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Pronunciation |
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(thye
oh THIKS
een) |
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U.S. Brand
Names |
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Navane® |
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Generic
Available |
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Yes |
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Synonyms |
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Tiotixene |
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Pharmacological Index |
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Antipsychotic Agent, Thioxanthene Derivative |
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Use |
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Management of psychotic disorders |
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Pregnancy Risk
Factor |
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C |
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Contraindications |
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Hypersensitivity to thiothixene or any component; severe CNS depression,
circulatory collapse, blood dyscrasias, coma |
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Warnings/Precautions |
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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. |
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Adverse
Reactions |
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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 |
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Overdosage/Toxicology |
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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. |
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Drug
Interactions |
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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
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Stability |
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Refrigerate |
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Mechanism of
Action |
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Elicits antipsychotic activity by postsynaptic blockade of CNS dopamine
receptors resulting in inhibition of dopamine-mediated effects; also has
alpha-adrenergic blocking activity |
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Pharmacodynamics/Kinetics |
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Metabolism: Extensive in the liver
Half-life: >24 hours with chronic use |
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Usual Dosage |
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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%) |
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Dietary
Considerations |
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Alcohol: Additive CNS effect, avoid use |
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Monitoring
Parameters |
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Liver function tests; for patients on prolonged therapy: CBC, ophthalmologic
exam |
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Test
Interactions |
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cholesterol (S),
glucose;
uric acid (S); may cause
false-positive pregnancy
test |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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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. |
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Dental Health:
Effects on Dental Treatment |
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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
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Patient
Information |
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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. |
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Nursing
Implications |
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Observe for extrapyramidal effects; concentrate should be mixed in juice
before administration |
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Dosage Forms |
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Capsule: 1 mg, 2 mg, 5 mg, 10 mg, 20 mg
Powder for injection, as hydrochloride: 5 mg/mL (2 mL) |
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References |
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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. |
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