thiothixene

thiothixene hydrochloride
Navane

Available forms
Available by prescription only
Capsules: 1 mg, 2 mg, 5 mg, 10 mg, 20 mg
Injection: 2 mg/ml, 5 mg/ml, 10 mg/ml
Oral concentrate: 5 mg/ml (7% alcohol)

Indications and dosages
 Acute agitation. Adults: 4 mg I.M. b.i.d. to q.i.d. Maximum dosage is 30 mg I.M. daily. Change to P.O. form as soon as possible.
 Mild to moderate psychosis. Adults: Initially, 2 mg P.O. t.i.d. May increase gradually to 15 mg daily. Maximum dose is 60 mg daily.
 Severe psychosis. Adults: Initially, 5 mg P.O. b.i.d. May increase gradually to 20 to 30 mg daily. Maximum recommended dose is 60 mg daily.

Pharmacodynamics
Antipsychotic action: Thiothixene is thought to exert antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects.
Thiothixene has many other central and peripheral effects; it also acts as an alpha blocker. Its most prominent adverse reactions are extrapyramidal.

Pharmacokinetics
Absorption: Rapidly absorbed.
Distribution: Widely distributed throughout the body. Drug is 91% to 99% protein-bound.
Metabolism: Metabolized in the liver.
Excretion: Mostly excreted as parent drug in feces by way of the biliary tract.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those experiencing circulatory collapse, coma, CNS depression, or blood dyscrasia.
  Use cautiously in geriatric or debilitated patients; in those with history of seizure disorders, CV disease, heat exposure, glaucoma, or prostatic hyperplasia; and in those in a state of alcohol withdrawal.

Interactions
Drug-drug. CNS depressants: Increases CNS depression. Avoid use together.
Drug-herb. Nutmeg: May cause loss of symptom control. Discourage use together.
Drug-food. Caffeine: Increases metabolism of drug. Discourage caffeine use.
Drug-lifestyle. Alcohol use: Increases CNS depression. Discourage alcohol use.
Heavy smoking: Increases metabolism of drug. Discourage smoking.
Sun exposure: May potentiate photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: neuroleptic malignant syndrome, extrapyramidal reactions, drowsiness, restlessness, agitation, insomnia, tardive dyskinesia, sedation, pseudoparkinsonism, EEG changes, dizziness.
CV: hypotension, tachycardia, ECG changes.
EENT: ocular changes, blurred vision, nasal congestion.
GI: dry mouth, constipation.
GU: urine retention, menstrual irregularities, inhibited ejaculation.
Hematologic: transient leukopenia, leukocytosis, agranulocytosis.
Hepatic: jaundice.
Metabolic: weight gain.
Skin: mild photosensitivity, allergic reactions, pain at I.M. injection site, sterile abscess.
Other: gynecomastia.

Effects on lab test results
• May increase liver enzyme levels.
• May decrease WBC and granulocyte counts.

Overdose and treatment
CNS depression is characterized by deep, unarousable sleep and possible coma, hypotension or hypertension, extrapyramidal symptoms, abnormal involuntary muscle movements, agitation, seizures, arrhythmias, ECG changes, hypothermia or hyperthermia, and autonomic nervous system dysfunction.
 Treatment is symptomatic and supportive and includes maintaining vital signs, airway, stable body temperature, and fluid and electrolyte balance.
 Don’t induce vomiting: Drug inhibits cough reflex, and aspiration may occur. Use gastric lavage, then activated charcoal and sodium chloride cathartics; dialysis doesn’t help. Regulate body temperature, as needed. Treat hypotension with I.V. fluids: Don’t give epinephrine. Seizures may be treated with parenteral diazepam or barbiturates; arrhythmias with parenteral phenytoin (1 mg/kg with rate titrated to blood pressure); and extrapyramidal reactions with benztropine at 1 to 2 mg or parenteral diphenhydramine at 10 to 50 mg.

Special considerations
• Liquid and injectable formulations may cause a rash if skin contact occurs.
• Because stomach upset may occur, administer oral form with food or fluid.
• Dilute the concentrate in 2 to 4 oz (60 to 120 ml) of liquid, preferably water, carbonated drinks, fruit juice, tomato juice, milk, or pudding.
• I.M. injection may cause skin necrosis.
• Solution for injection may be slightly discolored. Don’t use if excessively discolored or if a precipitate is evident.
• Drug is stable after reconstitution for 48 hours at room temperature.
• Protect liquid formulation from light.
• Dosage adjustments may be needed when changing from I.M. to P.O. or vice versa.
• Drug causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5-hydroxyindoleacetic acid because of darkening of urine by metabolites; it also causes false-positive urine pregnancy results in tests using human chorionic gonadotropin as the indicator.
• Monitor blood pressure before and after parenteral administration.
• Drug is linked to a high risk of extrapyramidal effects.
• Taper drug gradually. After abrupt withdrawal of long-term therapy, patient may experience gastritis, nausea, vomiting, dizziness, tremor, feeling of warmth or cold, diaphoresis, tachycardia, headache, and insomnia.
• Check patient regularly for abnormal body movements (at least once every 6 months).
Pregnant patients
• Hyperreflexia has been reported in infants following in utero exposure. Use drug during pregnancy only when potential benefit justifies risk to fetus.
Pediatric patients
• Drug isn’t recommended for children younger than age 12.
Geriatric patients
• Geriatric patients tend to require lower doses, adjusted to individual response. Adverse reactions, especially tardive dyskinesia and other extrapyramidal effects, are more likely to develop in such patients.

Patient education
• Explain risks of dystonic reactions and tardive dyskinesia, and tell patient to report abnormal body movements.
• Tell patient to avoid sun exposure and to wear sunscreen when going outdoors to prevent photosensitivity reactions. Remind him that heat lamps and tanning beds also may cause burning of the skin or skin discoloration.
• Instruct patient not to spill the liquid on skin. Contact with skin may cause rash and irritation.
• Tell patient to take drug exactly as prescribed, not to double missed doses, and not to share drug with others.
• Explain that many drug interactions are possible. Patient should seek medical approval before taking any OTC or herbal medication.
• Warn patient not to stop taking drug suddenly; most adverse reactions may be relieved by reducing the dose. Tell him to report difficulty urinating, sore throat, dizziness, or fainting.
• Warn patient against hazardous activities that require alertness until effect of drug is established. Reassure patient that sedation usually subsides after several weeks.
• Tell patient not to drink alcohol or take other medications that may cause excessive sedation.
• Explain which fluids are appropriate for diluting the concentrate and the dropper technique of measuring dose.
• Tell patient to shake concentrate before administration.
• Instruct patient to store drug away from children.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use