Chlorpromazine Hydrochloride

Class: Phenothiazines
VA Class: CN701
Chemical Name: 2-Chloro-10-[3-(dimethylamino)propyl]-phenothiazine monohydrochloride
Molecular Formula: C₁₇H₁₉CIN₂S HCL
CAS Number: 69-09-0

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

[Posted 06/16/2008] FDA notified healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics. Antipsychotics are not indicated for the treatment of dementia-related psychosis. The prescribing information for all antipsychotic drugs will now include the same information about this risk in a BOXED WARNING and the WARNINGS section. For more information visit the FDA website at: , and .

Introduction

Propylamino-derivative phenothiazine; conventional (prototypical, first-generation) antipsychotic agent.^{a b c d g i}

Uses for Chlorpromazine Hydrochloride

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Symptomatic management of psychotic disorders (i.e., schizophrenia).^{a b c d g}

Nausea and Vomiting

Management of nausea and vomiting, including during surgery.^{a b c d}

Preoperative Sedation

Relief of restlessness and apprehension before surgery.^{a b c}

Acute Intermittent Porphyria

Treatment of acute intermittent porphyria.^{a b c d}

Tetanus

Adjunct in the treatment of tetanus.^{a b c d}

Bipolar Disorder

Symptomatic management of manic phase of bipolar disorder.^{a b c}

Intractable Hiccups

Treatment of intractable hiccups.^{a b c d}

Disruptive Behavior Disorder and Attention Deficit Hyperactivity Disorder (ADHD)

Treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations).^{a b c}

Short-term treatment of hyperactive children who exhibit excessive motor activity with accompanying conduct disorders manifested as impulsivity, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance.^{a b c}

Chlorpromazine Hydrochloride Dosage and Administration

General

• 
  

  Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.^{a b c}

  
  


• 
  

  Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued.^{a b c} (See Tardive Dyskinesia under Cautions.)

  
  

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  For symptomatic relief of psychotic disorders, initial therapeutic response to antipsychotic therapy usually occurs within 1–4 weeks and optimum therapeutic response occurs within 6 months or longer.^{a b d g}

  
  


• 
  

  For prompt control of severe psychotic symptoms, administer IM; after symptoms are controlled, oral therapy should replace parenteral therapy.^{a b c d}

  
  


• 
  

  Once optimum dosage is achieved, continue this dosage for 2 weeks, then gradually reduce to lowest possible effective dosage.^{a b c}

  
  

Administration

Administer orally, by deep IM or direct IV injection, or by IV infusion.^{a b c}

Sub-Q administration not recommended because of local irritation.^{b c}

Avoid skin and clothing contact with chlorpromazine hydrochloride injection, since contact dermatitis has occurred rarely.^{b c}

Reserve parenteral therapy for recumbent patients;^{b c} however, if cautions are taken to avoid orthostatic hypotension (i.e., patient remains recumbent for ≥30 minutes after injection), acutely agitated ambulatory patients may receive the drug IM.^{b c}

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Direct IV injection for use only during surgery to control nausea and vomiting and in the adjunctive treatment of tetanus.^{b c}

IV infusion is intended only for use in adjunctive treatment of intractable hiccups in adults.^{b c}

Avoid IV administration of undiluted drug.^{b c}

Dilution

For direct IV injection, dilute with 0.9% sodium chloride injection to a concentration not exceeding 1 mg/mL.^{b c}

For IV infusion, add injection to 500–1000 mL of 0.9% sodium chloride.^{b c}

Rate of Administration

Children: For direct IV injection, administer diluted solution at a rate of 0.5 mg/minute.^{b c}

Adults: For direct IV injection, administer diluted solution at a rate of 1 mg/minute.^{b c} For IV infusion, administer diluted solution slowly.^{b c}

IM Administration

Inject slowly, deep into a large muscle mass such as the upper outer quadrant of the gluteus maximus.^{b c}

Dilution

If irritation at IM injection site occurs, may dilute with 0.9% sodium chloride injection or 2% procaine hydrochloride.^{b c}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as chlorpromazine hydrochloride; dosage expressed in terms of the hydrochloride salt.^{a b c}

Manufacturers state that the 100- and 200-mg tablets are intended for use in patients with severe neuropsychiatric conditions.^{a c}

Chlorpromazine should generally not be used in children <6 months of age unless the condition to be treated is potentially life-threatening; dosage in this age group has not been established.^{a b c}

Pediatric Patients

Adolescents 13–17 years of age: No specific dosage recommendations; dosage is based on patient weight and clinician judgment.^{k l}

