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MOLINDONE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Molindone is a dihydroindolone antipsychotic agent. It is not structurally related to the phenothiazines, the butyrophenones or the thioxanthenes.

Specific Substances

    1) EN-1733A
    2) Lidone
    3) Indol-4(5H)-one, 3-ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)-, monohydrochloride
    4) CAS 7416-34-4 (molindone)
    5) CAS 15622-65-8 (molindone hydrochloride)

Available Forms Sources

    A) FORMS
    1) Molindone hydrochloride is available as 5 mg, 10 mg, and 25 mg tablets (Prod Info molindone HCl oral tablets, 2014).
    B) USES
    1) Molindone hydrochloride is used to treat patients with schizophrenia (Prod Info molindone HCl oral tablets, 2014).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Molindone hydrochloride is used to treat patients with schizophrenia.
    B) PHARMACOLOGY: Molindone hydrochloride, a dihydroindolone compound, exerts its antipsychotic effects on the ascending reticular activating system in the absence of muscle relaxation and incoordination effects.
    C) TOXICOLOGY: Postsynaptic dopamine 2 receptor blockade may account for extrapyramidal symptoms and contribute to instigation of neuroleptic malignant syndrome.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) The following adverse effects have been reported with therapeutic use of molindone: drowsiness, hypotension, tachycardia, transient, non-specific T-wave changes, dry mouth, elevated liver enzymes, transient leukopenia, leukocytosis, extrapyramidal effects (rigidity, tremor, akathisia, major tonic spasms and tardive dyskinesia), fever, seizures. Especially in patients who have previous exposure to neuroleptics, therapeutic administration and overdose may facilitate rhabdomyolysis with high CPK levels, myoglobinuria, hyperkalemia, acid-base derangements and subsequent acute renal failure. Metabolic acidosis, hyperkalemia, hyperphosphatemia, hypocalcemia may occur as a complication of rhabdomyolysis or acute renal failure. Neuroleptic malignant syndrome (NMS), which can manifest clinically with hyperpyrexia, muscle rigidity, autonomic instability, and altered mental status, has been rarely reported after therapeutic use of molindone.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Experience with overdose is limited. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses. Extrapyramidal effects (rigidity, tremor, akathisia, major tonic spasms and tardive dyskinesia) are likely with overdose.
    2) SEVERE TOXICITY: Especially in patients who have previous exposure to neuroleptics, therapeutic administration and overdose may facilitate rhabdomyolysis with high CPK levels, myoglobinuria, hyperkalemia, acid-base derangements and subsequent acute renal failure.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Hyperpyrexia, hypotension and shallow, rapid respirations have occurred with therapeutic use in patients previously exposed to neuroleptics.
    0.2.20) REPRODUCTIVE
    A) Molindone has been classified as FDA pregnancy category C. Third-trimester antipsychotic drug exposure has been associated with extrapyramidal and/or withdrawal symptoms in neonates. Studies have found no significant teratogenic or reproductive risks for this chemical.

