Yes

Antipsychotic Agent, Thioxanthene Derivative

Management of psychotic disorders

C

Hypersensitivity to thiothixene or any component; severe CNS depression, circulatory collapse, blood dyscrasias, coma

May be sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; predisposition to seizures; subcortical brain damage; bone marrow suppression; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of neuroleptics. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is high relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Hypotension, tachycardia, syncope, nonspecific EKG changes

Central nervous system: Extrapyramidal signs (pseudoparkinsonism, akathisia, dystonias, lightheadedness, tardive dyskinesia), dizziness, drowsiness, restlessness, agitation, insomnia

Dermatologic: Discoloration of skin (blue-gray), rash, pruritus, urticaria, photosensitivity

Endocrine & metabolic: Changes in menstrual cycle, changes in libido, breast pain, galactorrhea, lactation, amenorrhea, gynecomastia, hyperglycemia, hypoglycemia

Gastrointestinal: Weight gain, nausea, vomiting, stomach pain, constipation, xerostomia, increased salivation

Genitourinary: Difficulty in urination, ejaculatory disturbances, impotence

Hematologic: Leukopenia, leukocytes

Neuromuscular & skeletal: Tremors

Ocular: Pigmentary retinopathy, blurred vision

Respiratory: Nasal congestion

Miscellaneous: Diaphoresis

Symptoms of overdose include muscle twitching, drowsiness, dizziness, rigidity, tremor, hypotension, cardiac arrhythmias

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required (eg, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response). Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

CYP1A2 enzyme substrate

Benztropine (and other anticholinergics) may inhibit the therapeutic response to thiothixene and excess anticholinergic effects may occur

Chloroquine may increase thiothixene concentrations

Cigarette smoking may enhance the hepatic metabolism of thiothixene. Larger doses may be required compared to a nonsmoker.

Concurrent use of thiothixene with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by thiothixene

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Thiothixene may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Thiothixene plus lithium may rarely produce neurotoxicity

Barbiturates may reduce thiothixene concentrations

Propranolol may increase thiothixene concentrations

Sulfadoxine-pyrimethamine may increase thiothixene concentrations

Thiothixene and low potency antipsychotics may reverse the pressor effects of epinephrine

Thiothixene and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Thiothixene and trazodone may produce additive hypotensive effects

Refrigerate

Elicits antipsychotic activity by postsynaptic blockade of CNS dopamine receptors resulting in inhibition of dopamine-mediated effects; also has alpha-adrenergic blocking activity

Metabolism: Extensive in the liver

Half-life: >24 hours with chronic use

Children <12 years: Oral: 0.25 mg/kg/24 hours in divided doses (dose not well established)

Children >12 years and Adults: Mild to moderate psychosis:

Oral: 2 mg 3 times/day, up to 20-30 mg/day; more severe psychosis: Initial: 5 mg 2 times/day, may increase gradually, if necessary; maximum: 60 mg/day

I.M.: 4 mg 2-4 times/day, increase dose gradually; usual: 16-20 mg/day; maximum: 30 mg/day; change to oral dose as soon as able

Rapid tranquilization of the agitated patient (administered every 30-60 minutes):

Oral: 5-10 mg

I.M.: 10-20 mg

Average total dose for tranquilization: 15-30 mg

Hemodialysis: Not dialyzable (0% to 5%)

Alcohol: Additive CNS effect, avoid use

Liver function tests; for patients on prolonged therapy: CBC, ophthalmologic exam

cholesterol (S), glucose; uric acid (S); may cause false-positive pregnancy test

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension

Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age; drug-induced Parkinson's syndrome occurs often; Akathisia is the most common extrapyramidal reaction in elderly

Increased confusion, memory loss, psychotic behavior, and agitation frequently occur as a consequence of anticholinergic effects

Antipsychotic associated sedation in nonpsychotic patients is extremely unpleasant due to feelings of depersonalization, derealization, and dysphoria

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. Do not discontinue without consulting prescriber. Tablets/capsules may be taken with food. Mix oral solution with 2-4 ounces of liquid (eg, juice, milk, water, pudding). Do not take within 2 hours of any antacid. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May turn urine red-brown (normal). You may experience excess drowsiness, lightheadedness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); urinary retention (void before taking medication); ejaculatory dysfunction (reversible); decreased perspiration (avoid strenuous exercise in hot environments); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; altered menstrual pattern, change in libido, swelling or pain in breasts (male or female); vision changes; skin rash, irritation, or changes in color of skin (gray-blue); or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Observe for extrapyramidal effects; concentrate should be mixed in juice before administration

Capsule: 1 mg, 2 mg, 5 mg, 10 mg, 20 mg

Powder for injection, as hydrochloride: 5 mg/mL (2 mL)

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Schneider SM, "Neuroleptic Malignant Syndrome: Controversies in Treatment," Am J Emerg Med, 1991, 9(4):360-2.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.

Wiener JM, "Psychopharmacology in Childhood Disorders," Psychiatr Clin North Am, 1984, 7(4):831-43.