thye-oh-RID-a-zeen

Therapeutic Classification: antipsychotics

Pharmacologic Classification: phenothiazines

• Treatment of 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. Crosses the placenta and enters breast milk.

Protein Binding: 90%.

Metabolism/Excretion: Highly metabolized by the liver (primarily by CYP2D6 isoenzyme) and GI mucosa; the CYP2D6 enzyme system 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
• Known alcohol intolerance (concentrate only)
• Concurrent use of fluvoxamine, propranolol, pindolol, fluoxetine, other agents known to inhibit the CYP2D6 enzyme, or agents known to prolong the QTc interval (risk of life-threatening arrrhythmias)
• Hypokalemia (correct prior to use)
• QTc interval >450 msec.

Use Cautiously in:

• Debilitated patients
• Glaucoma
• Urinary retention
• Diabetes mellitus
• Patients with risk factors for electrolyte imbalance (dehydration, diuretic therapy)
• Respiratory disease
• Prostatic hyperplasia
• CNS tumors
• Patients at risk for falls
• Epilepsy
• Intestinal obstruction
• OB: Lactation: Safety not established. Recommend discontinue drug or bottle feed
• Geri: May be at ↑ risk for extrapyramidal and CNS adverse effects; appears on Beers list; ↑ risk of mortality in elderly patients treated for dementia-related psychosis.

CNS: NEUROLEPTIC MALIGNANT SYNDROME, sedation, extrapyramidal reactions, tardive dyskinesia.

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

CV: ARRHYTHMIAS, QT INTERVAL PROLONGATION, hypotension, tachycardia.

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

GU: urinary retention, priapism.

Derm: photosensitivity, pigment changes, rash.

Endo: galactorrhea, amenorrhea.

Hemat: AGRANULOCYTOSIS, leukopenia.

Metab: hyperthermia.

Misc: allergic reactions.

Drug-Drug:

• Concurrent fluvoxamine, propranolol, pindolol, fluoxetine, other agents known to inhibit the CYP450 2D6 enzyme, or agents known to prolong the QTc interval↑ risk of life-threatening arrhythmias.
• 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↓ blood levels of thioridazine.
• 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 theerapy.
• 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: Geriatric patients 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 or if breastfeeding.
• 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

• Disturbed thought process (Indications).
• Sexual dysfunction (Side Effects).

NDC Code^*

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-0612- Thioridazine Hydrochloride
    • 0378-0612-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0612-01)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-0614- Thioridazine Hydrochloride
    • 0378-0614-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0614-01)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-0616- Thioridazine Hydrochloride
    • 0378-0616-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0616-01)

• 0378- Mylan Pharmaceuticals Inc.
  • 0378-0618- Thioridazine Hydrochloride
    • 0378-0618-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0618-01)

• 51079- Mylan Institutional Inc.
  • 51079-565- Thioridazine Hydrochloride
    • 51079-565-20- 100 BLISTER PACK in 1 CARTON (51079-565-20) > 1 TABLET, FILM COATED in 1 BLISTER PACK (51079-565-01)

• 51079- Mylan Institutional Inc.
  • 51079-566- Thioridazine Hydrochloride
    • 51079-566-20- 100 BLISTER PACK in 1 CARTON (51079-566-20) > 1 TABLET, FILM COATED in 1 BLISTER PACK (51079-566-01)

• 51079- Mylan Institutional Inc.
  • 51079-567- Thioridazine Hydrochloride
    • 51079-567-20- 100 BLISTER PACK in 1 CARTON (51079-567-20) > 1 TABLET, FILM COATED in 1 BLISTER PACK (51079-567-01)

• 51079- Mylan Institutional Inc.
  • 51079-580- Thioridazine Hydrochloride
    • 51079-580-20- 100 BLISTER PACK in 1 CARTON (51079-580-20) > 1 TABLET, FILM COATED in 1 BLISTER PACK (51079-580-01)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-148- Thioridazine Hydrochloride
    • 53489-148-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-148-01)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-148- Thioridazine Hydrochloride
    • 53489-148-10- 1000 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-148-10)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-149- Thioridazine Hydrochloride
    • 53489-149-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-149-01)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-149- Thioridazine Hydrochloride
    • 53489-149-10- 1000 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-149-10)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-150- Thioridazine Hydrochloride
    • 53489-150-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-150-01)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-150- Thioridazine Hydrochloride
    • 53489-150-10- 1000 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-150-10)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-01- 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-01)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-02- 50 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-02)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-03- 250 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-03)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-05- 500 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-05)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-06- 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-06)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-10- 1000 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-10)

• 53489- Sun Pharmaceutical Industries, Inc.
  • 53489-500- Thioridazine Hydrochloride
    • 53489-500-60- 20 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (53489-500-60)

• 70518- REMEDYREPACK INC.
  • 70518-0770- Thioridazine Hydrochloride
    • 70518-0770-0- 30 TABLET, FILM COATED in 1 BLISTER PACK (70518-0770-0)

• 70518- REMEDYREPACK INC.
  • 70518-1706- Thioridazine Hydrochloride
    • 70518-1706-0- 30 TABLET, FILM COATED in 1 BLISTER PACK (70518-1706-0)