Does Compazine (prochlorperazine) cause side effects?

Compazine (prochlorperazine) is an antiemetic (to control nausea and vomiting) and first-generation piperazine phenothiazine antipsychotic medication. 

Scientists believe phenothiazine antipsychotics may work by blocking the action of the neurotransmitter dopamine in the brain. Phenothiazine antipsychotics are used when patients do not respond to other antipsychotics. 

The antiemetic benefits of Compazine are due to dopamine blockade in the chemoreceptor trigger zone of the brain. Compazine also has moderate effects on other neurotransmitters and receptors. 

Blockade of certain receptors called alpha-adrenergic receptors causes

  • drowsiness,
  • muscle relaxation, and
  • adverse cardiovascular effects such as

Common side effects of Compazine include

Serious side effects of Compazine include

  • extrapyramidal symptoms (including motor restlessness, sustained or repetitive muscle contractions, pseudo-parkinsonism, and tardive dyskinesia), and
  • heart and liver abnormalities.

Drug interactions of Compazine include acetylcholinesterase inhibitors, which may decrease the effectiveness of Compazine.

  • Combining Compazine with alcohol, kava kava, central nervous system (CNS) depressants, and cannabis may increase the risk of CNS depressant side effects.
  • Antacids may decrease the absorption of Compazine.
  • Combining Compazine with other drugs that cause anticholinergic side effects such as dry mouth, constipation, dry eyes, decreased urinary output, and mental confusion increases the risk of experiencing these effects.
  • Compazine may increase the blood levels of dofetilide.
  • Deferoxamine may increase the risk of experiencing side effects of Compazine and may result in prolonged loss of consciousness.
  • Metoclopramide may increase the side effects of antipsychotic agents.
  • Compazine may increase the CNS depressant effects of orphenadrine or paraldehyde.
  • Combining Compazine and potassium chloride may result in an increase in the ulcerogenic effect of potassium chloride.
  • Combining Compazine with thalidomide may increase the risk of experiencing CNS depressant side effects.

Compazine has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, Compazine should be avoided in pregnancy except in cases of severe nausea and vomiting that requires treatment and where the potential benefit justifies the potential risk to the fetus.

It is unknown if Compazine is excreted into human milk. Other phenothiazines are excreted into breast milk. If clearly needed, Compazine should be used cautiously in females who are breastfeeding.

What are the important side effects of Compazine (prochlorperazine)?

Side effects associated with prochlorperazine treatment include:

The following also have been reported are movement disorders (extrapyramidal symptoms), including:

Additionally, cardiac (heart) and liver abnormalities have occurred in some patients.

Children are prone to develop extrapyramidal reactions more than adults.

Compazine (prochlorperazine) side effects list for healthcare professionals

Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions and hypotension may occur. Cholestatic jaundice has occurred.

If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. There have been a few observations of fatty changes in the livers of patients who have died while receiving the drug. No causal relationship has been established.

Leukopenia and agranulocytosis have occurred. Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate leukocyte depression, stop treatment and start antibiotic and other suitable therapy.

Neuromuscular (Extrapyramidal) Reactions

  • These symptoms are seen in a significant number of hospitalized mental patients. They may be characterized by motor restlessness, be of the dystonic type, or they may resemble parkinsonism.
  • Depending on the severity of symptoms, dosage should be reduced or discontinued.
  • If therapy is reinstituted, it should be at a lower dosage.
  • Should these symptoms occur in children or pregnant patients, the drug should be stopped and not reinstituted.
  • In most cases barbiturates by suitable route of administration will suffice. (Or, injectable diphenhydramine may be useful.)
  • In more severe cases, the administration of an anti-parkinsonism agent, except levodopa, usually produces rapid reversal of symptoms.
  • Suitable supportive measures such as maintaining a clear airway and adequate hydration should be employed.

Motor Restlessness

  • Symptoms may include agitation or jitteriness and sometimes insomnia.
  • These symptoms often disappear spontaneously.
  • At times these symptoms may be similar to the original neurotic or psychotic symptoms.
  • Dosage should not be increased until these side effects have subsided.
  • If these symptoms become too troublesome, they can usually be controlled by a reduction of dosage or change of drug.
  • Treatment with anti-parkinsonian agents, benzodiazepines or propranolol may be helpful.

Dystonia

Class Effect

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment.

Dystonic symptoms include:

  • spasm of the neck muscles,
  • sometimes progressing to tightness of the throat,
  • swallowing difficulty,
  • difficulty breathing,
  • and/or protrusion of the tongue.

While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Pseudo-parkinsonism

Symptoms may include:

  • mask-like facies;
  • drooling;
  • tremors;
  • pillrolling motion;
  • cogwheel rigidity; and
  • shuffling gait.

Reassurance and sedation are important. In most cases these symptoms are readily controlled when an antiparkinsonism agent is administered concomitantly.

