Largactil (Chlorpromazine) is a first-generation (typical) antipsychotic medicine that is used to treat the following conditions:

• Treatment of children 1 to 12 years of age with behavioral problems especially violent, hyperexcitable, and explosive in nature that is disproportionate to the stimulus provoking them.
• Manic episodes in patients with bipolar disorder.
• Intractable hiccups.
• Short-term Treatment of Hyperactivity in children with attention deficit, aggression, labile mood, frustration, and impulsivity.
• Treatment of Nausea & Vomiting
• Treatment of acute intermittent porphyria
• Schizophrenia and patients with Psychotic disorders.
• Restlessness and apprehension prior to a surgical procedure.
• As an adjunct to other therapies in patients with tetanus.

Off-Label Uses of chlorpromazine in Adults include:

• Nausea & vomiting of pregnancy
• Psychosis & agitation associated with dementia

Chlorpromazine Dose in Adults

Largactil Dosage:

• Chlorpromazine dose in patients with a bipolar disorder, psychotic disorders, and schizophrenia:

  • Oral dose:

    • 30 to 800 mg orally daily in 2 - 4 divided doses. Therapy should be initiated at lower doses and titrate as needed.
    • The usual dose is between 200 and 800 mg daily, however, some patients may require up to 1 or 2 gms daily

  • Intramuscular Dose:

    • 25 mg as Intramuscular injection. Additional doses may be required.
    • The dose may gradually be increased over several days. The usual dose is 200 mg/day.

Largactil Dose in Intractable hiccups:

• Oral dose:

  • 25 to 50 mg thrice or four times daily.

• Intramuscular dose (used in patients refractory to oral treatment):

  • 25 to 50 mg as a stat dose. Patients with persistent symptoms may require an intravenous dose.

• Intravenous dose ( used in patients refractory to oral or IM treatment):

  • 25 to 50 mg via slow intravenous infusion with patients lying flat in bed.
  • Monitor vital signs of the patient during the infusion.

Largactil Dose in Nausea and vomiting:

• Oral dose:

  • 10 to 25 mg every 4 - 6 hours.

• Intramuscular dose:

  • 25 mg initially. Based on tolerability and if the blood pressure does not fall, additional doses of 25 - 50 mg every 3-4 hours may be administered until vomiting stops.

• During surgery:

  • 12.5 mg initially. The dose may be repeated in 30 minutes if hypotension does not occur.

Largactil as Off-label use in refractory Nausea and vomiting of pregnancy [Ref]:

• Intravenous or Intramuscular use:

  • 25 to 50 mg every 4 - 6 hours

• Oral dose:

  • 10 to 25 mg every 4 - 6 hours

Largactil dose in Acute intermittent Porphyria:

• Oral dose:

  • 25 to 50 mg 3 - 4 times a day.
  • It may be discontinued after several weeks.

• Intramuscular dose:

  • 25 mg 3 - 4 times daily until the oral administration can be tolerated.

Largactil dose in presurgical apprehension:

• Oral:

  • 25 - 50 mg 2 or 3 hours before the surgery

• Intramuscular dose:

  • 12.5 - 25 mg 1 or 2 hours before the surgery

Largactil dose in patients with Tetanus:

• Intramuscular dose:

  • 25 - 50 mg 3 or 4 times a day

• Intravenous dose:

  • • 25 - 50 mg

      ---

How to Discontinue chlorpromazine (Largactil) therapy?

• Gradual tapering over a period of 6 to 24 months is recommended by most authorities to minimize the risk of relapse and avoid withdrawal symptoms. APA recommends reducing the dose by 10% per month.
• Antiparkinson medicines may be continued for sometime after discontinuation to prevent withdrawal symptoms.

The following three protocols are generally followed:

• Cross-titration (gradually discontinuing the first antipsychotic while increasing the new antipsychotic
• Overlap and taper (maintaining the dose of the first antipsychotic while increasing dose of the new antipsychotic gradually, and then tapering the first antipsychotic)
• Abrupt change (abruptly discontinuing the first antipsychotic and initiate the new antipsychotic at the treatment dose or gradually increase the dose of the new antipsychotic).

