Thioridazine

370.57

370.57

200-044-2

DTXSID6023656

Crystals from acetone|Colorless crystals

N - Nervous system

2934302300

57.1

5.9

Solid

1.2±0.1 g/cm3

72-74 °C

230 °C @ Press: 0.02 Torr

9℃

1.677

1.113mg/L(22.5 ºC)

-20°C

3.69X10-8 mm Hg at 25 deg C (est)

LD50 orally in rats: 995 ±39 mg/kg (Goldenthal)

Faint

Very bitter

9.5None

Henry's Law constant = 1.50X10-11 atm-cu m/mol at 25 °C (est)

9.5|pKa = 9.5

184.9 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

White to slightly yellow, granular powder; freely soluble in chloroform; slightly soluble in benzene /Thioridazine hydrochloride/

UN1230 - class 3 - PG 2 - Methanol, solution

1

11-23/24/25-39/23/24/25-52/53

16-36/37-45-61

SP2100000

F,T

STABLE IN MODERATE HEAT , DARKENS ON EXPOSURE TO LIGHT /THIORIDAZINE HYDROCHLORIDE/

P210-P260-P273-P280-P301 + P310-P311

H225-H301 + H311 + H331-H370-H412

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Incompatible with strog oxidizing agents

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including thioridazine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Thioridazine hydrochloride/

|Warning|H302 (99.49%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Aggregated GHS information provided by 197 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|Use safety glasses or goggles and protect exposed skin.

May cause irritation /to the eyes, skin, and mucous membranes/. Avoid inhalation. Remove to fresh air. Avoid contact. Flush /eyes/ with copious quantities of water for at least 15 minutes. Avoid /skin/ contact. Flush with copious quantities of soap and water.

LD50=956-1034 mg/kg (Orally in rats); Agitation, blurred vision, coma, confusion, constipation, difficulty breathing, dilated or constricted pupils, diminished flow of urine, dry mouth, dry skin, excessively high or low body temperature, extremely low blood pressure, fluid in the lungs, heart abnormalities, inability to urinate, intestinal blockage, nasal congestion, restlessness, sedation, seizures, shock

Liver test abnormalities have been reported to occur in a high proportion of patients on long term phenothiazine therapy, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to thioridazine, with some resemblance to cases of chlorpromazine jaundice. The onset of jaundice occurred within a few weeks to several months of therapy and the pattern of serum enzyme elevations was typically cholestatic, although hepatocellular patterns have also been reported. Immunoallergic manifestations (fever, rash and eosinophilia) were not prominent and autoantibodies were not detected. Some cases were associated with agranulocytosis which is a rare but known complication of the phenothiazines.

QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/|Concurrent use /of other photosensitizing medications/ with phenothiazines may cause additive photosensitizing effects. In addition, concurrent use of systemic methoxsalen, trixsalen, or tetracyclines with phenothiazines may potentiate intraocular photochemical damage to the choroid, retina, or lens. /Phenothiazines/|Prior administration of phenothiazines may decrease the pressor effect and shorten the duration of action of phenylephrine. /Phenothiazines/|In addition to increased CNS and respiratory depression, concurrent use /of opiod (narcotic) analgesics/ with phenothiazines increases orthostatic hypotension and increases the risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention. /Phenothiazines/|For more Interactions (Complete) data for Thioridazine (30 total), please visit the HSDB record page.

LD50 Rat oral 995 mg/kg

Geriatric patients appear to be particularly sensitive to adverse nervous system (eg, tardive dyskinesia, parkinsonian signs and symptoms, akathisia, sedation), anticholinergic, and cardiovascular (eg, orthostatic hypotension) effects of antipsychotic agents. Because the risk of falling and associated hip fracture in geriatric patients may be increased with use of antipsychotic agents, phenothiazine therapy should be initiated at reduced dosages and such patients observed closely. /Phenothiazine General Statement/

95%

Thioridazine's production and use as an antipsychotic drug(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+5(SRC), determined from a log Kow of 5.90(2) and a regression-derived equation(3), indicates that thioridazine is expected to be immobile in soil(SRC). The pKa of thioridazine is 9.5(4), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the base exists as an cation and cations do not volatilize. Thioridazine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.69X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+5(SRC), determined from a log Kow of 5.90(2) and a regression-derived equation(3), indicates that thioridazine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.5(4) indicates thioridazine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3,600(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), thioridazine, which has an estimated vapor pressure of 3.69X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phases in the ambient atmosphere. Particulate-phase thioridazine may be removed from the air by wet or dry deposition(SRC). Thioridazine does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Thioridazine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Thioridazine does not contain chromophores that absorb at wavelengths >290 nm(1), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3,600 was calculated in fish for thioridazine(SRC), using a log Kow of 5.90(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of thioridazine is estimated as 1.2X10+5(SRC), using a log Kow of 5.90(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that thioridazine is expected to be immobile in soil. The pKa of thioridazine is 9.5(4), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

