Navane (Thiothixene)

NAVANE™

Pfizer

Thiothixene

Antipsychotic

Action And Clinical Pharmacology: Thiothixene is an antipsychotic agent of the thioxanthene series. It possesses certain chemical and pharmacologic similarities to the piperazine phenothiazines and differences from the aliphatic group of phenothiazines. Thiothixene’s mode of action has not been clearly established.

Indications And Clinical Uses: An antipsychotic agent useful in the management of schizophrenia and other psychotic disorders.

As with other antipsychotic agents, some patients resistant to previous medication have responded favorably to thiothixene. It may also be of value in the management of withdrawn, apathetic schizophrenic patients.

Thiothixene is not recommended for the treatment of nonpsychotic mental and emotional disorders.

Contra-Indications: Children: Safety for use in children under 12 years of age has not yet been established.

Circulatory collapse, comatose states, CNS depression due to any cause and blood dyscrasias.

Known hypersensitivity to the drug. It is not known whether a cross sensitivity between the thioxanthenes and the phenothiazines exists, but this possibility should be considered.

Manufacturers’ Warnings In Clinical States: Occupational Hazards: As is true with many CNS drugs, thiothixene 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 drugs, patients should be cautioned about the possible additive effects (which may include hypotension) with CNS depressants and with alcohol. Potentiation of CNS depressants (sedatives, tranquilizers, narcotic analgesics, antihistamines, anesthetics, alcohol), atropine and organophosphorus insecticides, and reversal of epinephrine effect, have been observed with related drugs.

Pregnancy: Safe use in pregnancy has not been established. It should, therefore, not be used in women of childbearing potential unless, in the opinion of the physician, the expected benefits of the drug outweigh the potential hazard to the fetus.

Precautions: In consideration of the known capability of thiothixene and certain other antipsycotic drugs 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 it may lower the convulsive threshold. Although the drug potentiates the actions of the barbiturates, the dosage of the anticonvulsant therapy should not be reduced when it is administered concurrently.

Production or aggravation of ECG changes has occurred with thiothixene and therefore caution should be observed when there is increased risk to the patient (see Adverse Effects).

Though exhibiting rather weak anticholinergic properties, thiothixene should be used with caution in patients who are known or are suspected to have glaucoma, and in those who might be exposed to extreme heat or who are receiving atropine or related drugs. Undue exposure to sunlight should be avoided. Photosensitive reactions have been reported in patients.

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 thiothixene for prolonged periods). Blood dyscrasias (agranulocytosis, pancytopenia, thrombocytopenic purpura), and liver damage (jaundice, biliary stasis), have been reported with related drugs.

Caution as well as careful adjustment of the dosages is indicated when thiothixene is used in conjunction with other CNS depressants.

An antiemetic effect observed in animal studies may also occur in man; therefore, it is possible that thiothixene may mask signs of overdosage of toxic drugs and it may obscure conditions such as intestinal obstruction and brain tumor.

To lessen the likelihood of adverse reactions related to drug accumulation, patients on long-term therapy, particularly on high doses, should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued. Periodic blood counts and liver function tests should be performed. Sudden onset of severe CNS or vasomotor symptoms should be kept in mind.

Adverse Reactions: Since thiothixene has pharmacologic properties similar to those of the phenothiazines, all the known adverse reactions of that class of drugs should be borne in mind when it is used.

Behavioral: The most common side effects are initial and transient drowsiness, restlessness and agitation and insomnia. (The incidence of sedation appears to be similar to that of the piperazine group of phenothiazines, but less than that of certain aliphatic phenothiazines.)

Other adverse reactions reported less frequently are weakness or fatigue, excitement, depression and headache.

Psychic and motor hyperactivity may be desirable, except in an already agitated and excited patient. Activation of psychotic symptomatology has been observed, but it usually responds to reduction of dosage or temporary discontinuation of the drug. Toxic confusional states may occur on rare occasions.

Neurological: The incidence and nature of extrapyramidal symptoms, including akathisia, pseudo-parkinsonism and dystonic reactions, are similar to those encountered with the piperazine phenothiazines, but thiothixene is more likely to produce akathisia. They are usually controlled by reduction of dosage and/or administration of antiparkinson drugs depending on the type and severity of symptoms. Cerebral seizures have been reported (see Precautions). Phenothiazine derivatives have been associated with cerebral edema and cerebrospinal fluid abnormalities.

