Antipsychotic
Haloperidol (Haldol)
Also called Haldol
Indications
- Severe agitation in the ED or ICU, IM or IV, often with a benzodiazepine (off-label outside schizophrenia; IV is off-label)
- Delirium with distress or danger, short term (off-label; PADIS 2018 advises against routine use)
- Schizophrenia and acute psychosis (the injection's labeled use)
- Postoperative and palliative nausea and vomiting at low doses (off-label)
Dosing
| Where | Dose |
|---|---|
| Seizures and neuro | Haloperidol: 2–5 mg IV/IM; check QTc |
| Antiemetics | Haloperidol (low dose): Butyrophenone (D₂). 0.5–2 mg IV or IM for PONV (PONV 2025; IV use is off-label); QT, extrapyramidal effects |
On the quick cards
Mechanism of action
Haloperidol is a high-potency butyrophenone antagonist at dopamine D₂ receptors, with little muscarinic, histamine or α₁ activity. D₂ receptors are Gi-coupled, so blockade removes dopamine's brake on cAMP and firing. Mesolimbic blockade calms agitation and psychosis, chemoreceptor trigger zone blockade stops vomiting, and nigrostriatal and pituitary blockade cause EPS and raise prolactin. It also blocks cardiac hERG (IKr) potassium channels, lengthening the QT.
Pharmacology
- CNS: calms without much sedation; EPS (dystonia within hours to days, akathisia, parkinsonism); lowers the seizure threshold; impairs heat regulation
- Cardiovascular: dose-related QT prolongation; hypotension is uncommon
- Respiratory: little effect on drive or airway reflexes, which suits non-intubated patients
- Other: raises prolactin; antiemetic; almost no anticholinergic effect
Pharmacokinetics
| Onset | IM: sedation in about 15–30 min (median 17 min after 10 mg, Cole 2016); IV acts sooner |
|---|---|
| Peak | Plasma peak about 20 min after IM; 2–6 h orally |
| Half-life | About 14 h IV, 21 h IM, 12–37 h orally; decanoate about 3 weeks |
| Distribution | Lipophilic; Vd 9.5–21.7 L/kg |
| Protein binding | About 90–94% |
| Metabolism | Liver: glucuronidation and ketone reduction (to reduced haloperidol, partly converted back), plus CYP3A4 and some CYP2D6 oxidation (label) |
| Interactions | Rifampin cut levels by 70%; carbamazepine lowers them; CYP3A4 or 2D6 inhibitors raise them (label) |
| Elimination | Urine and bile as metabolites |
| Bioavailability | Oral 40–75% (first pass) |
Chemistry
- Butyrophenone: a 4-fluorophenyl ketone joined by a three-carbon chain to a 4-(4-chlorophenyl)-4-hydroxypiperidine; droperidol is a relative
- Achiral; weak base (pKa about 8.7), highly lipophilic (log P about 4)
- Lactate 5 mg/mL with methyl- and propylparaben, pH 3.0–3.8; protect from light (label)
- The decanoate is an ester prodrug in sesame oil for monthly IM depot: never IV
Adverse effects and cautions
In the one-pagers
- Mental Health: Meds and CommunicationAntipsychotics and Benzodiazepines: Typical antipsychotics: Most EPS (haloperidol): AIMS for tardive dyskinesia
- End of Life, Hospice, Pain and SleepComfort in the last days: Restlessness, moaning, picking: First check pain, full bladder, constipation, drug effects; calm quiet room with a soft light, familiar voices; haloperidol or benzodiazepine as prescribed; no restraints
- Rhythm GalleryVentricular rhythms and wide-complex tachycardia: Torsades is polymorphic VT twisting around the baseline on a long QT, typically started by a short–long–short sequence. Risk rises with QTc over 500 ms, female sex, bradycardia, low K⁺ or Mg²⁺, heart failure and QT drugs (class IA and III antiarrhythmics, haloperidol, ondansetron, macrolides, fluoroquinolones, methadone). Sustained polymorphic VT g
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Other antipsychotic drugs
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Sources
- FDA label: Haloperidol Injection, Fresenius Kabi (2026)
- PubChem: haloperidol
- Girard 2018 (MIND-USA); Andersen-Ranberg 2022 (AID-ICU)
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