Haloperidol

Pronunciation: (ha-loe-PER-i-dole)Class: Phenylbutylpiperadine derivative

Trade Names:Haldol- Tablets 0.5 mg- Tablets 1 mg- Tablets 2 mg- Tablets 5 mg- Tablets 10 mg- Tablets 20 mg- Solution, concentrate, oral 2 mg (as lactate)/mL- Injection, solution 5 mg (as lactate)/mL

Trade Names:Haldol Decanoate 50- Injection, oil, extended-release 50 mg (as decanoate 70.5 mg)/mL

Trade Names:Haldol Decanoate 100- Injection, oil, extended-release 100 mg (as decanoate 141.04 mg)/mL

Apo-Haloperidol (Canada)Haloperidol LA (Canada)

Pharmacology

Has antipsychotic effect, apparently caused by dopamine-receptor blockage in CNS.

Pharmacokinetics

Absorption

When administered in sesame oil, it results in the slow and sustained release of haloperidol. T _max is 6 days after injection. Steady-state plasma concentrations are achieved after the third or fourth dose. When taken orally, haloperidol is readily absorbed from the GI tract.

Distribution

The relationship between dose of haloperidol decanoate and plasma haloperidol concentration is roughly linear for doses below 450 mg. Vd is about 18 L/kg; C _max is 9.2 ng/mL and T _max about 1.7 h following a single 20 mg oral dose. Haloperidol is widely distributed in the body, including breast milk, and it crosses the blood-brain barrier.

Metabolism

Metabolized by the liver. Because of first-pass metabolism in the liver, plasma concentration after oral doses are lower than those after IM injection.

Elimination

Apparent half-life is approximately 3 wk for the decanoate and 18 h for oral.

Indications and Usage

Oral

Management of psychotic disorders; control of Tourette disorder in children and adults; management of severe behavioral disorders in children; short-term treatment of hyperactive children.

Injection Haloperidol lactate

Treatment of schizophrenia; control of Tourette disorder.

Haloperidol decanoate

Treatment of schizophrenia in patients requiring prolonged parenteral therapy.

Unlabeled Uses

Obsessive-complusive disorder; prevention of chemotherapy-induced nausea or vomiting; treatment of acute agitation in children.

Contraindications

Severe toxic CNS depression or comatose states from any cause; Parkinson disease; hypersensitivity to any component of the product.

Dosage and Administration

Psychotic disordersAdults Moderate symptoms, elderly or debilitated patients

PO 0.5 to 2 mg 2 or 3 times daily.

Severe symptoms, chronic or resistant patients

PO 3 to 5 mg 2 or 3 times daily. Dosages up to 100 mg/day may be necessary in some patients.

Children 3 to 12 yr of age (weight, 15 to 40 kg)

PO Initial dosage, 0.5 mg/day. If needed, increase dose in 0.5 mg increments at 5- to 7-day intervals up to 0.15 mg/kg/day or until therapeutic effect is obtained (usual dosage range, 0.05 to 0.15 mg/kg/day in 2 or 3 divided doses). IM Safety and efficacy not established in children.

Tourette disorderAdults Moderate symptoms, elderly or debilitated patients

PO 0.5 to 2 mg 2 or 3 times daily.

Severe symptoms, or chronic or resistant patients

3 to 5 mg 2 or 3 times daily. Dosages up to 100 mg/day may be necessary in some patients.

Children 3 to 12 yr of age (weight, 15 to 40 kg)

PO Initial dosage, 0.5 mg/day. If needed, increase dose in 0.5 mg increments at 5- to 7-day intervals up to 0.15 mg/kg/day or until therapeutic effect is obtained (usual dosage range, 0.05 to 0.075 mg/kg/day in 2 or 3 divided doses).

Behavioral disorders/hyperactivityChildren 3 to 12 yr of age (weight, 15 to 40 kg)

PO Initial dosage, 0.5 mg/day. If needed, increase dose in 0.5 mg increments at 5- to 7-day intervals or until therapeutic effect is obtained (usual dosage range, 0.05 to 0.075 mg/kg/day in 2 or 3 divided doses). In severely disturbed, nonpsychotic children or in hyperactive children with conduct disorder, short-term administration may suffice. There is little evidence to support dosages greater than 6 mg/day.

Haloperidol lactate injectionSchizophrenia Adults

IM 2 to 5 mg for prompt control of acutely agitated schizophrenic patients with moderately severe to very severe symptoms. Depending on response, subsequent doses may be needed within 60 min; although 4 to 8 h intervals may be satisfactory.

Haloperidol decanoate injection

The dose should be individualized under close supervision during initiation and stabilization of therapy. The recommended interval between doses is monthly or every 4 wk, but variations in patient response may dictate a need for adjustments in dose or dosing interval.

