CHLORPROMAZINE

CHLORPROMAZINE (klor-proe'ma-zeen) CHLORPROMAZINE HYDROCHLORIDE Sonazine, Thorazine Classifications: psychotherapeutic; antipsychotic; phenothiazine; antiemetic; Therapeutic: antipsychotic; antiemetic Pregnancy Category: C

Availability

10 mg, 25 mg, 50 mg, 100 mg, 200 mg tablets; 30 mg, 75 mg, 150 mg, 200 mg, 300 mg sustained-release capsules; 10 mg/5 mL syrup; 30 mg/mL, 100 mg/mL oral concentrate; 25 mg/mL injection

Action

Phenothiazine derivative with actions at all levels of CNS with a mechanism that produces strong antipsychotic effects. Exerts quinidine-like antiarrhythmic action. Antiemetic effect due to suppression of the chemoreceptor trigger zone (CTZ). Antipsychotic drugs are sometimes called neuroleptics because they tend to reduce initiative and interest in the environment, decrease displays of emotions or affect, suppress spontaneous movements and complex behavior, as well as decrease psychotic symptoms.

Therapeutic Effect

Mechanism that produces strong antipsychotic effects is unclear, but thought to be related to blockade of postsynaptic dopamine receptors in the brain. Also has antiemetic effects due to its action on the CTZ.

Uses

To control manic phase of manic-depressive illness, for symptomatic management of psychotic disorders, including schizophrenia, in management of severe nausea and vomiting, to control excessive anxiety and agitation before surgery, and for treatment of severe behavior problems in children (e.g., attention deficit disorder). Also used for treatment of acute intermittent porphyria, intractable hiccups, and as adjunct in treatment of tetanus.

Contraindications

Hypersensitivity to phenothiazine derivatives, sulfite, or benzyl alcohol; withdrawal states from alcohol; CNS depression; comatose states, brain damage, bone marrow depression, Reye's syndrome; children <6 mo; pregnancy (category C), lactation.

Cautious Use

Agitated states accompanied by depression, seizure disorders, respiratory impairment due to infection or COPD; glaucoma, diabetes, hypertensive disease, peptic ulcer, prostatic hypertrophy; thyroid, cardiovascular, and hepatic disorders; patients exposed to extreme heat or organophosphate insecticides; previously detected breast cancer.

Route & Dosage

Psychotic Disorders, Agitation Adult: PO 25–100 mg t.i.d. or q.i.d., may need up to 1000 mg/d IM/IV 25–50 mg up to 600 mg q4–6h Child: PO >6 mo, 0.55 mg/kg q4–6h prn up to 500 mg/d IM/IV >6 mo, 0.5–1 mg/kg q6–8h Nausea and Vomiting Adult: PO 10–25 mg q4–6h prn IM/IV 25–50 mg q4–6h prn Child: PO >6 mo, 0.55 mg/kg q4–6h prn up to 500 mg/d IM/IV >6 mo, 0.55 mg/kg q6–8h Dementia Geriatric: PO Initial 10–25 mg 1–2 times/d, may increase q4–7d by 10–25 mg/d (max: 800 mg/d) Intractable Hiccups Adult: PO/IM 25–50 mg t.i.d. or q.i.d. Tetanus Adult: IM/IV 25–50 mg q6–8h Child: IM/IV 0.5mg/kg q6–8h Nausea and Vomiting During Surgery Adult/Adolescent: IV 2 mg q2min prn (max total 25 mg) Child/Infant (>6 mo): IV 1 mg q2min prn (max total 0.25 mg/kg) Intractable Hiccups Adult/Adolescent: IV 25–50 mg in 500–1000 mL NS, not to exceed 1 mg/min

Administration

Oral

• Give with food or a full glass of fluid to minimize GI distress.
• Ensure that oral drug is swallowed and not hoarded. Suicide attempt is a constant possibility in depressed patients, particularly when they are improving.
• Mix chlorpromazine concentrate just before administration in at least ? glass juice, milk, water, coffee, tea, carbonated beverage, or with semisolid food.
• Ensure that sustained-release form of drug is not chewed or crushed. It must be swallowed whole.

Intramuscular/Intravenous

• Avoid parenteral drug contact with skin, eyes, and clothing because of its potential for causing contact dermatitis.
• Keep patient recumbent for at least ? h after parenteral administration. Observe closely. Report hypotensive reactions.

Intramuscular

• Inject IM preparations slowly and deep into upper outer quadrant of buttock. Avoid SC injection; it may cause tissue irritation and nodule formation. If irritation is a problem, consult physician about diluting medication with normal saline or 2% procaine. Rotate injection sites.

Intravenous PREPARE: Direct: Dilute 25 mg with 24 mL of NS to yield 1 mg/mL.  Continuous: May be further diluted in up to 1000 mL of NS.   ADMINISTER: Direct: Administer 1 mg or fraction thereof over 1 min for adults and over 2 min for children.  Continuous: Give slowly at a rate not to exceed 1 mg/min.   INCOMPATIBILITIES Solution/additive: Aminophylline, amphotericin B, ampicillin, chloramphenicol, chlorothiazide, methohexital, penicillin G, pentobarbital, phenobarbital. Y-site: Allopurinol, amifostine, amphotericin B cholesteryl complex, aztreonam, bivalirudin, cefepime, etoposide, fludarabine, furosemide, lansoprazole, linezolid, melphalan, methotrexate, paclitaxel, piperacillin/tazobactam, remifentanil, sargramostim. Lemon yellow color of parenteral preparation does not alter potency; if otherwise colored or markedly discolored, solution should be discarded.

• All forms are stored preferably between 15°–30° C (59°–86° F) protected from light, unless otherwise specified by the manufacturer. Avoid freezing.

Adverse Effects (≥1%)

Body as a Whole: Idiopathic edema, muscle necrosis (following IM), SLE-like syndrome, sudden unexplained death. CV: Orthostatic hypotension, palpitation, tachycardia, ECG changes (usually reversible): prolonged QT and PR intervals, blunting of T waves, ST depression. GI: Dry mouth; constipation, adynamic ileus, cholestatic jaundice, aggravation of peptic ulcer, dyspepsia, increased appetite. Hematologic: Agranulocytosis, thrombocytopenic purpura, pancytopenia (rare). Metabolic: Weight gain, hypoglycemia, hyperglycemia, glycosuria (high doses), enlargement of parotid glands. CNS: Sedation, drowsiness, dizziness, restlessness, neuroleptic malignant syndrome, tardive dyskinesias, tumor, syncope, headache, weakness, insomnia, reduced REM sleep, bizarre dreams, cerebral edema, convulsive seizures, hypothermia, inability to sweat, depressed cough reflex, extrapyramidal symptoms, EEG changes. Respiratory: Laryngospasm. Skin: Fixed-drug eruption, urticaria, reduced perspiration, contact dermatitis, exfoliative dermatitis, photosensitivity, eczema, anaphylactoid reactions, hypersensitivity vasculitis; hirsutism (long-term therapy). Special Senses: Blurred vision, lenticular opacities, mydriasis, photophobia. Urogenital: Anovulation, infertility, pseudopregnancy, menstrual irregularity, gynecomastia, galactorrhea, priapism, inhibition of ejaculation, reduced libido, urinary retention and frequency.

Diagnostic Test Interference

Chlorpromazine (phenothiazines) may increase cephalin flocculation, and possibly other liver function tests; also may increase PBI. False-positive result may occur for amylase, 5-hydroxyindole acetic acid, phenylketonuria, porphobilinogens, urobilinogen (Ehrlich's reagent), and urine bilirubin (Bili-Labstix). False-positive or false-negative pregnancy test results possibly caused by a metabolite of phenothiazines, which discolors urine depending on test used.