Nausea and Vomiting

Oral

Children 6 months to 12 years of age: Usually, 0.55 mg/kg every 4–6 hours as necessary.^{a c} Adjust dosage based on symptom severity and patient response.^{a c}

IM

Children 6 months to 12 years of age: Initially, 0.55 mg/kg every 6–8 hours as necessary; carefully adjust subsequent dosage based on symptom severity and patient response.^{b c}

Surgery

Preoperative Sedation

Oral

Children 6 months to 12 years of age: 0.55 mg/kg administered 2–3 hours before surgery.^{a c}

IM

Children 6 months to 12 years of age: 0.55 mg/kg administered 1–2 hours before surgery.^{b c}

Nausea and Vomiting During Surgery

IV

Children 6 months to 12 years of age: Fractional 1-mg doses may be given at 2-minute intervals up to a total dosage of 0.275 mg/kg;^{b c} may repeat fractional dosage regimen after 30 minutes if necessary and if hypotension does not occur.^{b c}

IM

Children 6 months to 12 years of age: 0.275 mg/kg;^{b c} may repeat dosage in 30 minutes if necessary and if hypotension does not occur.^{b c}

Tetanus

IM or IV

Children 6 months to 12 years of age: 0.55 mg/kg every 6–8 hours by IM or direct IV injection.^{b c}

In children weighing <22.7 kg, maximum parenteral dosage is 40 mg daily.^{b c} In children weighing 22.7–45.5 kg, maximum parenteral dosage is ≤75 mg daily, except in severe cases.^{b c}

Disruptive Behavior Disorder and ADHD

Outpatients

Oral or IM

Children 1–12 years of age: Initially, 0.55 mg/kg orally every 4–6 hours or IM every 6–8 hours as necessary;^{a b c} increase dosage gradually as required.^{a b c}

Hospitalized Patients

Oral or IM

Initiate with low dosage as with outpatients and increase dosage gradually.^{a b c} For severe behavior disorders, higher dosages (50–100 mg daily, and in older children: ≥200 mg daily) may be necessary.^{a b c} There is little evidence that behavior improvement in severely disturbed, mentally retarded patients is further enhanced at dosages >500 mg daily.^{a b c}

IM

Maximum 40 mg daily for children <5 years (or 22.7 kg).^{b c}

Maximum ≤75 mg daily for children 5–12 years of age (or 22.7–45.5 kg);^{b c} dosage may be further increased in unmanageable patients.^{b c}

Adults

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Usual oral dosage during maintenance therapy is 200 mg daily; however, oral dosages up to 800 mg daily may be required in some patients.^{a b c}

Outpatients with Relatively Mild Symptomatology

Oral

30–75 mg daily, given in 2–4 divided doses.^{a c}

Outpatients with More Severe Symptomatology

Oral

Initially, 25 mg 3 times daily.^{a c} After 1 or 2 days, may gradually increase dosage twice weekly by 20–50 mg until symptoms are controlled.^{a c}

If used to replace parenteral therapy after prompt control of symptoms achieved, initiate oral therapy at 25–50 mg 3 times daily.^{a b c}

IM

For prompt control of severe symptoms, 25 mg IM initially; may repeat in 1 hour if necessary. ^{b c} After symptoms are controlled, replace parenteral therapy with oral therapy at dosage of 25–50 mg 3 times daily.^{a b c}

Hospitalized Patients

Oral

Dosages of 500 mg daily are generally sufficient in most patients.^{a c} Dosages >2 g daily may be required in some patients; however, little therapeutic gain is achieved with dosages >1 g daily administered for extended periods.^{a c}

Less acutely agitated patients: Initially, 25 mg 3 times daily;^{a c} gradually increase subsequent dosage.^a Usually do not exceed 400 mg daily.^{a c}

IM

In acute schizophrenic or manic patients: Initially, 25 mg.^{b c} May administer an additional IM dose of 25–50 mg in 1 hour if necessary.^{b c} Increase subsequent dosage gradually over several days to a maximum of 400 mg every 4–6 hours in exceptionally severe cases until symptoms are controlled.^{b c}

Usually, patients become quiet and cooperative within 24–48 hours after therapy initiation;^{a b} oral therapy can then replace parenteral therapy. ^b

Nausea and Vomiting

Oral

10–25 mg every 4–6 hours;^{a c} may increase dosage if necessary.^{a c}

IM

Initially, usual dose is 25 mg.^{b c} If hypotension does not occur, may administer additional IM doses of 25–50 mg every 3–4 hours until symptoms subside; oral therapy should then replace parenteral therapy if necessary.^{b c}

