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Therapeutic Classification: antipsychotics

Pharmacologic Classification: phenothiazines

• Refractory schizophrenia (considered second line treatment after failure with atypical antipsychotics).

• Alters the effects of dopamine in the CNS.
• Possesses significant anticholinergic and alpha-adrenergic blocking activity.

• Diminished signs and symptoms of psychoses.

Absorption: Absorption from tablets is variable.

Distribution: Widely distributed, high concentrations in the CNS.

Protein Binding: 90%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism (7% of population may be poor metabolizers and may have significantly ↑ thioridazine concentrations and an ↑ risk of adverse effects).

Half-life: 21–24 hr.

(antipsychotic effects)

Contraindicated in:

• Hypersensitivity
• Cross-sensitivity with other phenothiazines may exist
• Angle-closure glaucoma
• Bone marrow depression
• Severe liver or cardiovascular disease
• Concurrent use of fluvoxamine, propranolol, pindolol, fluoxetine, or other agents known to inhibit the CYP2D6 enzyme, or agents known to prolong the QT interval (risk of life-threatening arrrhythmias)
• Poor CYP2D6 metabolizers
• Hypokalemia (correct prior to use)
• QTc interval >450 msec
• Lactation: Lactation.

Use Cautiously in:

• Glaucoma
• Urinary retention
• Diabetes mellitus
• Risk factors for electrolyte imbalance (dehydration, diuretic therapy)
• Respiratory disease
• Prostatic hyperplasia
• CNS tumors
• At risk for falls
• Seizure disorder
• Intestinal obstruction
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia.

CV: ARRHYTHMIAS, hypotension, QT interval prolongation, tachycardia.

Derm: photosensitivity, pigment changes, rash.

EENT: blurred vision, dry eyes, lens opacities, pigmentary retinopathy (high doses).

Endo: amenorrhea, galactorrhea.

GI: constipation, dry mouth, anorexia, drug-induced hepatitis, ileus.

GU: priapism, urinary retention.

Hemat: AGRANULOCYTOSIS, leukopenia.

Metab: hyperthermia, weight gain.

Neuro: sedation, extrapyramidal reactions, NEUROLEPTIC MALIGNANT SYNDROME, tardive dyskinesia.
Misc: allergic reactions.

Drug-Drug:

• Fluvoxamine, propranolol, pindolol, fluoxetine, other CYP2D6 inhibitors, or QT interval prolonging medications↑ risk of life-threatening arrhythmias; concurrent use contraindicated.
• Diuretics↑ the risk of electrolyte imbalance and arrhythmias.
• Additive hypotension with other antihypertensives, nitrates, and acute ingestion of alcohol.
• Additive CNS depression with other CNS depressants, including alcohol, antihistamines, opioid analgesics, sedative/hypnotics, and general anesthetics.
• Additive anticholinergic effects with other drugs possessing anticholinergic properties, including antihistamines, antidepressants, atropine, haloperidol, other phenothiazines, and disopyramide.
• Lithium↓ levels and effectiveness.
• Thioridazine may mask early signs of lithium toxicity and ↑ the risk of extrapyramidal reactions.
• ↑risk of agranulocytosis with antithyroid agents.
• Concurrent use with epinephrine may result in severe hypotension and tachycardia.
• May ↓ the effectiveness of levodopa.

• PO (Adults and Children >12 yr): 50–100 mg 3 times daily initially; may be gradually ↑ to a maintenance dose of up to 800 mg/day.
• PO (Children): 0.5 mg/kg/day in divided doses initially; may be gradually ↑ to a maintenance dose of up to 3 mg/kg/day.

(Generic available)

• Tablets: 10 mg; 25 mg; 50 mg; 100 mg;

• Assess mental status (orientation, mood, behavior) before and periodically during therapy.
• Assess positive (delusions, hallucinations, agitation) and negative (social withdrawal) symptoms of schizophrenia.
• Assess weight and BMI initially and throughout therapy.
• Monitor BP (sitting, standing, lying), ECG, pulse, and respiratory rate before and frequently during the period of dose adjustment. May cause Q-wave and T-wave changes in ECG.
• Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
• Assess patient for level of sedation after administration. Geri: Older adults are more likely to become oversedated.
• Monitor intake and output ratios and daily weight. Report significant discrepancies.
• Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Report these symptoms; reduction in dosage or discontinuation of medication may be necessary. Trihexyphenidyl, diphenhydramine, or benztropine may be used to control these symptoms. Benzodiazpines may alleviate akathisia.
• Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue; excessive eye blinking). Report immediately; may be irreversible.
• Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

• CBC, liver function tests, and ocular examinations should be evaluated periodically during therapy. May cause ↓ hematocrit, hemoglobin, leukocytes, granulocytes, platelets. May cause ↑ bilirubin, AST, ALT, and alkaline phosphatase. Agranulocytosis occurs between 4–10 wk of therapy with recovery 1–2 wk after discontinuation. May recur if medication is restarted. Liver function abnormalities may require discontinuation of therapy.
  • May cause false-positive or false-negative pregnancy test results and false-positive urine bilirubin test results.
  • May cause ↑ serum prolactin levels.

• PO: Administer with food, milk, or full glass of water to minimize gastric irritation.

• Advise patient to take medication as directed and not to skip doses or double up on missed doses. Take missed doses as soon as remembered unless almost time for the next dose. If more than 2 doses a day are ordered, the missed dose should be taken within 1 hr of the scheduled time or omitted. Abrupt withdrawal may lead to gastritis, nausea, vomiting, dizziness, headache, tachycardia, and insomnia.
• Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately to health care professional.
• Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
• May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to use sunscreen and protective clothing when exposed to the sun. Exposed surfaces may develop a blue-gray pigmentation, which may fade after discontinuation of the medication. Extremes in temperature should also be avoided, as this drug impairs body temperature regulation.
• Instruct patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth. Consult health care professional if dry mouth continues for >2 wk.
• Advise patient that increasing activity and bulk and fluids in the diet helps minimize the constipating effects of this medication.
• Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
• Advise patient not to take thioridazine within 2 hr of antacids or antidiarrheal medication.
• Inform patient that this medication may turn urine pink to reddish brown.
• Advise patient to notify health care professional of medication regimen before treatment or surgery.
• Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, visual disturbances, dark-colored urine, or clay-colored stools occur.
• Advise female patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
• Emphasize the importance of routine follow-up exams to monitor response to medication and to detect side effects. Periodic ocular exams are indicated. Encourage continued participation in psychotherapy.

• Decrease in positive symptoms (hallucinations, delusions, agitation) of schizophrenia.

Mellaril