Laboratory Monitoring

    A) Monitor ECG, vital signs, and perform neurologic exam.
    B) Monitor acid-base status, fluid and electrolyte balance, renal function, and liver enzymes.
    C) Closely monitor serum CPK, especially in patients with muscle pain, dark urine or muscle rigidity.
    D) Monitor for akathisia and possible extrapyramidal effects.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Management will primarily be symptomatic and supportive. Manage mild hypotension with IV fluids.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treat hypotension refractory to IV fluids with a pressor such as norepinephrine. Manage severe extrapyramidal symptoms with anticholinergics and/or benzodiazepines. Although rare, treat neuroleptic malignant syndrome with benzodiazepines, as well as cooling and supportive measures; consider bromocriptine and dantrolene in severe cases. Treat seizures with IV benzodiazepines; add propofol, or barbiturates if seizures recur or persist.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital decontamination is not recommended because of the possibility of a dystonic reaction or CNS depression and subsequent aspiration.
    2) HOSPITAL: Consider activated charcoal in a patient with a recent, significant overdose who is alert or in whom airway is protected.
    D) AIRWAY MANAGEMENT
    1) Insure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression.
    E) ANTIDOTE
    1) None
    F) RHABDOMYOLYSIS
    1) Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be needed to maintain urine output. Urinary alkalinization is NOT routinely recommended.
    G) NEUROLEPTIC MALIGNANT SYNDROME
    1) Although rare, treat neuroleptic malignant syndrome with benzodiazepines, as well as cooling and supportive measures; consider bromocriptine and dantrolene in severe cases.
    H) DYSTONIA
    1) ADULT: Benztropine 1 to 2 mg IV or diphenhydramine 1 mg/kg/dose IV over 2 minutes. CHILD: Diphenhydramine 1 mg/kg/dose IV over 2 minutes (maximum 5 mg/kg/day or 50 mg/m(2)/day).
    I) SEIZURES
    1) Administer IV benzodiazepines; add propofol, or barbiturates if seizures recur or persist.
    J) ENHANCED ELIMINATION
    1) Forced diuresis, dialysis, hemoperfusion, and hemodialysis are NOT expected to be useful.
    K) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management.
    2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be referred to a healthcare facility.
    3) ADMISSION CRITERIA: Patients with significant persistent central nervous system toxicity (eg, somnolence, extrapyramidal signs) or persistent tachycardia should be admitted. Patients with dysrhythmias, seizures, delirium, or coma should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, seizures, dysrhythmias, severe delirium, coma) or in whom the diagnosis is not clear.
    L) PITFALLS
    1) Consider the possibility that other psychiatric medications may have been involved in the ingestion. Failure to identify and treat neuroleptic malignant syndrome. Inadequate control of hyperthermia and hypotension can lead to end-organ damage and death.
    M) PHARMACOKINETICS
    1) ORAL: Rapidly absorbed and metabolized. Less than 2% to 3% of an administered dose of molindone is excreted as unchanged or unmetabolized drug in the urine. Elimination half-life: 1.5 hours.
    N) DIFFERENTIAL DIAGNOSIS
    1) Includes overdose of other atypical antipsychotic agents or other centrally acting agents (eg, tricyclic antidepressants, skeletal muscle relaxants).

Range Of Toxicity

    A) TOXICITY: A minimum toxic dose has not been established. Therapeutic doses as high as 400 mg/day in adults are well tolerated.
    B) THERAPEUTIC DOSES: ADULTS: Initial dose, 50 to 75 mg orally daily; may increase to 100 mg/day in 3 or 4 days. Patients with severe psychosis may need up to 225 mg/day of molindone. CHILDREN: The safety and effectiveness of molindone in children below the age of 12 years have not been established. In studies, doses of 1 to 2.5 mg/day were given to children (age range 3 to 5 years).

