Haloperidol, Haloperidol Decanoate , Haloperidol Lactate, Haldo®

• Haldo®
• Haldol Decanoate®
• Haloperidol La®
• Peridol®
• Aloperidin®
• Bioperidolo®
• Brotopon®
• Dozic®
• Duraperidol (Germany)®
• Einalon S®
• Eukystol®
• Haldol (common tradename in the US and UK)®
• Halosten®
• Keselan®
• Linton®
• Peluces®
• Serenace®
• Sigaperidol®

1th generation (Typical) anti-psychotics

Butyrophenones

Dopamin Antagonist

• Tablet: 0.5mg, 1mg, 2 mg, 5 mg, 10 mg, 20 mg
• Oral Concentrate: 2 mg/mL
• Injectable solution: 50 mg/mL, 100 mg/mL, Ampoule 5 mg/mL, 1 mL

Haloperidol:

Adults: Gilles de la Tourette’s syndrome (Tic disorder), , Schizophrenia

• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.

Pediatrics Older than 3 years of age: Gilles de la Tourette’s syndrome (Tic disorder), Psychotic disorder, Schizophrenia, Hyperactive disorder (Short-term use)

Haloperidol Lactate:

• Adults:
• Gilles de la Tourette’s Syndrome (Tic disorder)
• Psychotic disorder
• Schizophrenia
• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.
• Pediatrics: Not FDA approval

Pediatrics: Not FDA approval

Haloperidol Decanoate:

Adults:

• Chronic Schizophrenia
• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.

Pharmacodynamics:

• Mechanism of action: typical butyrophenone => D2 blocker, Alfa1 Blocker, Antagonist of 5-HT2 receptor, Muscarinic 1 receptor affinity (Anti-cholinergic effect), Histaminic 1 receptor affinity( Anti-histaminic effect)

Pharmacokinetics:

1. Absorption:

• Oral: Bioavailability is 60%-70%. 30-60 minutes in intramuscular- intravenous injection.
• Intramuscular injections: rapidly absorbed – high bioavailability almost 20 minutes.
• Intravenous injections: Bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds.

2. Distribution: 90% binds to plasma proteins.

3. Metabolism: Cytochrome p450 in liver (CYP3A4).

4. Excretion: 30% Urine + 15% feces

 Haloperidol (Adult Dose):

• Gilles de la Tourette’s syndrome: Moderate symptoms => 0.5 to 2 mg/ Severe symptoms => 3 to 5 mg (Po) orally2 to 3 times per day (Bid-Tid).
• Psychotic disorder: moderate symptoms => 0.5 to 2 mg / severe symptoms => 3 to 5 mg (Po) orally 2 to 3 times per day (Bid-Tid).
• Schizophrenia: moderate symptoms => 0.5 to 2 mg / severe symptoms 3 to 5 mg (Po) orally 2 to 3 times per day (Bid-Tid).

Haloperidol (Pediatrics dose – Do not use in children less than 3 years of age):

1. Gilles de la Tourette’s syndrome:

Age 3 to 12 years (Weight: 15 to 40 kg):

• Initial dose: lowest possible dose (0.5 mg per day) or weight-based dose (0.05 to 0.075 mg/kg/day) Orally (Po) in 2 to 3 divided doses, whichever is less.
• Incremental dose:5 mg at 5 to 7 day intervals to therapeutic effect.

 Over age 12 years:

• Moderate Symptoms => 0.5- 2 mg Orally (Po) 2 to 3 times per day (Bid-Tid)
• Severe Symptoms => 3-5 mg Orally (Po) 2 to 3 times per day (Bid-Tid).

2. Hyperactive behaviour: (Short term administration- If patient is not responded to non-antipsychotic medications and psychotherapy)

3 to 12 years (weight 15 to 40 kg):

• Initial dose:05 to 0.075 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid)
• Incremental dose:5 mg at 5 to 7 day intervals to therapeutic effect
• MAX daily dose: 0.075 mg/kg/day

Over age 12 years:

• Moderate symptoms: 0.5 to 2 mg
• Severe symptoms: 3 to 5 mg orally 2 to 3 times per day (Bid-Tid)

3. Psychotic disorder:

3 to 12 years (weight 15 to 40 kg)=>

• Initial dose:05 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid),
• Incremental dose5 mg/day at 5 to 7 day intervals to therapeutic effect
• MAX daily dose15 mg/kg/day

