Mechanism of effect
Triflupromazine binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone (CTZ) and vomiting centre. Triflupromazine blocks the neurotransmitter dopamine and the vagus nerve in the gastrointestinal tract. Triflupromazine also binds the muscarinic acetylcholine receptors (M1 and M2) and the tryptamine D receptors (5HT2B).
Pharmacodynamic
Triflupromazine reduces anxiety, emotional withdrawal, hallucinations, disorganized thoughts, blunted mood, and suspiciousness. Triflupromazine is used particularly to control violent behavior during acute episodes of psychotic disorders. It can also be used to control severe nausea and vomiting, severe hiccups, and moderate to severe pain in some hospitalized patients. Triflupromazine acts on the central nervous system.
Pharmacokinetics
Absorption: Absorption may be erratic and peak plasma concentrations show large interindividual differences.
Protein binding: Very high (90% or more).
Metabolism: Hepatic.
Drug indications
nauseaDosage
Usual adult and adolescent dose
Psychotic disorders
Intramuscular, initially 60 mg; additional doses may be administered as needed.
Nausea and vomiting
Intramuscular, 5 to 15 mg every four hours as needed.
Intravenous, 1 mg; additional doses may be administered as needed.
Psychotic disorders
Intramuscular, 150 mg per day.
Nausea and vomiting
Intramuscular, 60 mg per day.
Intravenous, 3 mg per day.
Usual pediatric dose
Psychotic disorders or Nausea and vomiting
Children up to 21/2 years of age: Dosage has not been established.
Children 21/2 years of age and older: Intramuscular, 200 to 250 mcg (0.2 to 0.25 mg) per kg of body weight, not to exceed 10 mg per day
Drug contraindications
cardiovascular conditions , Hypertension , hypotension , long QT syndrome , Severe CNS depressionInteractions
Acetylcholine , potassium citrate , Tapentadol , Dolasetron , vandetanib , Dofetilide , Halofantrine , Grepafloxacin , Oxymorphone , glycopyrrolate topical , Bepridil , bedaquilineAlerts
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol for preparation of medications for use in neonates.
Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.
Patients sensitive to one phenothiazine may be sensitive to other phenothiazines also
» Alcoholism, active (CNS depression and hypotension may be potentiated; risk of heatstroke may be increased; chronic alcohol abusers may be predisposed to hepatotoxic reactions during phenothiazine therapy; dosage reduction may be necessary)
Angina pectoris (pain may be increased if phenothiazine treatment leads to an increase in physical activity)
» Blood dyscrasias (may be exacerbated; treatment may have to be discontinued)
» Brain damage, subcortical or
» Cerebral atherosclerosis, marked (a severe hyperthermic reaction may occur, sometimes 14 to 16 hours after phenothiazine administration)
Breast cancer (potentially higher risk of disease progression and possible increased resistance to endocrine and cytotoxic treatment, due to phenothiazine-induced prolactin secretion)
» Cardiac reserve deficiency, such as mitral insufficiency, severe or
» Cerebrovascular insufficiency or
» Pheochromocytoma or
» Renal insufficiency (severe hypotension is more likely to occur)
Cardiovascular disease (increased risk of hypotension and/or exacerbation of condition by phenothiazine-induced hypotension; ECG changes related to repolarization have been seen in some patients without cardiovascular disease who were taking phenothiazines; myocardial depression, cardiomegaly, congestive heart failure [CHF], and arrhythmias may be induced)
Conditions for which vomiting is a sign, such as:
Brain tumor
Drug overdose
Intestinal obstruction
» Reye's syndrome (diagnosis may be obscured by the antiemetic effect of phenothiazines; less likely with thioridazine)
(increased risk of hepatotoxicity in children and adolescents with Reye's syndrome)
Glaucoma, or predisposition to (may be potentiated by anticholinergic effects of phenothiazines)
» Hepatic function impairment (phenothiazines can cause hepatic dysfunction)
(metabolism may be decreased; higher serum phenothiazine concentrations may increase CNS effects)
(patients with a history of hepatic encephalopathy due to cirrhosis have increased sensitivity to the CNS effects of phenothiazines)
Parkinson's disease (potentiation of extrapyramidal effects)
Peptic ulcer or
Urinary retention (may be exacerbated; phenothiazines have caused bladder paralysis in some patients)
Prostatic hypertrophy, symptomatic (increased risk of urinary retention)
Respiratory disorders, chronic, especially in children (may be potentiated due to CNS depressant effect of phenothiazines; also, cough-suppressant effects of phenothiazines may be especially problematic in these patients)
Seizure disorders, or history of (seizures may be precipitated)
» Sensitivity to any phenothiazine, or history of (may be potentiated upon re-exposure to any phenothiazine in patients with a history of phenothiazine-induced blood dyscrasias, jaundice, or skin reactions)
Sensitivity to parabens, sulfites, or tartrazine (some dosage forms of phenothiazines contain parabens, sulfites, or tartrazine [FD&C Yellow No. 5])
Caution should also be used in geriatric, emaciated, and debilitated patients, who usually require a lower initial dose , and in patients who will be exposed to organophosphate or carbamate pesticides , extreme heat , or extreme cold .
Points of recommendation
For oral dosage forms
Taking with food, milk, or water to reduce stomach irritation
Diluting each dose of medication that comes in dropper bottle with a recommended beverage immediately prior to use
Swallowing the extended-release dosage form whole
For rectal dosage forms
Chilling suppository if too soft to insert
» Compliance with therapy; not taking more or less medication than prescribed
» Several weeks of therapy may be required to produce desired effects in treatment of mental or emotional conditions
Missed dose when dosing schedule is:
• One dose a day—Taking as soon as possible if remembered the same day; skipping missed dose if not remembered until the next day; going back to regular dosing schedule; not doubling doses
• More than one dose a day—Taking as soon as possible if within an hour or so of missed dose; skipping missed dose if not remembered until later; going back to regular dosing schedule; not doubling doses
» Checking with physician before discontinuing medication; gradual dosage reduction may be needed
Avoiding use of antacids or antidiarrheal medication within 2 hours of taking phenothiazine
» Avoiding use of alcoholic beverages or other CNS depressants during therapy
Avoiding the use of over-the-counter medications for colds or allergies to prevent increased anticholinergic effects and risk of developing heatstroke
Caution if any laboratory tests required; possible changes in ECG readings, and interference with gonadorelin, metyrapone, phenylketonurea, and urine bilirubin test results
» Caution if any kind of surgery, dental treatment, or emergency treatment is required; telling physician or dentist in charge about phenothiazine because of possible drug interactions or hypotension
» Possible drowsiness or blurred vision; caution when driving, using machines, or doing other things requiring alertness or accurate vision
» Possible dizziness or lightheadedness (orthostatic hypotension); caution when getting up suddenly from a lying or sitting position
» Possible heatstroke: Caution during exercise, hot weather, or when taking hot baths
Possible hypothermia: Caution during prolonged exposure to cold
» Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks
» Possible skin photosensitivity; avoiding unprotected exposure to sun; using protective clothing; using a sunblock product that includes protection against both UVA-caused photosensitivity reactions and UVB-caused sunburn reactions; avoiding use of sunlamp, tanning bed, or tanning booth; checking with physician if severe reaction occurs
» Possible eye photosensitivity; wearing sunglasses that block ultraviolet light
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