chlorpromazine hydrochloride

chlorpromazine hydrochloride

Chlorpromanyl (CA), Largactil (CA) (UK), Novo-Chlorpromazine (CA)

Pharmacologic class: Phenothiazine

Therapeutic class: Antipsychotic, anxiolytic, antiemetic

Pregnancy risk category C

Action

Unknown. May block postsynaptic dopamine receptors in brain and depress areas involved in wakefulness and emesis. Also possesses anticholinergic, antihistaminic, and adrenergic-blocking properties.

Availability

Capsules (sustained-release): 30 mg, 75 mg, 150 mg, 200 mg, 300 mg

Injection: 25 mg/ml

Oral concentrate: 30 mg/ml, 40 mg/ml, 100 mg/ml

Suppositories: 25 mg, 100 mg

Syrup: 10 mg/5 ml, 25 mg/5 ml, 100 mg/5 ml

Tablets: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

⊘Indications and dosages

➣ Acute schizophrenia or mania

Adults: Hospitalized patients - Initially, 25 mg I.M; if necessary, give an additional 25 to 50 mg in 1 hour. Increase dosage gradually, as needed, for several days (up to 400 mg q 4 to 6 hours in exceptionally severe cases) until symptoms are controlled; then give 500 mg P.O. daily. In less acutely disturbed patients, 25 mg P.O. t.i.d., increased gradually until effective dosage is reached (usually 400 mg P.O. daily). Acutely disturbed outpatients - Initially, 10 mg P.O. three or four times daily or 25 mg P.O. two or three times daily. In more severe cases, 25 mg P.O. t.i.d.; after 1 or 2 days, increase daily dosage by 20 to 50 mg at semiweekly intervals until effective dosage is reached.

Children ages 6 months to 12 years: 0.55 mg/kg P.O. (15 mg/m²) q 4 to 6 hours as needed, or 0.55 mg/kg I.M. (15 mg/m²) q 6 to 8 hours (not to exceed 40 mg/day in children ages 6 months to 5 years, or 75 mg/day in children ages 6 to 12), or 1 mg/kg P.R. q 6 to 8 hours p.r.n.

➣ Nausea and vomiting

Adults: 10 to 25 mg P.O. q 4 to 6 hours, increased if necessary; or 25 mg I.M. If no hypertension occurs, give 25 to 50 mg I.M. q 3 to 4 hours as needed until vomiting stops; then switch to oral dosing or one 100-mg suppository q 6 to 8 hours p.r.n.

➣ Nausea and vomiting during surgery

Adults: 12.5 mg I.M., repeated in 30 minutes p.r.n. if no hypotension occurs; or 2 mg I.V. at 2-minute intervals (not to exceed 25 mg)

Children ages 6 months to 12 years: 0.275 mg/kg I.M.; may repeat in 30 minutes as needed

➣ Preoperative sedation

Adults: 25 to 50 mg P.O. 2 to 3 hours before surgery, or 12.5 to 25 mg I.M. 1 to 2 hours before surgery

Children ages 6 months to 12 years: 0.55 mg/kg P.O. (15 mg/m²) 2 to 3 hours before surgery, or 0.55 mg/kg I.M. 1 to 2 hours before surgery

➣ Intractable hiccups

Adults: 25 to 50 mg P.O. three to four times daily. If symptoms continue for 2 to 3 days, give 25 to 50 mg I.M.; if symptoms still persist, give 25 to 50 mg by slow I.V. infusion with patient positioned flat in bed.

➣ Acute intermittent porphyria

Adults: 25 to 50 mg P.O. three to four times daily. Drug is usually discontinued after several weeks, but some patients require maintenance doses. Or 25 mg I.M. t.i.d. until patient can tolerate oral doses.

➣ Tetanus

Adults: 25 to 50 mg P.O. three to four times daily (given with barbiturates, as prescribed). Total dosage and frequency determined by patient response.

