Thiothixene

Class: Thioxanthenes
VA Class: CN709
Chemical Name: N,N-dimethyl-9-[3-(4-methyl-1-piperazinyl)-propylidene]thioxanthene-2-sulfonamide
Molecular Formula: C₂₃H₂₉N₃O₂S₂
CAS Number: 5591-45-7
Brands: Navane

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

[Posted 06/16/2008] FDA notified healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics. Antipsychotics are not indicated for the treatment of dementia-related psychosis. The prescribing information for all antipsychotic drugs will now include the same information about this risk in a BOXED WARNING and the WARNINGS section. For more information visit the FDA website at: , and .

Introduction

Thioxanthene-derivative, conventional (prototypical, first-generation) antipsychotic agent; structurally and pharmacologically related to chlorprothixene (no longer commercially available in the US) and trifluoperazine.^{a b c d e g u}

Uses for Thiothixene

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Symptomatic management of psychotic disorders (i.e., schizophrenia).^{a b c d u}

Has been used in the management of refractory or treatment-resistant schizophrenia.^c

Mental Retardation

Efficacy not established for the management of behavioral complications in patients with mental retardation.^{a b c u}

Thiothixene Dosage and Administration

General

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.^{a b c u}

  
  


• 
  

  Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued.^{a b u w} (See Tardive Dyskinesia under Cautions.)

  
  


• 
  

  For symptomatic relief of psychotic disorders, initial therapeutic response to antipsychotic therapy usually occurs within 2–4 weeks and optimum therapeutic response occurs within 6 months or longer.^{d w}

  
  

Administration

Oral Administration

Thiothixene is administered orally once daily or in divided doses 2 or 3 times daily.^{a b c k t u} Thiothixene hydrochloride has been given orally and parenterally, but no longer is commercially available in the US.^{a c h v}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pediatric Patients

Psychotic Disorders

Oral

Children ≥12 years of age: Initially, 2 mg 3 times daily for mild to moderate psychotic disorders; may gradually increase dosage, if necessary, up to 15 mg daily.^{a b c u}

For more severe psychotic disorders in children ≥12 years of age: Initially, 5 mg twice daily; may then increase dosage until satisfactory response obtained.^{a b c u}

Optimal maintenance dosage usually 20–30 mg daily; may be increased up to 60 mg daily, if necessary; once-daily administration may be adequate.^{a b c k u}

Daily dosages >60 mg rarely provide additional therapeutic effect.^{a b c u}

Adults

Psychotic Disorders

Oral

For mild to moderate psychotic disorders: Initially, 2 mg 3 times daily; may gradually increase dosage, if necessary, up to 15 mg daily.^{a b c u}

For more severe psychotic disorders: Initially, 5 mg twice daily; may then increase dosage until satisfactory response obtained.^{a b c u}

Optimal maintenance dosage usually 20–30 mg daily; may be increased up to 60 mg daily, if necessary; once-daily administration may be adequate.^{a b c k u}

Daily dosages >60 mg rarely provide additional therapeutic effect.^{a b c u}

Prescribing Limits

Pediatric Patients

Psychotic Disorders

Oral

Children ≥12 years of age: Maximum 60 mg daily.^{a b c u}

Adults

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Oral

Maximum 60 mg daily.^{a b c u}

Special Populations

Geriatric Patients

No specific dosage recommendations for geriatric patients, but generally select dosage at the lower end of recommended range; increase dosage more gradually and monitor closely.^{a b d h u w} (See Geriatric Use under Cautions and see Special Populations under Pharmacokinetics.)

Cautions for Thiothixene

Contraindications

• 
  

  Circulatory collapse.^{a b c u}

  
  


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  Comatose states or CNS depression from any cause.^{a b c u} (See Specific Drugs and Laboratory Tests under Interactions.)

  
  


• 
  

  Blood dyscrasias.^{a b c u}

  
  


• 
  

  Known hypersensitivity to thiothixene.^{a b c u} Not known if cross-sensitivity exists between thioxanthenes and phenothiazines; consider possibility that cross-sensitivity may occur.^{a b c u}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Shares the toxic potentials of other antipsychotic agents (e.g., phenothiazines); observe the usual precautions associated with therapy with these agents.^{a b c u}

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, may develop in patients receiving antipsychotic agents, including thiothixene.^{a b c d u w} Consider reducing thiothixene dosage or discontinuing drug and switching to a second-generation (atypical) antipsychotic agent.^{a b c d u w}

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported with antipsychotic agents, including thiothixene.^{a b c u w}

CNS Depression

May impair mental and/or physical abilities, especially during the first few days of therapy; use caution with activities requiring alertness (e.g., operating vehicles or machinery).^{a b u}

Response to CNS depressants and alcohol may be potentiated.^{a b u} (See Specific Drugs and Laboratory Tests under Interactions.)

