Yes

Antipsychotic Agent, Phenothazine, Piperidine

Management of manifestations of psychotic disorders; short-term treatment of moderate to marked depression with variable degrees of anxiety in adult patients and for the treatment of agitation, anxiety, depression, tension, sleep disturbances, and fears in geriatric patients; behavioral problems in children

C

Hypersensitivity to thioridazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, circulatory collapse, severe hypotension, bone marrow suppression, blood dyscrasias, coma

Highly 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; bone marrow suppression; predisposition to seizures; subcortical brain damage; 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 phenothiazines. 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 low relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS). Doses exceeding recommended doses may cause pigmentary retinopathy.

Cardiovascular: Hypotension, orthostatic hypotension, peripheral edema, EKG changes

Central nervous system: EPS (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia), dizziness, drowsiness, neuroleptic malignant syndrome (NMS), impairment of temperature regulation, lowering of seizures threshold

Dermatologic: Increased sensitivity to sun, rash, discoloration of skin (blue-gray)

Endocrine & metabolic: Changes in menstrual cycle, changes in libido, breast pain, galactorrhea, amenorrhea

Gastrointestinal: Constipation, weight gain, nausea, vomiting, stomach pain, xerostomia, nausea, vomiting, diarrhea

Genitourinary: Difficulty in urination, ejaculatory disturbances, urinary retention, priapism

Hematologic: Agranulocytosis, leukopenia

Hepatic: Cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Tremor

Ocular: Pigmentary retinopathy, blurred vision, cornea and lens changes

Respiratory: Nasal congestion

Symptoms of overdose include deep sleep, coma, extrapyramidal symptoms, abnormal involuntary muscle movements, hypotension, 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); do not use epinephrine. 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 and 2D6 enzyme substrate; CYP2D6 enzyme inhibitor

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

Chloroquine may increase thioridazine concentrations

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

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

Antihypertensive effects of guanethidine and guanadrel may be inhibited by thioridazine

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

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

Thioridazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce thioridazine concentrations

Propranolol may increase thioridazine concentrations

Sulfadoxine-pyrimethamine may increase thioridazine concentrations

Thioridazine and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

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

Thioridazine and trazodone may produce additive hypotensive effects

Phenylpropanolamine in combination with thioridazine may result in cardiac arrhythmias; monitor

Naltrexone in combination with thioridazine has been reported to cause lethargy and somnolence

Protect all dosage forms from light

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones

Duration of action: 4-5 days

Half-life: 21-25 hours

Time to peak serum concentration: Within 1 hour

Oral:

Behavior problems: Initial: 10 mg 2-3 times/day, increase gradually

Severe psychoses: Initial: 25 mg 2-3 times/day, increase gradually

Adults:

Psychoses: Initial: 50-100 mg 3 times/day with gradual increments as needed and tolerated; maximum: 800 mg/day in 2-4 divided doses; if >65 years, initial dose: 10 mg 3 times/day

Depressive disorders, dementia: Initial: 25 mg 3 times/day; maintenance dose: 20-200 mg/day

Hemodialysis: Not dialyzable (0% to 5%)

Alcohol: Additive CNS effect, avoid use

For patients on prolonged therapy: CBC, ophthalmologic exam, blood pressure, liver function tests

Therapeutic: 1.0-1.5 mg/mL (SI: 2.7-4.1 mmol/L); Toxic: >10 mg/mL (SI: >27 mmol/L)

False-positives for phenylketonuria, urinary amylase, uroporphyrins, urobilinogen

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. Store away from light. 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). Avoid skin contact with liquid medication; may cause contact dermatitis (wash immediately with warm, soapy water). 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, vomiting, or dry mouth (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.

Avoid skin contact with oral suspension or solution; may cause contact dermatitis

Concentrate, oral: 30 mg/mL (120 mL); 100 mg/mL (3.4 mL, 120 mL)

Suspension, oral: 25 mg/5 mL (480 mL); 100 mg/5 mL (480 mL)

Tablet: 10 mg, 15 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

Aman MG, Marks RE, Turbott SH, et al, "Clinical Effects of Methylphenidate and Thioridazine in Intellectually Subaverage Children," J Am Acad Child Adolesc Psychiatry, 1991, 30(2):246-56.

Appell RA, Shield DE, and McGuire EJ, "Thioridazine-Induced Priapism," Br J Urol, 1977, 49(2):160.

Baker PB, Merigian KS, Roberts JR, et al, "Hyperthermia, Hypertension, Hypertonia, and Coma in Massive Thioridazine Overdose," Am J Emerg Med, 1988, 6(4):346-9.

Buckley NA, Whyte IM, and Dawson AH, "Cardiotoxicity More Common in Thioridazine Overdose Than With Other Neuroleptics," J Toxicol Clin Toxicol, 1995, 33(3):199-204.

Burgess KR, Jefferis RW, and Stevenson IF, "Fatal Thioridazine Cardiotoxicity," Med J Aust, 1979, 2(4):177-8.

Cowen TD and Meythaler JM, "Hypotensive Effects of Thioridazine in an Elderly Patient With Traumatic Brain Injury," Brain Inj, 1994, 8(8):735-7.

Goss JB, "Concomitant Use of Thioridazine With Risperidone," Am J Health Syst Pharm, 1995, 52(9):1012.

Oshika T, "Ocular Adverse Effects of Neuropsychiatric Agents. Incidence and Management," Drug Saf, 1995, 12(4):256-63.

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.

Weisdorf D, Kramer J, Goldbarg A, et al, "Physostigmine for Cardiac and Neurologic Manifestations of Phenothiazine Poisoning," Clin Pharmacol Ther, 1978, 24(6):663-7.