Trifluoperazine
Trifluoperazine is a generic medication for the drug :
Trifluoperazine medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Trifluoperazine 1 mg
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Trifluoperazine 2 mg
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Trifluoperazine 5 mg
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Trifluoperazine 10 mg
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Trifluoperazine 20 mg
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Drug Interactions
Drug-Herb Interactions
Avoid concurrent use of phenothiazines with kava kava, gotu kala, valerian and St. John's wort because these herbs may increase CNS depression. Kava kava may also provide additive dopamine antagonism. Dong quai should also be avoided because of a possible increased risk of photosensitization.
Drug-Laboratory Interactions
Trifluoperazine use may cause a false positive reading for phenylketonuria.
Trifluoperazine
Drug-Drug Interactions
| Interacting Drug | Effect | Clinical Comment |
|---|---|---|
| Anticholinergics (e.g., benztropine, trihexypyhenidyl, orphenadrine, procyclidine) | May inhibit the therapeutic response to trifluoperazine. May delay gastric emptying, decrease absorption and increase gut wall metabolism of trifluoperazine | Excess anticholinergic effects may occur. Reserve for situations where EPS occur and lowering of the antipsychotic dose is not possible. Re-evaluate anticholinergic use regularly (e.g., every 3 months) |
| Antihypertensives | Potential additive hypotension | Monitor blood pressure |
| Chloroquine | May increase trifluoperazine levels | Mechanism unknown; monitor for enhanced pharmacologic and adverse effects of trifluoperazine |
| CNS depressants (e.g., opioid analgesics, ethanol, barbiturates, cyclic antidepressants, antihistamines, sedative-hypnotics) | May produce additive CNS depression | Advise patients to monitor for additive effects and to modify activities accordingly (e.g., driving) |
| CYP1A2 inducers (e.g., carbamazepine, cigarette smoking, phenobarbital, rifampin) | Decreased plasma concentrations of trifluoperazine | Monitor for decreased therapeutic effects of trifluoperazine and adjust dose as indicated |
| CYP1A2 inhibitors (e.g., amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, ofloxacin, propranolol) | Increased plasma concentrations of trifluoperazine | Monitor for increased pharmacologic and adverse effects of trifluoperazine and adjust dose as indicated |
| Drugs that prolong the QTc (e.g., adenosine, antiarrhythmics, chloral hydrate, chloroquine, clarithromcyin, erythromycin, gatifloxacin, levofloxacin, pimozide) | Potential additive QTc prolongation | Coadministration of phenothiazines with other medications that might also prolong the QTc interval is not recommended |
| Epinephrine | May result in hypotension | Trifluoperazine may reverse the pressor effects of epinephrine; epinephrine should not be used to manage hypotension caused by phenothiazines |
| Levodopa, bromocriptine, cabergoline, guanethidine | May antagonize the pharmacologic effects of these medications resulting in loss of efficacy | Decreased therapeutic effects of both drugs |
| Lithium | Rarely, concurrent use of lithium with phenothiazines has resulted in acute encephalopathic syndrome, even with normal lithium levels | Caution and close monitoring for neurologic symptoms is advised |
| Metoclopramide | Potential additive EPS | Monitor for increased incidence of EPS |
Overview
Trifluoperazine is a major substrate of the CYP1A2. Inhibitors of CYP1A2 may increase the levels of trifluoperazine, enhancing its effects; CYP1A2 inducers produce the opposite effect. It is important to avoid alcoholic beverages as this combination may increase CNS depression and increase the risk of extrapyramidal reactions.
Special Handling Instructions
Avoid skin contact with oral suspension as contact dermatitis has been reported.
Dosage and Administration
Antiemetic
Adults (hospitalized or well-supervised)
Initial oral dose is 2 to 5 mg twice daily with optimum response usually seen in the 15 to 20 mg/day range. Maximum doses of 60 to 100 mg/day have been used.