Clinical Effects

Summary Of Exposure

    A) USES: Molindone hydrochloride is used to treat patients with schizophrenia.
    B) PHARMACOLOGY: Molindone hydrochloride, a dihydroindolone compound, exerts its antipsychotic effects on the ascending reticular activating system in the absence of muscle relaxation and incoordination effects.
    C) TOXICOLOGY: Postsynaptic dopamine 2 receptor blockade may account for extrapyramidal symptoms and contribute to instigation of neuroleptic malignant syndrome.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) The following adverse effects have been reported with therapeutic use of molindone: drowsiness, hypotension, tachycardia, transient, non-specific T-wave changes, dry mouth, elevated liver enzymes, transient leukopenia, leukocytosis, extrapyramidal effects (rigidity, tremor, akathisia, major tonic spasms and tardive dyskinesia), fever, seizures. Especially in patients who have previous exposure to neuroleptics, therapeutic administration and overdose may facilitate rhabdomyolysis with high CPK levels, myoglobinuria, hyperkalemia, acid-base derangements and subsequent acute renal failure. Metabolic acidosis, hyperkalemia, hyperphosphatemia, hypocalcemia may occur as a complication of rhabdomyolysis or acute renal failure. Neuroleptic malignant syndrome (NMS), which can manifest clinically with hyperpyrexia, muscle rigidity, autonomic instability, and altered mental status, has been rarely reported after therapeutic use of molindone.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Experience with overdose is limited. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses. Extrapyramidal effects (rigidity, tremor, akathisia, major tonic spasms and tardive dyskinesia) are likely with overdose.
    2) SEVERE TOXICITY: Especially in patients who have previous exposure to neuroleptics, therapeutic administration and overdose may facilitate rhabdomyolysis with high CPK levels, myoglobinuria, hyperkalemia, acid-base derangements and subsequent acute renal failure.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hyperpyrexia, hypotension and shallow, rapid respirations have occurred with therapeutic use in patients previously exposed to neuroleptics.
    3.3.2) RESPIRATIONS
    A) WITH THERAPEUTIC USE
    1) TACHYPNEA: Shallow, rapid respirations occurred with therapeutic use, secondary to metabolic acidosis, in a patient with probable neuroleptic malignant syndrome who had been previously exposed to other neuroleptics (Johnson et al, 1986).
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) HYPERPYREXIA has occurred with therapeutic use in patients who developed neuroleptic malignant syndrome and had previously been exposed to other neuroleptics (Johnson et al, 1986; Gradon, 1991).
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) HYPOTENSION has occurred with therapeutic use in patients who developed neuroleptic malignant syndrome and had previously been exposed to other neuroleptics (Johnson et al, 1986).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension has occurred with therapeutic use in patients previously exposed to neuroleptics (Prod Info MOBAN(R) oral tablets, 2010; Johnson et al, 1986; Turek, 1970).
    B) TACHYARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Tachycardia has been reported with molindone therapy (Abuzzahab, 1973a).
    C) ELECTROCARDIOGRAM ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Transient, non-specific T-wave changes, without clinical symptoms, have been rarely reported (Prod Info MOBAN(R) oral tablets, 2010).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) HYPERVENTILATION
    1) WITH THERAPEUTIC USE
    a) Shallow, rapid respirations have occurred with therapeutic use, secondary to metabolic acidosis, in a patient who developed neuroleptic malignant syndrome and had previously been exposed to other neuroleptics (Johnson et al, 1986).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROLEPTIC MALIGNANT SYNDROME
    1) WITH THERAPEUTIC USE
    a) Neuroleptic malignant syndrome (NMS), which can manifest clinically with hyperpyrexia, muscle rigidity, autonomic instability, and altered mental status, has been rarely reported after therapeutic use of molindone (Prod Info MOBAN(R) oral tablets, 2010).
    b) Neuroleptic malignant syndrome (NMS) possibly caused by molindone was reported to occur in a 40-year-old woman with a past history of two previous episodes of NMS due to other medications. The patient had received lithium 300 mg in the morning and 600 mg at bedtime and chlorpromazine 200 mg at bedtime for one week with no signs of improvement. Her medications were stopped and the next morning she received molindone 25 mg. By that afternoon she was febrile (temperature 40 degrees Celsius), rigid, and diaphoretic with a CPK of 1430 units/L. All medications were stopped and the patient was started on bromocriptine. Within 48 hours, she was afebrile and her CPK had fallen to 300 units/L (Gradon, 1991a).
    c) Neuroleptic malignant syndrome (NMS) possibly resulting from molindone was reported in a 36-year-old woman receiving haloperidol, chlorpromazine, and molindone. The patient made a full recovery upon discontinuation of the neuroleptics (Bernstein, 1979).
    B) EXTRAPYRAMIDAL DISEASE
    1) WITH THERAPEUTIC USE
    a) SIGNS: Rigidity, tremor, dysphagia, akathisia, dystonia and major tonic spasm have occurred with therapeutic use (Turek, 1970).
    b) TARDIVE DYSKINESIA
    1) A potentially irreversible tardive dyskinesia may develop in patients receiving antipsychotic drugs, and may be related to the duration of treatment and the cumulative dose. Less commonly, the syndrome can develop after brief treatment periods at low doses. Antipsychotics may mask the underlying process by suppressing the signs and symptoms of the syndrome. The prevalence of the syndrome appears to be highest among the elderly, especially elderly women; however, it is impossible to rely upon prevalence to estimate which patients are likely to develop the syndrome. The syndrome may remit partially or completely upon discontinuation of the antipsychotic medication (Prod Info MOBAN(R) oral tablets, 2010).
