The P-I-E-N-O Parkinsn's List Drug Database
prochlorperazine / CompazineTM , StemetilTM
ANTI-VOMITING:
Antiemitic: HIGH RISK
Description: Prochlorperazine, a piperazine phenothiazine, is an oral and parenteral antiemetic and antipsychotic agent. It is most closely related to the high-potency neuroleptics such as perphenazine. Prochlorperazine is mainly used for the management of nausea and vomiting but it shares many of the actions and adverse effects of the antipsychotics. Prochlorperazine was approved by the FDA in 1956.
Mechanism of action: Prochlorperazine blocks postsynaptic dopamine receptors in the mesolimbic system and increases dopamine turnover by blockade of the DA somatodendritic autoreceptor. After ~12 weeks of chronic therapy, depolarization blockade of dopamine tracts occurs. The decrease in dopamine neurotransmission has been found to correlate with the antipsychotic effects. This DA-blockade is also responsible for the strong extrapyramidal effects observed with this drug. Dopamine blockade in the chemoreceptor trigger zone accounts for the antiemetic effects. Prochlorperazine possesses moderate anticholinergic and ›-adrenergic receptor blocking effects. Blockade of ›A-adrenergic receptors produces sedation; muscle relaxation; and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns.
Pharmacokinetics: Prochlorperazine is rapidly absorbed following oral administration, but there is considerable individual variation in peak plasma concentrations because the drug undergoes metabolism in the gastric mucosa and on first pass through the liver. Following IM or PO administration (tablets or syrup), absorption is rapid. Onset of action occurs in about 3060 minutes. Antipsychotic effects are gradual, with considerable individual variation, and peak effects may not occur for 6 weeks to 6 months.
Prochlorperazine is widely distributed into body tissues and fluids, and crosses the blood-brain barrier. The drug is highly plasma protein-bound (91-99%), predominantly to ›A-acid glycoprotein. The drug crosses the placenta and is excreted into breast milk. Metabolism is extensive, but the metabolites have not been shown to have pharmacological activity. Some conjugation with glucuronides occurs, and these along with unconjugated metabolites account for most of the drug found in urine. Metabolites and unchanged drug can be detected for some months after discontinuation of the drug. Some excretion may occur via the biliary tract and feces. The duration of activity is 4-6 hours.
CONTRAINDICATIONS/PRECAUTIONS: All phenothiazines, including prochlorperazine can cause neuromuscular reactions, particularly dystonias. Children with acute illnesses, including varicella-zoster infections, CNS infections, measles, gastroenteritis, or dehydration, may be more susceptible to developing extrapyramidal symptoms, particularly dystonias.
Prochlorperazine is relatively contraindicated in patients with bone marrow depression. Marrow depression is rare with prochlorperazine, but preexisting neutropenia could be worsened by prochlorperazine.
Prochlorperazine can worsen conditions in patients with organic or traumatic brain damage. This is a relative contraindication, and the exact cause of this phenomenon is unknown. Patients with underlying temperature dysregulation can have this condition amplified by prochlorperazine.
In patients with underlying tardive dyskinesia, prochlorperazine can worsen the condition in the long term. An alternative antiemetic or antipsychotic should be considered. Similarly, patients who have experienced extrapyramidal symptoms with dopamine antagonists in the past can do so again with prochlorperazine. Prochlorperazine should be used cautiously in patients with Parkinson's disease.
Prochlorperazine can cause hypotension, so patients with cardiovascular disorders could have exacerbation of their conditions if administered prochlorperazine. Hypotension is most common with parenteral therapy and is usually short-lived when therapy is stopped.
Phenothiazines can lower the seizure threshold and should be used with caution in patients with a seizure disorder. Because of seizure risk, phenothiazines should not be used during intrathecal intravenous radiographic contrast administration. Phenothiazines should be discontinued at least 48 hours before myelography and not resumed until at least 24 hours after the procedure. Prochlorperazine should not be used for the control of nausea and vomiting associated with this procedure.
Because of mild anticholinergic activity, patients with glaucoma, urinary retention, and benign prostatic hypertrophy can experience exacerbation of symptoms when given prochlorperazine.
Prochlorperazine is hepatically metabolized. Hepatic disease could compromise prochlorperazine's metabolism, leading to excessive toxicity. Prochlorperazine can cause cholestatic jaundice and could exacerbate any underlying cholestatic dysfunction.
Prochlorperazine should be used cautiously in patients with pheochromocytoma because the prochlorperazine-induced buildup of neurotransmitters can have a cardiotoxic effect in these patients.
Limited information exists on prochlorperazine's effects during pregnancy or breast-feeding. Prochlorperazine is classifies as pregnancy category C. Caution should be used and this drug given only if the benefits outweigh the possible birth defects or other effects in the infant.
The use of phenothiazines in patients with GI obstruction can mask the symptoms of their condition (i.e., vomiting). Phenothiazines should be used cautiously in these patients.
DRUG INTERACTIONS: Concomitant administration of prochlorperazine and CNS agents (ethanol, opiate agonists, barbiturates, narcotics, tranquilizers, general anesthetics, parenteral magnesium sulfate) can result in additive depressant effects (e.g., oversedation, respiratory depression, and hypotension).
Concomitant administration of prochlorperazine and other anticholinergics, including atropine, monoamine oxidase inhibitors, phenothiazines, antihistamines, antidepressants, meperidine, and antiparkinsonian agents, can cause additive adverse effects such as oversedation, paralytic ileus, and severe constipation.
Animal data have shown that concurrent use of prochlorperazine and metrizamide can increase the risk of developing seizures. Patients should not receive prochlorperazine within 48 hours before or after metrizamide.
If lithium is administered concomitantly with prochlorperazine, an acute encephalopathy can ensue. Many patients have received phenothiazines and lithium without any adverse outcomes, but isolated reports of encephalopathy have been made.
Because prochlorperazine lowers the seizure threshold, anticonvulsants may require dosage adjustment. Concomitant administration of prochlorperazine can inhibit the metabolism of phenytoin, thereby increasing the risk of phenytoin toxicity if these agents are given concomitantly. Phenobarbital enhances renal excretion of prochlorperazine, resulting in pharmacokinetic changes and a decreased therapeutic response to prochlorperazine, so dosages may need to be adjusted.
Prochlorperazine can decrease the effectiveness of bromocriptine on prolactin secretion. Prolactin release requires dopamine antagonism activity, which prochlorperazine provides. Bromocriptine, acting as a dopamine agonist, impairs prolactin release by stimulating the release of prolactin inhibiting factor.
Patients receiving parenteral prochorperazine should be observed for an injection site reaction.
ADVERSE REACTIONS: The adverse effects of phenothiazines can affect all organ systems and may be attributed either to the drug's effects on the central and autonomic nervous system, or to hypersensitivity reactions to the drug.
Extrapyramidal symptoms (EPS) occur frequently during treatment with phenothiazines and appear to be the result of DA-receptor blockade. These symptoms occur with greater severity and frequency during high-dose therapy. Extrapyramidal symptoms are categorized as dystonia, akathisia (subjective and objective motor restlessness), and parkinsonism. Parkinsonian symptoms are more common in the elderly, whereas children most often develop dystonic reactions, which can be worsened by acute infections or severe dehydration. Dystonic reactions are seen during the first week of treatment. Akathisia and parkinsonian symptoms usually develop several days to weeks into therapy. Dystonia and pseudoparkinsonism usually are easily treated with concomitant benztropine, diphenhydramine, lorazepam, or amantadine. Akathisia may respond to dosage reduction or concomitant administration of a benzodiazepine (usually lorazepam) or propranolol. In rare patients, an alternate antipsychotic may be necessary.
Neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS is characterized by hyperthermia, severe extrapyramidal dysfunction, alterations in consciousness, altered mental status, and autonomic instability (sinus tachycardia, low blood pressure or hypertension, diaphoresis). Increased serum creatine phosphokinase (CPK), acute renal failure, and leukocytosis also have occurred. NMS does not appear to be dose-related. Severe cases have resulted in death 330 days after the onset of the syndrome. Several predisposing factors may contribute to the development of NMS including heat stress, physical exhaustion, dehydration, and organic brain disease. NMS occurs more frequently in young men. The phenothiazine should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered. Hypothermia and hyperthermia have been reported with phenothiazines independent of the neuroleptic malignant syndrome and may be caused by the effect of the phenothiazine on the hypothalamic control of temperature regulation. Hyperpyrexia and heat stroke unrelated to NMS also have occurred.
Tardive dyskinesia (TD) is characterized by involuntary movements of the perioral region (tongue, mouth, jaw, eyelids, or face) or choreoathetoid movements in the extremities. It can develop during long-term therapy or following discontinuation of phenothiazine therapy, and it is observed more frequently in elderly women. The incidence of TD may be higher in patients with bipolar disorder than with schizophrenia. Some cases can be irreversible. While contradictory evidence exists, it has been suggested that the likelihood of developing TD increases with prolonged treatment and cumulative doses. Although this complication often occurs following prolonged treatment or with administration of high dosages, it also has been reported to occur after short periods of time and with low dosages. Routine monitoring (at 3to 6-month intervals) of movement disorders is considered the standard practice when using phenothiazines. If signs or symptoms of TD develop, the neuroleptic should be reevaluated and possibly discontinued.
Phenothiazines can cause a variety of CNS effects. Drowsiness occurs occasionally during initial treatment with some phenothiazines. Tolerance usually develops with continued therapy. Dizziness may occur as a result of orthostatic hypotension. Other CNS effects reported less frequently include restlessness, insomnia, depression, headache, and cerebral edema. Seizures can occur and are of special significance in patients with preexisting seizure disorders or EEG abnormalities.
Anticholinergic effects of phenothiazines include blurred vision, xerostomia, mydriasis, nausea, adynamic ileus, urinary retention, impotence, and constipation. These effects can be enhanced by the concomitant administration of anticholinergic antiparkinsonian drugs, antidepressants, or other anticholinergic agents.
Leukopenia including agranulocytosis is the most common hematologic disturbance that has been reported during phenothiazine administration. Agranulocytosis has occurred rarely and has been associated with combination treatment with other agents. Other hematologic abnormalities that have been associated with phenothiazine therapy include leukocytosis (usually in association with the neuroleptic malignant syndrome), eosinophilia, thrombocytopenia, pancytopenia, aplastic anemia, and anemia.
Prolonged therapy with phenothiazines can lead to skin hyperpigmentation. Hyperpigmentation generally is restricted to areas of the body exposed to sunlight. Photosensitivity can result, and patients should be warned either to keep out of the sun or to use effective sunscreens (SPF 15+) on exposed areas of the body. Withdrawal of the drug can reverse the effects. Contact dermatitis is also possible in predisposed individuals if they come in contact with liquid dosage forms of phenothiazines.
Phenothiazines can cause ocular changes. Pigmentary retinopathy can occur with or without pigmentary changes in the skin during therapy with phenothiazines. Symptoms of blurred vision, difficulty with nighttime vision, or defective color vision should be investigated promptly. Wearing protective dark glasses can reduce the possibility of this reaction. Phenothiazines have been associated with deposition of fine particles in the lens and cornea, which can lead to corneal opacification and visual impairment.
Liver impairment in the form of cholestasis has been reported rarely with administration of phenothiazines. Jaundice is also possible and may even occur in neonates of mothers who received phenothiazines during pregnancy. Cholestatic jaundice from phenothiazines is generally considered a hypersensitivity reaction.
Adverse cardiovascular reactions that have occurred during antipsychotic therapy include hypotension, hypertension, ventricular tachycardia, ECG changes such as QT prolongation, and other cardiac arrhythmias such as torsade de pointes. Cardiac arrhythmias such as torsade de pointes secondary to antipsychotic therapy have mainly been associated with thioridazineI and haloperidol.
Dopamine blockade can lead to hyperprolactinemia. As a result, neuroleptics can cause galactorrhea. Other endocrine changes that can occur during therapy with neuroleptics include amenorrhea or other menstrual irregularity, breast enlargement or mastalgia, libido decrease, impotence, ejaculation dysfunction (no ejaculation), and priapism. Weight gain may also occur during therapy with phenothiazines.
Phenothiazines do not cause physical or psychological dependence. However, sudden withdrawal of prochlorperazine can produce nausea/vomiting, dizziness and trembling. These effects are only temporary, and can be reduced by a gradual reduction in dosage, or continuation of concomitant antiparkinsonian agents.
PATIENT INFORMATION:
What do prochlorperazine tablets do?
Prochlorperazine (CompazineTM ) helps to control nausea and vomiting that can occur after surgery, or with the treatment of cancer (chemotherapy). Prochlorperazine also treats psychological or mental disorders. Another use of prochlorperazine is the treatment of non-psychotic anxiety (nervousness). Generic prochlorperazine tablets are available.
What should my doctor, dentist, or pharmacist know before I take prochlorperazine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take prochlorperazine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children under 2 years old, or less than 20 lb in weight.
Elderly patients over age 65 years may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with prochlorperazine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking prochlorperazine?
Serious side effects with prochlorperazine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with prochlorperazine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take prochlorperazine?
Visit your doctor for regular checks on your progress. Do not stop taking prochlorperazine suddenly; this can cause nausea, vomiting, and dizziness. Ask your doctor for advice if you are to stop taking this medicine.
You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how prochlorperazine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can increase possible dizziness or drowsiness. Avoid alcoholic drinks.
Prochlorperazine can reduce the response of your body to heat or cold. Try not to get overheated. Avoid temperature extremes, such as saunas, hot tubs, or very hot or cold baths or showers. Dress warmly in cold weather.
Prochlorperazine can make your skin more sensitive to sun or ultraviolet light. Keep out of the sun, or wear protective clothing outdoors and use a sunscreen (at least SPF 15). Do not use sun lamps or sun tanning beds or booths. Wear sunglasses to protect your eyes.
Your mouth may get dry, chewing sugarless gum or sucking hard candy and drinking plenty of water will help.
Do not treat yourself for coughs, colds, sore throat, or allergies. Ask your doctor or pharmacist for advice.
If you are going to have surgery, tell your doctor or dentist that you are taking prochlorperazine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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