Psychotic Disorders
Dosing Considerations
Individualization of the dose is important when using trifluoperazine. Once the maximum response is achieved, the dose may need to be reduced gradually to a maintenance level. The lowest effective dose should be used. To prevent withdrawal syndromes, reduce gradually over 1-2 weeks.
In older adults, it is advisable to start low and titrate up gradually to minimize the risk of hypotension and neuromuscular reactions.
When using the oral concentrate (10 mg/mL syrup), add the required dose to at least 60 mL or more of either tomato or fruit juice, milk, simple syrup, orange syrup, carbonated beverage, coffee, tea, water, or semisolid food (soup, puddings) to enhance palatability. Take the medicine right away.
Elderly
Initial oral dose should start at the low end of the dosage range and increased more gradually. The daily maximum dose should not exceed 6 mg.
Adults (outpatients)
The oral dose is 1 to 2 mg twice daily.
Recommended Dose and Dosage Adjustment
Adults
Oral dose is 1 to 2 mg twice daily as needed.
Children (6 to 12 years)
If hospitalized or are well-supervised, the recommended initial oral dose is 1 mg once or twice daily. The dose is then gradually increased until symptoms are controlled or adverse effects become troublesome. Older children may require higher doses if they present with severe symptoms. Maximum daily dose is 15 mg.
Administration
Administer with food to minimize gastrointestinal distress.
Adverse Reactions
Hepatic/Biliary/Pancreatic
cholestatic jaundice (usually occurs in first 2 to 4 weeks of therapy).
Genitourinary
priapism.
Gastrointestinal
obstipation (severe constipation), paralytic ileus.
Hematologic
blood dyscrasias, agranulocytosis (1:3000 to 4000 to 1:250 000 and usually occurs in the first 2 months of therapy), leukocytopenia, thrombocytopenia.
Immune
systemic lupus erythematosus-like syndrome.
Tardive Dyskinesia (TD)
TD occurs in individuals who have been on long-term antipsychotic therapy. It is a syndrome that consists of persistent and involuntary hyperkinetic movements. It commonly involves the face (tics, blinking, grimacing), tongue (chewing, tremor, protrusion, writhing), lips (smacking, pursing, puckering), limbs (toe tapping, pill rolling, writhing), neck and trunk (rocking, swaying, rotational pelvic movements). The risk of developing TD varies with advancing age and duration of antipsychotic treatment. Although there is no standard treatment for TD, initial management usually involves discontinuing the antipsychotic or switching to an atypical antipsychotic. The earlier TD is diagnosed and the offending antipsychotic discontinued, the better the prognosis for reversal of the disorder. However, discontinuing antipsychotic therapy altogether is not an option for some patients.
Less Common Adverse Drug Reactions (<1%)
Neuroleptic Malignant Syndrome (NMS)
Though a rare adverse event, NMS is potentially fatal. It is usually reversible once the offending agent is discontinued. It is hypothesized that NMS is a consequence of a widespread blockade of dopaminergic activity in the brain. There is no correlation between NMS and the duration of exposure to antipsychotics; NMS can occur at any time during treatment. NMS evolves over 24 to 72 hours. Motor symptoms (e.g., rigidity, akinesia or bradykinesia), altered mental status (e.g., confusion, delirium, stupor to coma), hyperthermia (fever >38 to 41°C), and autonomic instability (e.g., respiratory irregularities, cardiac arrhythmias, alterations in blood pressure) characterize NMS. Additional signs include leukocytosis, elevated CK levels, decreased creatinine clearance, proteinuria and myoglobinuria. Young age, male gender and dehydration are associated with an increased risk of NMS.
Central Nervous System
neuroleptic malignant syndrome (0.5 to 1%), impairment of temperature regulation (heatstroke or hypothermia), seizures (<1%).
Ocular
abnormal ocular pigmentation.
