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thioridazine (Mellaril, Millazine, Melleretten)
Tradenames: Mellaril, Millazine. (thioridazine hydrochloride)
Indications:
- management of psychotic conditions (see chlorpromazine)
Contraindications:
1) severe CNS depression
2) narrow angle glaucoma
3) blood dyscrasias
4) severe liver disease
5) severe cardiac disease
Caution: seizure disorder
Dosage:
1) 50-200 mg PO TID
2) short term treatment of major depression: 25 mg PO TID
3) children < 2 years: 0.5-3 mg/kg/day divided BID-TID
4) no antacids within 1 hour
Tabs: 10, 15, 25, 50, 100, 150, 200 mg.
Suspension: 25, 30 & 100 mg/5 mL (118 mL).
Pharmacokinetics:
1) antipsychotics in general have varied absorption
2) highly bound to plasma proteins
3) widely distributed to tissues including CNS
4) extensively metabolized by the liver by cyt P450 2D6
5) mesoridazine (Serentil) is an active metabolite
6) 1/2 the dose is excreted in the urine, the other 1/2 through enterohepatic circulation
Adverse effects:
1) common (> 10%)
- pseudoparkinsonism, akathisia, dystonia, hypotension, pigmentary retinopathy, persistent tardive dyskinesia, constipation, decreased sweating, dizziness, orthostatic hypotension, nasal congestion
2) less common (1-10%)
- difficulty urinating, photosensitivity, rash, changes in menstrual cycle, sexual dysfunction, breast pain, weight gain, nausea/vomiting, epigastric pain, trembling of fingers
3) uncommon (< 1%)
- agranulocytosis, cholestatic jaundice, neuroleptic malignant syndrome, priapism, blue-gray discoloration of skin, impairment of temperature regulation, galactorrhea, leukopenia, hepatotoxicity, corneal & lens changes, pigmentary retinopathy
4) other
- anticholinergic symptoms
- sedation
- tardive dyskinesia
- 10-20% of patients on long term therapy
- generally irreversible
- agranulocytosis (rare)
- QT prolongation [5]
- lowering of seizure threshold
Drug interactions:
1) additive effects with:
a) CNS depressants
b) antihypertensives
c) anticholinergic agents
2) concurrent use of lithium has rarely caused acute encephalitis
3) tricyclic antidepressants (TCA): increased cardiac arrhythmias
4) epinephrine: hypotension
5) see chlorpromazine
6) increased risk of arrhythmias with:
a) serotonin-reuptake inhibitors
1] fluvoxamine (Luvox)
2] fluoxetine (Prozac)
3] paroxetine (Paxil)
b) beta-adrenergic receptor antagonists
1] propranolol
2] pindolol
c) quinidine
7) thioridazine inhibits cyt P450 2D6
a) inhibits its own metabolism
b) may increase levels of drugs metabolized by cyt P450 2D6
8) any drug that inhibits metabolism of cyt P450 2D6 may increase levels of thioridazine
Laboratory:
1) specimen: serum, plasma (EDTA)
2) methods: GLC, HPLC, fluorometry
3) interferences: fluorometric assay detects metabolites & parent compund
Mechanism of action:
- low potency dopamine D2 receptor antagonist
Interactions
drug interactions
drug adverse effects (more general classes)
Related
chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil)
cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
mesoridazine (Serentil, Calodal)
General
antipsychotic agent
dopaminergic receptor antagonist
phenothiazine
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 10-36 HOURS
therapeutic-range 1.0-1.5 UG/ML
toxic-range >10 UG/ML
protein-binding >99%
pregnancy-category C
safety in lactation ?
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Saunders Manual of Medical Practice, Rakel (ed),
WB Saunders, Philadelphia, 1996, pg 1147
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Prescriber's Letter 7(9):53 2000
- Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed,
WB Saunders, Philadelpha 1995