Surgery

Preoperative Sedation

Oral

25–50 mg, 2–3 hours before surgery.^{a c}

IM

12.5–25 mg, 1–2 hours before surgery.^{b c}

Nausea and Vomiting During Surgery

IV

Fractional 2-mg doses may be given IV at 2-minute intervals up to a maximum total dosage of 25 mg.^{b c}

IM

12.5 mg; may repeat dose in 30 minutes if hypotension does not occur.^{b c}

Acute Intermittent Porphyria

Oral

25–50 mg 3 or 4 times daily.^{a c} Can discontinue therapy after several weeks; however, some patients may require maintenance therapy.^{a c}

IM

25 mg 3 or 4 times daily until patient can take oral therapy.^{b c}

Tetanus

IV

25–50 mg by direct IV injection.^{b c}

IM

25–50 mg 3 or 4 times daily, usually in conjunction with barbiturates.^{b c} Determine total dosage and administration frequency by patient response, starting with low dosage and increasing gradually.^b

Intractable Hiccups

Oral or IM

Initially, 25–50 mg orally 3 or 4 times daily.^{a c} If symptoms persist for 2–3 days, may give 25–50 mg IM.^{a b c}

IV

If hiccups persist after oral and IM therapy, may administer 25–50 mg by slow IV infusion with patient in a supine position.^{b c} Closely monitor BP.^{b c}

Prescribing Limits

Pediatric Patients

Nausea and Vomiting

IM

Maximum 40 mg daily for children 6 months to <5 years of age (or <22.7 kg).^{b c}

Maximum 75 mg daily for children 5–12 years of age (or 22.7–45.5 kg), except in severe cases.^{b c}

Tetanus

IM or IV

Maximum 40 mg daily for children <22.7 kg.^{b c}

Maximum ≤75 mg daily for children 22.7–45.5 kg, except in severe cases.^{b c}

Disruptive Behavior Disorder and ADHD

Hospitalized Patients

Oral or IM

Maximum effective dosage not established, but there is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced at dosages >500 mg daily.^{a b c}

IM

Maximum 40 mg daily for children <5 years (or <22.7 kg).^{b c}

Maximum ≤75 mg daily for children 5–12 years of age (or from 22.7–45.5 kg); dosage may be further increased in unmanageable patients.^{b c}

Adults

Psychotic Disorders

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Hospitalized Patients

Oral

Little therapeutic gain achieved by dosages >1 g daily administered for extended periods.^{a c}

Less acutely agitated patients: Usually do not exceed 400 mg daily.^{a c}

IM

Maximum IM dosage of 400 mg every 4–6 hours.^{b c}

Surgery

Nausea and Vomiting During Surgery

IV

Maximum total dosage of 25 mg.^{b c}

Special Populations

Geriatric Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

No specific dosage recommendations for geriatric patients, but generally select dosage at the lower end of recommended range; increase dosage more gradually and monitor closely.^{a b c d} (See Geriatric Use Under Cautions.)

Debilitated or Emaciated Patients

Increase dosage more gradually.^{a b c d}

Cautions for Chlorpromazine Hydrochloride

Contraindications

• 
  

  Comatose states or in the presence of large amounts of CNS depressants (e.g., alcohol, barbiturates, opiates).^{a b d} (See Specific Drugs and Laboratory Tests under Interactions.)

  
  


• 
  

  Known hypersensitivity to phenothiazines.^{a b}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Shares the toxic potentials of other phenothiazines; observe the usual precautions of phenothiazine therapy.^{a b c d}

Extrapyramidal Reactions

Possible extrapyramidal reactions.^{a b d} Signs and symptoms may be similar to those accompanying certain disorders (e.g., encephalitis, Reye’s syndrome, encephalopathy, meningitis, tetanus); diagnosis of these disorders may be obscured or the disease-associated signs and symptoms may be incorrectly diagnosed as drug induced.^{a b d} Avoid use in children and adolescents whose signs and symptoms suggest Reye’s syndrome.^{a b}

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, may develop in patients receiving antipsychotic agents, including chlorpromazine.^{a b d g} Consider reducing chlorpromazine dosage or switching to a second-generation (atypical) antipsychotic agent.^{a b d g}

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported with antipsychotic agents, including chlorpromazine.^{a b d g}

Concomitant Therapy with Lithium

Although most patients receiving lithium and an antipsychotic agent concurrently do not develop unusual adverse effects, an acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present.^{a b d} (See Specific Drugs and Laboratory Tests under Interactions.)