Trifluoperazine
More Common Adverse Drug Reactions (≥1%)
| Body System | Effect | Clinical Comment |
|---|---|---|
| Cardiovascular | Hypotension, orthostatic hypotension, peripheral edema (1–3%) | Monitor BP during first few hour post-initiation of therapy. Use caution in patients (e.g., elderly, patients with cardiovascular disease) where a sudden drop in BP is undesirable. |
| Central Nervous System | Extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia)—rare with doses | Dose reduction may be warranted in patients experiencing parkinsonism or akathisia. Consider i.v. anticholinergics (e.g., benztropine) in acute dystonic reactions. To prevent development of tardive dyskinesia, lowest effective doses are recommended. If symptoms of tardive dyskinesia appear, discontinue trifluoperazine or decrease dose to increase reversibility. Bedtime dose may prevent daytime sedation. |
| Dermatologic | Rash, discoloration of skin (blue-gray), photosensitivity | |
| Endocrine and Metabolic | Changes in menstrual cycle, | |
| Gastrointestinal | Constipation, weight gain, nausea, vomiting, stomach pain, xerostomia | |
| Genitourinary | Difficult urination, ejaculatory disturbances, urinary retention | |
| Hematologic | Pancytopenia, eosinophilia, hemolytic anemia, aplastic anemia | |
| Hepatic | Hepatotoxicity, abnormal liver function tests (dose-related) | |
| Neuromuscular | Tremor | |
| Ocular | Pigmentary retinopathy, cornea and lens changes | |
| Respiratory | Nasal congestion |
Overview
Two of the most serious potential side effects of trifluoperazine therapy are neuroleptic malignant syndrome and tardive dyskinesia.
Cardiovascular
QT prolongation, torsades de pointes.
Supplied
Not currently available for CPhA monographs. Please consult individual product monographs.
Indications and Clinical Use
Trifluoperazine is indicated for:
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symptomatic treatment of psychotic disorders including schizophrenia
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prevention or treatment of nausea and vomiting
Overdosage
Recommended Management
Patients who have ingested trifluoperazine in overdose occasionally require respiratory and hemodynamic support. This may include intubation, ventilation, boluses of isotonic i.v. fluids and inotropic support. Patients who seize should be treated with benzodiazepines. Ventricular arrhythmias are uncommon, and should be treated with boluses of sodium bicarbonate as well as conventional arrhythmics such as lidocaine. In the rare patient with torsades de pointes, i.v. magnesium sulfate and/or a pacemaker should be used. Once the patient's airway is adequately protected, 1 dose of activated charcoal can be administered to minimize absorption of orally ingested trifluoperazine. Extrapyramidal reactions, which are associated more commonly with chronic administration than with overdose, may be treated with i.v. benztropine or diphenhydramine.
Signs and Symptoms
Symptoms of trifluoperazine overdosage are an extension of its pharmacologic action. The primary symptoms observed are sedation and hypotension. Mild or early intoxication may cause restlessness, confusion and excitement. CNS sedation may progress to coma. Disturbed temperature regulation can occur; both hypothermia and hyperthermia have been reported. Neuroleptic malignant syndrome can occur in overdose or with therapeutic doses. Other symptoms may include anticholinergic manifestations, tachycardia, cardiac arrhythmias, seizures and respiratory and/or vasomotor collapse.
Warnings and Precautions
Geriatrics
Older individuals may be more susceptible than younger adults to the CNS, anticholinergic and cardiovascular side effects of phenothiazines. Hypotension and sedation may increase the risk of falls and associated hip fractures. Lower doses should be used in older patients and therapy should be closely monitored.
Special Populations
Immune
The oral syrup contains sodium bisulfite. Caution is advised in patients with sulfite allergy.
General
To minimize the risk of dose-related or long-term side effects such as extrapyramidal reactions trifluoperazine should be used at the lowest effective dose for the shortest possible duration.