A pKa of 9.5(1) indicates thioridazine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). Volatilization from moist soil is not expected because the base exists as a cation and cations do not volatilize(2). Thioridazine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.17X10-6 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 430 workers (239 of these were female) were potentially exposed to thioridazine in the US(1). Occupational exposure to thioridazine may occur through inhalation and dermal contact with this compound at workplaces where thioridazine is produced or used. Exposure to thioridazine among the general population may be limited to those administered the drug Mellaril, an antipsychotic medication(SRC).|Thioridazine is a drug used in the management of psychotic disorders in adults and is administered orally as a tablet(2). Therefore, users are exposed through oral consumption. Pharmacists, physicians and nurses dispensing or administering thioridazine may be exposed to thioridazine through dermal contact(SRC).

For the treatment of schizophrenia and generalized anxiety disorder.

Thioridazine is a phenothiazine and antipsychotic agent that is no longer in common use. Thioridazine has been linked to rare instances of clinically apparent acute cholestatic liver injury.

Antipsychotic Agents

Antipsychotic Agents, Phenothiazine; Dopamine Antagonists|Thioridazine is indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with thioridazine, it is strongly recommended that a patient be given at least two trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration. /Included in US product label/|The prescriber should be aware that thioridazine has not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown. /Included in US product label/|The US Food and Drug Administration (FDA) currently advises clinicians that antipsychotic agents are not approved for the treatment of dementia-related psychosis. FDA further advises clinicians that no drugs currently are approved for the treatment of patients with dementia-associated psychosis and that other management options should be considered in such patients. /Phenothiazine General Statement/

... Extrapyramidal reactions ... fairly common, usually 3 types ... Parkinsonian-like syndrome ... dystonia and dyskinesia, including torticollis, tics, and other involuntary muscle movements ... akathisia, shown by restlessness ... hyperreflexia, reported in newborn ... ./Phenothiazines/|Thioridazine has been shown to prolong the QTc interval in a dose related manner, and drugs with this potential, including thioridazine, have been associated with Torsades de pointes type arrhythmias and sudden death. Due to its potential for significant, possibly life threatening, proarrhythmic effects, thioridazine should be reserved for use in the treatment of schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs|Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Thioridazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis|In common with other phenothiazines, thioridazine is contraindicated in severe central nervous system depression or comatose states from any cause including drug induced central nervous system depression. It should also be noted that hypertensive or hypotensive heart disease of extreme degree is a contraindication of phenothiazine administration.|For more Drug Warnings (Complete) data for Thioridazine (48 total), please visit the HSDB record page.

Antipsychotic drugs are not addicting ... however, some degree of physical dependence may occur. ... Some authors have reported occurrence of muscular discomfort and difficulty in sleeping that develop several days after abrupt discontinuation. /Phenothiazines/|Tolerance develops to sedative effects of chlorpromazine and other phenothiazines over a period of days or week. /Phenothiazines/|Phenothiazines produce varying degrees of sedation without hypnosis or anesthesia in normal and psychotic patients; however, the drugs potentiate the CNS depressant actions of sedatives, hypnotics, and anesthetics. Tolerance to the sedative effects develops over a period of days or weeks during long-term therapy. /Phenothiazine General Statement/

Thioridazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Thioridazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)|Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)

60%|Experimental studies in animals and in vitro have demonstrated that thioridazine has affinity for melanin granules and tends to accumulate in close association with uveal pigment ... .|... Pharmacokinetics and metabolism ... similar ... to chlorpromazine, but strong anticholinergic action of thioridazine on the gut may modify its own absorption ... . Concentrations of thioridazine in plasma are relatively high (hundreds of nanograms per milliliter), possibly owing to its relative hydrophilicity ... .|In 48 patients taking thiordazine the mean amount not bound to serum proteins was 0.15%, that of the side-chain sulfoxide 1.66%, side-chain sulfone 1.17%, and ring sulfoxide 1.7%.|Thioridazine and metabolites were measured in brain, liver, and kidney specimens, obtained postmortem from two subjects whose deaths were related to acute intoxication with thioridazine, by gas-liquid chromatography. Although the absolute concentration measured for thioridazine and metabolites differed in the two cases, the metabolic pattern for each tissue, expressed in terms of the percentage of total drug in each tissue, was quite similar. The brain, liver, and kidney metabolic patterns, however, are in sharp contrast to the plasma metabolite patterns observed for subjects on a therapeutic regimen of thioridazine. As this example demonstrates, postmortem specimens are a valuable (but seldom used) source of human pharmacological data.|For more Absorption, Distribution and Excretion (Complete) data for Thioridazine (10 total), please visit the HSDB record page.