    2) CASE REPORT: Tardive dyskinesia occurred in a 27-year-old man who, prior to molindone, had received haloperidol, trifluoperazine, and fluphenazine in short courses without symptoms. Dyskinesia developed 10 months after institution of molindone therapy and had persisted for 7 months at the time of the report (Ananth & Carrillo, 1983).
    3) CASE REPORT: A case of tardive dyskinesia associated with molindone was reported in a 29-year-old female who had received numerous antipsychotic drugs prior to initiation of molindone. During the third month of treatment with molindone, she developed symptoms of tardive dyskinesia. Three months after discontinuation of the drug, the symptoms were subsiding and she was transferred to outpatient care (Katz, 1990).
    4) Molindone has been reported to aggravate preexisting tardive dyskinesia (Kellner et al, 1976).
    c) DYSTONIA
    1) Dystonia, including neck muscle spasm (sometimes progressing to throat tightness), tongue protrusion, and difficulty breathing or swallowing, has been reported during the first few days of treatment with first generation antipsychotic drugs. Symptoms may occur with low doses, but are more common and severe with larger doses. Men and younger age groups of both sexes are at increased risk of acute dystonia (Prod Info MOBAN(R) oral tablets, 2010).
    d) AKINESIA
    1) Akinesia (including tremor, rigidity, and immobility and reduction of voluntary movements) has been reported with molindone hydrochloride therapy (Prod Info MOBAN(R) oral tablets, 2010).
    e) AKATHISIA
    1) One study reported oral-buccal-lingual masticatory movements and akathisia in an adult who received up to 225 mg/day molindone for three months (Katz, 1990a).
    2) WITH POISONING/EXPOSURE
    a) SIGNS: Rigidity, tremor, dysphagia, akathisia, dystonia and major tonic spasm have occurred with therapeutic use (Turek, 1970) and may occur in overdose.
    C) SEIZURE
    1) WITH THERAPEUTIC USE
    a) Seizures have been rarely reported with molindone hydrochloride use (Prod Info MOBAN(R) oral tablets, 2010).
    D) DROWSY
    1) WITH THERAPEUTIC USE
    a) Initial drowsiness was the most frequently-reported adverse event associated with molindone hydrochloride therapy. Drowsiness usually resolved with continued usage or dose reduction (Prod Info MOBAN(R) oral tablets, 2010).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) APTYALISM
    1) WITH THERAPEUTIC USE
    a) Dry mouth, contributing to dysphagia, has been reported during molindone therapy (Abuzzahab, 1973a).
    B) WEIGHT LOSS FINDING
    1) WITH THERAPEUTIC USE
    a) Both weight gain (Abuzzahab, 1973a) and weight loss (Kellner, 1976; Heikkinen et al, 1993) have been reported with therapeutic use.
    b) Although most neuroleptic drugs are associated with weight gain, molindone appears to be more often associated with weight loss (Allison et al, 1999).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Therapeutic use has been associated with increases in hepatic enzyme concentrations (SGPT, SGOT, alkaline phosphatase) in some patients (Abuzzahab, 1973a) 1973b; Bhatia et, 1985).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) Acute renal failure may develop in patients secondary to rhabdomyolysis; molindone's ability to cause these conditions alone is controversial (Pandurangi & Narasimhachari, 1988).
    b) SIGNS - Oliguria or anuria, elevated blood urea nitrogen and creatinine concentrations, hyperphosphatemia, hyperkalemia, hypocalcemia and acid-base disturbance.
    B) DISORDER OF MENSTRUATION
    1) WITH THERAPEUTIC USE
    a) One study reported menstrual abnormalities in 10 patients receiving molindone (25 to 150 mg/day) over a period of 6 weeks. Heavy menstrual flow which was not evident prior to therapy occurred in 4 of the patients. One patient developed amenorrhea (Krumholz, 1970).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH THERAPEUTIC USE
    a) Metabolic acidosis occurred in a patient therapeutically treated with molindone who developed rhabdomyolysis and renal failure (Johnson et al, 1986).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH THERAPEUTIC USE
    a) Transient leukopenia and leukocytosis have been reported with molindone therapy (Prod Info MOBAN(R) oral tablets, 2010; Kellner, 1976).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH THERAPEUTIC USE
    a) CONTROVERSY: Molindone alone has not been definitively proven to cause rhabdomyolysis (Pandurangi & Narasimhachari, 1988). In large doses, it has been implicated as one of several factors which combined to cause rhabdomyolysis in a therapeutically treated patient (Johnson et al, 1988).
    b) EFFECTS : Include muscle pain, weakness, myoglobinuria, brown or red discoloration of the urine, hyperkalemia, hypocalcemia, hyperuricemia, acid-base derangement and increased serum concentration of creatinine phosphokinase. Sequelae include acute renal failure.
    2) WITH POISONING/EXPOSURE
    a) HISTORY: Psychiatric patients may be more predisposed to developing rhabdomyolysis from molindone overdose. They have often been previously exposed to neuroleptics and other agents, may have increased muscle membrane permeability secondary to psychosis and may experience abnormal muscular activity during psychotic catatonic excitement (Melzer, 1968; (Lazarus, 1985).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOTHYROIDISM
    1) WITH THERAPEUTIC USE
    a) Hypothyroidism has been loosely associated with therapeutic use of molindone (Gradon, 1991; Peper, 1985).
    B) LACTATION
    1) WITH THERAPEUTIC USE
    a) Therapeutic use of molindone has been reported to cause an increase in release of prolactin and consequent galactorrhea (Wesp, 1979; Kahn, 1979).

