Haloperidol Comprehensive Study Outline

OUTLINE: HALOPERIDOL

Outline: Haloperidol (HALDOL)

Description

Haloperidol (marketed as HALDOL) is among the major antipsychotic medication (FDA, 2017)

Its chemical designation is 4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4-fluorobutyrophenone and the structural formula is:

HALDOL is administered as an intramuscular injection, which contains 5 mg Haloperidol as the lactate and PH-adjusting lactic acid with a PH of between 3.0 and 3.6 (FDA, 2017).

Indications

HALDOL is FDA-indicated for treating Schizophrenia

It is also indicated for controlling vocal utterances and tics of Tourette’s Disorder (FDA, 2017)

Although not FDA-indicated, HALDOL has also been found to be effective in the treatment of delirium in critical illness (Girard et al., 2018)

Mechanism of Action

HALDOL’s specific mechanism of action is not clearly established (FDA, 2017)

Drug-Drug Interactions

The risks of using HALDOL with other drugs could be either pharmacokinetics (altering plasma levels) or pharmacodynamic (FDA, 2017).

Pharmacokinetic Interactions

· HALDOL’s metabolism occurs through several routes, including the enzyme system of the cytochrome P450 and glucuronidation. Drugs that inhibit any of these routes may increase Haloperidol concentrations and consequently, adverse events, including QT prolongation and an increased risk of cardiac arrest (FDA, 2017).

· Thus, clinicians ought to carefully monitor patients’ clinical status for adverse events when any such drugs are prescribed to complement HALDOL therapy.

· Mild to moderate increases in haloperidol concentrations have been reported when Haloperidol is used with drugs that induce or inhibit CYP2D6 or CYP3A4 isoenzymes, such as Buspirone, fluoxetine, sertraline, promethazine, and quinidine (FDA, 2017)

· Haloperidol plasma levels have also been shown to reduce significantly when HALDOL therapy is complemented with drugs that cause enzyme inductions such as Carbamazepine and Rifampin (FDA, 2017).

Pharmacodynamic Interactions

· Haloperidol is associated with a heightened risk of QT-prolongation, thus clinicians are advised to be cautious and do regular clinical monitoring when developing prescriptions for patients with pre-existing QT-prolongation conditions such as electrolyte imbalance, hypokalemia, and QT syndrome (FDA, 2017).

· Anti-Parkinson medication have been associated with increased intraocular pressure when used with HALDOL therapy due to excretion rate differences (FDA, 2017). Thus, clinicians are advised to discontinue HALDOL therapy if they have to prescribe anti-Parkinson medication (FDA, 2017).

· Metabolic inhibitors Paroxetine (20mg/day) and Keteconazole (400mg/day) have been associated with QTc (corrected QT interval) increases when used in combination with haloperidol (FDA, 2017). Thus, it may be prudent to reduce the dosage of haloperidol when it is prescribed together with metabolic inhibitors (FDA, 2017).

· HALDOL, like other antipsychotic medication, has been shown to potentiate CNS depressants such as alcohol, opiates, and anesthetics

Dosage and Administration

· The FDA advises that the amount of medication used in treating schizophrenia patients depends on the individual patient’s needs (FDA, 2017). Clinicians can review dosages upwards and downwards depending on patients’ individualized responses and what is needed for effective therapeutic control (FDA, 2017).

· The initial dosage of haloperidol is 2 to 5 mg administered intramuscularly for prompt control of mild to moderately severe schizophrenic symptoms (FDA, 2017).

· Depending on the patient’s response, the clinician may give subsequent doses every hour or every four to eight hours without surpassing the maximum daily dosage of 20mg/day (FDA, 2017).

· To determine the initial dosage, the clinician gives consideration to the severity of symptoms, the patient’s current medication, previous responses to antipsychotic drugs, and age (FDA, 2017).

Dosage Considerations for Special Populations

· The use of haloperidol during pregnancy has been associated with a risk of fetus limb malformations, as well as withdrawal and extrapyramidal symptoms upon birth (FDA, 2017)

· Haloperidol should not be administered to nursing mothers as is excreted in breast milk (FDA, 2017)

· The safety of haloperidol in children has not yet been established

· There are no notable differences in the effectiveness of haloperidol between younger and geriatric patients, although the latter report higher prevalence of tardive dyskinesia and may be safer with low doses (FDA, 2017).

Half-Life

· A drug’s half-life is the time it takes for its active substance to reduce by 50 percent in the body (Smith et al., 2017).

· Half-life is important because it dictates daily dosage (Smith et al., 2017).

· Shorter half-life drugs may require more frequent dosing to be effective.

· Haloperidol has an estimated half-life of between 14 and 35 hours (Leon et al., 2004). Plasma concentrations peak after about 18 hours and then begin to fall (Leon et al., 2004).

· Long-acting forms of the drug, however, have a half-life of up to 21 days and peak close to 6 days after the injection (FDA, 2017; Smith et al., 2017).

Side Effects/Adverse Effects

Common Haloperidol adverse effects include:

· Connective tissues and musculoskeletal disorders – muscle twitching, trismus, torticollis

· Psychiatric disorders – restlessness, loss of libido

· Breast disorders and reproductive system – breast discomfort, menorrhagia, dysmenorrhea, galactorrhea, amenorrhea

· Skin reactions

· Hypotension

Contraindications for Use

Common contraindications include (FDA, 2017):

· Cardiovascular effects resulting from QT prolonging

· Tardive Dyskinesia, in which case the drug is to be discontinued

· Neuroleptic malignant syndrome, which manifests in altered mental status, muscle rigidity, hyperpyrexia, tachycardia, renal failure, and irregular blood pressure

· Falls, particularly among the elderly, resulting from orthostatic hypotension, somnolence, and motor instability

Overdose Considerations

Prominent symptoms of overdose include:

· Severe extrapyramidal reactions

· Sedation

· Hypotension

· Muscle rigidity or weakness

· The patient is comatose with hypotension and respiratory depression

Overdose treatment involves:

· creation of an oropharyngeal airway to counter respiratory depression using mechanical respirators or artificial respiration

· Use of vasopressor agents, concentrated albumin, and intravenous plasma and fluids to counter hypotension. The clinician should monitor the patient until the ECG normalizes

· Administering anti-Parkinson medication to counter severe extrapyramidal reactions

Comorbidities Considerations

· Haloperidol is contraindicated in individuals with Parkinson’s disease and hypertension due to QT prolongation and drug-drug interactions with anti-Parkinson medication (FDA, 2017).

· Effective ECG monitoring is crucial for hypertensive patients.

· The clinician may have to discontinue haloperidol before beginning anti-Parkinson medication

· Haloperidol is not approved for use with dementia patients due to a heightened risk of death (FDA, 2017).