Hepatic|Major metabolites include sulfoxy products at ring position 5 (inactive) or at substituent at position 2 (including active metabolite mesoridazine). Demethylation of piperidine ring is very rapid ... .|Although the exact metabolic fate of phenothiazines has not been clearly established, the drugs are extensively metabolized, principally in the liver via hydroxylation, oxidation, demethylation, sulfoxide formation, and conjugation with glucuronic acid; metabolic alterations in the side chain also may occur. /Phenothiazine General Statement/|Most metabolites of phenothiazines are pharmacologically inactive; however, certain metabolites (eg, 7-hydroxychlorpromazine, mesoridazine) show moderate pharmacologic activity and may contribute to the action of the drugs. There is limited evidence to indicate that some phenothiazines (eg, chlorpromazine) may induce their own metabolism. /Phenothiazine General Statement/|Thioridazine and metabolites were determined by a selective HPLC technique in blood from five post-mortem cases; two deaths attributed to drug overdose and three deaths due to natural causes or trauma. Additionally, total thioridazine-like compounds were determined in these blood samples and liver specimens by a nonspecific fluorometric technique. Blood concentrations were: thioridazine, 0.78-8.85 mg/L; mesoridazine, 0.52-26.8 mg/L; and sulforidazine, 0.00-0.87 mg/L. Thioridazine-5-sulfoxide stereoisomeric DL,LD, and DD,LL pair concentrations ranged from 0.02-0.56 and 0.03-0.83 mg/L, respectively. Thioridazine metabolite profiles were not helpful in differentiating therapeutic administration from severe overdose. Liver appears to be the specimen of choice in the assessment of thioridazine overdose.|For more Metabolism/Metabolites (Complete) data for Thioridazine (8 total), please visit the HSDB record page.|Thioridazine has known human metabolites that include N-desmethylthioridazine, Thioridazine 2-sulfoxide, and Thioridazine 5-sulfoxide.

21-25 hours|Serum half-life of thioridazine has been estimated to range from about 6 to over 40 hours.

Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.|The basic pharmacological activity of thioridazine is similar to that of other phenothiazines, but is associated with minimal extrapyramidal stimulation.|The principal pharmacologic effects of thioridazine are similar to those of chlorpromazine. On a weight basis, thioridazine is about as potent as chlorpromazine. Thioridazine has strong anticholinergic and sedative effects and weak extrapyramidal effects. Thioridazine has little antiemetic activity.|The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/|In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking, and adrenergic activity. The antipsychotic activity of phenothiazines may be related to any or all of these effects, but it has been suggested that the drugs' effects on dopamine are probably most important. It has also been suggested that effects of phenothiazines on other amines (eg, gamma-aminobutyric acid [GABA]) or peptides (eg, substance P, endorphins) may contribute to their antipsychotic effect. Further study is needed to determine the role of central neuronal receptor antagonism and of effects on biochemical mediators in the antipsychotic action of the phenothiazines and other antipsychotic agents. /Phenothiazine General Statement/|For more Mechanism of Action (Complete) data for Thioridazine (13 total), please visit the HSDB record page.

