No

Antipsychotic Agent, Dihydoindoline

Management of psychotic disorder

C

Hypersensitivity to molindone or any component (cross reactivity between phenothiazines may occur); severe CNS depression, coma

May be sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of neuroleptics. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate-high relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Orthostatic hypotension, tachycardia, arrhythmias

Central nervous system: Extrapyramidal reactions (akathisia, pseudoparkinsonism, dystonia, tardive dyskinesia), mental depression, altered central temperature regulation, sedation, drowsiness, restlessness, anxiety, hyperactivity, euphoria, seizures, neuroleptic malignant syndrome (NMS)

Dermatologic: Pruritus, rash, photosensitivity

Endocrine & metabolic: Change in menstrual periods, edema of breasts, amenorrhea, galactorrhea, gynecomastia

Gastrointestinal: Constipation, xerostomia, nausea, salivation, weight gain, weight loss

Genitourinary: Urinary retention, priapism

Hematologic: Leukopenia, leukocytosis

Ocular: Blurred vision, retinal pigmentation

Miscellaneous: Diaphoresis (decreased)

Symptoms of overdose include deep sleep, extrapyramidal symptoms, cardiac arrhythmias, seizures, hypotension

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required (eg, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response). Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Critical cardiac arrhythmias often respond to I.V. phenytoin (15 mg/kg up to 1 g), while other antiarrhythmics can be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

CYP2D6 enzyme substrate

Benztropine (and other anticholinergics) may inhibit the therapeutic response to molindone and excess anticholinergic effects may occur

Chloroquine may increase molindone concentrations

Cigarette smoking may enhance the hepatic metabolism of molindone. Larger doses may be required compared to a nonsmoker.

Concurrent use of molindone with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by molindone

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Molindone may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Molindone plus lithium may rarely produce neurotoxicity

Barbiturates may reduce molindone concentrations

Propranolol may increase molindone concentrations

Sulfadoxine-pyrimethamine may increase molindone concentrations

Molindone and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Molindone and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Molindone and trazodone may produce additive hypotensive effects

Protect from light; dispense in amber or opaque vials

Mechanism of action mimics that of chlorpromazine; however, it produces more extrapyramidal effects and less sedation than chlorpromazine

Metabolism: In the liver

Half-life: 1.5 hours

Time to peak serum concentration: Oral: Within 1.5 hours

Elimination: Principally in urine and feces (90% within 24 hours)

Oral:

3-5 years: 1-2.5 mg/day divided into 4 doses

5-12 years: 0.5-1 mg/kg/day in 4 divided doses

Adults: 50-75 mg/day increase at 3- to 4-day intervals up to 225 mg/day

Alcohol: Avoid use

Monitor blood pressure and pulse rate prior to and during initial therapy evaluate mental status; monitor weight

No information available to require special precautions

>10% of patients experience dry mouth; anticholinergic side effects can cause a reduction of saliva production or secretion. This may result in discomfort and dental disease (ie, caries, oral candidiasis and periodontal disease); molindone can cause extrapyramidal reactions which may appear as muscle twitching or increased motor activity of the face, neck or head

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); or decreased perspiration (avoid strenuous exercise in hot environments). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; changes in menstrual pattern or breast tenderness; vision changes; skin rash or yellowing of skin; difficulty breathing; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

May increase appetite and possibly a craving for sweets; recognize signs of neuroleptic malignant syndrome and tardive dyskinesia

Concentrate, oral, as hydrochloride: 20 mg/mL (120 mL)

Tablet, as hydrochloride: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg

Johnson SB, Alvarez WA, and Freinhar JP, "A Case of Massive Rhabdomyolysis Following Molindone Administration," J Clin Psychiatry, 1986, 47(12):607-8.

Katz SE, "Tardive Dyskinesia Associated With Molindone Treatment," Am J Psychiatry, 1990, 147(1):124-5, (letter).

Knight ME and Roberts RJ, "Phenothiazine and Butyrophenone Intoxication in Children," Pediatr Clin North Am, 1986, 33(2):299-309.

Malek-Ahmadi P and Allen SA, "Paroxetine-Molindone Interaction," J Clin Psychiatry, 1995, 56(2):82-3.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.