Indications and Usage
Thiothixene capsules are effective in the management of schizophrenia. Thiothixene capsules have not been evaluated in the management of behavioral complications in patients with mental retardation.
Dosage and Administration
Dosage of thiothixene capsules should be individually adjusted depending on the chronicity and severity of the symptoms of schizophrenia. In general, small doses should be used initially and gradually increased to the optimal effective level, based on patient response.
Some patients have been successfully maintained on once-a-day thiothixene capsules therapy.
The use of thiothixene capsules in children under 12 years of age is not recommended because safe conditions for its use have not been established.
In milder conditions, an initial dose of 2 mg three times daily is recommended. If indicated, a subsequent increase to 15 mg/day total daily dose is often effective.
In more severe conditions, an initial dose of 5 mg twice daily is recommended.
The usual optimal dose is 20 mg to 30 mg daily. If indicated, an increase to 60 mg/day total daily dose is often effective. Exceeding a total daily dose of 60 mg rarely increases the beneficial response.
Contraindications
Thiothixene capsules are contraindicated in patients with circulatory collapse, comatose states, central nervous system depression due to any cause, and blood dyscrasias. Thiothixene capsules are contraindicated in individuals who have shown hypersensitivity to the drug. It is not known whether there is a cross sensitivity between the thioxanthenes and the phenothiazine derivatives, but this possibility should be considered.
Adverse Reactions
NOTE: Not all of the following adverse reactions have been reported with thiothixene. However, since thiothixene has certain chemical and pharmacologic similarities to the phenothiazines, all of the known side effects and toxicity associated with phenothiazine therapy should be borne in mind when thiothixene is used.
Cardiovascular Effects
Tachycardia, hypotension, lightheadedness, and syncope. In the event hypotension occurs, epinephrine should not be used as a pressor agent since a paradoxical further lowering of blood pressure may result. Nonspecific EKG changes have been observed in some patients receiving thiothixene. These changes are usually reversible and frequently disappear on continued thiothixene therapy. The incidence of these changes is lower than that observed with some phenothiazines. The clinical significance of these changes is not known.
CNS Effects
Drowsiness, usually mild, may occur although it usually subsides with continuation of thiothixene therapy. The incidence of sedation appears similar to that of the piperazine group of phenothiazines but less than that of certain aliphatic phenothiazines. Restlessness, agitation and insomnia have been noted with thiothixene. Seizures and paradoxical exacerbation of psychotic symptoms have occurred with thiothixene infrequently.
Hyperreflexia has been reported in infants delivered from mothers having received structurally related drugs.
In addition, phenothiazine derivatives have been associated with cerebral edema and cerebrospinal fluid abnormalities.
Extrapyramidal Symptoms
Extrapyramidal symptoms, such as pseudoparkinsonism, akathisia and dystonia have been reported (see Dystonia, Class effect ). Management of these extra-pyramidal symptoms depends upon the type and severity. Rapid relief of acute symptoms may require the use of an injectable antiparkinson agent. More slowly emerging symptoms may be managed by reducing the dosage of thiothixene and/or administering an oral antiparkinson agent.
Dystonia
Class effect
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Persistent Tardive Dyskinesia
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy with thiothixene1 or may occur after drug therapy has been discontinued. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities.
Since early detection of tardive dyskinesia is important, patients should be monitored on an ongoing basis. It has been reported that fine vermicular movement of the tongue may be an early sign of the syndrome. If this or any other presentation of the syndrome is observed, the clinician should consider possible discontinuation of antipsychotic medication (see WARNINGS section).
Hepatic Effects
Elevations of serum transaminase and alkaline phosphatase, usually transient, have been infrequently observed in some patients. No clinically confirmed cases of jaundice attributable to thiothixene have been reported.
Hematologic Effects
As is true with certain other psychotropic drugs, leukopenia and leukocytosis, which are usually transient, can occur occasionally with thiothixene. Other antipsychotic drugs have been associated with agranulocytosis, eosinophilia, hemolytic anemia, thrombocytopenia and pancytopenia.
Allergic Reactions
Rash, pruritus, urticaria, photosensitivity and rare cases of anaphylaxis have been reported with thiothixene. Undue exposure to sunlight should be avoided. Although not experienced with thiothixene, exfoliative dermatitis and contact dermatitis (in nursing personnel) have been reported with certain phenothiazines.
Endocrine/Reproductive
Hyperprolactinemia3, lactation, menstrual irregularities, moderate breast enlargement and amenorrhea have occurred in a small percentage of females receiving thiothixene. If persistent, this may necessitate a reduction in dosage or the discontinuation of therapy. Phenothiazines have been associated with false positive pregnancy tests, gynecomastia, hypoglycemia, hyperglycemia and glycosuria.
Autonomic Effects
Dry mouth, blurred vision, nasal congestion, constipation, increased sweating, increased salivation and impotence have occurred infrequently with thiothixene therapy. Phenothiazines have been associated with miosis, mydriasis, and adynamic ileus.