Interactions

Drug: Alcohol, cns depressants increase CNS depression; antacids, antidiarrheals decrease absorption—space administration 2 h before or after administration of chlorpromazine; phenobarbital increases metabolism of phenothiazine; general anesthetics increase excitation and hypotension; antagonizes antihypertensive action of guanethidine; phenylpropanolamine poses possibility of sudden death; tricyclic antidepressants intensify hypotensive and anticholinergic effects; anticonvulsants decrease seizure threshold—may need to increase anticonvulsant dose. Herbal: Kava increased risk and severity of dystonic reaction.

Pharmacokinetics

Absorption: Rapid absorption with considerable first pass metabolism in liver; rapid absorption after IM. Onset: 30–60 min. Peak: 2–4 h PO; 15–20 min IM. Duration: 4–6 h. Distribution: Widely distributed; accumulates in brain; crosses placenta. Metabolism: In liver by CYP2D6. Elimination: In urine as metabolites; excreted in breast milk. Half-Life: Biphasic 2 and 30 h.

Nursing Implications

Assessment & Drug Effects

• Establish baseline BP (in standing and recumbent positions), and pulse, before initiating treatment.
• Monitor BP frequently. Hypotensive reactions, dizziness, and sedation are common during early therapy, particularly in patients on high doses and in the older adult receiving parenteral doses. Patients usually develop tolerance to these adverse effects; however, lower doses or longer intervals between doses may be required.
• Lab tests: Periodic CBC with differential, liver function tests, urinalysis, and blood glucose.
• Monitor cardiac status with baseline ECG in patients with preexisting cardiovascular disease.
• Be alert for signs of neuroleptic malignant syndrome (see Appendix G). Report immediately.
• Observe and record smoking since it increases metabolism of phenothiazines, resulting in shortened half-life and more rapid clearance of drug. Higher dosage in smokers may be required. Advise patient to stop or at least reduce smoking, if possible.
• Monitor I&O ratio and pattern: Urinary retention due to mental depression and compromised renal function may occur. If serum creatinine becomes elevated, therapy should be discontinued.
• Monitor for antiemetic effect of chlorpromazine, which may obscure signs of overdosage of other drugs or other causes of nausea and vomiting.
• Be alert to complaints of diminished visual acuity, reduced night vision, photophobia, and a perceived brownish discoloration of objects. Patient may be more comfortable with dark glasses.
• Monitor diabetics or prediabetics on long-term, high-dose therapy for reduced glucose tolerance and loss of diabetes control.
• Ocular examinations, and EEG (in patients >50 y) are recommended before and periodically during prolonged therapy.

Patient & Family Education

• Take medication as prescribed and keep appointments for follow-up evaluation of dosage regimen. Improvement may not be experienced until 7 or 8 wk into therapy.
• Do not alter dosing regimen, and do not give the drug to another person.
• May cause pink to red-brown discoloration of urine.
• Wear protective clothing and sunscreen lotion with SPF above 12 when outdoors, even on dark days. Photosensitivity associated with chlorpromazine therapy is a phototoxic reaction. Severity of response depends on amount of exposure and drug dose. Exposed skin areas have appearance of an exaggerated sunburn. If reaction occurs, report to physician.
• Practice meticulous oral hygiene. Oral candidiasis occurs frequently in patients receiving phenothiazines.
• Report extrapyramidal symptoms that occur most often in patients on high dosage, the pediatric patient with severe dehydration and acute infection, the older adult, and women.
• Avoid driving a car or undertaking activities requiring precision and mental alertness until drug response is known.
• Do not abruptly stop this drug. Abrupt withdrawal of drug or deliberate dose skipping, especially after prolonged therapy with large doses, can cause onset of extrapyramidal symptoms (see Appendix F) and severe GI disturbances. When drug is to be discontinued, dosage must be tapered off gradually over a period of several weeks.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug