thiothixene NAVANE
Class: First Generation Antipsychotic/ThioxantheneFDA Indications: Schizophrenia
Off-Label Use: Agitation And Aggression In Dementia, Bipolar Mania, Agitation And Psychosis Due To Delirium
Prescribing
Forms: 1, 2, 5, 10, 20mg capsule; 5 mg/ml po soln; 2 mg/ml, 5 mg/ml, 10 mg/ml IMDose Range: 10-60 mg/day
Starting: 5-10 mg/day; maximum dose generally 60 mg/day; higher doses may be given in divided doses
Stopping: Taper 6-8 weeks, rapid d/c can lead to rebound psychosis
Monitoring:
Precautions
Contraindications: Contraindicated in severe central nervous system depression (alcohol, barbiturates, narcotics, etc.) or comatose statesSerious Side Effects: , , Neutropenia and/or Agranulocytosis (rare), Hyperprolactinemia
Side Effects: anticholinergic side effects, EPS
Pharmacodynamics
1° MOA: Dopamine 2 (D2) receptor antagonism in mesolimbic areaTarget: D2 (very high), 5HT2A (low), α1 (moderate), H1 (very high), M1 (low)
Pharmacokinetics
t½: 34° TMAX: 1-3°Substrate of: 1A2; 2D6
Inhibits: ∅ ; Induces: ∅
Active Metabolites: N-demethylthiothixene, thiothixene sulfoxide
DDIs
- - 1A2 inhibitors can ↑ levels, likewise 1A2 inducers can ↓ levels
Misc
- - elimination is biphasic, with an initial t½ of 3.4 hours and a terminal t½ of 34 hours
- - may cause less weight gain than other antipsychotics
- - mid- to high-potency neuroleptic
- - there are some studies supporting off-label use for agitation in dementia
Special Populations
Category C—Thiothixene, a phenothiazine derivative, is structurally and pharmacologically related to trifluoperazine and chlorprothixene (see Trifluoperazine). Although occasional reports have attempted to link various phenothiazines with congenital malformations, most of the evidence suggests that these drugs are low risk for the embryo-fetus.
No reports describing the use of thiothixene during lactation have been located. The molecular weight (about 444) is low enough that excretion into breast milk should be expected. The effect on a nursing infant from exposure to the drug in milk is unknown. However, other phenothiazines are present in milk and have caused toxicity. Sedation is a possible effect in nursing infants.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Elderly and debilitated patients should be started on lower dosage.
2019 BEE℞S Recommendation: Avoid, except in schizophrenia or bipolar disorder. Increased risk of CVA and greater rate of cognitive decline and mortality in persons with dementia. Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options have failed or are not possible and the older adult is threatening substantial harm to self or others.
No dosage adjustment necessary.
No dosage adjustment necessary.