CNS
Because phenothiazines can lower the seizure threshold, trifluoperazine should be used with caution in patients with a history of seizures.
Phenothiazines, particularly high potency agents such as trifluoperazine, can cause extrapyramidal reactions (see Adverse Reactions).
Because phenothiazines can affect the hypothalamic regulation of body temperature, they should be used with caution in patients exposed to extreme heat or cold.
Phenothiazines should be used with caution in patients with Parkinson's disease.
Because of their anticholinergic properties, phenothiazines should be used with caution in patients with glaucoma, benign prostatic hyperplasia, or other conditions that could be aggravated by anticholinergic effects.
Endocrine and Metabolism
Patients with hypocalcemia may be more susceptible to dystonic reactions (see Adverse Reactions).
Occupational Hazards
Because trifluoperazine can cause drowsiness and dizziness, especially at the beginning of the therapy, it is important to avoid driving a car, operating machinery, or participating in activities that require mental alertness until this effect has subsided.
Pregnant Women
Trifluoperazine readily crosses the placenta. Though some reports have attempted to link trifluoperazine with congenital defects, most evidence suggests that it is safe for the mother with low risk to the fetus. The decision to use trifluoperazine during pregnancy should be based on whether the expected benefit of therapy justifies the potential risk to the exposed fetus, especially in the first trimester.
Pediatrics
Children may be more susceptible to extrapyramidal reactions than adults, particularly if they have acute infectious illnesses or are dehydrated. Use lower doses in children and monitor therapy closely.
Nursing Women
Because of its low molecular weight, it is anticipated that trifluoperazine may pass into breast milk. Caution is advised when using it during lactation because of potential toxicity to the infant.
Cardiovascular
Because phenothiazines can cause hypotension, including orthostatic hypotension, trifluoperazine should be used with caution in patients with cardiovascular disease, although it is more commonly associated with the lower potency agents.
Action and Clinical Pharmacology
Distribution
Trifluoperazine is >90% plasma protein bound. Because of its highly lipophilic nature, CNS trifluoperazine concentrations exceed those in plasma. The volume of distribution is 10 to 35 L/kg. It is anticipated that trifluoperazine is distributed into the breast milk because of its low molecular weight. Trifluoperazine readily crosses the placenta.
Absorption
Trifluoperazine is readily absorbed. Absorption from tablets is sometimes erratic; however, it may be less so with the liquid formulation. When taken orally, trifluoperazine reaches its peak concentration within 2 to 4 hours. The onset of action of trifluoperazine is 0.5 to 1 hour following tablet administration. Slightly faster onset is achieved with the oral suspension since no disintegration time is involved.
Mechanism of Action
Trifluoperazine is a high potency piperazine phenothiazine that blocks the postsynaptic mesolimbic dopaminergic (D2) receptors in the brain, improving the positive symptoms of schizophrenia. Due to its high potency it is associated with a relatively high risk of extrapyramidal reactions such as pseudoparkinsonism, acute dystonic reactions, akathisia and tardive dyskinesia. Potency of cholinergic blockade is low and it causes less sedation and orthostatic hypotension than lower potency phenothiazines. Though D2 blockade may occur hours after administration, maximal clinical effects may take several weeks to achieve.
Trifluoperazine inhibits indirect stimulation of the vomiting center, consequently preventing or treating nausea and vomiting. It is not effective in preventing vertigo or motion sickness.
Pharmacokinetics: Adults
Excretion
The inactive metabolites are excreted primarily in the urine. Trifluoperazine is not dialyzable.
Metabolism
Trifluoperazine is metabolized in the liver, primarily by CYP1A2. The half life of trifluoperazine is variable at 7 to 18 hours.
Contraindications
Patients who are hypersensitive to trifluoperazine or to any ingredient in the formulation or component of the container.
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Patients with severe CNS depression or coma, bone marrow suppression, blood dyscrasias, severe hepatic disease.