Sensitivity Reactions

Hypersensitivity and Cross-sensitivity

Possible sensitivity reactions reported with thiothixene (e.g., rash, pruritus, urticaria, anaphylactoid reactions) and related drugs (e.g., agranulocytosis, pancytopenia, thrombocytopenic purpura, jaundice, biliary stasis).^{a b c u w}

Not known if cross-sensitivity exists between thioxanthenes and phenothiazines; consider possibility that cross-sensitivity may occur.^{a b u}

Photosensitivity

Photosensitivity may occur; avoid excessive exposure to sunlight during therapy.^{a b u w}

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Seizures

Possible risk of seizures; may lower seizure threshold.^{a b c u} Use with extreme caution in patients with a history of seizures or during alcohol withdrawal.^{a b c u} (See Specific Drugs and Laboratory Tests under Interactions.)

Cardiovascular Effects

Possible hypotension, tachycardia, nonspecific ECG changes, dizziness, and/or syncope; use with caution in patients with cardiovascular disease.^{a b c u}

If severe hypotension occurs, administer norepinephrine or phenylephrine; epinephrine or dopamine should not be used.^{a b c u w} (See Specific Drugs and Laboratory Tests under Interactions.)

Anticholinergic Effects

Possible anticholinergic effects (e.g., dry mouth, blurred vision, constipation, increased perspiration, urinary retention, impotence).^{a b c u}

Use with caution in patients with glaucoma or prostatic hypertrophy.^c (See Specific Drugs and Laboratory Tests under Interactions.)

Ocular Effects

Pigmentary retinopathy and lenticular pigmentation reported with prolonged therapy with antipsychotic agents, including thiothixene.^{a b c u} Observe carefully.^{a b c u}

Prolactin Secretion

Elevated prolactin concentrations reported; elevation persists during chronic administration.^{a b c u w}

Clinical significance unknown; consider that approximately one-third of human breast cancers are prolactin dependent when prescribing thiothixene in patients with previously detected breast cancer.^{a b c u w}

Galactorrhea, amenorrhea, gynecomastia, and impotence reported.^{a b c u w}

Regulation of Body Temperature

Use with caution in patients exposed to extreme heat or cold.^{a b c u w}

Other Precautions

Antiemetic effects may mask signs of overdosage of other drugs (e.g., antineoplastic agents) or obscure cause of vomiting in various disorders (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).^{a b c u w}

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.^e

Lactation

Not known but considered likely to distribute into human milk; possible effects on nursing infant unknown.^{e h n o r s} Caution if used in nursing women; carefully assess potential benefits and risks.^{e n o}

Pediatric Use

Safety not established in children <12 years of age.^{a b c u}

Geriatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Geriatric patients appear to be particularly sensitive to adverse CNS (e.g., tardive dyskinesia, parkinsonian manifestations, akathisia, sedation), anticholinergic, and cardiovascular (e.g., orthostatic hypotension) effects of antipsychotic agents.^{a b d h i u w}

Use with caution.^h (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Drowsiness or sedation, extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia, tardive dyskinesia), anticholinergic effects (e.g., dry mouth, blurred vision), hypotension.^{a b c u}

Interactions for Thiothixene

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (increased or decreased plasma thiothixene concentrations) with concomitant use of CYP enzyme inhibitors or inducers.^{a b h j l u} (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Alcohol	Potential additive CNS effects and hypotensiona b u w	Use with cautiona b h u w
Anticholinergic drugs (e.g., atropine)	Possible potentiation of anticholinergic effectsa b c u	Use with cautiona b u
Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)	Anticonvulsants may decrease plasma thiothixene concentrationsa h j l Thiothixene may lower seizure thresholda b c u Barbiturates: Thiothixene does not appear to potentiate the anticonvulsant activity of barbituratesa b c u	Observe for signs and symptoms of reduced thiothixene effectivenessa Dosage adjustments of anticonvulsants may be necessary i Barbiturates: Do not reduce anticonvulsant dosage during concurrent usea b c u
Antidepressants, tricyclic (TCAs)	Possible increased plasma concentrations of thiothixenej l
β-Blockers (e.g., propranolol)	Possible decreased thiothixene clearancej l
Cimetidine	Possible decreased thiothixene clearanceh j l
CNS depressants (e.g., antihistamines, barbiturates, general anesthetics, opiate analgesics, sedative/hypnotics)	Possible additive CNS effects and hypotensiona b u	Use with caution to avoid excessive sedation or CNS depression; carefully adjust dosages of both agents as necessarya b h u
Epinephrine or dopamine	Possible further lowering of BPa b c u w	Do not use epinephrine or dopamine for thiothixene-induced hypotensiona b c u w (see Cardiovascular Effects under Cautions)
Hypotensive agents	Possible additive hypotensive effecta c	Observe closely for signs of excessive hypotensiona c
Isoniazid	Possible decreased thiothixene clearancel
Lithium	An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present h w	Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appearw
Paroxetine	Pharmacokinetic interaction unlikelym
Smoking	Possible decreased plasma thiothixene concentrations h j l
Tests for pregnancy	False-positive results reported in some patients receiving phenothiazines; less likely to occur when serum test is useda b u