Reproductive

    3.20.1) SUMMARY
    A) Molindone has been classified as FDA pregnancy category C. Third-trimester antipsychotic drug exposure has been associated with extrapyramidal and/or withdrawal symptoms in neonates. Studies have found no significant teratogenic or reproductive risks for this chemical.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) Several animal studies have failed to demonstrate a significant teratogenic risk (Prod Info Moban(R), Molindone, 1998).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Molindone has been classified as FDA pregnancy category C (Prod Info Moban(R), 1998).
    B) EXTRAPYRAMIDAL AND/OR WITHDRAWAL SYMPTOMS
    1) Maternal use of antipsychotic drugs during the third trimester of pregnancy has been associated with an increased risk of neonatal extrapyramidal and/or withdrawal symptoms (eg, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) following delivery. Severity of these adverse effects have ranged from cases that are self-limiting to cases that required prolonged periods of hospitalization and ICU care (Prod Info MOBAN(R) oral tablets, 2010).
    C) CASE REPORTS
    1) One patient received a total dose of 9.8 grams molindone throughout her entire pregnancy and delivered normal twins. Immediate post-birth examination revealed no detectable adverse effects secondary to maternal ingestion of molindone (Ayd, 1976).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) No data are available on the content of molindone in the breast milk of nursing mothers (Prod Info Moban(R), Molindone, 1998; Briggs et al, 1998).
    2) There is some suggestion that the adverse effect profile of molindone is not significantly different from "typical" antipsychotics, and these agents actually increase breast milk production (Bagnall A, Fenton M & Lewis R et al, 2000; Llewellyn & Stowe, 1998; Chisholm & Kuller, 1997).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor ECG, vital signs, and perform neurologic exam.
    B) Monitor acid-base status, fluid and electrolyte balance, renal function, and liver enzymes.
    C) Closely monitor serum CPK, especially in patients with muscle pain, dark urine or muscle rigidity.
    D) Monitor for akathisia and possible extrapyramidal effects.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Monitor acid-base status.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte balance, renal function, and liver enzymes. Closely monitor serum CPK, especially in patients with in patients with muscle pain, dark urine or muscle rigidity(Johnson et al, 1986; Johnson et al, 1988).
    4.1.3) URINE
    A) OTHER
    1) Monitor urine myoglobin in patients with elevated CK or evidence of renal toxicity (Johnson et al, 1986; Johnson et al, 1988).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with significant persistent central nervous system toxicity (eg, somnolence, extrapyramidal signs) or persistent tachycardia should be admitted. Patients with dysrhythmias, seizures, delirium, or coma should be admitted to an intensive care setting.
    6.3.1.2) HOME CRITERIA/ORAL
    A) There is no data to support home management.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, seizures, dysrhythmias, severe delirium, coma) or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be referred to a healthcare facility.

