dizziness appears to be related to the size of each dose. In a comparison of 900 mg/day given at 450 mg b.i.d. or 300 mg t.i.d., more than 20% of patients experienced dizziness on the b.i.d. regimen vs. 12% on the t.i.d. regimen.

Adverse reactions reported by less than 5%, but in 2% or greater of the patients were: sustained ventricular tachycardia, hypesthesias, abdominal pain, dyspepsia, vomiting, sweating, cardiac chest pain, asthenia, nervousness, paresthesias, congestive heart failure, muscoloskeletal pain, diarrhea, dry mouth, cardiac death, sleep disorders and blurred vision.

Adverse reactions infrequently reported (in less than 2% of the patients) were:

Cardiovascular hypotension, hypertension, syncope, supraventricular arrhythmias (including atrial fibrillation/flutter), cardiac arrest, bradycardia, pulmonary embolism, myocardial infarction, vasodilation, cerebrovascular events, thrombophiebitis;

Nervous System tremor, anxiety, depression, euphoria, confusion, somnolence, agitation, seizure, coma, abnormal gait, hallucinations, nystagmus, diplopia, speech disorder, akathisia, loss of memory, ataxia, abnormal coordination, dyskinesia, vertigo, tinnitus;

Genitourinary urinary retention or frequency, dysuria, urinary incontinence, kidney pain, impotence, decreased libido;

Respiratory hyperventilation, apnea, asthma, pharyngitis, cough, sinusitis;

Gastrointestinal anorexia, bitter taste, dysphagia, flatulence, ileus;

Other drug fever, hypothermia, temperature intolerance, eye pain, rash, pruritus, dry skin, urticaria, swelling of the lips and tongue, perorbital edema.

During Ethmozine® therapy, two patients developed thrombocytopenia that may have been drug-related. Clinically significant elevations in liver function tests (bilirubin, serum transaminases) and jaundice consistent with hepatitis were rarely reported. Although a cause and effect relationship has not been established, caution is advised in patients who develop unexplained signs of hepatic dysfunction, and consideration should be given to discontinuing therapy.

Three patients developed rechallenge-confirmed drug fever, with one patient experiencing an elevation above 103°F (to 105°F, with rigors). Fevers occurred at about 2 weeks in 2 cases, and after 21 weeks in the third. Fevers resolved within 48 hours of discontinuation of moricizine.

Adverse reactions were generally similar in patients over 65 (n=375) and under 65 (n=697), although discontinuation of therapy for reasons other than proarrhythmia was more common in older patients (13.9% vs. 7.7%). Overall mortality was greater in older patients (9.3% vs. 3.9%), but those were not deaths attributed to treatment and the older patients had more serious underlying heart disease.

The following table compares the most common (occurrence in more than 2% of the patients) non-cardiac adverse reactions (i.e. drug-related or of unknown relationship) in controlled clinical trials during the first one to two weeks of therapy with Ethmozine®, quinidine, placebo, disopyramide or propranolol in patients with ventricular arrhythmias.

Side Effects by Body System

Cardiovascular

Cardiovascular side effects have included exacerbation of old or induction of new atrial and ventricular arrhythmias (2% to 12%), heart failure (2%), hypotension (1%), and syncope (1%). Moricizine-induced arrhythmias may be lethal and more refractory to conversion to sinus rhythm than nondrug-induced arrhythmias. To reduce the proarrhythmic effect, it is recommended that the serum potassium, calcium, and magnesium concentrations be within normal limits prior to moricizine therapy.

Alteration in ventricular conduction, including new bundle branch patterns, has occurred in approximately 9.4% of patients. Second-degree heart block has occurred in patients without baseline conduction abnormalities (0.2%) as well as those with preexisting abnormalities (0.9%). Third-degree heartblock has been reported in 1.4% of patients with baseline conduction dysfunction.

Independent risk factors for the development of moricizine cardiotoxicity are advanced age, coronary artery disease, a history of myocardial infarction, low left ventricular ejection fraction (less than 0.40), and congestive heart failure.

Other cardiovascular effects have included hypertension, chest pain, congestive heart failure, myocardial infarction, vasodilation and thrombophlebitis.

The multicenter Cardiac Arrhythmias Suppression Trial (CAST) failed to show improved survival during use of moricizine to treat asymptomatic or mildly asymptomatic premature ventricular depolarizations in patients with a recent history of myocardial infarction.

In a prospective study using maximal dosages of moricizine (mean 831 mg per day) in 31 patients with a history of sustained ventricular tachyarrhythmias (mean ejection fraction 0.39), a significant proarrhythmic effect and lack of efficacy were observed. Six of the 31 experienced ventricular proarrhythmias within four days. Of the remaining 25 patients, 24 underwent electrophysiologic testing and four were found to be noninducible (16% efficacy). Seven patients were discharged on moricizine therapy. One patient developed a ventricular proarrhythmia, one developed complete AV heart block, and two experienced recurrent ventricular tachycardia.

Gastrointestinal

Gastrointestinal side effects occurred in up to 34% of patients, usually manifesting as nausea (10% to 34%), vomiting or diarrhea (2%), and abdominal discomfort (3%). Gastrointestinal effects were included in adverse reactions leading to discontinuation of therapy in 7% of patients. Anorexia, bitter taste, dysphagia, flatulence, and ileus have been reported.

Nervous system

Nervous system side effects have usually manifest as dose-related dizziness (15%) and headache (8%). Other nervous system side effects included hypoesthesias (4%), paresthesias (2%), anxiety (3%), fatigue (1%), and sleep disorders (2%). Tremor, abnormal gait and coordination, ataxia, dyskinesia, confusion, somnolence, agitation, seizure, coma, speech disorder, and loss of memory have been reported.

One case of increased parkinsonism has been reported. Moricizine is a phenothiazine derivative and suspected of exacerbating or inducing parkinsonian symptoms.

Hematologic

No evidence of bone marrow toxicity was present in the rare reports of thrombocytopenia. Patients were on other drugs with thrombocytopenia-associated potential.

Hematologic side effects have been rare, but have include thrombocytopenia.

Hepatic

Hepatic side effects, such as transiently elevated liver function tests, have been reported.

Genitourinary

Genitourinary side effects may be related to the chemical similarity of moricizine to phenothiazines. Phenothiazines can cause urinary retention.

Genitourinary side effects including urinary retention or frequency, incontinence, impotence and decreased libido occurred in less than 2% of patients.

Other

Drug fever, confirmed by rechallenge, has been reported in three patients. Hypothermia and temperature intolerance have occurred. Vertigo and tinnitus have been reported.

Hypersensitivity

Hypersensitivity side effects such as rash, pruritus, urticaria, swelling of the lips and tongue and periorbital edema have been reported.

General

Generally, cardiovascular effects have been reported most frequently. Noncardiac side effects occur in up to 45% of patients, usually in the first one or two weeks of therapy.

Psychiatric

Psychiatric symptoms of depression, euphoria, and hallucinations have been reported.

Ocular

Ocular side effects including nystagmus, diplopia, pain, and blurred vision have occurred.

Respiratory

Respiratory side effects including pulmonary embolism, hyperventilation, apnea, asthma, pharyngitis, cough, and sinusitis have been reported.

Dermatologic

Dermatologic symptoms of dry skin and rash have been reported.

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