Other Adverse Reactions
Hyperpyrexia, anorexia, nausea, vomiting, diarrhea, increase in appetite and weight, weakness or fatigue, polydipsia, and peripheral edema.
Although not reported with thiothixene, evidence indicates there is a relationship between phenothiazine therapy and the occurrence of a systemic lupus erythematosus-like syndrome.
Neuroleptic Malignant Syndrome (NMS)
Please refer to the text regarding NMS in the WARNINGS section.
NOTE: Sudden deaths have occasionally been reported in patients who have received certain phenothiazine derivatives. In some cases the cause of death was apparently cardiac arrest or asphyxia due to failure of the cough reflex. In others, the cause could not be determined nor could it be established that death was due to phenothiazine administration.
To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug Interactions
Hepatic microsomal enzyme inducing agents, such as carbamazepine, were found to significantly increase the clearance of thiothixene. Patients receiving these drugs should be observed for signs of reduced thiothixene effectiveness4,5.
Due to a possible additive effect with hypotensive agents, patients receiving these drugs should be observed closely for signs of excessive hypotension when thiothixene is added to their drug regimen6.
Overdosage
Manifestations include muscular twitching, drowsiness and dizziness. Symptoms of gross overdosage may include CNS depression, rigidity, weakness, torticollis, tremor, salivation, dysphagia, hypotension, disturbances of gait, or coma.
Treatment
Essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under careful observation and maintain an open airway, since involvement of the extrapyramidal system may produce dysphagia and respiratory difficulty in severe overdosage. If hypotension occurs, the standard measures for managing circulatory shock should be used (intravenous (I.V.) fluids and/or vasoconstrictors).
If a vasoconstrictor is needed, levarterenol and phenylephrine are the most suitable drugs. Other pressor agents, including epinephrine, are not recommended, since phenothiazine derivatives may reverse the usual pressor action of these agents and cause further lowering of blood pressure.
If CNS depression is marked, symptomatic treatment is indicated. Extrapyramidal symptoms may be treated with antiparkinson drugs.
There are no data on the use of peritoneal or hemodialysis, but they are known to be of little value in phenothiazine intoxication.
Description
Thiothixene is a thioxanthene derivative. Specifically, it is the cis isomer of N,N-dimethyl-9-[3-(4-methyl-1-piperazinyl)propylidene]thioxanthene-2-sulfonamide. It has a molecular formula C23H29N3O2S2 and the molecular weight is 443.63 g/mol.
The chemical structure is:
The thioxanthenes differ from the phenothiazines by the replacement of nitrogen in the central ring with a carbon-linked side chain fixed in space in a rigid structural configuration. An N,N-dimethyl sulfonamide functional group is bonded to the thioxanthene nucleus.
Each Thiothixene Capsules, USP contains 1 mg, 2 mg, 5 mg or 10 mg of thiothixene, USP and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium lauryl sulfate.
Each empty hard gelatin capsule contains gelatin, iron oxide red, iron oxide yellow, purified water and titanium dioxide. In addition, the 1 mg hard gelatin capsule contains D&C yellow 10, FD&C blue 1 and FD&C red 40. The 2 mg hard gelatin capsule also contains D&C yellow 10 and ferrosoferric oxide. The 5 mg and 10 mg hard gelatin capsule also contains ferrosoferric oxide.
The capsule is imprinted with black pharmaceutical ink which contains ferrosoferric oxide, potassium hydroxide, propylene glycol and shellac.
structureHow Supplied / Storage and Handling
Thiothixene Capsules USP, 1 mg are supplied as size ‘4’ hard gelatin capsules with a caramel opaque colored cap and a blue opaque colored body, imprinted 'AA10A' on body, with black ink containing white to off-white granular powder.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 60219-1673-1
Bottles of 1000: NDC 60219-1673-7
Thiothixene Capsules USP, 2 mg are supplied as size ‘4’ hard gelatin capsules with a caramel opaque colored cap and a yellow opaque colored body, imprinted 'AA11A' on body, with black ink containing white to off-white granular powder.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 60219-1674-1
Bottles of 1000: NDC 60219-1674-7
Thiothixene Capsules USP, 5 mg are supplied as size ‘4’ hard gelatin capsules with a caramel opaque colored cap and a white opaque colored body, imprinted 'AA12A' on body, with black ink containing white to off-white granular powder.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 60219-1675-1
Bottles of 1000: NDC 60219-1675-7
Thiothixene Capsules USP, 10 mg are supplied as size ‘4’ hard gelatin capsules with a caramel opaque colored cap and a peach opaque colored body, imprinted 'AA13A' on body, with black ink containing white to off-white granular powder.
They are available as follows:
Bottles of 100 with child-resistant closure: NDC 60219-1676-1
Bottles of 1000: NDC 60219-1676-7
Storage
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Patient Counseling Information
Given the likelihood that some patients exposed chronically to antipsychotics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.