Thiothixene Pharmacokinetics

Absorption

Bioavailability

Rapidly and well absorbed from GI tract following oral administration.^{c i k} Peak plasma concentrations usually occur within 1–3 hours.^{i k t}

Onset

Antipsychotic effects usually are apparent within 2–4 weeks after initiation of oral therapy and optimum therapeutic response usually occurs within 6 months or longer.^{c d w}

Plasma Concentrations

Optimal therapeutic plasma concentrations not well defined, but clinical improvement associated with peak plasma concentrations of 2–15 mcg/L.^{t y}

Distribution

Extent

Widely distributed into body tissues.^{c i}

Crosses placenta in animals; considered likely to cross placenta in humans.^{p x} Not known if distributed into human milk but distribution into breast milk considered likely.^{e h o r}

Plasma Protein Binding

>99%.ⁱ

Elimination

Metabolism

Principally metabolized in the liver; undergoes extensive oxidative first-pass metabolism to form thiothixene sulfoxide and N-desmethylthiothixene.^{c h i j}

Elimination Route

Excreted mainly in feces via biliary elimination as unchanged drug and as demethyl, sulfoxide, demethylated sulfoxide, and hydroxylated metabolites.^{c i}

Unlikely to be removed by hemodialysis and peritoneal dialysis.^{a b u w}

Half-life

34–35 hours.^{d i k m t}

Special Populations

Clearance is reduced in females and in patients >50 years of age.^h

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 20–25°C; protect from light and moisture.^{b c u}

ActionsActions

• 
  

  Produces pharmacologic effects similar to those of other conventional antipsychotic agents (e.g., phenothiazines, butyrophenones, chlorprothixene).^{a b c u w}

  
  


• 
  

  Precise mechanism(s) of antipsychotic action not determined, but may be principally related to antidopaminergic effects.^w Acts principally at subcortical levels on the reticular formation, hypothalamus, and limbic system.^{c w}

  
  


• 
  

  Exhibits weak anticholinergic, antihistaminic, α-adrenergic, and sedative effects and strong extrapyramidal effects; appears to possess antiemetic activity.^{a b c h u}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.^{a b c h u}

  
  


• 
  

  Importance of clinicians informing patients in whom chronic use is contemplated of risk of tardive dyskinesia, taking into account clinical circumstances and competency of patient to understand information provided.^{a b u}

  
  


• 
  

  Importance of clinicians informing patients of risk of extrapyramidal reactions and providing reassurance that these reactions usually can be controlled by administration of antiparkinsonian drugs (e.g., benztropine) and by subsequent dosage reduction.^{a b c u w}

  
  


• 
  

  Advise patients to avoid excessive sunlight.^{a b u w}

  
  


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  Importance of avoiding exposure to temperature extremes.^{a b c w}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{a b u}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{a b u}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{a b u} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Thiothixene

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	1 mg*	Navane	Pfizer
			Thiothixene Capsules	Mylan, Sandoz
		2 mg*	Navane	Pfizer
			Thiothixene Capsules	Mylan, Sandoz
		5 mg*	Navane	Pfizer
			Thiothixene Capsules	Mylan, Sandoz
		10 mg*	Navane	Pfizer
			Thiothixene Capsules	Mylan, Sandoz
		20 mg	Navane	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Navane 10MG Capsules (PFIZER U.S.): 90/$189.99 or 270/$565.95

Navane 2MG Capsules (PFIZER U.S.): 90/$92.99 or 270/$266.98

Navane 20MG Capsules (PFIZER U.S.): 90/$266 or 270/$779.99

Navane 5MG Capsules (PFIZER U.S.): 90/$139.99 or 270/$409.96

Thiothixene 1MG Capsules (SANDOZ): 90/$22.99 or 270/$49.97

Thiothixene 2MG Capsules (MYLAN): 90/$26.99 or 270/$71.97

Thiothixene 5MG Capsules (SANDOZ): 90/$25.99 or 270/$59.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions March 15, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. Roerig, Division of Pfizer Inc. Navane (thiothixene) capsules and solution, concentrate prescribing information. New York, NY. 2008 Mar.

