thioridazine (Mellaril, Millazine, Melleretten)
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Introduction
Tradenames: Mellaril, Millazine. (thioridazine hydrochloride)
Indications
- management of psychotic conditions (see chlorpromazine)
Contraindications
- severe CNS depression
- narrow angle glaucoma
- blood dyscrasias
- severe liver disease
- severe cardiac disease
Caution: seizure disorder
Dosage
- 50-200 mg PO TID
- short term treatment of major depression: 25 mg PO TID
- children < 2 years: 0.5-3 mg/kg/day divided BID-TID
- no antacids within 1 hour
Tabs: 10, 15, 25, 50, 100, 150, 200 mg.
Suspension: 25, 30 & 100 mg/5 mL (118 mL).
Pharmacokinetics
- antipsychotics in general have varied absorption
- highly bound to plasma proteins
- widely distributed to tissues including CNS
- extensively metabolized by the liver by cyt P450 2D6
- mesoridazine (Serentil) is an active metabolite
- 1/2 the dose is excreted in the urine, the other 1/2 through enterohepatic circulation
elimination via liver
elimination via kidney
1/2life = 10-36 hours
protein binding = >99 %
Adverse effects
- common (> 10%)
- 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
- 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
- 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 adverse effects of antipsychotic agents
- drug adverse effects of psychotropic agents
- drug adverse effects of dopaminergic receptor antagonists
- drug adverse effects of antihypertensive agents
Drug interactions
- additive effects with:
- concurrent use of lithium has rarely caused acute encephalitis
- tricyclic antidepressants (TCA): increased cardiac arrhythmias
- epinephrine: hypotension
- see chlorpromazine
- increased risk of arrhythmias with:
- thioridazine inhibits cyt P450 2D6
- inhibits its own metabolism
- may increase levels of drugs metabolized by cyt P450 2D6
- any drug that inhibits metabolism of cyt P450 2D6 may increase levels of thioridazine
- drug interaction(s) of lithium carbonate with phenothiazine
- drug interaction(s) of antipsychotics & dopamine receptor agonists
- drug interaction(s) of antipsycotics with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
- drug interaction(s) of NSAIDs & antihypertensives
Laboratory
- specimen: serum, plasma (EDTA)
- methods: GLC, HPLC, fluorometry
- interferences: fluorometric assay detects metabolites & parent compund
Mechanism of action
- low potency dopamine D2 receptor antagonist
More general terms
Additional terms
- chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
- mesoridazine (Serentil, Calodal)
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
- ↑ 5.0 5.1 Prescriber's Letter 7(9):53 2000
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995