Schizophrenia Adults

IM (deep injection) Initial dose should not exceed 100 mg. If conversion from oral haloperidol to IM haloperidol decanoate requires more than 100 mg as an initial dose, administer that dose in 2 injections (max, 100 mg initially followed by the balance in 3 to 7 days). In patients stabilized on low oral doses (10 mg or less per day), the initial recommended dose of haloperidol decanoate is 10 to 15 times the daily dose. In patients stabilized on higher oral doses, in risk of relapse or tolerant to oral haloperidol, the recommended dose is 20 times the daily dose. Recommended monthly maintenance dose of haloperidol decanoate is 10 to 15 times the previous oral daily dose.

General Advice

• Measure prescribed dose of oral concentrate using calibrated dropper or dosing syringe.
• Injection is for IM administration only. Not for intradermal, subcutaneous, or IV administration.
• Double-check injection doseform. Haloperidol decanoate is designed for monthly injection only.
• The maximum volume per injection site for haloperidol decanoate should not exceed 3 mL.
• Do not administer injection if particulate matter or marked discolorations noted. A slight yellowish discoloration is normal and will not alter potency.

Storage/Stability

Store tablets and oral concentrate between 68° and 77°F. Store injection between 59° and 86°F and protect from light. Do not freeze oral concentrate or injection.

Drug Interactions

Anesthetics, opiates, alcohol

May increase CNS depressant effects. Use with caution and closely monitor the response of the patient.

Anticholinergics

May increase anticholinergic effects. Coadministration may worsen schizophrenic symptoms, decrease haloperidol serum concentrations, and lead to tardive dyskinesia. In addition, the risk for intestinal pseudo-obstruction may be increased. If these agents are coadministered, adjust the dose of both drugs as needed. Monitor for signs and symptoms of GI hypomotility.

Anticonvulsants

Use with caution in patients receiving anticonvulsant medications because haloperidol may lower the convulsive threshold. Monitor the response of the patient and adjust the anticonvulsant dose as needed.

Antiparkinson medication (eg, levodopa)

Haloperidol is contraindicated in patients with Parkinson disease. Antiparkinson medication may have to be given after haloperidol is discontinued because of the difference in excretion rates. The risk of extrapyramidal symptoms may be increased if both drugs are discontinued simultaneously. In addition, coadministration of haloperidol and antiparkinson medication may increase IOP.

Azole antifungal agents (eg, itraconazole)

Plasma levels of haloperidol may be elevated, increasing the risk of adverse effects. Monitor the clinical response to haloperidol when an azole antifungal agent is started or stopped. Adjust the haloperidol dose as needed.

Beta-blockers (eg, propranolol)

Coadministration of beta-blockers and haloperidol may cause an unexpected severe hypotensive reaction, which may be because of additive or synergistic pharmacologic effects. If severe hypotension occurs, provide supportive treatment.

Cabergoline

Pharmacologic effects of cabergoline may be decreased. Coadministration is not recommended.

Carbamazepine

May decrease effects of haloperidol while the effects of carbamazepine may be increased. Monitor plasma concentrations of both drugs and the clinical response of the patient. Adjust the dosage of either drug as needed.

Drugs that prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, disopyramide, dofetilide, flecainide, procainamide, quinidine], arsenic trioxide, chloroquine, chlorpromazine, cisapride, dolasetron, droperidol, fluconazole, halofantrine, haloperidol, lapatinib, macrolide and related antibiotics [eg, clarithromycin, telithromycin], maprotiline, mefloquine, mesoridazine, methadone, nilotinib, paliperidone, pentamidine, perflutren, phosphodiesterase type 5 inhibitors [eg, sildenafil], pimozide, propafenone, quinolone antibiotics [ie, gatifloxacin, moxifloxacin], tacrolimus, tetrabenazine, thioridazine, tricyclic antidepressants [eg, doxepin, nortriptyline], tyrosine kinase receptor antagonists [eg, lapatinib], ziprasidone)

The risk of cardiovascular toxicity, including, fatal cardiac arrhythmias (torsades de pointes), may be increased. Coadministration is not recommended.

Epinephrine

In patients who develop hypotension, do not administer epinephrine because haloperidol may block the vasopressor activity of epinephrine, paradoxically lowering BP.

Guanethidine

The antihypertensive effectiveness of guanethidine may be decreased. Avoid this drug combination when possible. If coadministration is required, a larger dose of guanethidine may control BP. Monitor BP and adjust the guanethidine dose as needed.

Lithium

May induce disorientation, unconsciousness, extrapyramidal symptoms, and hyperthermia. Monitor neurologic function closely and discontinue immediately if impaired consciousness or hyperthermia develops.

Rifamycins (eg, rifampin)

Plasma levels of haloperidol may be reduced, decreasing the clinical effectiveness. Closely monitor the clinical response of the patient when starting or stopping rifamycins. Adjust the haloperidol dose as needed.