Children ages 6 months to 12 years: 0.55 mg/kg I.M. or 0.55 mg/kg I.V. q 6 to 8 hours

Dosage adjustment

• Age over 60

Off-label uses

• Anxiety disorders
• Migraine
• Phencyclidine (PCP) psychosis

Contraindications

• Hypersensitivity to drug, other phenothiazines, sulfites (injection), benzyl alcohol (sustained-release capsules)
• Angle-closure glaucoma
• Bone marrow depression
• Severe hepatic or cardiovascular disease

Precautions

Use cautiously in:
• cardiac disease, diabetes mellitus, respiratory disease, prostatic hypertrophy, CNS tumors, epilepsy, intestinal obstruction
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

☞ Know that I.V. infusion is recommended only for severe hiccups.
• When giving by I.V. infusion for intractable hiccups, dilute in 500 to 1,000 ml of normal saline solution and infuse slowly.
• For direct I.V. injection, dilute to 1 mg/ml using normal saline solution. Administer at a rate of at least 1 mg/minute for adults or 2 mg/minute for children.
• When giving I.M., use Z-track injection method to minimize tissue irritation.
• Don't inject subcutaneously.
• Know that in preoperative use, drug increases risk of neuromuscular excitation and hypotension when followed by barbiturate anesthestics.

Route	Onset	Peak	Duration
P.O.	30-60 min	Unknown	4-6 hr
P.O. (sustained)	30-60 min	Unknown	10-12 hr
I.V.	Rapid	Unknown	Unknown
I.M.	Unknown	Unknown	4-8 hr
P.R.	1-2 hr	Unknown	3-4 hr

Adverse reactions

CNS: sedation, drowsiness, extrapyramidal reactions, tardive dyskinesia, pseudoparkinsonism, neuroleptic malignant syndrome, seizures

CV: tachycardia, hypotension (especially with I.M. or I.V. use)

EENT: blurred vision, dry eyes, lens opacities, nasal congestion

GI: constipation, ileus, anorexia, dry mouth

GU: urinary retention, menstrual irregularities, galactorrhea, gynecomastia, inhibited ejaculation, priapism

Hematologic: eosinophilia, agranulocytosis, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenia

Hepatic: jaundice, hepatitis

Skin: rash, photosensitivity, pigmentation changes, sterile abscess

Other: allergic reactions, hyperthermia, pain at injection site

Interactions

Drug-drug. Activated charcoal, adsorbent antidiarrheals, antacids: decreased chlorpromazine absorption

Antidepressants, antihistamines, general anesthetics, MAO inhibitors, opioids, sedative-hypnotics: additive CNS depression

Antihistamines, disopyramide, quinidine, tricyclic antidepressants (TCAs): increased anticholinergic effects

Antihypertensives: additive hypotension

Barbiturates: increased metabolism and decreased efficacy of chlorpromazine

Bromocriptine: decreased bromocriptine efficacy

Epinephrine: antagonism of peripheral vasoconstriction, epinephrine reversal

Guanethidine: inhibition of antihypertensive effects

Lithium: disorientation, loss of consciousness, extrapyramidal symptoms

Meperidine: excessive sedation and hypotension

Norepinephrine: reduced pressor effect, elimination of bradycardia

Phenytoin: altered phenytoin blood level, lowered seizure threshold

Pimozide: increased risk of potentially serious CV reactions

Propranolol: increased blood levels of both drugs

TCAs: increased TCA blood levels and effects

Valproic acid: decreased elimination and increased effects of valproic acid

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin: increased levels

Granulocytes, hematocrit, hemoglobin, platelets, white blood cells: decreased values

Pregnancy tests: false-positive or false-negative result

Urine bilirubin: false-positive result

Drug-herbs. Angel's trumpet, jimsonweed, scopolia: increased anticholinergic effects

Chamomile, hops, kava, skullcap, valerian: increased CNS depression

St. John's wort: photosensitivity

Yohimbe: increased risk of toxicity

Drug-behaviors. Alcohol use: increased CNS depression

Sun exposure: increased risk of photosensitivity

Patient monitoring

• Monitor blood pressure closely during I.V. infusion.
☞ Stay alert for signs and symptoms of neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis, and arrhythmias). Stop drug immediately if these occur.
• Assess for extrapyramidal symptoms.

Patient teaching

• Tell patient to take capsules or tablets with a full glass of water, with or without food.
• Instruct patient not to crush sustained-release capsules.
• Tell patient to mix oral concentrate in juice, soda, applesauce, or pudding.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.