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THIXIT is available as thiothixene hydrochloride blue round flat tablets engraved with "2" and a breakline on one face & "dp" on the other containing 2mg thiothixene; & cream round flat tablets engraved with "10" and a breakline on one face & "dp" on the other containing 10mg thiothixene.
THIXIT is a psychotropic agent of the thioxanthene series. THIXIT possesses certain chemical and pharmacological similarities to the piperazine phenothiazines and differences from the aliphatic group of phenothiazines.
The exact mechanism of action of thiothixene is unknown. It is hypothesized that THIXIT produces a postsynaptic dopamine receptor blockage leading to a compensatory increase in dopamine synthesis and turnover rate.
Thiothixene appears to be well absorbed orally, rapidly distributed and metabolised to a variety of related compounds, which are excreted mainly in the bile. There is a 5:2 ratio of biliary to urinary excretion after thiothixene administration to dogs. Based on animal studies, the liver appears to be a major site of metabolism.
Although metabolized to a variety of compounds, only N-dimethyl-thiothixene has been identified. THIXIT has an absorption half time of about 0.5 hours, an early disappearance half life of 3.5 hours and a late disappearance half life of 34 hours.
Schizophrenia: THIXIT is a major antipsychotic agent for the treatment of schizophrenia. It is effective in chronically ill schizophrenic patients as well as those with acute symptomatology. Withdrawn, apathetic schizophrenic patients benefit specifically from the activating properties of THIXIT.
Increased co-operation, social competence and interest, and greater personal neatness have also been noted. Schizophrenic patients refractory to currently available psychotherapeutic agents may benefit through treatment with THIXIT.
Other psychoses: THIXIT is also useful in the treatment of patients with diagnoses of involutional psychosis, senile psychosis and psychosis associated with alcoholism.
Some patients have been successfully maintained on once-a-day THIXIT therapy.
In milder conditions, an initial dose is 2mg three times daily. If indicated, a subsequent increase to 15mg daily is often effective.
In more severe conditions, an initial dose of 5mg twice daily is recommended.
The usual optimal dose is 20 to 30mg daily. If indicated, an increase to 60mg/day total daily dose is often effective. As is customary with this class of agent, further titration above 60mg is generally unnecessary. However, THIXIT has been shown to be beneficial at doses above 60mg for severely depressed patients or chronic refractory patients unresponsive to lower dosages.
Use in children under 12 years of age is not recommended.
It may be necessary to adjust the dosage when changing from the intramuscular to oral dosage forms.
THIXIT is contraindicated in patients with circulatory collapse, comatose states, central nervous system depression due to any cause, and blood dyscrasias. THIXIT is contraindicated in individuals who have shown hypersensitivity to the agent.
An antiemetic effect was observed in animal studies with THIXIT; since this effect may also occur in man, it is possible that THIXIT may mask signs of overdosage of toxic agents and may obscure conditions such as intestinal obstruction and brain tumour.
In consideration of the known capability of THIXIT and certain other psychotropic agents to precipitate convulsions, extreme caution should be used in patients with a history of convulsive disorders or those in a state of alcohol withdrawal, since THIXIT may lower the convulsive threshold.
Though exhibiting rather weak anticholinergic properties, THIXIT should be used with caution in patients who are known or suspected to have glaucoma, or who might be exposed to extreme heat, or who are receiving atropine or related agents.
Use with caution in patients with cardiovascular disease.
Caution as well as careful adjustment of the dosage is indicated when THIXIT is used in conjunction with other CNS depressants other than anticonvulsant agents.
Also, careful observation should be made for pigmentary retinopathy, and lenticular pigmentation (fine lenticular pigmentation has been noted in a small number of patients treated with THIXIT for prolonged periods). Blood dyscrasias (agranulocytosis, pancytopenia, thrombocytopenic purpura), and liver damage (jaundice, biliary stasis), have been reported with related agents.
Undue exposure to sunlight should be avoided. Photosensitive reactions have been reported in patients on THIXIT.
As is true with many CNS agents, THIXIT may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, especially during the first few days of therapy. Therefore, the patient should be cautioned accordingly.
As in the case of other CNS-acting agents, patients receiving THIXIT should be cautioned about the possible additive effects, (which may include hypotension) with CNS depressants and with alcohol.
Safe use of THIXIT during pregnancy has not been established. THIXIT should be given to pregnant patients only when, in the judgement of the physician, the expected benefits from the treatment exceed the possible risks to mother and foetus. Animal reproduction studies and clinical experience to date have not demonstrated any teratogenic effects.