b. Sandoz Inc. Thiothixene capsules prescribing information. Princeton, NJ. 2007 Feb.

c. AHFS drug information 2008. McEvoy GK, ed. Thiothixene. Bethesda, MD: American Society of Health-System Pharmacists; 2008:2516-7.

d. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. From the APA website

e. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:1577-8.

f. American Academy of Pediatrics. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics. 2000; 105:880-87. [PubMed 10742343]

g. The United States Pharmacopeial Convention, Inc. USAN and the USP Dictionary drug names. Rockville, MD: United States Pharmacopeial Convention, Inc; 2007:853.

h. AMA Division of Drugs. AMA drug evaluations. Chicago: American Medical Association; 1994:2:1-2:29.

i. Balant-Gorgia AE, Balant L. Antipsychotic drugs: clinical pharmacokinetics of potential candidates for plasma concentration monitoring. Clin Pharmacokinet. 1987: 13:65-90.

j. Ereshefsky L, Saklad SR, Watanabe MD, et al. Thiothixene pharmacokinetic interactions: a study of hepatic enzyme inducers, clearance inhibitors, and demographic variables. J Clin Psychopharmacol. 1991; 11:296-301. [PubMed 1765572]

k. Hobbs DC, Welch WM, Short MJ, et al. Pharmacokinetics of thiothixene in man. Clin Pharmacol Ther. 1974; 16:473-8. [PubMed 4415039]

l. Ereshefsky L, Jann MW, Saklad SR, et al. Bioavailability of psychotropic drugs: historical perspective and pharmacokinetic overview. J Clin Psychiatry. 1986; 47 (Suppl):6-15. [PubMed 3528134]

m. Guthrie SK, Hariharan M, Kumar AA, et al. The effect of paroxetine on thiothixene pharmacokinetics. J Clin Pharm Ther. 1997; 22:221-6. [PubMed 9447478]

n. Webb RT, Howard L, Abel KM. Antipsychotic drugs for non-affective psychosis during pregnancy and postpartum. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD004411. DOI: 10.1002/14651858.CD004411.pub2.

o. Cohen LS, Heller VL, Rosenbaum JF. Treatment guidelines for psychotropic drug use in pregnancy. Psychosomatics. 1989; 30:25-33. [PubMed 2643809]

p. Altshuler LL, Cohen L, Szuba MP, et al. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996; 153:592-606. [PubMed 8615404]

q. Mortola JF. The use of psychotropic agents in pregnancy and lactation. Psychiatr Clin North Am. 1989; 12:69-87. [PubMed 2652114]

r. Goldberg H, Nissim R. Psychotropic drugs in pregnancy and lactation. Int J Psychiatry Med. 1994; 24:129-49. [PubMed 7960421]

s. Calabrese JR, Gulledge AD. Psychotropics during pregnancy and lactation: a review. Psychosomatics. 1985; 26:413-26. [PubMed 2859631]

t. Milton GV, Jann MW. Emergency treatment of psychotic symptoms: pharmacokinetic considerations for antipsychotic drugs. Clin Pharmacokinet. 1995; 28:494-504. [PubMed 7656507]

u. Mylan Pharmaceuticals Inc. Thiothixene capsules prescribing information. Morgantown, WV; 2003 Oct.

v. Roerig, Division of Pfizer Inc. Navane (thiothixene hydrochloride) intramuscular for injection prescribing information. New York, NY. 2008 Jan.

w. AHFS drug information 2008. McEvoy GK, ed. Phenothiazines general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 2497-508.

x. Schmidt MH, Lee T. Investigation of striatal dopamine D2 receptor acquisition following prenatal neuroleptic exposure. Psychiatry Res. 1991; 36:319-28. [PubMed 1676523]

y. Mavroidis ML, Kanter DR, Hirschowitz J et al. Clinical relevance of thiothixene plasma levels.J Clin Psychopharmacol. 1984; 4:155-7. [PubMed 6736276]

More Thiothixene resources

• Thiothixene Side Effects (in more detail)
• Thiothixene Dosage
• Thiothixene Use in Pregnancy & Breastfeeding
• Drug Images
• Thiothixene Drug Interactions
• Thiothixene Support Group
• 3 Reviews for Thiothixene - Add your own review/rating

• Thiothixene Professional Patient Advice (Wolters Kluwer)


• Thiothixene Prescribing Information (FDA)


• Thiothixene MedFacts Consumer Leaflet (Wolters Kluwer)


• thiothixene Concise Consumer Information (Cerner Multum)


• thiothixene Advanced Consumer (Micromedex) - Includes Dosage Information


• Navane Advanced Consumer (Micromedex) - Includes Dosage Information


• Navane Prescribing Information (FDA)

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