Hyperreflexia has been reported in infants delivered from mothers having received structurally related drugs.

Tardive Dyskinesias: As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible. 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.

There is no known effective treatment for tardive dyskinesia; antiparkinsonian agents usually do not alleviate the symptoms of this syndrome. All antipsychotic agents should be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. The physician may be able to reduce the risk of this syndrome by minimizing the unnecessary use of neuroleptics and reducing the dose or discontinuing the drug, if possible, when manifestations of this syndrome are recognized, particularly in patients over the age of 50. Fine vermicular movements of the tongue may be an early sign of the syndrome. If the medication is stopped at that time, the syndrome may not develop.

Autonomic: Dry mouth, blurred vision, nasal congestion, constipation, increased salivation and sweating, and impotence have occurred infrequently. Phenothiazines have been associated with miosis, mydriasis and adynamic ileus.

Cardiovascular: 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 thiothixene. These changes are usually reversible and frequently disappear on continued therapy. The clinical significance of these changes is not known. Cardiac arrhythmias, including AV block, paroxysmal tachycardia and ventricular fibrillation have been observed with some phenothiazines.

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.

Endocrine: Lactation, 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.

Allergic: Rash, pruritus, urticaria, and rare cases of anaphylaxis have been reported. Undue exposure to sunlight should be avoided. Although not experienced with thiothixene, exfoliative dermatitis, contact dermatitis (in nursing personnel), have been reported with certain phenothiazines.

Hematologic: As is true with certain other antipsychotic drugs, leukopenia and leukocytosis, which are usually transient, can occur occasionally. Other antipsychotic drugs have been associated with agranulocytosis, eosinophilia, hemolytic anemia, thrombocytopenia and pancytopenia.

Hepatic: Elevations of serum transaminase and alkaline phosphatase, usually transient, have been infrequently observed in some patients. No clinically confirmed cases of jaundice attributable to the drug have been reported.

Ophthalmological: fine lenticular pigmentation after prolonged therapy.

Miscellaneous: 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.

Symptoms And Treatment Of Overdose: Symptoms: 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 may be 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 (i.v. fluids and/or vasoconstrictors).

If a vasoconstrictor is needed, norepinephrine and phenylephrine are the most suitable drugs. Other pressor agents, including epinephrine, are not recommended, since phenothiazine derivatives may reverse the usual pressor elevating action of these agents and cause further lowering of blood pressure.

If CNS depression is present, recommended stimulants include caffeine and sodium benzoate. Picrotoxin or pentylenetetrazol should be avoided. 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.

Dosage: The usual optimal dosage of thiothixene is in the range of 15 to 30 mg daily. In most conditions, the initial dosage should be 5 to 10 mg daily. The dosage should be gradually increased to the optimally effective level based on patient response. An increase to 60 mg/day may be necessary; however, exceeding a total daily dosage of 60 mg/day rarely increases beneficial response. Patients on the average therapeutic dosage may be maintained on once a day therapy. Higher dosage can be given in 2 or 3 equally divided doses. The dosage should be reduced to the lowest possible maintenance level as soon as possible.

Availability And Storage: 2 mg: Each white, hard gelatin capsule contains: thiothixene 2 mg. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and sodium lauryl sulfate; capsule shell: gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Tartrazine-free. Bottles of 100.

5 mg: Each orange and white, hard gelatin capsule contains: thiothixene 5 mg. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and sodium lauryl sulfate; capsule shell: FD&C Red No. 3, FD&C Yellow No. 6, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Tartrazine-free. Bottles of 100.

10 mg: Each orange, hard gelatin capsule contains: thiothixene 10 mg. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and sodium lauryl sulfate; capsule shell: FD&C Red No. 3, FD&C Yellow No. 6, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide. Tartrazine-free. Bottles of 100.

Store between 15 and 30°C. (Shown in Product Recognition Section)

NAVANE™ Pfizer Thiothixene Antipsychotic

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