CNS Depression

May impair mental and/or physical abilities, especially during the first few days of therapy; use caution with activities requiring alertness (e.g., operating vehicles or machinery).^{a b d g}

Because of CNS depressant effects, use with caution in patients with chronic respiratory disorders (e.g., severe asthma, emphysema, acute respiratory tract infections), particularly in children 1–12 years of age.^{a b d}

Fetal/Neonatal Morbidity

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Safety of use during pregnancy not established.^{a b d} Jaundice, prolonged extrapyramidal signs and symptoms, hyperreflexia, and hyporeflexia reported in some neonates born to women who received phenothiazines during pregnancy.^{a b d} Generally, use during pregnancy only when the potential benefits justify the possible risks to the fetus.^{a b d}

Sensitivity Reactions

Hypersensitivity and Cross-sensitivity

Possible sensitivity reactions (e.g., cholestatic jaundice, blood dyscrasias, skin reactions, anaphylactoid reactions).^{a b d} Use generally not recommended in patients who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) to a phenothiazine, unless potential benefits outweigh the possible risks.^{a b d}

Contact dermatitis occurs rarely following skin contact with chlorpromazine hydrochloride injection; use care to avoid skin contact with injection.^{b c}

Photosensitivity

Photosensitivity may occur; avoid excessive exposure to sun during therapy.^{a b d}

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^{b c}

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Nervous System Effects

Possible suppression of the cough reflex and aspiration of gastric contents.^{a b d}

Possible risk of seizures; may lower seizure threshold.^{a b d} Use with caution in patients with a history of seizures or EEG abnormalities or in those receiving anticonvulsant agents.^{a b d} Maintain adequate anticonvulsant therapy.^{a b d} Chlorpromazine does not intensify anticonvulsant action of barbiturates; dosage of anticonvulsants should not be reduced.^{a d}

Prolactin Secretion

Elevated prolactin concentrations reported; elevation persists during chronic administration.^{a b d g}

Clinical importance unknown; consider that approximately one-third of human breast cancers are prolactin dependent when prescribed in patients with previously detected breast cancer.^{a b d g}

Galactorrhea, amenorrhea, gynecomastia, and impotence reported.^{a b d g}

Hematologic Effects

Blood dyscrasias, including leukopenia, agranulocytosis, thrombocytopenic purpura, eosinophilia, hemolytic anemia, aplastic anemia, and pancytopenia, reported with phenothiazine derivatives.^{a b d g} Perform hematologic evaluations periodically in patients receiving long-term therapy.^d

If bone marrow suppression occurs during therapy, discontinue drug and institute appropriate therapy.^{a b d}

Hepatic Effects

Cholestatic jaundice or liver damage reported.^{a b d g}

Perform hepatic function tests immediately in patients who develop fever accompanied by flu-like symptoms (e.g., nausea, vomiting, anorexia) during therapy; if hepatic function tests results are abnormal, discontinue drug.^{a b d g}

Anticholinergic Effects

Possible anticholinergic effects (e.g., dry mouth, blurred vision, mydriasis, constipation, obstipation, nausea, adynamic ileus, atonic colon, urinary retention, decreased perspiration, and impotence).^{a b d}

Use with caution in patients with glaucoma or prostatic hypertrophy.^{a b d}

Cardiovascular Effects

Possible hypotension (including orthostatic hypotension), tachycardia, momentary fainting and dizziness, and ECG changes.^{a b d g}

To minimize hypotension following IM administration, patient should remain in supine position under observation for ≥30 minutes.^b

If hypotension occurs, place patient in Trendelenburg’s position and, if required, administer norepinephrine or phenylephrine; epinephrine or dopamine should not be used.^{a b d} (See Specific Drugs and Laboratory Tests under Interactions.)

Use with caution in patients with cardiovascular disease.^{a b d}

Ocular Effects

Consider possibility of pigmentary retinopathy and lenticular and corneal deposits in patients receiving prolonged therapy.^{a b d g} Periodic ophthalmic examinations recommended in patients receiving prolonged phenothiazine therapy with moderate to high dosages.^{a b d g}

Regulation of Body Temperature

Phenothiazines depress the hypothalamic mechanism for body temperature regulation; possible hyperthermia or hypothermia when exposed to temperature extremes.^{a b d g}

Use with caution in patients exposed to extreme heat or cold.^{a b d}

Mutagenicity

Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents receiving certain antipsychotic agents.^{a b d}

Abrupt Withdrawal

Possible gastritis, nausea and vomiting, dizziness, and tremulousness after abrupt discontinuance of high-dose therapy;^{a b d} may avoid or reduce symptoms by gradual withdrawal or by continuing antiparkinsonian agents for several weeks after therapy is withdrawn.^{a b d}