In the animal reproduction studies with THIXIT, there was some decrease in conception rate and litter size, and an increase in resorption rate in rats and rabbits. Similar findings have been reported with other psychotropic agents.
After repeated oral administration of THIXIT to rats (5 to 15 mg/kg/day), rabbits (3 to 50 mg/kg/day), and monkeys (1 to 3 mg/kg/day) before and during gestation, no teratogenic effects were seen.
It is not known whether this agent is excreted in human milk. Because many agents are excreted in human milk, and the possibility of serious adverse reactions occurring in breastfeeding infants, THIXIT should be used only when in the opinion of the physician, potential benefit outweighs potential risk.
The use of THIXIT in children under 12 years of age is not recommended because safety and efficacy in the paediatric age group have not been established.
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 ECG changes have been observed in some patients receiving THIXIT. These changes are usually reversible and frequently disappear on continued THIXIT therapy. The incidence of these changes is lower than that observed with some phenothiazines. The clinical significance of these changes is not known.
Drowsiness, usually mild, may occur, although it usually subsides with continuation of THIXIT 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 THIXIT. Seizures and paradoxical exacerbation of psychotic symptoms have occurred infrequently with THIXIT.
Extrapyramidal symptoms, such as pseudoparkinsonism, akathisia and dystonia have been reported. Management of these extrapyramidal 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 THIXIT and/or administering an oral antiparkinson agent.
As with all antipsychotic agents tardive dyskinesia may appear in some patients on long-term therapy 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 neuroleptic medication. (See Warnings and Precautions section.)
Elevations of serum transaminase and alkaline phosphatase, usually transient, have been infrequently observed in some patients. No clinically confirmed cases of jaundice attributable to THIXIT have been reported.
As is true with certain other psychotropic agents, leukopenia and leukocytosis, which are usually transient, can occur occasionally with THIXIT. Blood dyscrasias (agranulocytosis, pancytopenia, thrombocytopenic purpura) have been reported with related agents.
Rash, pruritus, urticaria, photosensitivity and rare cases of anaphylaxis have been reported with THIXIT. Undue exposure to sunlight should be avoided.
Lactation, moderate breast enlargement and amenorrhoea have occurred in a small percentage of females receiving THIXIT. If persistent, this may necessitate a reduction in dosage or the discontinuation of therapy.
Dry mouth, blurred vision, nasal congestion, constipation, increased sweating, increased salivation and impotence have occurred infrequently with THIXIT therapy.
Hyperpyrexia, anorexia, nausea, vomiting, diarrhoea, increase in appetite and weight, weakness or fatigue, polydipsia, and peripheral oedema.
It is not known whether there is a cross sensitivity between the thioxanthenes and the phenothiazine derivatives, but this possibility should be considered. THIXIT potentiates the actions of the barbiturates, but the dosage of the anticonvulsant therapy should not be reduced when THIXIT is administered concurrently.
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.
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. Extrapyramidal symptoms may be treated with antiparkinsonian agents. If hypotension occurs, the standard measures for managing circulatory shock should be used (I.V. fluids and/or vasoconstrictors).
If a vasoconstrictor is needed, levarterenol and phenylephrine are the most suitable agents. Other pressor agents, including adrenaline, 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 present resulting in respiratory depression, endotracheal or nasotrachael intubation and assisted ventilation may be necessary.
No data are available on the use of peritoneal dialysis or haemodialysis, but they are known to be of little value in phenothiazine intoxication.
Store below 30°C.
Prescription Medicine
Tablets 2mg x 100
Tablets 10mg x 100
THIXIT brand of thiothixene hydrochloride is a thioxanthene derivative. Specifically, thiothixene is the cis isomer of N,N-dimethyl-9-[3-(4-methyl-l-piperazinyl)-propylidene] thioxanthene-2-sulfonamide.
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.
Thiothixene occurs as a white, odourless crystalline powder. The thiothixene base has a melting range between 147°C and 152°C.
Other ingredients of the tablets are:
2mg tablets: Lactose, Maize Cornflour, Magnesium stearate, Calcium hydrogen phosphate dihydrate, Sodium lauryl sulphate and FD & C Blue No. 2 Lake.
10mg tablets: Wheat starch, Glycine, Sodium chloride, Saccharin sodium, Vanillin, Magnesium Stearate, Calcium hydrogen phosphate dihydrate and Sodium lauryl sulphate.
Lincoln Pharmaceuticals
A Division of Douglas Pharmaceuticals Ltd
Central Park Drive
Lincoln
PO Box 45027
Auckland 8
NEW ZEALAND
Telephone: (09) 835-0660
Fax: (09) 835-0665
19 August 1999