Monitoring

    A) Monitor ECG, vital signs, and perform neurologic exam.
    B) Monitor acid-base status, fluid and electrolyte balance, renal function, and liver enzymes.
    C) Closely monitor serum CPK, especially in patients with muscle pain, dark urine or muscle rigidity.
    D) Monitor for akathisia and possible extrapyramidal effects.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital decontamination is not recommended because of the possibility of a dystonic reaction or CNS depression and subsequent aspiration.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor ECG, vital signs, and perform neurologic exam.
    2) Monitor acid-base status, fluid and electrolyte balance, renal function, and liver enzymes.
    3) Closely monitor serum CPK and urine myoglobin, especially in patients with muscle pain or rigidity, dark urine, prolonged coma or seizures, or known previous exposure to neuroleptics or history of psychosis or schizophrenia.
    4) Monitor for akathisia and possible extrapyramidal effects.
    B) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    C) RHABDOMYOLYSIS
    1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    6) MANNITOL/INDICATIONS
    a) Osmotic diuretic used in the management of rhabdomyolysis and myoglobinuria (Zimmerman & Shen, 2013).
    7) RHABDOMYOLYSIS/MYOGLOBINURIA
    a) ADULT: TEST DOSE: (for patients with marked oliguria or those with inadequate renal function) 0.2 g/kg IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase within 2 to 3 hours. The patient should be reevaluated if there is inadequate response following the second test dose (Prod Info MANNITOL intravenous injection, 2009). TREATMENT DOSE: 50 to 100 g IV as a 15% to 25% solution may be used. The rate should be adjusted to maintain urinary output at 30 to 50 mL/hour (Prod Info mannitol IV injection, urologic irrigation, 2006) OR 300 to 400 mg/kg or up to 100 g IV administered as a single dose (Prod Info MANNITOL intravenous injection, 2009).
    b) PEDIATRIC: Dosing has not been established in patients less than 12 years of age(Prod Info Mannitol intravenous injection, 2009). TEST DOSE (for patients with marked oliguria or those with inadequate renal function): 0.2 g/kg or 6 g/m(2) body surface area IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase; TREATMENT DOSE: 0.25 to 2 g/kg or 60 g/m(2) body surface area IV as a 15% to 20% solution over 2 to 6 hours; do not repeat dose for persistent oliguria (Prod Info MANNITOL intravenous injection, 2009).
    8) ADVERSE EFFECTS
    a) Fluid and electrolyte imbalance, in particular sodium and potassium; expansion of the extracellular fluid volume leading to pulmonary edema or CHF exacerbations(Prod Info MANNITOL intravenous injection, 2009).
    9) PRECAUTION
    a) Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia; do not add to whole blood for transfusions(Prod Info Mannitol intravenous injection, 2009); enhanced neuromuscular blockade observed with tubocurarine(Miller et al, 1976).
    10) MONITORING PARAMETERS
    a) Renal function, urine output, fluid balance, serum potassium, serum sodium, and serum osmolality (Prod Info Mannitol intravenous injection, 2009).
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    E) NEUROLEPTIC MALIGNANT SYNDROME
    1) May be successfully managed diphenhydramine, oral bromocriptine, benzodiazepines, or intravenous or oral dantrolene sodium in conjunction with cooling and other supportive care (May et al, 1983; Mueller et al, 1983; Leikin et al, 1987; Schneider, 1991; Barkin, 1992).
