THIORIDAZINE HYDROCHLORIDE- thioridazine hydrochloride tablet, film coated
Mylan Pharmaceuticals Inc.
WARNING
Thioridazine has been shown to prolong the QTc interval in a dose related manner, and drugs with this potential, including thioridazine, have been associated with Torsades de pointes type arrhythmias and sudden death. Due to its potential for significant, possibly life threatening, proarrhythmic effects, thioridazine should be reserved for use in the treatment of schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs (see WARNINGS, CONTRAINDICATIONS, and INDICATIONS).
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Thioridazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).
DESCRIPTION
Thioridazine hydrochloride is 2-methylmercapto-10-[2-(N-methyl-2-piperidyl) ethyl] phenothiazine
Thioridazine hydrochloride, USP is available as tablets for oral administration containing 10 mg, 25 mg, 50 mg or 100 mg.
Each tablet for oral administration contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, FD&C Yellow No. 6 Aluminum Lake, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium lauryl sulfate and titanium dioxide.
CLINICAL PHARMACOLOGY
The basic pharmacological activity of thioridazine is similar to that of other phenothiazines, but is associated with minimal extrapyramidal stimulation.
However, thioridazine has been shown to prolong the QTc interval in a dose dependent fashion. This effect may increase the risk of serious, potentially fatal, ventricular arrhythmias, such as Torsades de pointes type arrhythmias. Due to this risk, thioridazine is indicated only for schizophrenic patients who have not been responsive to or cannot tolerate other antipsychotic agents (see WARNINGS and CONTRAINDICATIONS). However, the prescriber should be aware that thioridazine has not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.
INDICATIONS AND USAGE
Thioridazine hydrochloride tablets are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine hydrochloride tablets should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with thioridazine hydrochloride tablets, it is strongly recommended that a patient be given at least two trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration (see WARNINGS and CONTRAINDICATIONS).
However, the prescriber should be aware that thioridazine hydrochloride tablets have not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.
CONTRAINDICATIONS
Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias.
ADVERSE REACTIONS
In the recommended dosage ranges with thioridazine hydrochloride most side effects are mild and transient.
Central Nervous System
Drowsiness may be encountered on occasion, especially where large doses are given early in treatment. Generally, this effect tends to subside with continued therapy or a reduction in dosage. Pseudoparkinsonism and other extrapyramidal symptoms may occur but are infrequent. Nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, and headache have been reported but are extremely rare.
Autonomic Nervous System
Dryness of mouth, blurred vision, constipation, nausea, vomiting, diarrhea, nasal stuffiness, and pallor have been seen.
Endocrine System
Galactorrhea, breast engorgement, amenorrhea, inhibition of ejaculation, and peripheral edema have been described.
Skin
Dermatitis and skin eruptions of the urticarial type have been observed infrequently. Photosensitivity is extremely rare.
Cardiovascular System
Thioridazine produces a dose related prolongation of the QTc interval, which is associated with the ability to cause Torsades de pointes type arrhythmias, a potentially fatal polymorphic ventricular tachycardia, and sudden death (see WARNINGS). Both Torsades de pointes type arrhythmias and sudden death have been reported in association with thioridazine. A causal relationship between these events and thioridazine therapy has not been established but, given the ability of thioridazine to prolong the QTc interval, such a relationship is possible. Other ECG changes have been reported
DOSAGE AND ADMINISTRATION
Since thioridazine hydrochloride tablets are associated with a dose related prolongation of the QTc interval, which is a potentially life threatening event, its use should be reserved for schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Dosage must be individualized and the smallest effective dosage should be determined for each patient.
Thioridazine Hydrochloride: Package Insert and Label Information (Page 3 of 3)
By Mylan Pharmaceuticals Inc. | Last revised: 28 November 2016
Adults
The usual starting dose for adult schizophrenic patients is 50 mg to 100 mg three times a day, with a gradual increment to a maximum of 800 mg daily if necessary. Once effective control of symptoms has been achieved, the dosage may be reduced gradually to determine the minimum maintenance dose. The total daily dosage ranges from 200 mg to 800 mg, divided into two to four doses.
Pediatric Patients
For pediatric patients with schizophrenia who are unresponsive to other agents, the recommended initial dose is 0.5 mg/kg/day given in divided doses. Dosage may be increased gradually until optimum therapeutic effect is obtained or the maximum dose of 3 mg/kg/day has been reached.
