Drug Interactions
Specific Drugs
| Drug |
Interaction |
Comments |
| Anticholinergic agents |
Increases in intraocular pressure may occur in patients receiving anticholinergic drugs, including antiparkinsonian agents, concurrently with haloperidol |
|
| Anticoagulants |
Antagonism of anticoagulant activity of phenindione (no longer commercially available in US) reported in 1 patient |
Further study needed to determine the clinical importance |
| CNS depressants (e.g., alcohol, anesthetics, barbiturates or other sedatives, opiates or other analgesics) |
Possible additive effects or potentiated action of other CNS depressants |
Use concomitantly with caution to avoid excessive sedation |
| Lithium |
An acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present |
Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear |
| Methyldopa |
Possible dementia in patients receiving haloperidol and methyldopa concomitantly |
Clinical importance of this possible interaction not determined; carefully observe patients for adverse psychiatric symptoms if used concurrently |
| Rifampin |
Decreased (70%) mean plasma haloperidol concentrations and decreased antipsychotic efficacy with concomitant use Following discontinuance of rifampin in other schizophrenic patients treated with oral haloperidol, mean haloperidol concentrations increased 3.3-fold |
Careful monitoring of clinical status and appropriate dosage adjustment are warranted whenever rifampin is initiated or discontinued in patients stabilized on haloperidol |
Pharmacokinetics
Absorption
Bioavailability
Well absorbed from GI tract following oral administration, but appears to undergo first-pass metabolism in the liver. Oral bioavailability reported to average 60%.
Peak plasma concentrations occur within 2–6 hours after oral administration. Following IM administration of haloperidol lactate, peak plasma haloperidol concentrations occur within 10–20 minutes.
Following IM administration of haloperidol decanoate, plasma haloperidol concentrations are usually evident within 1 day and peak concentrations generally occur within about 6–7 days (range: 1–9 days).
Onset
Following IM administration of haloperidol lactate, peak pharmacologic action occurs within 30–45 minutes; in acutely agitated patients, control of psychotic manifestations may become apparent within 30–60 minutes, with substantial improvement often occurring within 2–3 hours.
Duration
Haloperidol decanoate: Esterification of haloperidol results in slow and gradual release of haloperidol decanoate from fatty tissues, thus prolonging duration of action; administration of the ester in a sesame oil vehicle further delays rate of release.
Distribution
Distribution into human body tissues and fluids not fully characterized. In animals, the drug is distributed mainly into the liver, with lower concentrations being distributed into the brain, lungs, kidneys, spleen, and heart.
Following IM administration of haloperidol decanoate, the esterified compound is initially distributed into fatty tissue stores, from which the drug is then slowly and gradually released .
Distributed into milk.
Plasma Protein Binding
About 92%.
Elimination
Metabolism
Exact metabolic fate not clearly established, but appears to be principally metabolized in the liver by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive), and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol.
Limited data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be less than that of haloperidol.
After distribution and slow and gradual release from fatty tissue stores following IM administration of haloperidol decanoate, the drug undergoes hydrolysis by plasma and/or tissue esterases to form haloperidol and decanoic acid. Subsequent distribution, metabolism, and excretion of haloperidol appears to be similar to those of orally administered drug.
Elimination Route
Excreted slowly in urine and feces as unchanged drug and metabolites. Approximately 40% of a single oral dose is excreted in urine within 5 days. About 15% of an oral dose is excreted in feces via biliary elimination. Small amounts are excreted for about 28 days following oral administration.
Half-life
After IM administration of the decanoate, apparent half-life is approximately 3 weeks.
Special Populations
Pharmacokinetics of haloperidol generally warrant the use of reduced dosages in geriatric patients.
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