Chlorpromazine Dose in Children

Largactil Dose in Severe Behavior Problems:

• Infants older than 6 months, Children, and Adolescents weighing less than 45.5 kg:

  • Oral:
    • 0.55 mg/kg/dose every 4 - 6 hours as needed. Higher doses up to (50 to 100 mg/day) may be required in severe cases. Older children may be administered up to 200 mg/ day.
    • The maximum daily dose is 500 mg/day.
  • Intravenous or Intramuscular dose:
    • 0.55 mg/kg/dose every 6 - 8 hours as needed to a maximum recommended daily dose of:
    • 40 mg/day in Children <5 years or weighing <22.7 kg
    • 75 mg/day in Children ≥5 years and Adolescents or weighing 22.7 to 45.5 kg

• Adolescents weighing more than 45.5 kg:

  • Oral:
    • 30 to 800 mg/day in 2 - 4 divided doses
    • The usual dose is 200 mg/day
  • Intravenous or Intramuscular dose:
    • An initial dose of 25 mg. The dose may be repeated in 1 - 4 hours to a maximum dose of 400 mg/dose every 4 - 6 hours.

Largactil Dose for the treatment of Nausea and vomiting:

• Infants older than 6 months, Children, and Adolescents weighing less than 45.5 kg:

  • 0.55 mg/kg/dose every 6 to 8 hours as needed. Higher doses may be needed in severe cases.
  • The Usual maximum daily dose in children:
    • Less than 5 years or weighing less than 22.7 kg is 40 mg/day
    • More than 5 years and Adolescents or weighing 22.7 to 45.5 kg is 75 mg/day

• Adolescents weighing more than 45.5 kg:

  • 10 to 25 mg orally every 4 to 6 hours as needed or
  • 25 mg Intramuscular or intravenous. Additional doses may be given based on tolerability.

Largactil Use in the prevention of Chemotherapy-induced nausea and vomiting (CINV):

• Infants older than 6 months, Children, and Adolescents:

  • 0.5 mg/kg/dose intravenous every 6 hours to a maximum dose of 1 mg/kg/dose (or 50 mg).
  • Patients should be monitored for sedation.
  • It should be used in situations where corticosteroids are contraindicated.

Largactil Use in abortive therapy of Cyclic vomiting syndrome:

• Infants older than 6 months, Children, and Adolescents:

  • 0.5 to 1 mg/kg/dose intravenous every 6 hours to a maximum dose of 50 mg in combination with diphenhydramine (to avoid possible dystonic reactions).

Largactil dose in ICU-associated delirium:

• Infants older than 6 months, Children, and Adolescents:

  • 2.5 - 6 mg/kg/day orally every 4 to 6 hours in divided doses to a maximum daily dose of:
    • 50 mg/day in children less than 5 years
    • 200 mg/day in children older than 5 years and Adolescents

Or

• 2.5 to 4 mg/kg/day  intramuscular in three or four divided doses to a maximum daily dose of 40 mg/day

Largactil Dose in Preoperative sedation and anxiety:

• Infants older than 6 months, Children, and Adolescents:

  • 0.55 mg/kg/dose orally as a single dose 2 to 3 hours before surgery to a maximum dose of 50 mg OR
  • 0.55 mg/kg/dose Intramuscular as a single dose 1 - 2 hours before surgery to a maximum dose of 25 mg.

Largactil Dose in Tetanus:

• Infants older than 6 months, Children, and Adolescents weighing less than 45.5 kg:

  • Intramuscular/ Intravenous dose:
    • 0.55 mg/kg/dose every 6 - 8 hours. Higher doses may be used in severe cases.
    • The Usual maximum daily dose in children:
      • Less than 5 years or weighing less than 22.7 kg is  40 mg/day
      • older than 5 years and Adolescents or weighing 22.7 to 45.5 kg is 75 mg/day

• Adolescents weighing more than 45.5 kg:

  • Intramuscular and Intravenous dose:
    • 25 - 50 mg every 6 - 8 hours.
    • Therapy should be initiated in a low dose and titrated based on the response to therapy.

How to Discontinue chlorpromazine (Largactil) therapy used for psychosis and severe behavior therapy?

• Gradual tapering over a period of 6 to 24 months is recommended by most authorities to minimize the risk of relapse and avoid withdrawal symptoms. APA recommends reducing the dose by 10% per month.
• Antiparkinson medicines may be continued for sometime after discontinuation to prevent withdrawal symptoms.

The following three protocols are generally followed:​​​​​​​

• Cross-titration (gradually discontinuing the first antipsychotic while increasing the new antipsychotic
• Overlap and taper (maintaining the dose of the first antipsychotic while increasing dose of the new antipsychotic gradually, and then tapering the first antipsychotic)
• Abrupt change (abruptly discontinuing the first antipsychotic and initiate the new antipsychotic at the treatment dose or gradually increase the dose of the new antipsychotic).

