MH PHARM | Haldol

1. Medication Name and Class Haloperidol (Haldol) is a high-potency first-generation (conventional) antipsychotic structurally related to droperidol.2. Mechanism of Action Haloperidol blocks central postsynaptic dopamine (D-2) receptors in the mesolimbic pathway, which treats positive symptoms of schizophrenia like hallucinations and delusions. However, dopamine blockade in the nigrostriatal pathway causes extrapyramidal symptoms (EPS), while blockade in the tuberoinfundibular tract causes hyperprolactinemia. It has weak affinity for muscarinic, alpha-1, and H-1 receptors, meaning it causes less sedation, reflex tachycardia, and orthostatic hypotension compared to other antipsychotics.3. Indications FDA-approved uses include schizophrenia, Tourette's disorder, severe behavioral disorders in children, and acute agitation. Off-label uses include ICU delirium, persistent hiccups, chemotherapy-induced nausea, and severe behavioral symptoms of dementia.4. Boxed Warning and Geriatric Precautions Haloperidol carries a Boxed Warning regarding its use in geriatric patients with dementia-related psychosis. It is not FDA-approved for this population due to an increased risk of mortality, primarily from heart failure, sudden death, and infections like pneumonia. Additionally, there is an increased risk of cerebrovascular adverse events, including fatal strokes and transient ischemic attacks. The Beers Criteria considers it potentially inappropriate for elderly patients except in specific cases like schizophrenia or chemotherapy-induced nausea. Use for dementia behavioral symptoms must meet strict federal OBRA guidelines, primarily when the patient is a substantial threat to self or others. Due to the risk of hyponatremia and SIADH, sodium levels should be monitored closely.5. Pharmacokinetics and Administration Oral formulations should be taken with food to minimize GI irritation. Oral concentrates can be mixed with food or beverages, but not coffee or tea, which cause precipitation. Nurses should avoid skin contact with the concentrate to prevent contact dermatitis. Intramuscular (IM) lactate is an immediate-release injection that peaks in 20 to 40 minutes. Max adult dose is 20 mg/day. Intramuscular (IM) decanoate is a depot injection in sesame oil used for prolonged therapy. It must be administered deep IM, never IV, with a maximum of 3 mL per site using a 21-gauge needle. Peak concentrations occur after about 6 days, and the half-life is roughly 3 weeks. Patients must be stabilized on oral haloperidol before converting to the depot formulation. Intravenous (IV) administration of haloperidol is not FDA-approved in any population. If used off-label (e.g., for ICU delirium), it carries a high risk of QT prolongation, Torsade de Pointes (TdP), and arrhythmias, requiring strict ECG monitoring.6. Major Adverse Effects Severe, life-threatening adverse effects include neuroleptic malignant syndrome (NMS), tardive dyskinesia, QT prolongation, Torsade de Pointes, cardiac arrest, seizures, and agranulocytosis. Moderate effects include severe EPS (pseudoparkinsonism, akathisia, dystonic reactions) and hyperprolactinemia (galactorrhea, amenorrhea, impotence). Mild effects include drowsiness, dry mouth, and tremors.7. Drug Interactions and Metabolism Haloperidol is extensively metabolized in the liver by CYP2D6 and CYP3A4. Slow metabolizers of CYP2D6 are at increased risk for EPS due to delayed drug clearance. Co-administration with CYP3A4 or CYP2D6 inhibitors can increase haloperidol concentrations and the risk of QT prolongation. Avoid or reduce dosage in patients with severe hepatic impairment. No dosage adjustments are needed for renal impairment.