12 years and older =>

• Moderate symptoms:5 to 2 mg
• Severe symptoms: 3 to 5 mg Orally (Po) 2 to 3 times (Bid-Tid)

4. Schizophrenia:

3 to 12 years (weight 15 to 40 kg) =>

• Initial dose:05 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid)
• Incremental dose:5 mg/day at 5 to 7 day intervals to therapeutic effect
• MAX daily dose15 mg/kg/day

12 years and older:

• Moderate symptoms:5 to 2 mg 3 to 5 mg
• Severe symptoms: Orally (Po) 2 to 3 times daily (Bid-Tid)

Geriatric and debilitated patients:

• May require higher doses (0.5 to 2 mg 2 to 3 times/day (Bid-Tid)
• Chronic refractory schizophrenia: Initial dose:5 to 1.5 mg/day orally (Po) => Gradually increased to maintenance dose of 2 to 8 mg/day
• Mentally retarded with hyperkinesia: Initial dose:5 to 6 mg/day orally (Po) in divided doses. Gradually increased to maintenance (minimally effective maintenance dose).
• Maximum dose: 15 max/day to achieve control => Decrease to minimally clinically effective dose.

Haloperidol Decanoate:

Adult Dose:

Chronic Schizophrenia: (Two methods recommended)

• Initial dose: stabilized on low daily oral doses (up to 10 mg/day), 10 to 15 times previous daily oral dose IM monthly or every 4 weeks.
• Initial dose: stabilized on high daily oral doses, 20 times previous daily oral dose IM for the first month, then 10 to 15 times previous daily oral dose IM monthly or every 4 weeks,
• MAX initial dose 100 mg

Pediatrics Dose: Not safe in this group

Haloperidol Lactate:

1. Adult Dose:

Gilles de la Tourette’s syndrome:

• Initial dose: 2 to 5 mg IM, may repeat every 4 to 8 hours depending on patient response
• Incremental dose: every 1 hour if needed

Schizophrenia:

• Initial dose: 2 to 5 mg IM, may repeat every 4 to 8 hours depending on patient response
• Incremental dose: every 1 hour if needed

2. Pediatrics Dose: Not safe in this group

Tricyclic antidepressants (Haloperidol is enzyme Enzyme inhibitor)

Carbamazepine (Carbamazepine is Enzyme inducer)

Anti-parkinsonism agents:e.g Levodopa

Amiodarone

Cizapride

Terfenadine

Sotalol

Quinidine

Pimozide

Pentamidine

Procainamide

More frequent:

• Acute dystonia
• Extra pyramidal symptoms – Rigidity (Parkinsonism)
• Akathisia
• Tardive dyskinesia (long term administration)

Less frequent:

• Paralytic ileus
• Priapism
• Seizure
• Sudden cardiac death
• Tardive dyskinesia
• Torsades de pointes
• Prolonged QT interval
• Jaundice
• Hepatitis
• Cholestasis
• Acute hepatic failure
• Liver function test abnormal
• Hypoglycemia
• Hyperglycemia
• Hyponatremia
• Anaphylactic reaction
• Hypersensitivity
• Neutropenia
• Leukopenia
• Thrombocytopania
• Pancytopenia
• Confusional state
• Depression
• Insomnia
• Seizure
• Ventricular fibrillation
• Ventricular tachycardia
• Extrasystoles
• Bronchospasm
• Laryngospasm
• Laryngeal edema
• Dyspnea
• Nausea
• Vomiting
• Leukocytoclastic vasculitis
• Dermatitis exfoliative
• Urticaria
• Photosensitivity reaction
• Rash
• Itchiness
• Increased sweating
• Urinary retention
• Gynecomastia
• Sudden death
• Face edema
• Edema
• Hypothermia
• Hyperthermia
• Injection site abscess
• Anorexia
• Pulmonary embolism
• Tardive dyskinesia
• Cataracts
• Retinopathy
• Neuroleptic malignant syndrome

• Comatose state from any cause
• Known Hypersensitivity to Haloperidol
• Parkinson’s disease
• Central nervous system depression
• Patients with dementia-related psychosis
• Narrow angle glaucoma
• Bone marrow suppression/failure patients
• Leukopenic / Neutropenic patients due to any cause

Pregnancy: Category C

Lactation: Not recommended in nursing mother

1. Haloperidol Decanoate is in a sesame seed oil base and must not be given intravenously (Absolute contraindication). => Only deep intramuscular injection (21G needle) into the gluteal region. Maximum recommended volume is 3 milliliters per injection site.