    a) BENZODIAZEPINES: In conjunction with cooling measures and supportive care, initial management of NMS should include administration of intravenous benzodiazepines for muscle relaxation (Goldfrank et al, 2002) Benzodiazepines may also be helpful in controlling agitation or reversal of catatonia (Caroff & Mann, 1993; Gratz et al, 1992).
    1) DIAZEPAM DOSE: 3 to 5 mg intravenous bolus to slow push initially, followed by 1 to 2.5 mg intravenously in 10 minutes.
    b) BROMOCRIPTINE DOSE: 5 mg three times a day orally (Mueller et al, 1983).
    c) DANTROLENE LOADING DOSE: 2.5 mg/kg, to a maximum of 10 mg/kg intravenously (Barkin, 1992).
    d) DANTROLENE MAINTENANCE DOSE: 2.5 mg/kg intravenously every 6 hours (Barkin, 1992); 1 mg/kg orally every 12 hours, up to 50 mg/dose has also been successful (May et al, 1983).
    1) EFFICACY: Variable; often ineffective as sole agent. Most efficacious in reducing rigidity and the fever that may be produced at a muscular level; will not always resolve mental status changes or psychotic symptoms that probably are more central in origin. Efficacy may be improved if given with a dopamine agonist (Granato et al, 1983; Blue et al, 1986; May et al, 1983).
    2) Some studies report NO beneficial effects and suggest that dantrolene might even worsen the course of NMS (Rosebush & Stewart, 1989).
    e) NON-PHARMACOLOGIC METHODS: Rapid cooling, hydration, and serial assessment of respiratory, cardiovascular, renal and neurologic function, and fluid status are used in conjunction with drug therapy and discontinuation of the antipsychotic agent (Knight & Roberts, 1986).
    2) In a review of 67 case reports of neuroleptic malignant syndrome, the onset of clinical response was shorter after treatment with DANTROLENE (mean 1.15 days) or BROMOCRIPTINE (1.03 days) than with supportive measures alone (6.8 days).
    a) The time to complete resolution was also shorter with these therapeutic interventions (Rosenberg & Green, 1989).
    3) RETROSPECTIVE STUDY: A study comparing 438 untreated patients with neuroleptic malignant syndrome and 196 treated cases found that administration of dantrolene, bromocriptine, or amantadine significantly reduced the death rate in these cases (Sakkas et al, 1991).
    a) Death rate of untreated cases was 21%; administration of dantrolene alone (no dosage reported) decreased death rate to 8.6% (n=58); with bromocriptine alone death rate was 7.8% (n=51); and with amantadine alone death rate was 5.9% (n=17).
    b) In combination with other drugs, each of these drugs significantly decreased the NMS-related death rate, although the decrease was slightly less than for single administrations.
    F) DRUG-INDUCED DYSTONIA
    1) ADULT
    a) BENZTROPINE: 1 to 4 mg once or twice daily intravenously or intramuscularly; maximum dose: 6 mg/day; 1 to 2 mg of the injection will usually provide quick relief in emergency situations (Prod Info benztropine mesylate IV, IM injection, 2009).
    b) DIPHENHYDRAMINE: 10 to 50 mg intravenously at a rate not exceeding 25 mg/minute or deep intramuscularly; maximum dose: 100 mg/dose; 400 mg/day (Prod Info diphenhydramine hcl injection, 2006).
    2) CHILDREN
    a) DIPHENHYDRAMINE: 5 mg/kg/day or 150 mg/m(2)/day intravenously divided into 4 doses at a rate not to exceed 25 mg/min, or deep intramuscularly; maximum dose: 300 mg/day. Not recommended in premature infants and neonates (Prod Info diphenhydramine hcl injection, 2006).
    G) AMANTADINE
    1) In rats, amantadine reversed molindone-induced catalepsy and ptosis, which are dopamine-dependent behaviors. In addition, amantadine reversed molindone-induced inhibition of traction response in mice. However, its routine use is not recommended, as patients generally respond well to supportive care alone (Dhaware et al, 2000).

