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.

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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.

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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.

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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

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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.

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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

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Largactil dose in patients with Tetanus:

• Intramuscular dose:

  • 25 - 50 mg 3 or 4 times a day

• Intravenous dose:

  • • 25 - 50 mg

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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.

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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.

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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.

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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).

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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

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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.

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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.

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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)

Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Aminolevulinic Acid (Topical)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Antacids	May decrease the absorption of Antipsychotic Agents (Phenothiazines).
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Antimalarial Agents	May increase the serum concentration of Antipsychotic Agents (Phenothiazines).
Antipsychotic Agents (Second Generation [Atypical])	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Beta-Blockers	Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of BetaBlockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of Antipsychotic Agents (Phenothiazines).
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
Darunavir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Desmopressin	ChlorproMAZINE may enhance the adverse/toxic effect of Desmopressin.
Deutetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fingolimod	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
Guanethidine	Antipsychotic Agents may diminish the therapeutic effect of Guanethidine.
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lithium	May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine.
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Methylphenidate	Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
MetyroSINE	May enhance the adverse/toxic effect of Antipsychotic Agents.
Mianserin	May enhance the anticholinergic effect of Anticholinergic Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirabegron	Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroglycerin	Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Perhexiline	CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Porfimer	Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
QT-prolonging Agents (Indeterminate Risk - Avoid)	May enhance the QTc-prolonging effect of QTprolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Agents (Indeterminate Risk - Caution)	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin Modulators	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Serotonin Reuptake Inhibitor/Antagonists	Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Serotonin Reuptake Inhibitor/Antagonists. Specifically, this may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Serotonin Reuptake Inhibitor/Antagonists may enhance the hypotensive effect of Antipsychotic Agents (Phenothiazines).
Tetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Thiopental	Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Thiopental.
Tobacco (Smoked)	May decrease the serum concentration of ChlorproMAZINE.
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Valproate Products	ChlorproMAZINE may increase the serum concentration of Valproate Products.
Verteporfin	Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.

Risk Factor D (Consider therapy modification)

Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
Amiodarone	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Anti-Parkinson Agents (Dopamine Agonist)	Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). AntiParkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents.
Arsenic Trioxide	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Astemizole	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Astemizole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Azithromycin (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Bedaquiline	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Bedaquiline. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Bepridil	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Bepridil. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Chloroquine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Clofazimine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CloZAPine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
CYP2D6 Inhibitors (Strong)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Dasatinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Doxepin-Containing Products	QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Droperidol	May enhance the CNS depressant effect of ChlorproMAZINE. Droperidol may enhance the QTc-prolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, dose reductions are recommended. Monitor for additive toxicities such as QTc interval prolongation, ventricular arrhythmias, and CNS depression.
Encorafenib	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Escitalopram	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Flecainide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Fluconazole	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Fluconazole. Fluconazole may enhance the QTc-prolonging effect of QT prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
GadobenateDimeglumine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of GadobenateDimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gemifloxacin	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gilteritinib	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias.
Halofantrine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Haloperidol	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
InotuzumabOzogamicin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of InotuzumabOzogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Levofloxacin-Containing Products (Systemic)	May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Lofexidine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Mequitazine	Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged.
Methadone	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
Midostaurin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
OLANZapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Ondansetron	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Osimertinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Pentamidine (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Pilsicainide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
Propafenone	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class IA Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class III Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Dronedarone.
QT-prolonging Kinase Inhibitors (Highest Risk)	May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Miscellaneous Agents (Highest Risk)	May enhance the QTc-prolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Arsenic Trioxide; Astemizole; Bedaquiline; Bepridil.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Fluconazole; Nilotinib; Ribociclib.
RisperiDONE	QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Secretin	Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Sodium Stibogluconate	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Vemurafenib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid us with other CNS depressants at bedtime; avoid use with alcohol.

Risk Factor X (Avoid combination)

Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Aminolevulinic Acid (Systemic)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
Citalopram	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram.
Clarithromycin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin.
Domperidone	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone.
Dronedarone	May enhance the QTc-prolonging effect of ChlorproMAZINE.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
Flupentixol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol.
Glycopyrrolate (Oral Inhalation)	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Ipratropium (Oral Inhalation)	May enhance the anticholinergic effect of Anticholinergic Agents.
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Moxifloxacin (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic).
Nilotinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pimozide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Piperaquine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine.
Piribedil	Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
Potassium Chloride	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
Probucol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol.
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Exceptions: Clarithromycin.
QUEtiapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Ribociclib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib.
Sparfloxacin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Thioridazine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.

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:

Chlorpromazine injection 25 mg/ml
LARGACTIL	SANOFI AVENTIS (PAKISTAN) LTD.

 

Chlorpromazine Syrup 25 mg/5ml
LARGACTIL	SANOFI AVENTIS (PAKISTAN) LTD.

 

Chlorpromazine Tablets 10 mg
CHLOROTIL	UNEXO LABS (PVT) LTD.

 

Chlorpromazine Tablets 25 mg
CHLOROTIL	UNEXO LABS (PVT) LTD.
CHLORPROMAZINE	STAR LABORATORIES (PVT) LTD.

 

Chlorpromazine Tablets 50 mg
LARGACTIL	SANOFI AVENTIS (PAKISTAN) LTD.
RALGECTIL	REGENT LABORATORIES LTD.

 

Chlorpromazine Tablets 100 mg
LARGACTIL	SANOFI AVENTIS (PAKISTAN) LTD.
RALGECTIL	REGENT LABORATORIES LTD.
SEDECTIL	USAWA PHARMACEUTICALS

 

Chlorpromazine Tablets 100 mg
LARGACTIL	SANOFI AVENTIS (PAKISTAN) LTD.
RALGECTIL	REGENT LABORATORIES LTD.
SEDECTIL	USAWA PHARMACEUTICALS

 

Chlorpromazine Tablets 500 mg
SECDEL	DELTA PHARMA (PVT) LTD.