Usage
Haloperidol decanoate is an antipsychotic medication primarily prescribed for the long-term maintenance treatment of schizophrenia in adults who are already stabilized on oral haloperidol. It is also used for the treatment of schizoaffective disorder. Haloperidol is classified as a butyrophenone antipsychotic. Its mechanism of action involves blocking dopamine D2 receptors in the brain, which helps to reduce the symptoms of psychosis.
Alternate Names
The active ingredient is haloperidol. Haloperidol decanoate is the long-acting, injectable formulation. Brand names include Haldol Decanoate and Haldol.
How It Works
Pharmacodynamics: Haloperidol primarily acts as a dopamine D2 receptor antagonist in the mesolimbic and mesocortical pathways of the brain. This D2 receptor blockade is thought to be responsible for its antipsychotic effects. It also has some activity at alpha-1 adrenergic, histamine H1, and serotonin 5-HT2 receptors. However, its antipsychotic effects appear primarily mediated through dopamine D2 antagonism.
Pharmacokinetics: Haloperidol decanoate is administered intramuscularly. Following injection, the decanoate ester is slowly hydrolyzed to release haloperidol. It is highly lipophilic and widely distributed throughout the body, with a large volume of distribution. Haloperidol is extensively metabolized in the liver, mainly by CYP2D6 and CYP3A4 enzymes. It is primarily excreted in the urine and feces. The elimination half-life is around three weeks and steady state concentrations are typically reached after 3-6 months of regular administration.
Mode of Action: Haloperidol binds to and blocks dopamine D2 receptors, decreasing dopaminergic neurotransmission. This primarily affects the mesolimbic and mesocortical pathways, which are implicated in psychosis.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: As described above, it primarily acts as a D2 receptor antagonist and demonstrates some binding to alpha-1 adrenergic, histamine H1, and serotonin 5-HT2 receptors. Haloperidol is a CYP2D6 inhibitor and thus can affect the metabolism of other drugs metabolized by this enzyme.
Dosage
Standard Dosage
Adults:
The initial dose is typically 10 to 15 times the patient’s current daily oral haloperidol dose, administered intramuscularly every 4 weeks. The maximum recommended initial dose is 100 mg. Doses above 100 mg should be divided and administered as two injections 3-7 days apart. The usual maintenance range is 10-15 times the oral dose. Doses can be adjusted upwards by 50 mg every 4 weeks to achieve optimal therapeutic effect based on individual patient response. The maximum dose should not exceed 300mg every 4 weeks.
Children:
The safety and efficacy of haloperidol decanoate have not been established in children under 18 years of age.
Special Cases:
- Elderly Patients: A lower initial dose of 12.5 mg to 25 mg is recommended, with subsequent adjustments up to 25mg every 4 weeks as needed, to a maximum dose of 75 mg.
- Patients with Renal Impairment: Dosage adjustments are not typically required, but caution is advised.
- Patients with Hepatic Dysfunction: Although dose adjustment guidelines are not specific, caution and careful monitoring are needed in patients with hepatic impairment.
- Patients with Comorbid Conditions: Caution should be exercised in patients with cardiovascular disease, epilepsy, or other conditions. Pre-existing medical conditions may necessitate dosage adjustments or more frequent monitoring.
Clinical Use Cases
Haloperidol decanoate is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations. It is specifically for long-term maintenance therapy of schizophrenia and schizoaffective disorder. For acute situations, other formulations of haloperidol, such as the intravenous or intramuscular lactate formulation, would typically be used.
Dosage Adjustments
Dosages may be adjusted based on patient-specific factors such as tolerability, renal or hepatic dysfunction, and response to therapy. Drug interactions may also necessitate dose adjustments. CYP2D6 and CYP3A4 interactions can affect haloperidol concentrations.
Side Effects
Common Side Effects
- Extrapyramidal symptoms (EPS): Parkinsonism, dystonia, akathisia, tardive dyskinesia.
- Restlessness
- Sleep disturbances
- Dry mouth
Rare but Serious Side Effects
- Neuroleptic Malignant Syndrome (NMS)
- Torsades de pointes
- Seizures
- Severe dyskinesia
Long-Term Effects
Adverse Drug Reactions (ADR)
- NMS
- Agranulocytosis
- Severe allergic reactions
Contraindications
- Hypersensitivity to haloperidol
- Comatose states
- CNS depression
- Parkinson’s disease
- Dementia with Lewy bodies
- Prolonged QT interval
- Recent acute myocardial infarction
Drug Interactions
Haloperidol interacts with numerous medications. It is a CYP2D6 inhibitor and can increase levels of drugs metabolized by this enzyme. It can also interact with drugs that prolong the QT interval, including certain antiarrhythmics and antidepressants. Concurrent use of CNS depressants can potentiate sedation. Concomitant administration with inducers of CYP3A4 can reduce haloperidol levels and impact effectiveness.
Pregnancy and Breastfeeding
Haloperidol is generally avoided during pregnancy due to the potential risk of adverse effects on the developing fetus. If haloperidol is used during breastfeeding, the infant should be monitored for adverse effects.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist.
- Side Effects: EPS, sedation, dry mouth, NMS, tardive dyskinesia.
- Contraindications: Hypersensitivity, coma, CNS depression, Parkinson’s disease, dementia with Lewy bodies, prolonged QT.
- Drug Interactions: CYP2D6 inhibitors, QT prolonging drugs, CNS depressants, CYP3A4 inducers.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Initial: 10-15 times daily oral dose IM every 4 weeks (max 100mg for initial dose). Maintenance: Titrate to effect, max 300mg/4 weeks.
- Monitoring Parameters: ECG, EPS, mental status.
Popular Combinations
Haloperidol is sometimes used in combination with antidepressants in patients experiencing both psychosis and depression.
Precautions
- Monitor for EPS, NMS, and other side effects.
- Caution in patients with cardiovascular, hepatic, or renal disease.
- Avoid abrupt discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Haloperidol Decanoate?
A: The initial dose is usually 10-15 times the daily oral dose administered every 4 weeks, not to exceed 100 mg. The maintenance dose is titrated to optimal effect, with a maximum of 300mg every 4 weeks. Elderly patients should receive lower initial doses.
Q2: What are the most common side effects?
A: Extrapyramidal symptoms (EPS) are common, including parkinsonism, dystonia, akathisia, and tardive dyskinesia. Other common side effects include sedation, dry mouth, restlessness, and difficulty sleeping.
Q3: What are the contraindications?
A: Contraindications include hypersensitivity to haloperidol, coma, CNS depression, Parkinson’s disease, Dementia with Lewy Bodies, Long QT Syndrome and conditions predisposing to QT prolongation, recent myocardial infarction.
Q4: What are the serious side effects?
A: Neuroleptic malignant syndrome (NMS), Torsades de Pointes, seizures, and severe dyskinesias are rare but potentially serious side effects.
Q5: How should Haloperidol Decanoate be administered?
A: It is administered via deep intramuscular injection into the gluteal muscle. It is important to alternate injection sites.
Q6: Can Haloperidol Decanoate be used during pregnancy?
A: It is generally avoided during pregnancy due to potential fetal risks. Consult with an obstetrician to weigh the benefits and risks.
Q7: What should be monitored in patients receiving this medication?
A: Patients should be monitored for EPS, NMS, cardiac effects (including QT prolongation), and changes in mental status.
A: It is metabolized in the liver, mainly by CYP2D6 and CYP3A4.
Q9: Can this medication be used in children?
A: Safety and efficacy have not been established in children under 18.
Q10: What if a patient misses a dose?
A: Contact a healthcare professional for guidance as soon as possible.