Antiparkinsonism agents should be used only when required. Generally, therapy of a few weeks to 2 or 3 months will suffice.

After this time patients should be evaluated to determine their need for continued treatment. (Note: Levodopa has not been found effective in pseudo-parkinsonism.) Occasionally it is necessary to lower the dosage of prochlorperazine or to discontinue the drug.

Tardive Dyskinesia

  • As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued.
  • The syndrome can also develop, although much less frequently, after relatively brief treatment periods at low doses.
  • This syndrome appears in all age groups. Although its prevalence appears to be highest among elderly patients, especially elderly women, it is impossible to rely upon prevalence estimates to predict at the inception of neuroleptic treatment which patients are likely to develop the syndrome.
  • The symptoms are persistent and in some patients appear to be irreversible.
  • The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements).
  • Sometimes these may be accompanied by involuntary movements of extremities.
  • In rare instances, these involuntary movements of the extremities are the only manifestations of tardive dyskinesia.
  • A variant of tardive dyskinesia, tardive dystonia, has also been described.
  • There is no known effective treatment for tardive dyskinesia; anti-parkinsonism agents do not alleviate the symptoms of this syndrome.
  • It is suggested that all antipsychotic agents be discontinued if these symptoms appear.
  • Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked.
  • It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time the syndrome may not develop.

Adverse Reactions Reported With Prochlorperazine Or Other Phenothiazine Derivatives

Adverse reactions with different phenothiazines vary in type, frequency and mechanism of occurrence, i.e., some are dose-related, while others involve individual patient sensitivity.

Some adverse reactions may be more likely to occur, or occur with greater intensity, in patients with special medical problems, e.g., patients with mitral insufficiency or pheochromocytoma have experienced severe hypotension following recommended doses of certain phenothiazines.

Not all of the following adverse reactions have been observed with every phenothiazine derivative, but they have been reported with 1 or more and should be borne in mind when drugs of this class are administered:

  • extrapyramidal symptoms (opisthotonos, oculogyric crisis, hyperreflexia, dystonia, akathisia, dyskinesia, parkinsonism) some of which have lasted months and even years- particularly in elderly patients with previous brain damage;
  • grand mal and petit mal convulsions, particularly in patients with EEG abnormalities or history of such disorders;
  • altered cerebrospinal fluid proteins;
  • cerebral edema;
  • intensification and prolongation of the action of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol), atropine, heat, organophosphorus insecticides;
  • autonomic reactions (dryness of the mouth, nasal congestion, headache, nausea, constipation, obstipation, adynamic ileus, ejaculatory disorders/impotence, priapism, atonic colon, urinary retention, miosis and mydriasis);
  • reactivation of psychotic processes, catatonic-like states;
  • hypotension (sometimes fatal);
  • cardiac arrest;
  • blood dyscrasias (pancytopenia, thrombocytopenic purpura, leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia);
  • liver damage (jaundice, biliary stasis);
  • endocrine disturbances (hyperglycemia, hypoglycemia, glycosuria, lactation, galactorrhea, gynecomastia, menstrual irregularities, false-positive pregnancy tests);
  • skin disorders (photosensitivity, itching, erythema, urticaria, eczema up to exfoliative dermatitis);
  • other allergic reactions (asthma, laryngeal edema, angioneurotic edema, anaphylactoid reactions);
  • peripheral edema; reversed epinephrine effect;
  • hyperpyrexia; mild fever after large I.M. doses; increased appetite;
  • increased weight;
  • a systemic lupus erythematosus-like syndrome;
  • pigmentary retinopathy;
  • with prolonged administration of substantial doses, skin pigmentation, epithelial keratopathy, and lenticular and corneal deposits.

EKG changes-particularly nonspecific, usually reversible Q and T wave distortions - have been observed in some patients receiving phenothiazine tranquilizers.

Although phenothiazines cause neither psychic nor physical dependence, sudden discontinuance in long-term psychiatric patients may cause temporary symptoms, e.g., nausea and vomiting, dizziness, tremulousness.

Note: There have been occasional reports of sudden death in patients receiving phenothiazines. In some cases, the cause appeared to be cardiac arrest or asphyxia due to failure of the cough reflex.

To report suspected adverse reactions, contact Perrigo at 1-800-328-5113, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

What drugs interact with Compazine (prochlorperazine)?

No information provided.

Summary

Compazine (prochlorperazine) is an antiemetic (to control nausea and vomiting) and first-generation piperazine phenothiazine antipsychotic medication. Common side effects of Compazine include drowsiness, dizziness, missed menstrual periods (amenorrhea), blurred vision, skin reactions, and low blood pressure. Compazine has not been adequately evaluated in pregnant women. It is unknown if Compazine is excreted into human milk, but other phenothiazines are excreted into breast milk.

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Medically Reviewed on 7/1/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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