2. Do NOT administer Haloperidol Lactate intravenously (Relative contraindication). Although it is recommended not to inject intravenously (Not FDA approval- off label), some centers (Coronary care unites) administer it:

• Initial infusion doses of 2 to 25 milligrams per hour (Initial bolus dose of 10 milligrams followed by continuous infusion beginning as 10 milligrams per hour is recommended.)
• Maximum infusion rate: 40mg/hr
• Caution: administer Haloperidol Lactate intravenous continuous dose in patients not effectively managed by first line sedatives and in those attempted reversal of the cause of agitation has been unsuccessful.

3. Switching from injectable to oral haloperidol:

the first oral dose should be administered within 12- 24 hours following the last parenteral dose.

4. Caution is advised in patients with phaeochromocytoma and conditions predisposing to epilepsy such as alcohol withdrawal and brain damage. Haloperidol may lower the convulsive threshold.

5. Caution in administration of Haloperidol in patients with bone marrow suppression disorders, failures due to any cause => close observation (Complete blood count with differential and absolute neutrophil count in mandatory)

6. Caution in patients with Cognitive diseases => Alzheimer disease. May prone the patient to pneumonia.

7. Caution for Tardive Dyskinesia: 

• Rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements)  Irreversible in some patients in patients treated with neuroleptics with antipsychotic properties and other drugs with substantial neuroleptic activity. The risk of developing tardive dyskinesia may minimize by reducing the dose of the neuroleptic drug used and its duration of administration => anti-Parkinson agents usually do not alleviate the symptoms of this syndrome.

8. Do not do abrupt discontinuation => gradual withdrawal of antipsychotic drugs will decrease the incidence of withdrawal emergent neurological signs.

9. Administer cautiously to patients with severe impairment of liver or kidney

10. Haloperidol may interfere with the anticoagulant properties of phenindione. Possibility should be kept in mind of a similar effect occurring when Haloperidol is used with other anticoagulants.

11. Haloperidol may antagonize the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure-lowering effects of adrenergic-blocking agents such as guanethidine.

 12. Caution in concomitant use with methyldopa: Enhanced CNS effects have seen.

13. Caution in concomitant use with Tricyclic antidepressants: Haloperidol inhibits the metabolization of Tricyclic antidepressants => increasing plasma levels of these drugs => increased tricyclic antidepressant toxicity (anticholinergic effects, cardiovascular toxicity, lowering of seizure threshold).

14. Caution in concomitant use with Carbamazepine (Carbamazepine has enzyme inducer effect) => May cause significant reduction of plasma level of Haloperidol => do a dose adjustment.

15. Caution in concomitant use with Levodopa (Anti-parkinsonism agent) => it may have a synergistic effect! (Increase extrapyramidal symptoms: akathisia, Tardive dyskinesia, dystonia, hyperreflexia, rigidity, opisthotonos, and occasionally, oculogyric crisis):

• Administration of an anti-Parkinson agent is usually, but not always effective in preventing or reversing neuromuscular reactions associated with Haloperidol Decanoate.

16. Watch out for Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also taking antipsychotic medications: Haloperidol.

17. Neuroleptic drugs (Anti-psychotics including Haloperidol) elevate prolactin levels; the elevation persists during chronic administration. => galactorrhea, amenorrhea, gynecomastia and impotence may occur.

18. Caution for Neuroleptic Malignant Syndrome (NMS): hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure), elevated CPK, myoglobinuria (rhabdomyolysis), and acute renal failure. NMS is potentially fatal, requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment:

• Hyperpyrexia and heat stroke, not associated with the above symptom complex, has also been reported.

19. Over-dosage:

• Symptoms: Severe extrapyramidal reactions, Hypotension (can produce shock like state), Sedation
• Treatment: No specific antidote, do a supportive therapy, Heart monitoring, ECG (QT Prolongation), Pulse-Oxymetery, Observe Airway, Breathing, circulation.