Other Precautions

Antiemetic effects may mask signs of overdosage of other drugs (e.g., antineoplastic agents) or obscure cause of vomiting in various disorders (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).^{a b d}

Use phenothiazines with caution in debilitated patients, patients with renal or hepatic disease, and patients exposed to organophosphate insecticides.^{a b d}

Use phenothiazines with caution in patients with hypocalcemia, since susceptibility to dystonic reactions may be increased.^d

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.^e (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk.^{a b c d e i} Discontinue nursing or the drug.^{a b d}

Pediatric Use

Safety and efficacy in children <6 months of age not established; generally, do not use unless condition to be treated is potentially life-threatening.^{a b c} Do not use in conditions for which pediatric dosage not established.^{a b c}

Geriatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Geriatric patients appear to be particularly sensitive to adverse CNS (e.g., tardive dyskinesia, parkinsonian manifestations, akathisia, sedation), anticholinergic, and cardiovascular (e.g., orthostatic hypotension) effects of antipsychotic agents.^{a b d g} Possible increased risk for falls and consequent hip fractures.^d

Use with caution.^d (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia, tardive dyskinesia), drowsiness, dizziness, skin reactions or rash, dry mouth, orthostatic hypotension, amenorrhea, galactorrhea, weight gain.^{a b c d g}

Interactions for Chlorpromazine Hydrochloride

Metabolized principally by CYP2D6 and to a lesser extent CYP1A2.^{d f j}

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions with substrates, inhibitors, or inducers of CYP2D6 are possible.^{d f j}

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Alcohol	Potential additive CNS effects; concomitant use with alcohol potentiates hypotension observed with chlorpromazinea b d	Advise patients to avoid alcohola b
Anticoagulants, oral	Potential decreased effect of oral anticoagulantsa b
Anticonvulsants (phenytoin, phenobarbital)	Chlorpromazine may lower seizure threshold; CNS depressant effects do not potentiate anticonvulsant activity of anticonvulsantsa b d Chlorpromazine may interfere with phenytoin metabolism and precipitate phenytoin toxicitya b d Phenobarbital may decrease plasma chlorpromazine concentrationsd	Dosage adjustments of anticonvulsants may be necessarya b d
Atropine and other anticholinergic drugs	Possible potentiated anticholinergic effects a b i	Use with cautiona b
CNS depressants (e.g., antihistamines, barbiturates, general anesthetics, opiate analgesics, sedative/hypnotics)	Possible additive effects or potentiated action of other CNS depressantsa b c i	Use concomitantly with caution to avoid excessive sedation or CNS depressiona b d When administered concomitantly, about one-fourth to one-half the usual dosage of CNS depressant generally is neededa b i
Epinephrine or dopamine	Possible further lowering of BPa b d	Do not use epinephrine or dopamine for phenothiazine-induced hypotension a b d (see Cardiovascular Effects under Cautions)
Guanethidine and related compounds	Potential for decreased effectiveness of guanethidine and related compoundsa b i
Lithium	An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present a b d	Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appeara b d
Propranolol	Possible increased plasma concentrations of chlorpromazine and propranolola b
Test for phenylketonuria (PKU)	Potential false-positive test results may occur during phenothiazine usea b d
Tests for pregnancy	False-positive results reported in some patients receiving phenothiazines; less likely to occur when serum test is useda b d
Thiazide diuretics	Potential for increased orthostatic hypotension a b

Chlorpromazine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract and from parenteral sites of injection.^{c i} Appears to undergo substantial first-pass metabolism.^{c h} Peak plasma concentrations generally attained within 2–4 hours after oral administration;^{h i} considerable interindividual variation in peak concentrations reported.^{c i}

Onset

Usually occurs within 30–60 minutes following oral administration.^c

Duration

4–6 hours following oral administration.^c Following IM administration for nausea and vomiting in pediatric patients, may last up to 12 hours.^b

Distribution

Extent

Widely distributed into most body tissues and fluids.^{c d h i} Crosses blood-brain barrier; brain concentrations exceed those in plasma.^{c h i}

Crosses the placenta.^{c d e i} Distributed into breast milk.^{a b c d e i}

Plasma Protein Binding

92–97% (mainly albumin).^{c i}

Elimination

Metabolism

Metabolic fate not fully elucidated.^{c h} Appears to be extensively metabolized, principally in the liver and kidneys.^{c h}

Elimination Route

Phenothiazines and their metabolites are excreted in urine and feces.^{c d}

Unlikely to be substantially removed by hemodialysis and peritoneal dialysis.^{a b d}

Half-life

Biphasic half-life; half-life of initial phase is 2 hours and hal