Serotonin reuptake inhibitors (eg, fluoxetine)

Haloperidol plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Additional clinical monitoring is indicated. If toxic signs occur, stop one or both agents.

Tacrine

The risk of occurrence of severe extrapyramidal symptoms may be increased. Monitor the patient. If an interaction is suspected, stop one or both drugs.

Tramadol

Risk of seizures may be increased. Coadministration is not recommended.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

ECG changes; hypertension; hypotension; QT prolongation; tachycardia; torsades de pointes.

CNS

Agitation; anxiety; confusion; depression; drowsiness; dystonia; euphoria; exacerbation of psychotic symptoms; extrapyramidal symptoms; headache; insomnia; lethargy; restlessness; seizures; tardive dyskinesia; tardive dystonia; vertigo.

Dermatologic

Hair loss; maculopapular and acneiform skin reactions; photosensitivity.

EENT

Blurred vision; cataracts; retinopathy; visual disturbances.

GI

Anorexia; constipation; diarrhea; dry mouth; dyspepsia; hypersalivation; nausea; vomiting.

Genitourinary

Breast engorgement; gynecomastia; impotence; increased libido; lactation; mastalgia; menstrual irregularities; priapism; urinary retention.

Hematologic

Agranulocytosis; anemia; leukocytosis; leukopenia; lymphomonocytosis.

Hepatic

Jaundice; impaired liver function.

Local

Local tissue reactions (haloperidol decanoate).

Metabolic-Nutritional

Hyperglycemia; hypoglycemia; hyponatremia; hyperammonemia (postmarketing).

Respiratory

Bronchospasm; increased depth of respiration; laryngospasm.

Miscellaneous

Diaphoresis; heat stroke; hyperpyrexia; NMS.

Precautions

Warnings Increased mortality Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with those taking placebo. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Haloperidol is not approved for the treatment of dementia-related psychosis.

Monitor Monitor for improvement in symptoms of psychotic disorders, control of tics and vocal utterances in Tourette disorder, or improvement of behavioral problems or hyperactivity. Monitor for electrolyte imbalances (eg, hypokalemia, hypomagnesemia) as needed. Provide close clinical supervision during initiation and stabilization of therapy.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Do not use in children younger than 3 yr of age. Safety and efficacy of IM form not established.

Elderly

More susceptible to effects; consider lower dose.

Special Risk Patients

Use drug with caution in patients with CV disease or mitral insufficiency, history of glaucoma, EEG abnormalities or seizure disorders, prior brain damage, or hepatic or renal impairment.

Abrupt withdrawal

Abrupt withdrawal in patients on maintenance therapy has been associated with transient dyskinetic signs, which may be indistinguishable from tardive dyskinesia.

Bronchopneumonia

Has occurred, including fatal cases, in some patients following the use of antipsychotic drugs, including haloperidol.

CNS effects

May impair mental or physical abilities, especially during first few days of therapy.

CV effects

Cases of sudden death, QT prolongation, and torsades de pointes have been reported.

Cyclic disorders

When haloperidol is used to control mania, there may be a rapid mood swing to depression.

Debilitated patients

More susceptible to effects; consider lower dose.

Hyperprolactinemia

Prolactin levels may be elevated.

NMS

Has occurred and is potentially fatal. Signs and symptoms are hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, irregular BP, tachycardia, and diaphoresis.

Severe neurotoxicity

Severe neurotoxicity may occur in patients with thyrotoxicosis who are also receiving antipsychotics, including haloperidol.

Sudden death

Has been reported; predisposing factors may be seizures or previous brain damage. Flare up of psychotic behavior may precede death.

Tardive dyskinesia

Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is highest in elderly patients, especially women. Use smallest effective dose for shortest period of time needed.

Overdosage

Symptoms

Autonomic reactions; cardiac arrhythmias; CNS depression; coma; ECG changes associated with torsades de pointes; extrapyramidal symptoms; hypertension; hypotension; shock-like state; somnolence.

Patient Information

• Advise patient, family, or caregiver that dose will be adjusted periodically until max benefit has been obtained.
• Advise patient, family, or caregiver not to change the dose or stop taking unless advised by health care provider.
• Instruct patient, family, or caregiver to measure prescribed dose of oral concentrate using calibrated dropper or dosing syringe.
• Instruct patient not to stop taking haloperidol when feeling better.
• Instruct patient, family, or caregiver to immediately report fainting or loss of consciousness, dizziness, high fever, muscle rigidity, or altered mental status to health care provider.
• Advise patient, family, or caregiver to notify health care provider of the following: excessive drowsiness, increased agitation or anxiety, or involuntary body or facial movements.
• Advise patient to avoid strenuous activity during periods of high temperature or humidity.
• Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
• Instruct patient to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may make dizziness worse.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient that drug may cause drowsiness and impaired judgment or thinking skills and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Caution patient that medication may cause sensitivity to sunlight and to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.

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