Treatment of phenothiazine overdosage generally involves symptomatic and supportive care. There is no specific antidote for phenothiazine intoxication; however, anticholinergic antiparkinsonian drugs may be useful in controlling extrapyramidal reactions associated with phenothiazine overdosage. Following acute ingestion of the drugs, the stomach should be emptied by gastric lavage and consideration also should be given to repeated doses of activated charcoal. If the patient is comatose, having seizures or a dystonic reaction, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. Gastric lavage may be useful even several hours after the drug has been ingested, since GI motility may be greatly reduced following overdosage of phenothiazines. Induction of emesis should generally not be attempted, since a phenothiazine-induced dystonic reaction of the head or neck may result in aspiration of vomitus during emesis. Administration of a saline cathartic may be beneficial in enhancing evacuation of the drug from the GI tract, especially following ingestion of extended-release preparations (eg, Spansules). /Phenothiazine General Statement/|Cardiovascular monitoring should begin immediately and should include continuous ECG monitoring to detect possible arrhythmias. Treatment may include correction of electrolyte abnormalities and acid-base balance, lidocaine, phenytoin, isoproterenol, ventricular pacing, and defibrillation. Antiarrhythmic agents that can prolong the QT interval (eg, class IA [disopyramide, procainamide, quinidine] or III agents) should be avoided in treating overdosage-associated arrhythmias in which prolongation of QTc is a manifestation. Appropriate therapy (IV fluids and a vasopressor) should be instituted if hypotension occurs; epinephrine, bretylium, or dopamine should not be used. For the management of refractory hypotension, vasopressors such as phenylephrine, levarterenol, or metaraminol may be used. Appropriate therapy should be instituted if excessive sedation occurs; CNS stimulants that may cause seizures should be avoided. If seizures occur, treatment should not include barbiturates because these drugs may potentiate phenothiazine-induced respiratory depression. Hypothermia is common and sometimes difficult to control. In some patients with acute toxicity, exchange transfusions may be useful, but hemodialysis, forced diuresis, hemoperfusion, or manipulation of urine pH is of little value in enhancing elimination of phenothiazines. /Phenothiazine General Statement/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ Thioridazine is a phenothiazine derivative that has been used as an antipsychotic; it rarely causes photosensitization. However, /investigators/ noticed that this drug induced an erythematous reaction in a photopatch test. Six volunteers were patch tested with various concentrations of thioridazine and irradiated with a range of UVA doses, and the time courses of the color of and blood flow to the test sites were monitored. The free-radical metabolites of thioridazine generated under UVA irradiation and its effects on ascorbate radical formation were examined with an electron paramagnetic resonance (EPR) spectrometer in vitro. As a result, immediate erythema developed during UVA irradiation in most subjects when 1% thioridazine was applied for 48 hr and irradiation doses were higher than 4 J cm(-2). Another peak of erythematous reaction was observed 8-12 hr after irradiation. ... Thioridazine-derived oxidants and/or thioridazine radicals generated during UVA irradiation seem to play an important role in this unique phototoxic reaction.|/SIGNS AND SYMPTOMS/ Effects and clinical complications of acute overdose involving phenothiazines may include: Cardiovascular: Cardiac arrhythmias, hypotension, shock, ECG changes, increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, atrioventricular block, ventricular tachycardia, ventricular fibrillation, Torsades de pointes, myocardial depression. Central Nervous System: Sedation, extrapyramidal effects, confusion, agitation, hypothermia, hyperthermia, restlessness, seizures, areflexia, coma. Autonomic Nervous System: Mydriasis, miosis, dry skin, dry mouth, nasal congestion, urinary retention, blurred vision. Respiratory: Respiratory depression, apnea, pulmonary edema. Gastrointestinal: Hypomotility, constipation, ileus. Renal: Oliguria, uremia. Toxic dose and blood concentration ranges for the phenothiazines have not been firmly established.|/SIGNS AND SYMPTOMS/ In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia or CNS stimulation with convulsions followed by respiratory depression may occur; patients with early or mild intoxication may experience drowsiness, restlessness, disorientation, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included shock (eg, ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, bilateral bundle branch block, atrioventricular block, ventricular tachycardia, ventricular fibrillation, torsades de pointes, myocardial depression, agitation, dry skin, nasal congestion, urinary retention, oliguria, uremia, blurred vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, constipation, ileus, dry mouth, vomiting, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, and pulmonary edema, possibly with sudden apnea. /Phenothiazine general Statement/|/SIGNS AND SYMPTOMS/ Thioridazine has been shown to prolong the QTc interval in a dose related manner, and drugs with this potential, including thioridazine, have been associated with Torsades de pointes type arrhythmias and sudden death. Due to its potential for significant, possibly life threatening, proarrhythmic effects, thioridazine should be reserved for use in the treatment of schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs|For more Human Toxicity Excerpts (Complete) data for Thioridazine (29 total), please visit the HSDB record page.

Aldazine

Thioridazine preparations: (AHFS, 2010)

PHENOTHIAZINE DETERMINATION BY GAS CHROMATOGRAPHY. /PHENOTHIAZINES/|IN PRESENCE OF SUITABLE OXIDIZING AGENT, PHENOTHIAZINES DEVELOP CHARACTERISITIC COLOR THAT CAN BE USED FOR QUALITATIVE DETERMINATION. /PHENOTHIAZINES/|TLC OF BASIC DRUGS /INCL THIORIDAZINE/ ON SILICA GEL.|THIORIDAZINE DETERMINATION BY SPECTROPHOTOFLUOROMETER.|Dissolve 300 mg Thioridazine in 60 ml glacial acetic acid and titrate with 0.1 N perchloric acid. Determining the end-point potentiometrically.

Gas liquid chromatograpy determination in plasma.|FLUOROMETRY, SPECIFIC TO ABOUT 0.5 UG/ML IN URINE.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals