Opsonil

Approved Indications:

• Schizophrenia and Other Psychotic Disorders:
  Management of schizophrenia, acute psychosis, and chronic psychotic conditions. Effective in treating positive symptoms such as hallucinations, delusions, and agitation.
• Manic Episodes in Bipolar Disorder:
  Short-term treatment of acute mania.
• Behavioral Disorders in Children (Over 6 months):
  Treatment of severe behavioral problems including hyperactivity, aggression, and explosive behavior unresponsive to other measures.
• Severe Nausea and Vomiting:
  Used when symptoms are refractory to standard antiemetics.
• Preoperative Anxiety and Sedation:
  To reduce anxiety and produce sedation prior to anesthesia or surgery.
• Intractable Hiccups:
  Treatment of persistent hiccups not responding to conventional therapy.
• Tetanus (Adjunctive Use):
  As supportive therapy to control rigidity and spasms.
• Acute Intermittent Porphyria:
  Used to manage acute porphyric attacks.

Clinically Accepted Off-Label Uses:

• Delirium with Agitation (Short-Term):
  For control of severe agitation or aggression in delirium, especially in intensive care settings.
• Tourette Syndrome (Severe Cases):
  For suppression of severe motor and vocal tics in cases resistant to first-line agents.

Route of Administration: Oral, Intramuscular (IM), Intravenous (IV), Rectal
Dosage Forms: Tablets, Syrup, Suppositories, Injections

Adults:

• Psychosis/Schizophrenia (Oral):
  Initial: 25–50 mg 2 to 4 times daily
  Maintenance: 100–800 mg/day in divided doses
  Maximum: 1000 mg/day in severe cases
• Acute Agitation (IM):
  25–50 mg IM every 4–6 hours as needed
  IV use only in emergencies: 25 mg slowly under continuous cardiac monitoring
• Nausea and Vomiting:
  Oral: 10–25 mg every 4–6 hours
  IM: 25–50 mg as a single dose or as needed
• Hiccups (Intractable):
  Oral: 25–50 mg 3–4 times daily
  IM: 25 mg every 6–8 hours
• Preoperative Sedation:
  IM: 25–50 mg 1–2 hours before surgery

Pediatrics (Children >6 months):

• Behavioral Disorders/Nausea:
  Oral: 0.55 mg/kg every 4–6 hours (Max: 40 mg/day)
  IM: 0.55 mg/kg/dose every 6–8 hours

Geriatrics:

• Start at 1/3 to 1/2 of the adult dose
• Titrate cautiously with close monitoring for hypotension and sedation

Renal or Hepatic Impairment:

• Use with caution
• Start with the lowest possible dose
• Regular monitoring of hepatic and renal function is required

Chlorpromazine hydrochloride is a typical antipsychotic from the phenothiazine class. It exerts its antipsychotic effect primarily by blocking postsynaptic dopamine D2 receptors in the mesolimbic and mesocortical pathways of the brain, reducing excessive dopaminergic activity that contributes to psychosis. It also exhibits significant antagonism at histamine H1, muscarinic M1, and alpha-1 adrenergic receptors, accounting for its sedative, anticholinergic, and hypotensive effects. Additionally, its dopamine receptor blockade in the chemoreceptor trigger zone (CTZ) underlies its antiemetic properties.

• Absorption: Well absorbed orally, though subject to significant first-pass hepatic metabolism
• Bioavailability: Approximately 10–35%
• Onset of Action: Oral: 30–60 minutes; IM: 10–20 minutes
• Time to Peak Concentration: 2–4 hours (oral)
• Protein Binding: >90%
• Distribution: Widely distributed in tissues; crosses blood-brain barrier and placenta
• Metabolism: Extensive hepatic metabolism via CYP2D6 and other isoenzymes
• Active Metabolites: Yes
• Elimination Half-life: 16–30 hours
• Excretion: Primarily in urine and feces, mostly as metabolites

• Pregnancy:
  Classified as Category C (legacy FDA classification).
  Use only if clearly needed. There is a risk of extrapyramidal and withdrawal symptoms in neonates exposed during the third trimester. Use should be avoided during late pregnancy unless the benefit outweighs the risk.
• Lactation:
  Chlorpromazine is excreted in breast milk. There is potential for adverse effects in the nursing infant, such as sedation or extrapyramidal symptoms. Breastfeeding is generally not recommended during treatment.

• Primary Class: Typical (First-Generation) Antipsychotic
• Subclass: Phenothiazine Derivative
• Additional Pharmacologic Roles: Antiemetic, Sedative, Antihistaminic, Anticholinergic

• Hypersensitivity to chlorpromazine or other phenothiazines
• Severe CNS depression or coma
• Bone marrow suppression
• Pheochromocytoma
• Children <6 months of age
• Narrow-angle glaucoma
• Severe cardiovascular disease with hypotension
• Concurrent use with large doses of CNS depressants or alcohol

• Tardive Dyskinesia: Risk increases with prolonged use; may be irreversible
• Neuroleptic Malignant Syndrome (NMS): Rare but potentially fatal; discontinue immediately if suspected
• QT Prolongation and Ventricular Arrhythmias: Avoid use in patients with risk factors (e.g., electrolyte imbalance, pre-existing QT prolongation)
• Orthostatic Hypotension: Use caution in elderly or volume-depleted patients
• Seizure Risk: May lower seizure threshold
• Hepatotoxicity: Periodic liver function testing recommended
• Photosensitivity: May cause skin reactions; advise avoidance of strong sunlight
• Agranulocytosis: Rare; monitor blood counts periodically
• Extrapyramidal Symptoms: Including dystonia, akathisia, parkinsonism
• Black Box Warning (Elderly Dementia): Increased mortality in elderly patients with dementia-related psychosis

Common:

• Central Nervous System: Drowsiness, sedation, dizziness, extrapyramidal symptoms (e.g., rigidity, tremor)
• Cardiovascular: Orthostatic hypotension, tachycardia
• Gastrointestinal: Dry mouth, constipation, nausea
• Dermatologic: Photosensitivity, skin pigmentation changes
• Endocrine: Weight gain, amenorrhea, galactorrhea

Serious/Rare:

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Agranulocytosis
• Seizures
• Cholestatic jaundice
• QT prolongation and torsades de pointes
• Hypothermia or hyperthermia
• Urinary retention, paralytic ileus

• CNS Depressants (e.g., opioids, benzodiazepines, alcohol): Enhanced sedation and respiratory depression
• Antihypertensive Agents: Additive hypotensive effect
• Anticholinergics: Increased risk of anticholinergic side effects
• Levodopa and Dopaminergic Drugs: Antagonism of antiparkinsonian effects
• QT-Prolonging Drugs (e.g., macrolides, amiodarone): Increased risk of ventricular arrhythmias
• Lithium: Risk of neurotoxicity (confusion, tremor)
• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): May increase chlorpromazine levels
• MAO Inhibitors: Avoid concomitant use due to additive CNS effects

Enzyme System Involvement:
Primarily metabolized by CYP2D6, with minor contributions from CYP1A2 and CYP3A4.

• FDA Black Box Warning (Ongoing): Elevated risk of mortality in elderly patients with dementia-related psychosis; not approved for this use
• Clinical Monitoring (Updated 2023): Regular ECGs and electrolyte monitoring recommended for patients on high doses or with cardiac risk factors
• Practice Guidelines (APA/NICE): Chlorpromazine is not first-line for psychosis; reserved for patients intolerant to or unresponsive to second-generation antipsychotics
• EPS Awareness: Guidelines emphasize early recognition and management of extrapyramidal symptoms

• Tablets and Syrup: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Injection (Ampoules): Store at 15°C to 30°C; protect from light; do not freeze
• Suppositories: Store in a cool, dry place below 25°C; avoid excessive heat
• Light and Humidity: Protect all dosage forms from excessive light and moisture
• Handling: Use aseptic technique for injection; discard opened vials appropriately