Enhanced Elimination

    A) SUMMARY
    1) Forced diuresis, dialysis, hemoperfusion, and hemodialysis are NOT expected to remove enough molindone from the patient to influence clinical course.
    B) CASE REPORT
    1) An adult patient who had received a total dose of 350 mg molindone over 4 days became cyanotic, unresponsive to pain, hypotensive, and acidotic, with a serum molindone level of 152 nanograms/mL. After developing acute renal failure secondary to rhabdomyolysis, the patient received several courses of dialysis. The authors did not comment on possible removal of molindone during dialysis; the patient continued to experience complications of renal failure (Johnson et al, 1986).

Abstracts

Case Reports

    A) ADULT
    1) PREGNANCY: One patient received a total dose of 9.8 grams molindone throughout her entire pregnancy and delivered normal twins. Immediate post-birth examination revealed no detectable adverse effects secondary to maternal ingestion of molindone (Ayd, 1976).
    2) RHABDOMYOLYSIS: A 32-year-old man, previously treated with haloperidol and fluphenazine, was given 50 milligrams molindone orally twice daily for four days. On the second day after treatment was initiated, he became cyanotic, unresponsive, and hypotensive, with serum molindone level of 152 nanograms/milliliter. He was myoglobinuric, and CPK increased to a peak of 914,000 international units/liter; sequelae included acute oliguric renal failure and prolonged prothrombin time. After dialysis, bromocriptine, and symptomatic treatment, the patient was discharged without medication (Johnson et al, 1986).
    3) NEUROLEPTIC MALIGNANT SYNDROME: A 40-year-old woman, previously treated with lithium and chlorpromazine, received one 25 milligram dose of molindone orally. Six hours later, she became febrile, rigid, and diaphoretic. Serum CPK peaked at 1430 international units/liter. Upon discontinuation of molindone and initiation of bromocriptine therapy, she became afebrile with normal CPK level (Gradon, 1991).

Range Of Toxicity

Summary

    A) TOXICITY: A minimum toxic dose has not been established. Therapeutic doses as high as 400 mg/day in adults are well tolerated.
    B) THERAPEUTIC DOSES: ADULTS: Initial dose, 50 to 75 mg orally daily; may increase to 100 mg/day in 3 or 4 days. Patients with severe psychosis may need up to 225 mg/day of molindone. CHILDREN: The safety and effectiveness of molindone in children below the age of 12 years have not been established. In studies, doses of 1 to 2.5 mg/day were given to children (age range 3 to 5 years).

Therapeutic Dose

    7.2.1) ADULT
    A) The usual starting dose for molindone is 50 to 75 milligrams (mg) orally daily. The dose can be increased to 100 mg/day after 3 or 4 days. The following maintenance doses may be used: Patients with mild psychosis 5 to 15 mg orally 3 to 4 times a day; moderate psychosis 10 to 25 mg orally 3 to 4 times a day; severe psychosis up to 225 mg/day of molindone orally in divided doses (Prod Info MOBAN(R) oral tablets, 2008).
    7.2.2) PEDIATRIC
    A) The safety and effectiveness of molindone in children below the age of 12 years have not been established (Prod Info MOBAN(R) oral tablets, 2008).
    B) Campbell et al (1971) administered doses of 1 to 2.5 milligrams/day to children (age range 3 to 5 years) (Campbell, 1971). Greenhill et al (1981) administered doses up to 1 milligram (mg)/kilogram/day to school age children; the optimal dose appeared to be 0.5 mg/kilogram/day, divided in 4 doses (Greenhill, 1981).

Maximum Tolerated Exposure

    A) Therapeutic doses as high as 400 mg/day in adults, may be well tolerated (Pandurangi & Narasimhachari, 1988).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) One study reported therapeutic serum molindone levels of 44 to 374 ng/mL in clinically normal adult patients (Pandurangi & Narasimhachari, 1988). A therapeutic serum molindone range of 27 to 69 ng/mL has also been reported (Johnson et al, 1986).
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) A 32-year-old man, previously exposed to other neuroleptics and subsequently treated with 100 mg molindone/day for two days, suffered massive rhabdomyolysis and probable neuroleptic malignant syndrome. His serum molindone level, two days after treatment initiation and at the peak of clinical signs, was 152 ng/mL (Johnson et al, 1986).
    b) Toxic molindone levels are controversial and not well documented; some authors have reported therapeutic serum molindone levels of up to 374 ng/mL in clinically normal patients (Pandurangi & Narasimhachari, 1988).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 243 mg/kg (RTECS , 2001)
    2) LD50- (ORAL)MOUSE:
    a) 670 mg/kg (RTECS , 2001)
    3) LD50- (ORAL)RAT:
    a) 261 mg/kg (RTECS , 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Molindone hydrochloride is a dihydroindolone compound differing structurally from other antipsychotic drugs such as the phenothiazines, thioxanthenes, and butyrophenones. It exerts its antipsychotic effects on the ascending reticular activating system in the absence of muscle relaxation and incoordination effects (Prod Info MOBAN(R) oral tablets, 2010). Molindone blocks postsynaptic dopamine receptors. It has a lower affinity for cholinergic, noradrenergic, and histaminic receptors in vitro than other antipsychotic agents (Gradon, 1991).

Toxicologic Mechanism

    A) Postsynaptic dopamine 2 receptor blockade may account for extrapyramidal symptoms and contribute to instigation of neuroleptic malignant syndrome (Gradon, 1991).

References

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