Pregnancy Risk Factor C​​​​​​​

• Women with severe nausea or vomiting may use chlorpromazine.
• The newborn's reaction to maternal use of chlorpromazine during pregnancy has been described as hyper, hypo or jaundice.
• Infants who were exposed to maternal Chlorpromazine during the third trimester may experience withdrawal symptoms or abnormal muscle movements.
• The newborn might also have the following symptoms:
  • Agitation
  • Feeding disorder
  • Hypertonia
  • Hypotonia
  • Respiratory distress
  • Sleepiness
  • Tremor

Use of chlorpromazine while breastfeeding​​​​​​​

• Breastmilk contains chlorpromazine.
• Breastmilk concentrations are often higher than serum concentrations and can cause serious adverse drug reactions in infants.
• Manufacturer recommends that lactating mothers stop breastfeeding and discontinue using chlorpromazine.

Chlorpromazine Dose in Kidney disease:

The manufacturer has not recommended any dose adjustment in patients with renal disease, however, it should be used with caution. It is not dialyzable.

Chlorpromazine Dose in Liver disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease, however, it should be used with caution 

Common Side Effects of Largactil (chlorpromazine):

• Cardiovascular:

  • ECG abnormality (nonspecific QT changes)
  • Orthostatic hypotension
  • Tachycardia

• Central nervous system:

  • Akathisia
  • Dizziness
  • Drowsiness
  • Dystonia
  • Neuroleptic malignant syndrome
  • Parkinsonian-like syndrome
  • Seizure
  • Tardive dyskinesia

• Dermatologic:

  • Dermatitis
  • Skin photosensitivity
  • Skin pigmentation

• Endocrine & metabolic:

  • Amenorrhea
  • Gynecomastia
  • Hyperglycemia
  • Hypoglycemia

• Gastrointestinal:

  • Constipation
  • Nausea
  • Xerostomia

• Genitourinary:

  • Breast engorgement
  • Ejaculatory disorder
  • False-positive pregnancy test
  • Impotence
  • Lactation
  • Urinary retention

• Hematologic & oncologic:

  • Agranulocytosis
  • Aplastic anemia
  • Eosinophilia
  • Hemolytic anemia
  • Immune thrombocytopenia
  • Leukopenia

• Hepatic:

  • Jaundice

• Ophthalmic:

  • Blurred vision
  • Corneal changes
  • Epithelial keratopathy
  • Retinitis pigmentosa

Largactil Contraindications:

• Allergy to Phenothiazines
• Consumption of CNS depressants such as alcohol, barbiturates and opioids in combination with other drugs can cause a host of side effects.
• Patients who are not conscious.

Warnings and Precautions

• Anomalies in cardiac conduction:

  • It can lead to conduction abnormalities, including life-threatening arrhythmias.
  • It can prolong the QT interval, which could lead to torsade-de-pointes. Patients with congenital long QT syndrome should not use it.

• Anticholinergic effects

  • It can cause anticholinergic reactions in elderly patients, such as constipation, xerostomia and blurred vision.
  • Patients with reduced gastrointestinal motility, urinary retention, paralytic ileus or visual impairments should not use it.

• Aspiration to vomit

  • Alternate mentation patients may aspirate vomitus to suppress the cough reflex.

• Blood dyscrasias

  • Chlorpromazine can cause severe blood dyscrasias such as Leukopenia and neutropenia. Patients with blood disorders or preexisting conditions should not use it.
  • If the absolute neutrophil count drops to below 1000/ul, therapy should be stopped

• Depression in the CNS:

  • The drug may cause a suppression of the CNS in patients who are using heavy machinery or performing tasks that require mental alertness.

• Extrapyramidal symptoms

  • Extrapyramidal symptoms (EPS) may be caused by chlorpromazine, including tardive dyskinesia and acute dystonia.

• Falls

  • It can also increase the risk of falls among seniors due to somnolence and postural dizziness, motor instability, and sensory instability.

• Hyperprolactinemia

  • Although it may lead to an increase in prolactin, its clinical significance is unknown.

• Hypotension

  • Hypotension can occur in patients with preexisting heart disease, cerebrovascular diseases, hypovolemia, and those who use concurrent medications that cause volume depletion, vasodilation or depress myocardium.
  • Patients are asked to remain upright for at least 30 minutes after receiving intravenous chlorpromazine injections.

• Neuroleptic malignant Syndrome (NMS).

  • NMS symptoms such as mental status changes, rigidity, fever, or autonomic instability should be closely monitored.

• Ocular effects

  • Extended therapy with chlorpromazine can cause corneal, lenticular, and pigmentary retinopathy.

• Photosensitivity

  • Avoid excessive sun exposure for patients because of the risk of photosensitivity, rash and exfoliative dermatitis.

• Temperature regulation

  • Patients should avoid heat exposure, heat, dehydration and any concomitant anticholinergic medication as they may affect heat regulation.

• Dementia[US Boxed Warning]

  • For the treatment of dementia-related psychosis, Chlorpromazine has not been approved.
  • Second-generation antipsychotics should always be preferred to the first because of serious adverse drug reactions.
  • Patients with dementia-related psychosis, who are older than 65 years old, may be at greater risk for sudden and unexpected death.
  • Patients suffering from Parkinson's disease or Lewy body dementia are more sensitive than others to the cognitive impairment and extrapyramidal effects of its use.

• Hepatic and renal impairment

  • Patients with renal and liver disease should be cautious.

• Respiratory disease

  • It can impair mentation so it should not be used in severe asthma or patients who are at risk of developing respiratory failure.

• Seizure disorder

  • Patients at high risk for seizures include those who have had seizures in the past, are suffering from brain damage or head trauma, and those taking medications that could lower the seizure threshold.

Chlorpromazine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)

Risk Factor D (Consider therapy modification)

Risk Factor X (Avoid combination)

Monitoring Parameters:​​​​​​​

• Chlorpromazine long-term patients should be aware of the following:

  • Mental health
  • Weight
  • At baseline, body mass index and waist circumference were measured at each visit, for the first six months and then every three months thereafter.
  • CBC (monitor often during the first few weeks of therapy, especially for patients with low blood counts at baseline).
  • Annual serum electrolytes and liver function testing (annually or as clinically indicated).
  • Glycated hemoglobin and fasting plasma glucose levels at baseline, and then every year (monitor more often in patients with diabetes risk factors).
  • Baseline lipid profile, six months if LDL is greater than 130 mg/dl; every 2 years for patients with normal LDL levels.
  • Each visit is for a gynecological and sexual history.
  • Watch out for signs of Parkinson's disease and tardive dyskinesia in patients at high risk.
  • Annual Eye Examination for patients over 40 years old and 2 yearly for younger patients

How to administer Largactil (Chlorpromazine)?

• You should administer the intravenous solution at a steady 1 mg/minute rate.
• To avoid hypotension, the patient should lie down for 30 minutes immediately after intravenous injection/infusion.

Treatment of persistent hiccups

• It should be administered intravenous as a slow infusion.
• If given as anIntramuscular injectionIt should be slowly injected into the upper quadrant of your buttock.
• Avoid subcutaneous injectionsIt can cause tissue damage. 

Mechanism of action of Largactil (Chlorpromazine):

• Chlorpromazine, an antipsychotic drug belonging to the phenothiazine class, blocks postsynaptic dopaminergic nerves in the brain.
• It has a strong alpha–adrenergic blocking action and depresses hormones released from the hypothalamus.
• It also affects the reticular activating systems, thereby affecting the basal metabolism and body temperature.

After intramuscular injection, the Onset of Action isAfter Oral administration, it takes between 30 and 60 minutes. Antipsychotic effects can take several weeks, and the maximum antipsychotic effect may take 6 weeks to 6 month. The time taken to complete an action. It can be taken in between 4 and 6 hours after oral intake. It is quickly absorbed into the body and distributed throughout most tissues and fluids. It crosses the blood-brain boundary.

92% to 97% are the estimated drug contentsProtein-boundIt is bioavailable at 32%.

Metabolizedextensively by the liver.

The terminal half-life for children is 7.7 hours, while it is for adults at around 30 hours.

Within 24 hours, less than 1% of the drug is eliminated via urine as an unchanged drug. 

Chlorpromazine Brand Names (International):

• Aminazin
• Ampliactil
• Amplictil
• Aspersinal
• Bellacina
• Cepezet
• Chlorazin
• Chlorpromed
• Clonactil
• Clorpromaz
• Clozine
• Esmind
• Fenactil
• Gevril
• Globazine
• Hibernal
• Klorproman
• Laractyl
• Largactil
• Largo
• Lenison
• Matcine
• Megatil
• Meprosetil
• Morefine
• Neurazine
• Neurogel
• Opsonil
• Plegomazin
• Plegomazine
• Pogetol
• Promacid
• Promactil
• Promexin
• Propaphenin
• Prozil
• Prozin
• Psynor
• Reizer
• Winsumin
• Zycloran

Chlorpromazine Brand Names in Pakistan: